Endocrine
Abstracts
May 2017 Volume 49
ISSN 1479-6848 (online)
19th European Congress of
Endocrinology 2017
20 -23 May 2017, Lisbon, Portugal
published by
Online version available at
bioscientifica
Volume 49
Endocrine Abstracts
May 2017
19th European Congress of
Endocrinology 2017
20 - 23 May 2017
EDITORS
The abstracts were marked by the Abstract marking Panel selected by the Programme Organising Committee
Programme Organising Committee
Bulent Yildiz (Turkey) Chair
Evi Diamanti-Kandarakis (Greece)
Djuro Macut (Serbia)
Guillaume Assié (France) Co-chair
Andrea Giustina (Italy)
Rod Mitchell (UK)
Riccarda Granata (Italy) Co-chair
Ilpo Huhtaniemi (Finland/UK)
Barbara Obermayer-Pietsch (Austria)
Joa˜o Jácome de Castro (Portugal)
Irena Ilovayskaya (Russia)
Pedro Oliveira (Portugal)
Carlo Acerini (UK)
Tatjana isailovic (Serbia)
Robin Peeters (The Netherlands)
Richard Bergman (USA)
Gregory Kaltsas (Greece)
Duarte Pignatelli (Portugal)
Charlotte Bevan (UK)
Beata Kos-Kudla (Poland)
Matti Poutanen (Finland)
Heike Biebermann (Germany)
Cesar Luiz Boguszewski (Brazil)
Manuel Puig (Spain)
Local Organising Committee (LOC)
Joa˜o de Castro (Lisbon, Portugal) (Chair)
José Silva Nunes (Lisbon, Portugal)
Maria Joa˜o Oliveira (Porto, Portugal)
Duarte Pignatelli (Porto, Portugal)
Leonor Gomes (Coimbra, Portugal)
Mário Mascarenha (Lisbon, Portugal)
Jorge Dores (Porto, Portugal)
Mafalda Marcelino (Lisbon, Portugal)
Miguel Melo (Coimbra, Portugal)
Abstract Marking Panel
T Battelino Slovenia
C Dayan UK
F Kelestimur Turkey
G Raverot France
K Chatterjee UK
W de Herder Netherlands
R Kineman USA
M Reincke Germany
D Cuthbertson UK
W Dhillo UK
M Korbonits UK
S Rice UK
E de Koning The Netherlands
G Di Dalmazi Germany
B Kos-Kudla Poland
M Robledo Spain
M Dentice Italy
E Diamanti-Kandarakis Greece
N Krone UK
P Rodien France
D Fuhrer Germany
F Dotta Italy
H Krude Germany
H Romijn The Netherlands
R Gartner Germany
J Drouin Canada
M Laan Germany
C Ronchi Italy
J Jacome de Castro Portugal
L Duntas Greece
E Lalli France
R Ross UK
C Jazdzewski Poland
G Eisenhofer Germany
J Laven The Netherlands
G P Rossi Italy
C Kanaka-Gantenbein Greece
F Fallo Italy
G Lavery UK
M Ruchala Poland
S Pearce UK
P Farahani Canada
J Leger France
E Rutten Belgium
G Roman Romania
S Farooqi UK
T Links The Netherlands
D Salvatore Italy
E Stener-Victorin Sweden
M Fassnacht Germany
P Lips Netherlands
S Sanlioglu Turkey
E Visser The Netherlands
R Feelders The Netherlands
S Llahana UK
P Saunders UK
M-C Zennaro Spain
U Feldt-Rasmussen Denmark
A Luger Austria
S Schmid Germany
C Acerini UK
E Fliers The Netherlands
C Luiz Boguszewski Brazil
J Schopohl Germany
M Alevizaki Greece
C Flueck Switzerland
R M Luque Spain
D Schulte Germany
W Arlt UK
C Follin Sweden
M Luster Germany
M Sherlock Ireland
G Assié France
S Franks UK
D Macut Serbia
M Simoni Italy
S Aylwin UK
W Fraser UK
M Maggi Italy
J Smit The Netherlands
S Babajko France
J Frystyk Denmark
J Magre France
A Spada Italy
K Badenhoop Germany
L Fugazzolla Italy
M Mannelli Italy
G Stalla Germany
P Beck-Peccoz Italy
F Gabalec Czech Republic
F Mantero Italy
C Stratakis USA
R Bergman USA
A Gimenez-Roqueplo France
D Marks USA
T Tankova Bulgaria
J Bertherat France
F Giorgino Italy
G Mastorakos Greece
M Tena-Sempere Spain
F Beuschlein Germany
A Giustina Italy
C McCabe UK
M Terzolo Italy
C Bevan UK
J Gomez-Ambrosi Spain
R Mitchell UK
M Theodoropoulou Germany
H Biebermann Germany
R Granata Italy
J Mittag Germany
C Thompson Ireland
M Bluher Germany
A Grossman UK
L Morin-Papunen Finland
H Timmers The Netherlands
K Boelaert UK
R Hampl Czech Republic
N Morton UK
J Toppari Finland
A Boelen The Netherlands
M Heikinheimo Finland
A Mukherjee UK
M Toth Hungary
R Bouillon Belgium
C Hoefig Sweden
E Nagy Hungary
S Tsagarakis Greece
J-P Bourguignon Belgium
A Hoeflich Germany
J Newell-Price UK
M Tzanela Greece
G Brabant Germany
W Hoegler UK
B Obermayer-Pietsch Austria
E Valassi Spain
M L Brandi Italy
L Hofland Netherlands
P Oliveira Portugal
E van den Akker Netherlands
K Briot France
I Huhtaniemi UK
U Pagotto Italy
A van der Klaauw UK
G Brunetti Italy
E Husebye Norway
J J Palvimo Finland
A J van der Lelij Netherlands
C Buchanan UK
P Igaz Hungary
R Peeters The Netherlands
J van Eck The Netherlands
P Burman Sweden
I Ilovayskaya Russia
L Persani Italy
W van Hul Belgium
S Cannavo Italy
S Inzucchi USA
T Pieber Austria
J Visser The Netherlands
J Cap Czech Republic
T Isailovic Serbia
V Pirags Latvia
V Volke Estonia
G Carmeliet Belgium
E R Isenovic Serbia
N Pitteloud Switzerland
R Voutilainen Finland
J Castano Spain
M Jaffrain-Rea Italy
M Poutanen Finland
I Wilkinson UK
P Chanson France
B Jarzab Poland
D Power Portugal
Z Wu Germany
F Chiarelli Italy
D Jezova Slovakia
V Prevot France
P Yeoh UK
B Chini Italy
A Kalsbeek Netherlands
S Radian UK
B Yildiz Turkey
J Chowen Spain
G Kaltsas Greece
N Rahman Finland
J Young France
C Daousi UK
A Karlsson Sweden
B Rainey USA
M Zatelli Italy
M Dattani UK
M Keil USA
E Rajpert-De Meyts Denmark
19th European Congress of Endocrinology 2017
SPONSORS
The ESE would like to thank its Corporate Members and the ECE 2017 sponsors
ECE Corporate Members
Aegerion
Chiasma
Ipsen
Laboratoire HRA Pharma
Novartis Pharmaceuticals
Novo Nordisk
Pfizer
Sandoz International Gmbh
Shire Services BVBA
Strongbridge Biopharma
Gold Sponsors
Ipsen
Novartis Pharmaceuticals
Pfizer
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Contact:
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Euro House
Tel:
+44 (0)1454 642247
22 Apex Court
Fax:
+44 (0)1454 642222
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E-mail:
info@euro-endo.org
Bradley Stoke
Web site:
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Contact:
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+44 (0)1454 640467
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Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
CONTENTS
19th European Congress of Endocrinology 2017
PRIZE LECTURES AND BIOGRAPHICAL NOTES
The European Journal of Endocrinology Prize Lecture
EJE1
The Geoffrey Harris Prize Lecture
GH1
European Hormone Medal Lecture
EHM1
Clinical Endocrinology Trust Lecture
CET1
IPSEN1
PLENARY LECTURES
The fantastical world of hormones
P1
The secret life of FGF21
. . . . . P2
Update on regulation of steroidogenesis by aberrant hormone receptors
P3
The role of brain insulin resistance for the development of prediabetic phenotypes
P4
Browning of adipose tissue and metabolic regulation
P5
Thyroid oncology in the crossroads of precision and narrative medicine
P6
SYMPOSIA
Clinical Updates in Hypoparathyroidism
S1.1 - S1.3
Evolving diagnostics in adrenal and neuroendocrine tumours
S2.1 - S2.3
From the pituitary to the periphery
S3.1 - S3.3
2nd Joint Global Symposium on Obesity - The Many Dimensions of the Childhood Obesity Problem
S4.1 - S4.3
Turn your face to the sunshine
S5.1 - S5.3
Treatment of hypothyroidism: what have we learned?
S6.1 - S6.3
Crosstalk between bone & other organ(ism)s
S7.1 - S7.3
Predictors of therapeutic response in functioning pituitary tumours
S8.1 - S8.3
Novel type 2 diabetes treatment: Beyond glycaemic control
S9.1 - S9.3
The Challenges of Male Fertility
S10.1 - S10.3
New Roles for Nuclear Receptors
S11.1 - S11.3
New development in Graves’ Orbitopathy
S12.1 - S12.3
Challenging pituitary diseases
S13.1 - S13.3
Searching for the cause and approach in ectopic hormone syndromes
S14.1 - S14.3
Metabolic surgery mechanisms to clinical results (Endorsed by the European Journal of Endocrinology)
S15.1 - S15.3
Late-breaking: the PCSK9 revolution
S16.1 - S16.3
What endocrinologists should know about the genomics of endocrine tumors
S17.1 - S17.3
Hyperandrogenism: challenges in clinical management
S18.1 - S18.3
How to incorporate the new guidelines for thyroid cancer in my clinical practice
S19.1 - S19.3
Beta cell replacement and plasticity (Endorsed by Endocrine Connections)
S20.1 - S20.3
Environmental influences on endocrine systems
S21.1 - S21.3
Rare bone diseases (Endorsed by the European Journal of Endocrinology)
S22.1 - S22.3
Endo Oncology: prolactin, GH and metabolic hormones in oncology pathogenesis
(Endorsed by Endocrine Connections)
S23.1 - S23.3
Obesity: Pharmacological solutions
S24.1 - S24.3
HPA axis regulation during a woman’s life: impact on metabolic outcomes
S25.1 - S25.3
Tissue specific defects in thyroid hormone action
S26.1 - S26.3
Vitamin D beyond bone (Endorsed by Endocrine Connections)
S27.1 - S27.3
Sleep, love and reproduction (Endorsed by Endocrine Connections)
S28.1 - S28.3
Novel predictors of diabetes
S29.1 - S29.3
Moving away from old-fashioned steroidogenesis: what are the clinical implications?
S30.1 - S30.3
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Guided session 1
. . GS1.1-GS1.6
Guided session 2
. . GS2.1-GS2.6
NEW SCIENTIFIC APPROACHES
NSA1 - NSA6
DEBATES
Is there a role for medical therapy for non-functioning pituitary adenomas?
. . . D1.1-D1.2
Incidentally discovered nonfunctioning pancreatic NETs: Surgery or not?
(Endorsed by the European Journal of Endocrinology)
D2.1 - D2.2
Drug holiday in osteoporosis (Endorsed by the European Journal of Endocrinology)
D3.1 - D3.2
Is cardiovascular risk increased in women with PCOS?
D4.1 - D4.2
Should we still ablate all patients undergoing total thyroidectomy for thyroid cancer?
. . . D5.1-D5.2
Is it time for initial combination in type 2 diabetes?
. . . D6.1-D6.2
MEET THE EXPERT SESSIONS
. MTE1 - MTE16
MTNE1 - MTNE2
MTBS1 - MTBS3
NURSE SESSIONS
. . . N1.1-N1.4
. . . N2.1-N2.4
. . . N3.1-N3.3
ORAL COMMUNICATIONS
Adrenal - Basic & Clinical
OC1.1 - OC1.5
Diabetes Prediction and Complications
. . OC2.1-OC2.5
Receptors & Signalling
OC3.1 - OC3.5
Thyroid Disease 1
OC4.1 - OC4.5
Cardiovascular Endocrinology
OC5.1 - OC5.5
Diabetes therapy and complications . .
. . OC6.1-OC6.5
Cardiovascular endocrinology
OC7.1 OC7.5
Neuroendocrinology
OC8.1 - OC8.5
Thyroid Disease 2
OC9.1 - OC9.5
Bone & Calcium Homeostasis
OC10.1 - OC10.5
Obesity
OC11.1 - OC11.5
Pituitary Clinical
OC12.1 - OC12.5
Reproduction & Endocrine Disruption .
OC13.1 - OC13.5
Thyroid Cancer
OC14.1 - OC14.5
Guided Posters
Adrenal 1
GP1 - GP10
Adrenal 2
GP11 - GP20
Adrenal 3
GP21 - GP32
Bone & Calcium Homeostasis 1
. . GP33-GP42
Bone & Calcium Homeostasis 2
. . GP43-GP51
Cardiovascular & Lipid Endocrinology
. . GP52-GP61
Developmental & Protein Endocrinology
. . GP62-GP70
Diabetes & complications 1
. . GP71-GP82
Diabetes & complications 2
. . GP83-GP92
Diabetes therapy & complications 1
GP93 - GP102
Diabetes therapy & complications 2
GP103 - GP112
Endocrine Nursing
GP113 - GP117
Endocrine Tumours
GP118 - GP130
Female Reproduction
GP131 - GP142
Male Reproduction and Endocrine Disruptors
. GP143 - GP150
Neuroendocrinology & Growth Hormones . .
GP151 - GP160
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Obesity
GP161 - GP172
Pituitary
GP173 - GP184
Pituitary & endocrine Tumours
GP185 - GP196
Thyroid 1
GP197 - GP205
Thyroid 2
GP206 - GP216
Thyroid 3
GP217 - GP224
Thyroid Cancer
GP225 - GP235
Thyroid Cancer & Thyroid Case Reports
GP236 - GP245
EPOSTER PRESENTATIONS: ADRENAL AND NEUROENDOCRINE TUMOURS
Adrenal cortex (to include Cushing’s)
EP1 - EP86
Adrenal medulla
EP87 - EP107
Cardiovascular Endocrinology and Lipid Metabolism
EP108
Clinical case reports - Pituitary/Adrenal
EP109 - EP140
Clinical case reports - Thyroid/Others
EP141 - EP145
Endocrine tumours and neoplasia
EP146 - EP195
Neuroendocrinology
EP196 - EP204
Paediatric endocrinology
EP205 - EP206
Pituitary - Clinical
EP207
Steroid metabolism + action
EP208
Thyroid cancer
EP209
EPOSTER PRESENTATIONS: CALCIUM AND BONE
Bone & Osteoporosis
EP210 - EP246
Calcium & Vitamin D metabolism
EP247 - EP311
Cardiovascular Endocrinology and Lipid Metabolism
EP312 - EP313
Clinical case reports - Pituitary/Adrenal
EP314
Clinical case reports - Thyroid/Others
EP315 - EP342
Developmental endocrinology
EP343
Endocrine tumours and neoplasia
EP344 - EP350
Endocrine tumours and neoplasia
EP351
Paediatric endocrinology
EP352
Steroid metabolism + action
EP353
EPOSTER PRESENTATIONS: DIABETES, OBESITY AND METABOLISM
Calcium & Vitamin D metabolism
EP354
Cardiovascular Endocrinology and Lipid Metabolism
EP355 - EP383
Clinical case reports - Pituitary/Adrenal
EP384
Clinical case reports - Thyroid/Others
EP385 - EP400
Developmental endocrinology
EP401 - EP402
Diabetes (to include epidemiology, pathophysiology)
EP403 - EP497
Diabetes complications
EP498 - EP578
Diabetes therapy
EP579 - EP630
Endocrine Disruptors
EP631 - EP632
Endocrine tumours and neoplasia
EP633 - EP634
Female Reproduction
EP635 - EP637
Growth hormone IGF axis - basic
EP638 - EP640
Neuroendocrinology
EP641
Nuclear receptors and Signal transduction
EP642
Obesity
EP643 - EP723
Paediatric endocrinology
EP724 - EP726
Steroid metabolism + action
EP727 - EP730
EPOSTER PRESENTATIONS: ENVIRONMENT, SOCIETY AND GOVERNANCE
Cardiovascular Endocrinology and Lipid Metabolism
EP731
Clinical case reports - Thyroid/Others
EP732
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Developmental endocrinology
EP733 - EP734
Diabetes (to include epidemiology, pathophysiology)
EP735
Diabetes complications
EP736 - EP737
Endocrine Disruptors
EP738 - EP745
Endocrine tumours and neoplasia
EP746
Female Reproduction
EP747
Pituitary - Clinical
EP748
Thyroid (non-cancer)
EP749
EPOSTER PRESENTATIONS: INTERDISCIPLINARY ENDOCRINOLOGY
Adrenal cortex (to include Cushing’s)
EP750
Calcium & Vitamin D metabolism
EP751 - EP752
Cardiovascular Endocrinology and Lipid Metabolism
EP753 - EP761
Clinical case reports - Thyroid/Others
EP762 - EP774
Developmental endocrinology
EP775
Diabetes (to include epidemiology, pathophysiology)
EP776 - EP777
Diabetes complications
EP778
Endocrine Disruptors
EP779 - EP783
Endocrine tumours and neoplasia
EP784 - EP792
Female Reproduction
EP793 - EP795
Growth hormone IGF axis - basic
EP796
Male Reproduction
EP797
Neuroendocrinology
EP798 - EP800
Nuclear receptors and Signal transduction
EP801 - EP807
Obesity
EP808 - EP810
Paediatric endocrinology
EP811 - EP818
Pituitary - Basic
EP819
Steroid metabolism + action
EP820 - EP824
Thyroid (non-cancer)
EP825 - EP829
EPOSTER PRESENTATIONS: PITUITARY AND NEUROENDOCRINOLOGY
Adrenal cortex (to include Cushing’s)
EP830 - EP831
Clinical case reports - Pituitary/Adrenal
EP832 - EP872
Developmental endocrinology
EP873
Endocrine tumours and neoplasia
EP874 - EP877
Growth hormone IGF axis - basic
EP878 - EP887
Male Reproduction
EP888
Neuroendocrinology
EP889 - EP921
Paediatric endocrinology
EP922 - EP923
Pituitary - Basic
EP924 - EP936
Pituitary - Clinical
EP937 - EP1081
Steroid metabolism + action
EP1082
EPOSTER PRESENTATIONS: REPRODUCTIVE ENDOCRINOLOGY
Bone & Osteoporosis
EP1083
Cardiovascular Endocrinology and Lipid Metabolism
EP1084
Clinical case reports - Pituitary/Adrenal
EP1085 - EP1089
Clinical case reports - Thyroid/Others
EP1090 - EP1091
Developmental endocrinology
EP1092
Endocrine tumours and neoplasia
EP1093 - EP1094
Female Reproduction
EP1095 - EP1156
Male Reproduction
EP1157 - EP1182
Neuroendocrinology
EP1183 - EP1184
Obesity
EP1185 - EP1187
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Paediatric endocrinology
EP1188
Steroid metabolism + action
EP1189 - EP1191
EPOSTER PRESENTATIONS: THYROID
Clinical case reports - Thyroid/Others
EP1192 - EP1221
Nuclear receptors and Signal transduction
EP1222
Paediatric endocrinology
EP1223 - EP1227
Thyroid (non-cancer)
EP1228 - EP1487
INDEX OF AUTHORS
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Prize Lectures and
Biographical Notes
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
European Journal of Endocrinology Prize Winner
The European Journal of Endocrinology Prize is awarded to a candidate who has contributed
significantly to the advancement of knowledge in the field of endocrinology through publication. This
year’s recipient is Dr Miguel Lopez who will receive his prize and deliver his lecture as part of the ECE
2017 Opening Ceremony on Saturday 20 May 2017. Further information on the prize can be found at
Dr. Miguel López received his PhD in Molecular Biology (2002) from the
University of Santiago de Compostela (USC, Spain) and made his postdoctoral
training (2002-2006) in the Department of Clinical Biochemistry in the University
of Cambridge (UK). Currently, Dr. Miguel López is Associate Professor in
Department of Physiology at the School of Medicine and the Research Centre of
Molecular Medicine and Chronic Diseases (CIMUS) of USC. Since the beginning
of his PhD, he has focussed his research on the regulation of energy balance and
obesity, with his current interest on hypothalamic energy sensors in the modulation
of energy balance and metabolism. He has published around 150 peer-reviewed
papers. He currently serves on the editorial board of Endocronology, Journal of
Molecular Endocrinology, Molecular Metabolism, Journal of Endocrinology, several Frontiers journals
and PLoS ONE, and as a reviewer for several international biomedical journals and funding agencies.
For his work in this area, Dr. López received the awards for Basic Research in Obesity from Spanish
Endocrinology and Nutrition Society (SEEN, 2006 and 2009) and the Spanish Society for the Study of
Obesity (SEEDO, 2009), Spanish Award on Neuroendocrinology (2012), as well as the European
Association for the Study of Obesity (EASO) Young Investigator Award for Basic Science (2008; first
Spanish citizen to be awarded with that price) and the European Journal of Endocrinology Prize for the
European Society of Endocrinology (2017). He has been PI of 12 national and international grants,
among them an ERC Starting Grant. He teaches Endocrinology in the Schools of Medicine and
Pharmacy of USC. He has supervised 14 Master Thesis and 10 PhD Thesis.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
The European Journal of Endocrinology Prize Lecture
adipose tissue
(WAT), as well as muscle metabolism, hepatic function and
glucose homeostasis. The relevance of these data is interesting from a therapeutic
EJE1
point of view since several agents with potential anti-obesity and/or antidiabetic
Hypothalmic AMPK: a golden target against obesity?
effects, some currently in clinical use, such as nicotine, metformin and liraglutide
Miguel López
are known to act through AMPK, either peripherally or centrally. Furthermore,
Spain.
the orexigenic and weight-gaining effects of the worldwide use of antipsychotic
drugs, such as olanzapine, are also mediated by hypothalamic AMPK. Overall,
this evidence makes hypothalamic AMPK signaling an interesting target for drug
AMP-activated protein kinase (AMPK) is a cellular gauge that is activated under
development, with its potential for controlling both sides of the energy balance
conditions of low energy, increasing energy production and reducing energy
equation, namely feeding and energy expenditure via defined metabolic
waste. Centrally, the AMPK pathway is a canonical route regulating energy
pathways.
homeostasis, by integrating peripheral signals, such as hormones and metabolites,
with neuronal networks. Current evidence links hypothalamic AMPK with
DOI: 10.1530/endoabs.49.EJE1
feeding, brown adipose tissue (BAT) thermogenesis and browning of white
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Geoffrey Harris Prize Winner
The prestigious Geoffrey Harris Prize is awarded to an established researcher in the field of
neuroendocrinology and is the first of its kind in Europe. This years recipient is Professor Matthias
Tschop who will receive his prize and deliver his lecture as part of the ECE 2017 Opening Ceremony on
prizes/.
Professor Matthias H. Tschop received his M.D. from Ludwig-Maximilians
Universität in Munich, where he also trained as a physician in internal medicine.
In 1998 he accepted an invitation for a postdoctoral fellowship at the Eli Lilly
Research Laboratories in Indianapolis, USA before returning to Europe in 2002 to
establish his independent research laboratory at the German Institute of Human
Nutrition (DIfE) Potsdam. He later returned to the United States where he
joined the University of Cincinnati to ultimately serve as the Director of the
Diabetes and Obesity Center of Excellence and Arthur Russell Morgan Endowed
Chair of Medicine. In 2011 Prof. Tschop accepted the position as Scientific
Director of the Helmholtz Diabetes Center at Helmholtz Center Munchen and was
named Chair of the Division of Metabolic Diseases at Technische Universität
Munchen. Prof. Tschop is the first German physician to receive the prestigious Alexander-von-
Humboldt Professorship (2012). He was elected into the German National Academy of Science
(Leopoldina) in 2013 and one year later was named adjunct Professor at Yale University, USA.
He started the peer-reviewed open access journal Molecular Metabolism, which he leads as the
Editor-in-Chief (first impact factor 2016: 5.4). In 2016 Matthias Tschop received an honorary doctorate
of the University of Leipzig and was named Director for Biomedicine of the Helmholtz Pioneer Campus
in Munich, which he co-founded.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
The Geoffrey Harris Prize Lecture
a few compound mixtures has set the precedent for combinatorial treatment of
obesity. On the other hand, double or triple therapeutic combinations are more
GH1
difficult to advance to regulatory approval. Following an improved understanding
Toward hormone-based precision medicines for metabolic diseases
of the molecular basis for metabolic benefits following bariatric surgery
Matthias Tschop
interventions, several classes of novel unimolecular or independent combination
Germany.
therapeutics were discovered. These new classes of drug candidates are based on
gastrointestinal hormones, offer efficacy superior to currently prescribed options
and seem to have potential to fully reverse human obesity and type 2 diabetes.
After decades of research unraveling complex metabolic control networks,
Moreover, gut peptide-based cell-specific targeted delivery of small molecules
medicines capable of a safe reversal of morbid human obesity and type 2 diabetes
offer additional potential for novel metabolic precision medicines and reduced
are still not available. Historically, complex diseases have repeatedly proven to be
systemic side effects. In this presentation the discovery, pre-clinical validation
defiant to the best mono-therapeutic approaches. Several examples of
and first clinical test of peptide hormone poly-agonist drug candidates as well as
combination therapies have largely overcome such challenges, notably for the
of combinatorial single molecule therapeutic candidates will be summarized,
treatment of severe hypertension and tuberculosis. Obesity and its consequences,
including previously unpublished observations.
such as type 2 diabetes, have proven to be equally resistant to therapeutic
approaches based on single medicines. Appropriate management of type 2
DOI: 10.1530/endoabs.49.GH1
diabetes often requires adjunctive medications, and the recent registration of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
European Hormone Medal Lecture
The European Hormone Medal is awarded to an international scientist who has made significant
contributions to the field of basic or clinical endocrinology. This year’s recipient is Professor Evi
Diamanti-Kandarakis who will receive her prize and give her lecture as part of the European Congress
of Endocrinology (ECE), beginning on the 20th May. Further information on the prize can be found at
Dr. Evanthia Diamanti-Kandarakis is professor of Internal Medicine-
Endocrinology & Metabolism and Chairman of the Endocrine Department of
Euroclinic Athens. She received her MD from Medical School of Athens and
her PhD in experimental Endocrinology on the effects of androgens in
hypophysectomised rats, from the same University. She was trained in
Internal Medicine in England (1974-1980), and in Endocrinology-Diabetes,
Metabolism & Obesity in USA (1980-1986). Her research interests have
focused for the last 25 years on clinical, molecular and environmental aspects
of metabolic & hormonal abnormalities in obesity Diabetes and Polycystic
ovarian syndrome. This work has generated 181 publications and more than
12000 citations, classifying her among the 27 worldwide best Greek scientists
and the first Greek woman endocrinologist with the greatest international
contribution. In 2016 she has received the award of the best teacher in endocrinology in Greece.
Dr. Diamanti-Kandarakis has been invited by the international academic community as a speaker and
Tutor and has given more than 250 lectures, in Europe, Asia, Africa, North & South America.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
European Hormone Medal Lecture
disrupting chemicals
(EDCs) such as plasticizers, bisphenol A
(BPA) or
phthalates, and food toxins like advanced glycation end products
(AGEs),
EHM1
which may affect women’s health in everyday, industrialized life, will be
Endocrine disruptors: Is it all Greek to us?
discussed. Acute or prolonged exposure to EDCs and AGEs may result in
Evi Diamanti-Kandarakis
destabilization of the hormonal and metabolic homeostasis and lead to disruption
of reproductive functions in females. Strategies and strong recommendations
The main achievement at present, on Endocrine-Disruptors (EDCs) effects on
should be considered to protect present and future generations from their adverse
human health and disease development, is that it becomes a less /of a foreign
health effects. Understandably, Rachel Carson, said in an international language:
language[ issue. The widespread distribution of environmental chemicals in the
‘In nature nothing exists alone.’
atmosphere and the detection of these substances within human body, converge to
the concept that humans are continually exposed to EDCs. This presentation will
DOI: 10.1530/endoabs.49.EHM1
focus on the possible role of the most common and studied environmental toxins
in female reproductive disorders and especially in PCOS. Exposure to endocrine
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Endocrinology Trust Lecture
The Clinical Endocrinology Trust (CET) Award is given for clinical research that addresses aspects of
endocrinology at the forefront of clinical practice. This year’s recipient is Professor Renato Pasquali
who will receive his prize and give his lecture as part of the European Congress of Endocrinology
(ECE), beginning on the 20th May. The award is sponsored by the Clinical Endocrinology Trust and
Renato Pasquali is full professor of Endocrinology at of University Alma Mater Studiorum of Bologna
(UNIBO), Italy. In the 90’s In 2000 he established the division of Endocrinology in the S. Orsola-
Malpighi Hospital of Bologna (who was not present before), and served for a long period of time as
Director. In addition, he was director of the School of Specialization in Endocrinology and Metabolism
of UNIBO for fifteen years. Its clinical activity has covered over the years, all the major areas of
Endocrinology and Metabolic diseases. He is a member of numerous national and international
scientific societies and of the editorial boards of international journals. His scientific work was
dedicated, in particular, to (i) the pathophysiology and treatment of the polycystic ovary syndrome, and
(ii) the endocrinology of obesity (sex hormones, the hypothalamic-pituitary-adrenal axis, and the
endocannabinoid system). He has authored 285 original papers and review articles published in
international journals (PubMed) (HI 51) and 18 chapters in international textbooks. In particular, he
participated as co-author, to the writing group of Clinical Guidelines in “Position” and “Consensus”
statements.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Endocrinology Trust Lecture
androgen excess may play a crucial role in disrupting the metabolic pathway, in
favouring aberrant visceral fat morphology and function, in favouring the
CET1
development of insulin resistance and in increasing the susceptibility to develop
Prospects for a new assessment of polycystic ovarian syndrome
glucose intolerance states and type 2 diabetes. Hirsutism is common in PCOS,
Renato Pasquali
however its correlation with blood androgen levels is weak or absent. Apart from
Italy.
the opportunity to use more objective methodologies to define it, much more
research is needed on the potential role of cutaneous androgens. Finally, due to
the relevant impact of obesity on PCOS and the fact that in many developed
PCOS is the most common hyperandrogenic disorder, with a high prevalence of
countries most PCOS women are obese, it can be suggested that a secondary form
metabolic comorbidities, including obesity and central fat distribution, insulin
of PCOS related to obesity may exist. The concept of secondary PCOS can be
resistance and the metabolic syndrome. With this background, it should be
extended to other pathological entities, particularly to the severe insulin resistant
accepted that androgen excess must be present in all women with PCOS. Thanks
states, but also to other endocrinopathies and, finally, to specific drugs
to the advance in measuring blood androgen levels by LC-MS/MS, it has become
(particularly antiepileptics). As with other endocrine syndromes, we should
clear that almost all typical cases of PCOS have a variable pattern of androgen
therefore consider that PCOS, precisely because it is a ‘syndrome’, may include
excess. An androgen profile including all major androgens should therefore be
many different phenotypes, ranging from the classic to milder forms, and that a
used for research purposes and clinical practice. The phenotype characterized by
secondary PCOS may occur. Additional mild phenotypes without well defined
menses abnormalities and polycystic ovarian morphology but without androgen
androgen excess may have different pathophysiological mechanisms.
excess should be regarded as a separate entity. The presence of a dysmetabolic
profile should also be used in the characterization of PCOS, specifically insulin
DOI: 10.1530/endoabs.49.CET1
resistance, which is commonly present in obese PCOS women but can also be
detected in their normal-weight counterpart. In fact, there is evidence that
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
IPSEN1
Redefining neuroendocrinology: stress, sex and cognitive and emotional
regulation
Bruce McEwan
USA.
Abstract unavailable.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Plenary Lectures
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
The Fantastical World of Hormones
by the aberrant adrenal expression of several hormone receptors, particularly
G-protein coupled hormone receptors (GPCR) and their ligands. Screening for
P1
aberrant expression of GPCR in bilateral macronodular adrenal hyperplasia
The fantastical world of hormones
(BMAH) and unilateral adrenal adenomas of patients with overt or subclinical CS
John Wass
demonstrates the frequent co-expression of several aberrant receptors. In addition,
USA.
the aberrant GPCR can also exert their activity by regulating the paracrine
secretion of ACTH or other ligands for those receptors in BMAH or unilateral
tumors. The molecular mechanisms underlying the abnormal tissue-specific
We all know that endocrinology is the most amazing specialty. However although
expression of the aberrant GPCR remains unclear but may be secondary to
some of the discoveries in the last 3-400 years have been amazing, some of the
dedifferentiation of progenitor cells at the origin of hyperplasia or tumors or to
wrong turns have exhibited opportunism and quackery. Perhaps we should start
specific genetic alterations. The aberrant expression of hormone receptors is not
with testosterone and the effects of castration. We know that removal of the testes
limited to primary adrenal CS but can be implicated in other endocrine tumors
before puberty has irreversible affects and that in 16th and 17th centuries these
including primary aldosteronism (aldosteronoma or bilateral idiopathic hyper-
were exploited for music. Popes did not come out of this covered in glory and the
aldosteronism) and Cushing’s disease. Targeted therapies to block the aberrant
last papal castrato was singing in the Sistine Chapel choir in the early 1900s. In
receptors or their ligands have been effective in selected limited cases to date, but
the late 1840s Berthold a German physiologist in Gottingen experimented on
development of novel specific antagonists could become useful in the future.
capons showing that if he removed their testes and transplanted them into the
abdomen, where they regained their blood supply, the effects of castration were
DOI: 10.1530/endoabs.49.P3
not seen. He did not recognize the importance of his observation. Later in the late
1880s Brown-Séquard, the famous French neurologist, reported at the French
Royal Society injecting himself with a mixture of the bloods from the testes of
dogs and guinea pigs. His reported marked improvement in strength and stamina
was a placebo effect because of the shorter half-life of testosterone. Thyroxine
from sheep given to patients with hypothyroidism, again in the late 1880s had a
remarkable effect in women with hypothyroidism because of the longer half-life
of thyroxine. In the late 1880s the ovary was thought to be part of the nervous
The Role of Brain Insulin Resistance for the Development
system. Oophorectomy at that time was used to treat conditions in women
including hysteria and anorexia and anxiety and even nymphomania. Ernest
of Prediabetic Phenotypes
Starling was the first person to coin the term ‘hormone’ and ‘Ormao’ is the Greek
P4
word to ‘excite or stir up’. This was the founding of endocrinology. We have then
The role of brain insulin resistance for the development of prediabetic
gone from strength to strength with the discovery of insulin and more recent
phenotypes
leptin, pioneered amongst others by Steve O’Rahilly and Sadaf Farooqi in
Hans-Ulrich Häring
Cambridge.
Germany.
DOI: 10.1530/endoabs.49.P1
Abstract Unavailable
The Secret Life of FGF21
P2
The secret life of FGF21
David Mangelsdorf
Browning of Adipose Tissue and Metabolic Regulation
USA.
P5
Browning of adipose tissue and metabolic regulation
Fibroblast growth factor 21 (FGF21) is an endocrine and paracrine factor that is
Jan Nedergaard
produced in many tissues in response to metabolic stress, including several
Sweden.
nutrient and dietary conditions. In addition to its physiologic role in regulating the
adaptive response to these conditions, pharmacologic administration of FGF21 to
In most countries in the world, an increasing number of people suffer from the
obese animals causes weight loss and improves insulin sensitivity. The diverse
metabolic syndrome, normally defined as obesity, high blood sugar, high blood
actions of FGF21 are mediated through a unique receptor complex that is
fats and high blood pressure. The new understanding that adult humans possess
composed of a classic FGF receptor and the novel co-receptor, beta-Klotho.
active brown adipose tissue has led to hope that a (re)activation of this tissue
Investigation of the tissue-specificity of this FGF21
signaling pathway has
(browning) may be helpful in ameliorating the metabolic syndrome. Brown
revealed the existence of a complex peripheral and neural endocrine circuit that
adipose tissue has the ability to combust (extra) food intake in a direct way, due to
regulates metabolism, nutrient preference, and reward behaviors. We have also
the unique presence in this tissue of the UnCoupling-Protein-1 (UCP1). Thus, if
found an unexpected role for FGF21 in the exocrine pancreas as a secretagogue
activated - normally through the release of norepinephrine from the sympathetic
that protects acinar cells from proteotoxicity.
nervous system - the tissue will burn away food energy, leaving only heat, water
DOI: 10.1530/endoabs.49.P2
and CO2. Thus, it protects against the development of obesity. When the tissue is
chronically activated, the stored lipid reserves in the tissue will not suffice for
continued heat production, and the tissue will take up large amounts of sugar from
the circulation, through a unique adrenergic mechanism, leading to lowering of
blood sugar levels through a large glucose disposal. It will similarly activate the
synthesis of lipoprotein lipase, leading in parallel to a large increase in lipid
uptake from the circulation, diminishing blood triglyceride levels. During
prolonged stimulation, the constant burning of food in the tissue will lead to the
Update on Regulation of Steroidogenesis by Aberrant
mobilization of the body’s lipid reserves (the white adipose tissue) that will be
Hormone Receptors
broken down and the released fatty acids will be transported to the brown adipose
P3
tissue for combustion, i.e. the brown adipose tissue is slimming (and all these
effects together will likely also result in lowering of blood pressure). Although the
Update on regulation of steroidogenesis by aberrant hormone receptors
acute activity of the tissue is determined by norepinephrine, it would seem that
Andre Lacroix
sex hormones (positively) and glucocorticoids (negatively) can affect the tissue.
Canada.
The tendency to a worsening of the metabolic syndrome with age could then
partly be explained by a diminished sex hormone stimulation and an unaltered but
The mechanisms regulating cortisol production when ACTH of pituitary origin is
increasingly dominating negative effect of glucocorticoids, together leading to
suppressed in primary adrenal causes of Cushing’s syndrome (CS) include diverse
brown adipose tissue inactivity, and thus to obesity.
genetic and molecular mechanisms. These can lead either to constitutive
DOI: 10.1530/endoabs.49.P5
activation of the cAMP system and steroidogenesis or to its regulation exerted
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Thyroid Oncology in the Crossroads of Precision and
thyroid carcinomas: BRAF-life (Conventional and tall cell PTC, mainly), RAS-
like (Follicular variant PTC and follicular carcinoma) and No BRAF/No RAS.
Narrative Medicine
Precision medicine is playing a major role in thyroid oncology but its
P6
shortcomings are becoming evident. Somatic copy number alterations play also
Thyroid oncology in the crossroads of precision and narrative medicine
a role in some tumour subtypes and, furthermore, one is progressively aware of
Manuel Sobrinho Sim
˜ es
the important role played by host factors: Stromal reaction
(including
Portugal.
extracellular matrix characteristics, subsets of fibroblasts and degree of
desmoplasia), ‘social’ RNAs, immune cells, hormones, growth factors. The
data brought in by the latter narrative medicine approach is turning easier the
Thyroid cancers are the solid tumours of mankind with the lowest mutational
diagnosis and treatment of thyroid cancer patients.
load. This holds particularly true for papillary carcinomas
(PTC) whose
DOI: 10.1530/endoabs.49.P6
pathogenesis appears to be understandable by a limited number of genetic
alterations (That is why they are so frequently multifocal). The utilization of NGS
allowed the establishment of three molecular subtypes of well differentiated
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Symposia
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Updates in Hypoparathyroidism
hypoparathyroidism may be associated with the presence of anti-parathyroid
gland antibodies, and some patients harbor antibodies against the calcium-sensing
S1.1
receptor
(CaSR). Acquired hypoparathyroidism may also be caused by
Congenital hypoparathyroidism
hypomagnesaemia, which impairs PTH secretion; and can rarely be due to
Agnes Linglart
exposure to ionizing radiation, or result from infiltrative diseases affecting the
France.
parathyroids such as metastases or iron/copper overload.
DOI: 10.1530/endoabs.49.S1.2
The most common causes of hypoparathyroidism in children are the lack of or the
impaired development of the parathyroid glands due to genetic/chromosomal
alterations and the abnormal signaling of the Ca(2C)-sensing receptor (CaSR).
The latter refers to autosomal dominant hypocalcemia (ADH) mainly caused by
heterozygous activating mutations in CASR encoding CaSR (ADH type 1), and
exceptionally caused by activating mutations of GNA11 encoding the Gq/11
S1.3
protein (ADH type 2). Hypoparathyroidism can also be caused by an autoimmune
Clinical updates in hypoparathyroisism
process, mainly in the context of AIRE mutations. However, in many children, the
Erik Fink Eriksen
origin of the hypoparathyroidism remains undiscovered. In a recent national
Norway.
French survey gathering
142
children affected with hypoparathyroidism
performed by MAC, 43% of the patients were diagnosed before the age of
1 year. The main causes of the PTH insufficiency were 22q1.1 deletion (31%),
The spectrum of symptoms associated with hypoparathyroidism span from
ADH1 (13%), AIRE mutations (10%) and cervical surgery (7%). The etiology is
virtually none to severely debilitating fatigue, memory loss, muscle cramps, and
still unknown in 23% of the children. Due to the high calcium needs of the
paresthesia. Until recently disease management has focused on securing stable
skeleton during infancy and childhood, hypoparathyroidism in children is often
serum calcium values at the lower end of the reference range using potent active
symptomatic and is diagnosed because of the clinical symptoms of hypocalcemia
vitamin D analogues like Etalpha and Rocaltrol, together with calcium
(muscle spasms, laryngospasm, seizures). Children may present with unspecific
supplementation. Recently maintenance of adequate levels of 25(OH)D have
features such as cognitive and or motor delay, slowness, ungueal, dental and skin
also been mentioned as being important. Adequate intracellular magnesium levels
anomalies. In addition, clinical characteristics due to the disease itself causing the
seem to be pivotal for PTH secretion and action at the receptor level, and should
hypoparathyroidism may be present such as candidosis, conotruncal cardiac
therefore be kept at the upper end of the normal range if possible. It is one few
defect, renal and/or uterine malformation. Once hypoparathyroidism has been
endocrine diseases where supplementation of missing hormone was impossible
diagnosed in a child, a comprehensive work-up should be performed to identify
about
10 years ago. Now we have access to recombinant PTH(1-34) and
the disease-causing defect. The investigations depends on the age of the child
PTH(1-84), and I will review the potential use of and differences between these
(neonate, child, adolescent), and on the clinical features associated with the
analogues in the treatment of hypoparathyroidism. In terms of symptomatic relief
hypocalcemia. The diagnosis is of importance for the management of follow-up
the results of controlled studies using these analogues as sc. injections have been
and treatment. The management of hypoparathyroidism in children relies upon
disappointing. A more physiological pattern can be achieved with continuous
calcium supplements and vitamin D analogs. Following the initial period of
subcutaneous infusion using insulin pumps, and I will review the results obtained
profound hypocalcemia which may require IV infusion of calcium and high doses
with this technique so far.
of vitamin D analogs (up to 4 mg/day of alfacalcidol), the conventional therapy
DOI: 10.1530/endoabs.49.S1.3
should aim at absence of clinical symptoms, low-normal level of serum calcium
(2-2.2 mmol/l), avoiding hyperphosphatemia and having normal urinary calcium
excretion. In some children, this may be a challenging management requiring the
use of thiazide diuretics, phosphate binders, calcium supplements and in
refractory cases, recombinant PTH. It has become obvious in the past ten years
that we need to i- obtain more data on the long-term evolution of children affected
with hypoparathyroidism, ii- adjust our decision rules for the identification of the
Evolving Diagnostics in Adrenal and Neuroendocrine
cause of hypoparathyroidism in the context of next generation sequencing and
Tumours
gene panels or whole exome sequencing, and iii- develop guidelines for the
S2.1
management of hypoparathyroidism in children including the specificity of ADH.
Role of genetic and biomarker tests for diagnosis of neuroendocrine
DOI: 10.1530/endoabs.49.S1.1
tumours (NETs)
Raj Thakker
UK.
Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms that
S1.2
occur in different organs and give rise to tumours including carcinoids, pancreatic
Acquired hypoparathyroidism
tumours
(PNETs), pituitary adenomas, medullary thyroid carcinoma, and
Fadil Hannan
phaeochromocytomas. NETs usually occur as isolated non-familial tumours,
Uk.
but can also occur as hereditary and syndromic disorders, such as multiple
endocrine neoplasia
(MEN types 1-4), Von Hippel Lindau
(VHL) and
Hypoparathyroidism is characterized by absent or low circulating concentrations
phaeochromocytoma/paraganglioma. Patients with NETs such as PNETs that
of parathyroid hormone
(PTH), which results in hypocalcaemia, hyperpho-
do not secrete hormones (referred to as non-secreting or non-functioning PNETs)
sphataemia and impaired renal reabsorption of calcium. Hypoparathyroidism has
are often asymptomatic, and this may result in late diagnosis and presentation
a prevalence of w20-40 cases per 100 000 individuals, and anterior neck surgery
with metastases. Thus, there is an unmet need for new, reliable and specific
accounts for around 75% of cases. Postsurgical hypoparathyroidism may arise in
biomarkers for early diagnosis that would improve patient survival and quality of
patients undergoing total thyroidectomy, radical neck dissection for head and
life. Biomarkers, which are defined by the World Health Organisation as a
neck malignancies, and after total parathyroidectomy. Hypoparathyroidism
substance, structure or process that can be measured in the body or its products
following surgery is caused by intraoperative trauma, and inadvertent gland
and influence or predict the incidence of outcome or disease, for non-secreting
removal or devascularisation. Transient postsurgical hypoparathyroidism, defined
NETs include pancreatic polypeptide, chromogranins, carcinoembryonic antigen,
as lasting !6 months, affects 25-30% of patients following total thyroidectomy;
a-foetoprotein, neuron specific enolase and synaptophysin. However, these
whilst permanent postsurgical hypoparathyroidism, defined as lasting O6
current biomarkers have poor sensitivity and specificity for non-secreting NETs
months, affects up to 3% of patients after total thyroidectomy. Decreases in
thereby limiting their use for clinical decision making. Recently, detection of
pre-operative serum calcium and 25-hydroxyvitamin D concentrations, reduced
germline mutations of the MEN1 and VHL genes have been established as useful
intraoperative PTH concentrations, and longer duration of surgery represent
predictive biomarkers for the development of PNETs in families with these
independent predictors of transient hypoparathyroidism. Permanent hypopar-
disorders. However, such familial mutations account for only approximately 3%
athyroidism following thyroid surgery is associated with: inability to identify R2
of NETs. Additional biomarker development has also focussed on studying
parathyroid glands during surgery; hypocalcaemia at 24-h post-surgery; and
altered expression of the epigenome, transcriptome, proteinome and metabolome,
reoperation for bleeding. Occasionally, postsurgical hypoparathyroidism may
as well as circulating DNA, microRNAs and tumour cells that can be released
have a delayed-onset and present several years after neck surgery. Autoimmune-
from tumours into the vasculature. These advances will be reviewed. Dr Kate E
mediated destruction of the parathyroids represents the next most common cause
Lines, Dr Mark Stevenson & Professor Rajesh V Thakker.
of acquired hypoparathyroidism and is considered in patients with a personal
DOI: 10.1530/endoabs.49.S2.1
or family history of autoimmune diseases. Autoimmune acquired
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S2.2
S3.2
Current status in morphological imaging in adrenal and
GHR: are there benefits of endocrine defects?
gastrointestinal neuroendocrine tumours
John Kopchick
Sundin Anders
USA.
Sweden.
The effects of conditional mouse growth hormone receptor gene disruption or
Computed Tomography (CT) constitutes the basic technique for imaging of
‘knock-out’ on metabolic parameters and longevity will be presented. Tissues
adrenal tumours and neuroendocrine tumours (NETs). The major work-load in
investigated include muscle, adipose, heart, and liver. Also, data on adult onset
adrenal imaging is characterisation of adrenal incidentalomas, i.e. adrenal
growth hormone gene disruption will be presented.
tumours diagnosed on imaging performed for other reasons than adrenal disease.
DOI: 10.1530/endoabs.49.S3.2
Myelolipomas, which have a typical appearance with areas of macroscopic fat,
and simple cysts are easy to characterize and require no follow-up.
Morphologically benign adrenal tumours (rounded, sharply delineated, hom-
ogenous internal structure) with an attenuation of %10HU in the native CT
images are characterized as benign adrenocortical adenomas and require no
additional imaging. With an attenuation R10HU, follow-up of tumour size is
S3.3
recommended for 6 months. In young (!40 years) patients this should preferably
Somatostatin receptors: news in the pituitary, lessons for the periphery
be performed by MRI. Calculation of contrast medium wash-out is no longer
Justo Pastor Casta
˜o
applied. For tumours O4 cm surgical resection is recommended unless in cases of
Spain.
a typical myelolipoma or cyst. CT is for NETs used for the initial localization of
the primary tumour, for staging of the disease, detection of recurrence and for
The pituitary has been classically considered the ‘Master Gland’, owing to its
monitoring of therapy. It is also used in hybrid imaging in conjunction with PET
ability to regulate the function of the other endocrine glands of the body.
(PET/CT) and SPECT (SPECT/CT). MRI is superior for imaging of liver,
However, the hypophysis also served over the years as a master, guiding example
pancreas, brain and bone. In metastatic NETs,
68Ga-DOTA-somatostatin
to enlighten multiple fields of experimental biology and medicine, from classic
analogue PET/CT generally shows several additional lesions as compared to
physiology to modern cell biology, biochemistry and molecular biology.
CT/MRI and small lesions such as lymph nodes may be characterized as
Somatostatin and its receptors (sst1-5) comprise a classic regulatory system,
metastatic/not metastatic lesions. Contrast-enhanced US is excellent for
initially discovered and characterized at the hypothalamo-pituitary interface,
diagnosis and characterization of liver lesions and to guide the biopsy needle
which subsequently expanded to influence multiple bodily functions, from
for the histopathological NET diagnosis. Endoscopic US is the best method
neurotransmission to digestive function and metabolic homeostasis, and also
for detection of pancreatic NETs.
tumour biology. In this scenario, our group discovered an aberrantly spliced
DOI: 10.1530/endoabs.49.S2.2
variant of sst5, sst5TMD4, which lacks 3 of the typical 7 transmembrane domains
of GPCRs, but retains unique functional abilities and tisular and subcellular
distribution. Initial studies revealed sst5TMD4
overexpression in pituitary
tumors, particularly in acromegaly, where its presence is associated to a reduced
response to somatostatin analogues, both in vitro and in vivo, and is linked to
enhanced aggressiveness features, such as cell proliferation in vitro and tumor
invasion in vivo. These findings led us to explore the possible presence and
activity of sst5TMD4 in other hormone-related tumors. Interestingly, a series of
collaborative studies demonstrated that this truncated receptor is overexpressed
S2.3
in multiple tumors and cancers, including, so far, breast cancer, pancreatic
Current status in functional imaging
neuroendocrine tumors, poorly differentiated thyroid cancer, medullary thyroid
Vickas Prassad
carcinoma, and prostate cancer. In these pathologies, studies on patient samples
Germany.
and clinical features, an on tumor-derived primary cells or model cell lines have
demonstrated that sst5TMD4 presence is directly linked to enhanced aggressive-
ness features, such as increased cell proliferation, migration and invasion,
Abstract unavailable.
hormonal secretion, etc. Further analysis on the molecular underpinnings of these
observed features have revealed a number of activated oncogenic or inactivated
tumor-suppressing pathways and molecular players, some of which seem to be
shared by most tumor types studied, whereas others seem to be unique for a given
type of tumor/cancer. These results, coupled to our observation that other
misspliced variants related to pituitary pathophysiology (namely, In1-grelin and
GHS-R1b) are also present in the same tumors prompted us to study the splicing
machinery. Of note, ongoing studies have revealed that the splicing machinery is
dysregulated in these pathologies. Thus, the pituitary served, once again, to pave
the way to scientific discovery for the periphery.
DOI: 10.1530/endoabs.49.S3.3
From the Pituitary to the Periphery
S3.1
Implication of the prolactin receptor in humans
Nadine Binart
France.
2nd Joint Global Symposium on Obesity - The Many
Dimensions of the Childhood Obesity Problem
While prolactin
(PRL) is known as the pituitary hormone of lactation,
S4.1
accumulating evidence shows that PRL acts on many tissues and in many
Efficacy and effectiveness of physical activity and nutrition
pathophysiological conditions. The major isoform, 23 kDa PRL, acts via a
interventions in childhood obesity treatment
membrane receptor, the prolactin receptor
(PRL-R), a member of the
Hollie Raynor
hematopoietic cytokine superfamily, and for which the mechanism of activation
USA.
has been elucidated. The aim of this symposium is to present and discuss data
supporting actions of PRL in hyperprolactinemia in the context of gonadotropic
deficiency. High levels of PRL in humans may interfere with reproductive
While several organizations have recommended that multicomponent, behavioral
function mainly by actions at the hypothalamus. Our data suggest that Kisspeptin
family-based programs delivered at a moderate- to high-intensity contact
neurons appear to be the missing link between hyperprolactinemia and GnRH
frequency have a moderate to high rating of efficacy for improving weight status
deficiency. Otherwise, germline PRLR mutations have been suspected to be a
in children, these types of programs are difficult to translate into many practice-
specific genetic cause of prolactinoma in humans. This will be discussed in light
based settings. This presentation will review areas that have been identified within
of our recent results.
childhood obesity treatment programs that may assist with translation to practice-
DOI: 10.1530/endoabs.49.S3.1
based settings, and discuss research that has been conducted that examine these
factors. An example of a current randomized trial translating a multi-component,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
behavioral family-based program into an integrated primary care setting in the
S5.2
USA will be provided.
Vitamin D and rickets in African children
DOI: 10.1530/endoabs.49.S4.1
Vickie Braithwaite
UK.
Rickets is the most common non-communicable disease in low and middle
income countries and is re-emerging in countries such as the UK where it was
once thought to be eradicated. Rickets is a bone disease which affects growing
children and is caused by the undermineralisaton of the growth plate of long
bones. Rickets can lead to osteomalacia, disabling bone deformities of the lower-
S4.2
limbs, stunting, increased fracture risk and in severe cases circulating bone
The hunger genes: pathways to obesity
mineral disturbances can result in hypocalcaemic seizures and death. The
Sadaf Farooqi
majority of nutritional rickets worldwide is thought to be driven by vitamin D
deficiency due to inadequate skin exposure to UVB-containing sunshine. In many
countries in Africa however, 25-hydroxyvitamin D concentrations (the status
Abstract unavailable.
marker for vitamin D) are above those generally associated with vitamin D
deficiency thus indicating alternative causes of rickets. This presentation will
explore some of our work on the role of the vitamin D-calcium-phosphate axis on
nutritional rickets in a selection of African countries; highlighting the potential
roles of calcium and iron deficiency. This presentation will also explore whether
aetiology may differ depending on setting i.e. urban vs rural and the various
treatment methods for rickets including surgical correction of bone deformities,
nutritional supplementation and prophylactic treatment strategies for rickets
prevention.
Funded by MRC programmes U105960371, U123261351, MC-A760-5QX00 and
S4.3
DfID under the MRC/DfID Concordat.
Can we prevent childhood obesity?
DOI: 10.1530/endoabs.49.S5.2
Tim Lobstein
UK.
Childhood obesity prevalence continues at a high level in most developed
economies and is rising strongly in emerging middle-income countries. This rise
in prevalence shows strong links to the exposure of populations to mass-marketed
S5.3
foods and beverages and the use of motorised transport. In Europe the prevalence
Carbohydrate metabolism in patients with Cushing disease: a glance at
tends to be higher, and rising faster, among children from lower-income
the incretin system
households. The prevention of obesity is essential but clearly we are not doing
Lubov Matchekhina
very well - no country in Europe has successfully and sustainably reduced
Russia.
childhood obesity prevalence. We need to ask: What are the major social,
commercial and political barriers which need to be overcome? What steps can we
take to overcome these barriers and create a truly health-promoting society?
The relevance of carbohydrate metabolism studying in patients with Cushing
disease (CD) and acromegaly can be explained by frequent occurrence of glucose
DOI: 10.1530/endoabs.49.S4.3
metabolism disturbances on the one hand, and difficulties in glucose-lowering
therapy in these patients on the other. The effectiveness of hyperglycaemia
treatment may be reduced due to difficulties in remission/cure of the underlying
disease, as well as to the use of specific drug-therapy, leading to hyperglycaemia.
There is a growing interest in research aimed at studying the role of incretin
system in the pathogenesis of secondary hyperglycemia associated with
neuroendocrine diseases recently.
Aim of the study
Turn Your Face to the Sunshine
To analyze the rhythm and levels of incretins and neuropeptides secretion in
S5.1
patients with CD and acromegaly and therefore to specify the pathogenesis of
carbohydrate metabolism disturbances.
Effects of maternal thyroid function on infant neurodevelopment
Methods
Tim Korevaar
42 patients with Cushing disease and acromegaly were included; the mean age
The Netherlands.
was 37.5 years. All of the patients were newly diagnosed with Cushing disease
(using urinary free cortisol levels, evening saliva cortisol levels and low-dose
In this talk I aim to provide a helicopter view of clinical studies on maternal
dexamethasone suppression test) and acromegaly (in absence of GH suppression
thyroid function and child neurodevelopment and use this to pinpoint out how
during OGTT and high IGF1 levels); none of them had a history of previous drug
different viewpoints on the results can help to interpret the clinical relevance of
therapy, radiotherapy or pituitary surgery. All patients underwent OGTT, during
the currently available data and provide handles to make personal but informed
which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and
clinical decisions. It is well-established that thyroid hormone plays an important
120 min respectively.
role during early stages of fetal brain development. Thyroid hormone-dependent
Results
stages of brain development occur from the 5th week of pregnancy onwards while
During OGTT glucose levels were not significantly different in all groups. The
the fetal thyroid is not functionally matured until week 18-20. This implicates
mean HbA1c level was 5.8% (5.3-6.2). However the relevance of prediabetes was
that adequate maternal thyroid hormone concentrations are important for
higher in CD patients. In CD patients glucagon levels were significantly higher at
achieving optimal early fetal brain development. After the initial link between
all cut off points compared to controls (PZ0.001). In acromegaly patients, no
iodine deficiency and cretinism was first identified, a wide range of experimental
significant differences were found. GIP secretion was slightly lower in CD
studies further established underlying (patho)physiological mechanisms. Sub-
patients; in acromegaly patients, no differences were found. Acromegaly group
sequently, clinical studies were set-up to translate these findings and quantify the
was characterized by inverse rhythm of GIP secretion, with no peak level at 30’:
extent of effects in humans. During this presentation I aim take the audience
GIP 0 min - 194.2 pg/ml, GIP 30 min - 178.8 pg/ml. GLP-1 levels were
through a brief timeline of clinical studies published since the late 1990s until this
significantly higher in CD patients
(PZ0.047). In acromegaly group, no
year. The interpretation of clinical outcomes used to study the hypothesis that
significant differences in GLP-1
secretion were found. GLP-2
levels were
maternal thyroid hormones are important for fetal brain development, such as
significantly higher in CD patients compared to acromegaly and controls
child IQ, will be discussed. The timeline of clinical studies together with the
(PZ0.001). Ghrelin levels were significantly higher in CD (PZ0.013) and
interpretation of the results of recent studies, including clinical trials, could help
acromegaly (PZ0.023) patients.
to weigh the potential clinical benefits and harms, and make for a better informed
Conclusion
decision making.
More pleotropic actions of glucocorticoids can possibly explain higher relevance
DOI: 10.1530/endoabs.49.S5.1
of carbohydrate metabolism disturbances in CD patients. This can be also
explained by higher levels of glucagon secretion, which does not depend on type
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
of carbohydrate metabolism disorder and is stimulated by a direct action of
field may lead to new therapeutic options in congenital or post-surgical
glucocorticoids on glucagon receptor. GIP and GLP-1 secretion in CD and
hypothyroidism.
acromegaly patients are characterized by inverse rhythm with no peak levels
DOI: 10.1530/endoabs.49.S6.3
which means that these hormones are not playing the crucial role in carbohydrate
disturbances development in these patients. On the contrary, GLP-2 and ghrelin
seem to influence and potentially regulate glucose homeostasis in CD and
acromegaly patients.
DOI: 10.1530/endoabs.49.S5.3
Crosstalk between Bone & Other Organ(ism)s
S7.1
Immune system
Patrizia D’Amelio
Italy.
Treatment of Hypothyroidism: What Have We Learned?
The immune system has been recognized as one of the most important regulators
S6.1
of bone turnover and its de-regulation is implicated in several bone diseases as
What is the clinical relevance of deiodinase polymorphisms?
post-menopausal osteoporosis and inflammatory bone loss. The study of the
Antonio Bianco
relationship between immune system and bone metabolism is generally indicated
USA.
under the term ‘osteoimmunology’, the vast majority of these studies have been
performed in animal models, however several data have been confirmed also in
humans. Post-menopausal osteoporosis (PMO) is the most frequent metabolic
Abstract unavailable.
skeletal disease, it is characterized by reduced bone mineral density and micro
architectural deterioration of bone with increased fracture risk. In PMO the
uncoupling between osteoblast (OB)-mediated bone formation and osteoclast
(OC)-mediated bone resorption results in bone loss. Estrogen deficiency is the
main driver of post-menopausal bone loss: during estrogen depletion OCs
formation and activity are increased, this increase is partially mediated trough the
effect of estrogen deficiency on immune system. Estrogen deficiency influences
immune response, in particular T cells, become more active and able to produce
S6.2
inflammatory and pro-osteoclastogenic cytokines as TNFa and RANKL. Despite
T4/T3 combination therapy: is there a true effect?
of some inverse reports, the main body of literature firmly supports the essential
Wilmar Wiersinga
role of activated T cells in regulating bone loss induced by estrogen deficiency,
The Netherlands.
both in animal models and in humans. We recently demonstrated that immune
system, and in particular T cells mediate the effect of PTH on bone turnover, in
particular we demonstrated that during treatment with teriparatide for PMO T
L-T4 monotherapy remains the standard treatment of hypothyroidism, as RCTs
cells mediates osteoblastogenesis trough the production of Wnt10b, whereas
comparing T4 and T4CT3 did not indicate superiority of the combination
primary hyperparathyroidism do not increase this molecule. Moreover we
therapy. However, the issue is far from settled, as these RCTs can be criticized
demonstrated that, both in mice and humans, continuous infusion of PTH and
and 5-10% of patients on T4 have persistent complaints.
primary hyperparathyroidism increases the differentiation of T helper (TH) cells
i) Has T4CT3 therapy a true effect on serum thyroid hormones? Under T4
in TH17. These cells are responsible for increased OCs formation and activity
monotherapy serum FT4 is higher and serum FT3 is lower than in healthy
both in inflammatory diseases and in PMO. In conclusion The interactions
subjects, giving rise to abnormal T3/T4 ratio’s in 29% of patients. T4CT3
between immune system and bone are complex and play significant role in both
therapy produces lower FT4 and higher FT3 values, and thereby T3/T4 ratio’s are
health and disease, nevertheless not all the pathways discovered in animal models
closer to normal values. There is conflicting data whether T3/T4 ratio’s are related
have been fully demonstrated in humans, and several challenging questions
to SNPs (e.g. in DIO2) and to persistent complaints.
remains unsolved.
ii) Has T4CT3 therapy a true effect on thyroid-hormone dependent actions?
There is emerging but weak evidence that markers of thyroid hormone action
DOI: 10.1530/endoabs.49.S7.1
(such as LDL-cholesterol, SHBG, bone alkaline phosphatase) are closer to normal
under T4CT3 therapy than under T4 monotherapy.
iii) Has T4CT3 therapy a true effect on the clinical condition? Patients were
asked for their preference in 4 RCTs. Preference for T4 was 25% and for T4CT3
48%; no preference was expressed by 27%. Preference has been related to loss of
S7.2
body weight and to combined SNPs in MCT10 and DIO2.
iv) Has T4CT3 therapy a true effect on clinical practice? Yes, absolutely. Many
Osteocalcin signaling in myofibers is necessary and sufficient to increase
patients demand T4CT3 therapy, sometimes in a aggressive manner. Prescription
exercise capacity
of T3 tablets have increased, and pharmacy has discovered the potentially big
Gerard Karsenty
market for T3, among others resulting in a steep price increase of T3 tablets but
USA.
also in availability of 5 microgram T3 tablets. Only the ETA published detailed
guidelines how to start the still experimental T4CT3 regimen (Eur Thyroid J
The observation that circulating osteocalcin levels double during exercise in
2012;1:55). The many unresolved issues call for many more clinical trials.of
young mice suggests that this hormone might be a long sought after endocrine
different designs.
regulator of exercise capacity. We addressed this question by analyzing mice
DOI: 10.1530/endoabs.49.S6.2
lacking either osteocalcin or its receptor in myofibers only. This analysis showed
that osteocalcin signaling in myofibers enhances adaptation to exercise because it
increases uptake and utilization of glucose into the tricarboxylic acid cycle and
promotes fatty Osteocalcin signaling in myofibers favors adaptation to exercise
through a second mechanism. Indeed it up-regulates the expression of Interleukin-
6 a myokine that favors adaptation to exercise in part by signaling in bone to
S6.3
promote the production of bioactive osteocalcin. Acids utilization. In the course
of these studies we noticed that circulating osteocalcin levels decline sharply
Rebuilding your own thyroid from stem cells; the future therapy of
before mid-life and do not increase during exercise in older mice. This
hypothyroidism?
observation raised the prospect that osteocalcin may also be sufficient to correct
Anthony Hollenberg
the age-related decline in muscle function. In support of this hypothesis, our
USA.
experiments show that exogenous osteocalcin increases the exercise capacity of
young wilt-type mice and confers to 15 month-old mice the exercise capacity of
Advances in stem cell biology and thyroid development have opened up the
3 month-old mice. This study uncovers an osteocalcin-interleukin-6 axis that
possibility of developing tissue replacement therapy for hypothyroidism. Indeed,
increases muscle function during exercise and can reverse the age-induced
in this session the development from stem cells of functioning thyroid tissue in
decline in exercise capacity.
mice will be reviewed. In addition new insight into the development of this
DOI: 10.1530/endoabs.49.S7.2
technology in human cells will also be discussed. Importantly, advances in this
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S7.3
levels of GH-hypersecretion (Fig. 1). Treatment with somatostatin analogues,
both before and after surgery, leads to different responses of T2-hypointense
Gut microbiota and bone metabolism
adenomas versus non-hypointense tumours. The T2-hypointense adenomas have
Klara Sjogren
higher GH and IGF1 decreases and more important tumour shrinkage rates (1). It
Sweden.
is therefore interesting to have high quality T2-weighted MRI images at the
diagnosis of acromegaly, as it allows to estimate disease evolution and to orient
The gut microbiota (GM), the commensal bacteria living in our intestine,
the management strategy.
performs numerous useful functions, including modulating host metabolism and
Reference
immune status. Our recent studies demonstrate that the GM is also a regulator of
1. Potorac, J et al. T2-weighted MRI signal predicts hormone and tumor responses
bone mass and we propose that the effect of the GM on bone mass is mediated via
to somatostatin analogs in acromegaly. Endocr Relat Cancer 23(11):871-881.
effects on the immune system, which in turn regulates osteoclastogenesis. A role
DOI: 10.1530/endoabs.49.S8.2
of the GM in bone metabolism is further supported by studies demonstrating that
antibiotic, probiotic, and prebiotic treatments that impact GM composition
regulate bone metabolism. Collectively, these studies suggest that the GM may be
a novel therapeutic target for osteoporosis. Treatment with probiotics has already
been shown to improve bone mass in rodent models of bone loss, but future
randomized clinical trials are required to determine the possible effect of
S8.3
probiotics and other novel therapies modulating the GM composition on bone
Predictors of therapeutic response in functioning pituitary tumours
mass and fracture risk in patients with osteoporosis. Access to cheaper sequencing
Marek Bolanowski
and improved bioinformatics tools will allow metagenomic sequencing for the
Poland.
analysis of the GM composition in large prospective clinical cohort studies. This
can be used to evaluate the predictive value of the GM composition as a
biomarker for low bone mass and fracture risk. In addition, metatranscriptomics
Therapeutic response for medical therapy in hormonally functioning pituitary
and metaproteomics will most likely be used to identify the microbial genes and
tumours is different in various types of tumours. While majority of prolactinomas
proteins that have an impact on bone mass and fracture risk. We propose a new
respond well for medical therapy using dopamine agonists, in other tumours like
cross-disciplinary GM-bone research field called ‘osteo-microbiology’, bridging
somatotropinoma or corticotropinoma their response is significantly lower. In
the gaps between bone physiology, gastroenterology, immunology, and
some case therapy resistance can occur. There are various factors determining the
microbiology. Future studies are clearly warranted in this new research field to
efficacy of medical therapy in patients harboring functioning pituitary adenomas.
determine if the GM composition might be used as a biomarker for fracture risk
They are different for certain type of tumour. Among clinical aspects, gender, age
prediction and to validate the GM as a possible novel therapeutic target for
and extent of hormonal hypersecretion are important factors. In general, response
osteoporosis.
for the therapy in acromegaly is poor in younger male patients with larger
DOI: 10.1530/endoabs.49.S7.3
tumours and greater GH hypersecretion. Pituitary imaging using MRI can show
tumour size and invasiveness, together with T2
intensity. Histological and
molecular analyses assess granulation pattern, somatostatin and dopamine
receptors number and expression, Ki-67 index, mitotic activity, p53 immunor-
eactivity, AIP expression, genetic mutations and polymorphisms. The knowledge
of possible factors influencing therapeutic response is important and may be
Predictors of Therapeutic Response in Functioning
helpful in the choice of optimal individualized therapy.
Pituitary Tumours
DOI: 10.1530/endoabs.49.S8.3
S8.1
Molecular profiling
Monica Gadelha
Brazil.
Novel Type 2 Diabetes Treatment: Beyond Glycaemic Control
Abstract unavailable.
S9.1
Experimental models
Jens Holst
Denmark.
S8.2
One of the most surprising and inspiring experimental models for type 2 diabetes
therapy is gastric bypass surgery. Recent
5-year results have demonstrated
MRI predictors of therapeutic response in GH-secreting pituitary
massive improvements in glycaemic control and body weight, lipids and quality
tumours
of life after surgery compared to intensive medical therapy (the Stampede trial).
Jean Francois Bonneville
Therefore, it is imperative to identify the responsible factors with a view to utilize
Belgium.
this knowledge for future therapy without surgery. Substantial evidence suggests
that increased secretion of gut hormones plays an important role for both weight
The T2-weighted characteristics of GH-secreting pituitary adenomas have
loss
(inhibition of appetite C food intake) and glucose metabolism
(by
recently received particular attention from the research community. It now
stimulating glucose-induced insulin secretion). The appetite inhibition seems to
appears that somatotropinomas can be divided into groups with different behavior
involve hypersecretion of PYY, GLP-1 and perhaps CCK, oxyntomodulin, and
according to their T2-weighted signal. T2-hypointense adenomas are generally
neurotensin. Decreased secretion of ghrelin may also play a role. The improved
smaller, invade the cavernous sinus less frequently and are responsible for higher
glycaemic control is due to a combination of (i) dramatically improved insulin
sensitivity (initially improved hepatic sensitivity in parallel with reduction in
steatosis) and secondly peripheral sensitivity in parallel with general weight loss -
and (ii) improved postprandial insulin secretion due to improved beta cell glucose
sensitivity as well as a stronger glycaemic stimulus caused by accelerated glucose
absorption. The latter is also the major driving force for postprandial release of the
insulinotropic hormone GLP-1, whereas lipids
(bile salts) may explain
neurotensin secretion while protein derivatives drive CCK secretion. Further
experiments using isolated primary gut cells and perfused gut preparations have
identified certain bile salts to potently stimulate secretion while amino acids
transporters including Pept-1
and basolateral calcium-sensing receptors are
important for protein-induced secretioin. The most important lesson so far is that
stimulated secretion predominantly depends on absorption of nutritional
elements. Some of these elements may form the basis for new therapeutic
approaches.
Figure 1 Hyperintense (a) and hypointense (b) GH-secreting
DOI: 10.1530/endoabs.49.S9.1
adenomas on T2 W MRI.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S9.2
survivors. Male sterility is a relative common side effect of cancer treatment. This
adverse fertility effect is caused by gonadotoxic effects as the cancer treatments
Clinical studies on GLP1 - cardiovascular outcomes
not only effectively kill cancer cells but also destroy the progenitors of sperm.
Baptist Gallwitz
Spermatogenesis is the process of sperm production starting from spermatogonial
Germany.
stem cells that are extremely sensitive to treatments with alkylating agents or
irradiation. Damage to these stem cells results in temporary or permanent sterility
The incretin hormone Glucagon-like peptide-1
(GLP-1) has various non-
depending on the doses. For this reason, adult men diagnosed with cancer are
glycaemic properties. Among those, cardiovascular effects have been described
offered cryopreservation of semen before starting cancer treatment. However, for
in animal studies and in clinical studies in patients with type 2 diabetes that have
pre-pubertal and young boys, this is not an option as sperm is not yet produced in
been treated with GLP-1 receptor agonists (GLP-1RA). In animal studies, GLP-1
these boys. As spermatogonial stem cells are already present in the testis, these
and GLP-1RA have lead to a decrease in ischaemic areas in artificial myocardial
cells are a source for fertility preservation. A potential future clinical application
infarct models. Additionally, in some clinical studies, an improvement in left
to preserve fertility in these boys with cancer is to cryopreserve a small testis
ventricular function was observed as well as a decrease for catecholamine
biopsy prior to cancer treatment for later isolation and propagation of
requirement in post-surgical patients after coronary bypass graft surgery. The
spermatogonial stem cells from this biopsy and transplantation of these cells
pathophysiological explanations for these effects are a possible improvement in
back after cure of cancer. Studies in animal models have provided evidence that
substrate utilization of the myocardium as well as vascular effects mediated by the
this method indeed restores fertility. It is shown that spermatogonial stem cells
activation of cardiovascular GLP-1 receptors and a consecutive amelioration of
can be transplanted to the testis, where they migrate to their niche and colonize the
hypertension. In recent years, randomized, prospective cardiovascular safety
testis, giving full spermatogenesis of which sperm was able of fertilizing eggs and
trials have been initiated or performed with GLP-1RA in patients with type 2
producing offspring. Using this transplantation as readout, spermatogonial stem
diabetes and concomitant cardiovascular disease or cardiovascular risk factors.
cell characteristics could be studied in more detail, resulting in the establishment
Results from three of these studies have been published so far. In the ELIXA-trial,
of a long term in vitro propagation system for mouse spermatogonial stem cells
the short acting GLP-1RA lixisenatide was given as add on to a standard
that upon transplantation could produce sperm to generate offspring. This
antidiabetic therapy in patients after an acute cardiovascular event. In comparison
presentation will give an overview on the state of art of the translation of these
to an established diabetes therapy, lixisenatide demonstrated non-inferiority and
techniques to the human situation to establish a clinical application for fertility
cardiovascular safety. The LEADER-study performed with liraglutide in patients
preservation in young boys suffering from cancer.
with type 2 diabetes and concomitant cardiovascular risk or disease showed a
DOI: 10.1530/endoabs.49.S10.2
highly significant 13% relative risk reduction in the 3-point MACE (MACE Z
multiple adverse cardiovascular events; combined endpoint of cardiovascular
death, non-fatal myocardial infarction and non-fatal stroke) after 54 months. This
result was primarily driven by a significant reduction of cardiovascular death by
22%. Semaglutide, a long-acting GLP-1RA for once weekly injection that is not
approved yet, lead to a significant 26% relative risk reduction in the 3-point
MACE in its clinical phase III study programme. From these data, the hypothesis
S10.3
that the activation of the GLP-1 receptor has beneficial cardiovascular effects, is
strongly supported and it has now been demonstrated in two studies, that patients
Pubertal induction and hormone replacement in young males
with type 2 diabetes and cardiovascular disease may profit from a therapy with
Nelly Pitteloud
GLP-1RA regarding their cardiovascular outcomes.
Congenital gonadotropin-releasing hormone deficiency is a rare disorder
DOI: 10.1530/endoabs.49.S9.2
characterized by incomplete or absent puberty and infertility. This condition is
both clinically and genetically heterogeneous and presents with a broad spectrum
of phenotypes ranging from mild to severe. This presentation will provide a
review of hypogonadotropic hypogonadism, including the clinical presentation of
HH, a rational approach to evaluating HH patients, and an update on treatment
options. In particular, the speaker will focus on the choice of the most appropriate
S9.3
treatment in hypogonadotropic hypogonadism based on clinical presentation
SGLT2 long term protective effects
including the use of rFSH to enhance treatment outcome.
Javier Escalada
DOI: 10.1530/endoabs.49.S10.3
Spain.
Abstract unavaialble.
New Roles for Nuclear Receptors
S11.1
The Challenges of Male Fertility
Identification of nuclear receptors network in male fertility
S10.1
David Volle
France.
Manipulating testicular androgen production to promote lifelong male
health
Lee Smith
Male fertility is controlled by complex interactions among the hypothalamus,
UK.
pituitary, and testis. The major functions of the testis include production of
spermatozoa
(male gametes) and synthesis of testosterone. Testosterone is
produced by the testicular Leydig cells and is responsible for the development of
Abstract unavailable.
gonad, the attainment of puberty, and the maintenance of secondary sexual
characteristics. It is also involved in the maintenance of of spermatogenesis and
thus ensuring male fertility. Many studies have highlighted the complexity of the
regulations of testicular homeostasis at both tissue and cellular levels. Among the
involved molecular mechanisms, several nuclear receptors (NRs) have been
identified as key regulators of testicular physiology. NRs are a family of
S10.2
transcription factors with a conserved structure that within testis control
steroidogenesis and germ cell differentiation. Since several years, using both
Fertility preservation in pre-pubertal and young males
genetic and pharmacologic strategies, we have been implicated in the
Ans van Pelt
identification of the multiple roles of particular members of the NR superfamily.
The Netherlands.
Here we will give an overview of our research highlighting the identification of a
complex network showing the interactions of these NRs in the regulation of the
Survival rates for patients with cancer have continuously increased over the past
exocrine and endocrine functions of the testis.
decade as a result of more advanced cancer treatment. As a consequence, adverse
DOI: 10.1530/endoabs.49.S11.1
side effects of cancer therapy becomes an important health issue for these cancer
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S11.2
orbital fibroblasts fulfil in GO pathogenesis as well as the potential of direct
targeting of the orbital fibroblast in the treatment of GO.
Crosstalk between estrogen signalling and DNA damage repair
Simak Ali
DOI: 10.1530/endoabs.49.S12.1
UK.
Estrogen receptors (ER) are expressed in the majority of breast cancers, are key
drivers of breast cancer development and progression and hence therapies to
inhibit their activities are a mainstay of treatment for breast cancer. A large
proportion of patients develop resistance to these therapies, so determining the
S12.2
mechanisms of ER action is important for improving patient management and for
identifying new therapies. In defining the mechanisms by which ER regulates
Management of Graves orbitopathy
gene expression, we and others find that proteins involved in DNA damage
Luigi Bartalena
recognition and repair (DDR), including components of base excision repair
Italy.
(BER) and non-homologous end-joining (NHEJ) are central to the promotion of
gene expression by ER. Most recently, we have demonstrated that the cytosine
Management of Graves’ orbitopathy (GO) depends on the severity and activity of
deaminase APOBEC3B (A3B) is recruited to the regulatory regions of estrogen-
the disease. Guidelines for the management of GO have recently been published
responsive genes in an ER-dependent manner. We have shown that A3B
by EUGOGO (European Group on Graves’ Orbitopathy) (European Thyroid
recruitment promotes transient C-to-U changes at ER/A3B binding regions,
Journal 2016 5 9-26). Assessment of GO by standardized criteria is fundamental
repaired by BER/NHEJ pathways, with the cytosine deamination and its repair
to determine the type of intervention. General measures for all patients with GO,
facilitating chromatin remodeling that aids expression of ER target genes.
irrespective of the degree of severity and activity, include restoration and stable
Importantly, we have now extended these studies to demonstrate an important
maintenance of euthyroidism, refrain from smoking, use of local measures (e.g.
role for A3B in transcription regulation in ER-negative, as well as ER-positive
artificial tears, ocular gels). All GO patients, except for the mildest cases, should
breast cancer cell lines, indicating that A3B has a general role in regulating gene
be referred to specialists. Mild GO is not treated actively, except for a 6-month
expression in human cells. These findings highlight the therapeutic potential of
course of selenium supplementation, shown in a randomized clinical trial (RCT)
A3B inhibitors for the treatment of ERC and ER-negative breast cancer. Recent
to be more effective than placebo also in terms of prevention of progression to
reports have implicated A3B as the enzyme responsible for acquisition of
more severe forms of GO. Sight-threatening GO, due to dysthyroid optic
mutations and tumour evolution in diverse cancer types, highlighting the inherent
neuropathy and/or corneal breakdown, is an endocrine emergency and should be
dangers associated with the cellular role of DNA damage and repair in the
treated immediately with very high doses of intravenous glucocorticoids (ivGCs)
regulation of gene expression. These findings also raise the question of whether
and measures to protect the corneal surface. If, however, response is absent or
targeting of A3B to gene regulatory regions might promote non-coding mutations
poor within
2 weeks, the patient should be promptly submitted to orbital
that modify gene enhancer function and provide further impetus for the
decompression. Treatment of moderate-to-severe GO depends on disease activity.
development of A3B inhibitors for cancer.
If GO is stably inactive, there is no place for medical treatment, and rehabilitative
DOI: 10.1530/endoabs.49.S11.2
surgery (orbital decompression, squint surgery, eyelid surgery) can be performed,
as needed. For moderate-to-severe AND active GO, ivGCs represent, for the time
being, the first-line treatment. ivGCs are given as 12 weekly, slow infusions of
methylprednisolone (MP). Most commonly, the cumulative dose of MP is 4.5 g,
but the dose should be tailored to the patient conditions, avoiding a cumulative
dose O8 g and a single dose O0.75 g, to minimize the risk of toxicity. If response
is not satisfactory in terms of regression and inactivation of GO, second-line
therapies include a second course of ivGCs, a course of oral glucocorticoids
S11.3
combined with either orbital radiotherapy or cyclosporine, treatment with
The role of androgens in bone
rituximab. The choice of second-line treatments should be part of a shared
Frank Claessens
decision-making process with the informed patient. In addition to rituximab, the
Belgium.
effectivess and safety of which should be confirmed in larger RCTs, ongoing
studies are investigating the effectiveness and safety of other biologics, including
teprotumumab and tolicizumab. Results of these studies are not available yet.
Abstract unavailable.
DOI: 10.1530/endoabs.49.S12.2
S12.3
New Development in Graves’ Orbitopathy
How to predict progression in Graves orbitopathy?
S12.1
Petros Perros
The orbital fibroblast: a key player and target for therapy in graves’
UK.
orbitopathy
Wim Dik
The Netherlands.
Graves’ orbitopathy (GO) is a relatively rare condition, but can cause
significant morbidity, poor quality of life, socioeconomic cost and
Graves’ orbitopathy
(GO) is characterized by orbital tissue inflammation,
occasionally impaired vision. Some studies indicate that nearly all patients
expansion, remodelling and fibrosis. Although the initiating trigger of GO is
with Graves’ hyperthyroidism, even those without overt GO, have
still indistinct, excessive orbital fibroblast activity is at the heart of its
subclinical eye disease. It is becoming increasingly evident that early
pathogenesis. Orbital fibroblasts are activated by cellular interactions with
recognition of GO and early interventions can affect the long-term outcome
immune cells and the soluble factors they secrete as well as autoantibodies (e.g.
favourably. Predicting which patients will develop clinical manifestations of
TSH-receptor autoantibodies). Activated orbital fibroblasts produce inflammatory
GO is therefore important. Clinical tools for early recognition of GO in a
mediators thereby contributing to the inflammatory process in GO. Moreover,
population of patients with Graves’ hyperthyroidism attending endocrine
orbital fibroblasts exhibit robust proliferative activity and extracellular matrix
clinics have been developed and are being further validated. A number of
(especially hyaluronan) synthesizing capacity and can differentiate into
clinical and biochemical parameters have been shown to be associated with
adipocytes and myofibroblasts with disease progression, thereby contributing to
progression of GO and can be used clinically to identify such cases. They
tissue expansion/remodelling and fibrosis in GO. Orbital fibroblasts, especially
include age, gender smoking status, severity of thyrotoxicosis, dysthyroid
those from GO patients, exhibit a hyper-responsive phenotype when compared to
status, use of radioiodine and the level of TSH receptor antibodies.
fibroblasts from other anatomical regions, which may further contribute to GO
DOI: 10.1530/endoabs.49.S12.3
pathogenesis. This presentation will address our current view on the role that
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Challenging Pituitary Diseases
laboratory and morphological evaluation. ES, in fact, represents a complex
syndrome which requires a multidisciplinary and dedicated team, as to ensure
S13.1
integrated therapy charge and as to prevent the occurrence of the severe disease
Hypophysitis
complications.
Niki Karavitaki
DOI: 10.1530/endoabs.49.S13.2
UK.
Hypophysitis is a rare inflammatory condition of the pituitary gland. Its
pathogenesis is poorly understood and new variants have been recently described.
It can be primary
(isolated inflammation of the gland, not related with
medications, systemic inflammatory disorders, infections, or other diseases), or
secondary (associated with systemic inflammatory processes (as sarcoidosis,
Wegener’s granulomatosis, Crohn’s disease, Takayasu’s arteritis, Cogan’s
syndrome), inflammatory cell proliferative disorders (Langerhans cell histiocy-
S13.3
tosis, Erdheim-Chester disease), infections (as tuberculosis, syphilis), tumour-
Imaging of sellar masses
associated inflammatory infiltrate
(as in germinoma), immunotherapy
(as
Michael Buchfelder
medications targeting cytotoxic T-lymphocyte antigen-4
(CTLA-4) or pro-
Germany.
grammed cell death 1 (PD-1)), rupture of sellar cysts (Rathke’s cleft cysts and
craniopharyngiomas)). The histological subtypes are lymphocytic, granuloma-
tous, xanthomatous, and plasmacytic (also termed IgG4-related hypophysitis
To date, magnetic resonance tomography is generally considered the imaging
which is often a manifestation of systemic disease). The inflammation may
method of choice for its premium resolution of lesions and surrounding anatomic
involve the anterior pituitary gland (adenohypophysitis), posterior gland and stalk
structures. This is mainly due to the improved soft tissue contrast this method
(infundibulo-neurohypophystis), or entire gland (pan-hypophysitis). Patients with
offers. Other advantages are the possibility of direct multiplanar imaging in
hypophysitis present with manifestations related to mass effect from the gland
sagittal, coronal, and axial orientations and the avoidance of ionizing radiation.
enlargement and hypothalamo-pituitary dysfunction. The severity of hormone
The goal of all imaging studies in this region is to indicate precisely the location,
deficiencies may be out of proportion to imaging findings. Radiological findings
extent, and size of a sella region tumor. These features, along with signal
include homogenous enhancement of the pituitary, diffuse symmetric gland
characteristics, frequently not only allow us to determine the presence of a lesion
enlargement, midline stalk thickening, and absence of a posterior pituitary bright
but also indicate the nature of the lesion. For this purpose, its extension in relation
spot. The diagnosis is established by biopsy and pathological examination. There
to the various surrounding structures, its structure, and its enhancement pattern
are no prospective controlled studies on the optimal management of hypophysitis
must be recognized in order to help in differential diagnosis and in treatment
and treatment remains controversial; potential options include surgery (if visual
planning. A proper set of images is required. A stepwise analysis of the images is
deterioration), glucocorticoids (at variable dosages and duration), immunosup-
suggested. For various types of lesions, typical examples are shown. In this
pressive agents and radiotherapy. Spontaneous resolution of pituitary enlarge-
context, monitoring of treatment effects is shown by using repeat imaging with
ment has been observed in a number of cases and improvement of pituitary
comparable data acquisitions. The common artifacts are discussed as well as
hormone deficits may occur after the resolution of hypophysitis.
enhancement of depiction of minute tumours. Of course, the common features
DOI: 10.1530/endoabs.49.S13.1
that allow differential diagnosis, are presented.
DOI: 10.1530/endoabs.49.S13.3
S13.2
Empty sella
Laura De Marinis
Italy.
Searching for the Cause and Approach in Ectopic Hormone
Syndromes
Empty Sella (ES) represents a heterogeneous syndrome, with a completely
S14.1
unknown pathogenesis. Defects in the organogenesis or hypoplasia of the sellar
Rare Cushing’s
diaphragm
(associated with stable or intermittent variation of intracranial
Stephen Petersenn
pressure and/or with pituitary volume variation) can facile the herniation of the
Germany.
arachnoid space into pituitary fossa and the consequently pituitary compression.
ES can be the sequel of necrosis of pituitary adenomas, of hypophysitis or of
brain/head trauma. In these condition, ES is defined secondary. In cases with
Ectopic ACTH syndrome accounts for approximately 20% of all cases of ACTH-
unknown aetiology ES is defined Primary. However, actually, obesity, systemic
dependent Cushing’s syndrome. The most common causes are oat cell
hypertension, multiple pregnancies, diabetes mellitus and pseudotumor cerebri
carcinomas, bronchial and foregut carcinoid tumors, pancreatic islet cell tumors
are considerate factor risks for the occurrence of primary ES (PES). In 50% of
and pheochromocytomas. Rarely, ectopic CRH-secretion occurs by peripheral
cases with PES a coexistent intracranial hypertension is associated, with the
tumors, especially carcinoids. Whereas the screening for hypercortisolism
occurrence of neurological signs and symptoms. The clinical manifestation of
followed by analysis of ACTH is well established, the distinction between
PES can be insidious, with subclinical or severe symptoms, as headache or
pituitary adenomas and ectopic sources in ACTH-dependent Cushing’s syndrome
papilledema, as visual disturbance or diplopia or optic neuritis, as partial or
is more challenging. Ectopic tumors producing ACTH with already suppressed
complete hypopituitarism, also associated to hyper-prolactinemia. Pituitary
pituitary ACTH levels do generally not respond even to high doses of
Magnetic Resonance is crucial for the diagnosis and allow to distinguish between
glucocorticoids. Measuring response to CRH or vasopressin may also be useful
partial or complete empty sella. A complete pituitary function clinical and
in the differential diagnosis. Inferior petrosal sinus venous sampling allows
laboratory evaluation is required to identify and diagnose hypopituitarism
definite identification of a pituitary source of ACTH, especially in combination
condition, with basal and, if necessary, dynamic test. Moreover, measurement of
with a CRH-test administered during catheterization. Localization of the source
intracranial pressure is suggested, though direct or indirect test, as lumbar
of ectopic ACTH secretion may be especially difficult. In addition to CT, MRI
puncture or optical nerve ultrasound to evaluate the thickness of the optic nerves.
and endoscopic ultrasound, nuclear medicine techniques can help greatly in
In ES affected patients, hormonal replacement therapy is required for the
identifying the source of ectopic ACTH production. Treatment often requires a
management of hypopituitarism. Moreover, treatment of intracranial hyperten-
combination of different approaches, including surgery, medical therapies to
sion is strongly suggested, though diuretic drugs, as acetazolamide. In cases of
control hypercortisolism and/or proliferation, local ablation techniques, and
drug-resistant intracranial hypertension or in cases of neurological emergencies,
PRRT. As hypercortisolism may cause more clinical problems than the
intracranial hypertension neurosurgery treatment, as ventricular shunt placement,
underlying tumor itself, bilateral adrenalectomy is performed in selected cases.
is recommended. A semestral or at least annual follow-up is suggested in these
DOI: 10.1530/endoabs.49.S14.1
patients, with endocrinological, ophthalmological and neurosurgical clinical,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S14.2
bioavailability modification is causal since a bile acid sequestrant suppresses
the beneficial effects of bile diversions on glucose control. In agreement with the
Searching for the cause and approach in ectopic hormone syndromes:
inhibitory role of bile acids on gluconeogenesis, bile diversions promote a
rare acromegaly
blunting in HGP, whereas IGN is increased in the gut segments devoid of bile. In
Franc¸oise Borson-Chazot
obese rats fed a high fat-high sucrose diet, bile diversions improve glucose control
France.
and dramatically decrease food intake. This is due to an acquired disinterest for
fatty food, leading the animals to prefer starch-enriched diet. These data suggest a
Acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) is
key role of bile and of gluconeogenesis in the favorable outcomes of metabolic
rare accounting for less than 1% of cases of acromegaly. Less than 100 cases have
surgery.
been reported in the literature mainly as case reports, except for a nationwide
DOI: 10.1530/endoabs.49.S15.2
French series of 21 cases. Ectopic acromegaly occurs more frequently in women
who represent 2/3 of cases. Median age at diagnosis is 41 years but ranges from
adolescence to elderly. GHRH secreting neuroendocrine tumors are usually well
differentiated, originating in 90% of cases from pancreas or lung. Pheochromo-
cytomas or paragangliomas have been reported in a small proportion of cases.
Positive immunoexpression for GHRH is found in most tumors. Clinical and
hormonal features of ectopic acromegaly are very similar to that of somatotropic
S15.3
adenomas and differentiating between both may be challenging. Pituitary may be
normal or enlarged at MRI which may be difficult to interpret especially in MEN1
Long term effects of metabolic surgery
patients where the association of a microprolactinoma to a pancreatic tumor
Josep Vidal
secreting GHRH may be misleading. GHRH plasmatic measurement has an
Spain.
excellent specificity for the diagnosis. Tumors are usually large and easy to
localize by conventional imaging or somatostatin receptor scintigraphy.
Abstract unavailable.
Prognosis is usually favorable, even in metastatic forms which represent 50%
of cases. Surgical approach is recommended and, when a complete tumoral
resection is feasible, results, in most patients, in long-lasting remission. In such
cases, GHRH concentration is normalized and its increase is an accurate indicator
of recurrence. In uncured patients, somatostatin analogs control GH secretion but
inhibit, only partially, GHRH secretion. MEN1 mutation should be systematically
investigated in patients with a pancreatic tumor.
DOI: 10.1530/endoabs.49.S14.2
Late-breaking: The PCSK9 Revolution
S16.1
Beyond LDL lowering: the pleiotropic roles of PCSK9
Bertrand Cariou
S14.3
France.
Rare hypoglycemia
Kimberley Kamp
Abstract unavailable.
The Netherlands.
Abstract unavailable.
S16.2
New strategies for inhibiting PCSK9
Metabolic Surgery Mechanisms to Clinical Results (Endorsed
TBC
by the European Journal of Endocrinology)
Abstract unavailable.
S15.1
The upper gut anti-incretin theory
Geltrude Mingrone
France.
Abstract unavailable.
S16.3
PCSK9 inihibition in clinical practice: present and future
Alberico Catapono
Italy.
Abstract unavailable.
S15.2
The role of bile in metabolic surgery
Gilles Mithieux
France.
Gastric bypass surgery (GBP) promotes early benefits in energy homeostasis in
What Endocrinologists Should Know about the Genomics of
obese diabetic patients, including decreased hunger and improved glucose
Endocrine Tumors
control. A suggested mechanism associates a decrease in hepatic glucose
production (HGP) with an enhanced intestinal gluconeogenesis (IGN), the latter
S17.1
promoting metabolic benefits in energy homeostasis. In addition, bile acids (BA)
Clinical consequences of the recent genomics findings in thyroid cancer
have emerged as key metabolic regulators, which might account for several anti-
Thomas Giordano
diabetic effects. Moreover, plasma bile acids are elevated after GBP and are
known to inhibit gluconeogenesis. Bile diversions mimicking GBP in lean rats
Abstract unavailable.
(re-insertion of bile in the mid-jejunum or the mid-ileum) promote an increase in
plasma bile acids and a marked improvement in glucose control. Bile
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S17.2
pathways, and production of oncogenic proteins. As regards the neoplasms
morphologically classified as poorly differentiated neuroendocrine carcinomas,
Clinical implications of SDHx mutations
concurrent results show that they might be associated with three different
Anne-Paule Gimenez-Roqueplo
molecular signatures:
(a) typical
‘high grade neuroendocrine’ signatures,
France.
characterized by mutations in TP53
and Rb, and corresponding to
‘true’
neuroendocrine carcinomas; (b) ‘adenocarcinoma-like’ signatures, corresponding
Paragangliomas and pheochromocytomas (PPGL) are neuroendocrine tumors
to aggressive carcinomas maskerading as neuroendocrine neoplasms, (c) ‘well
with a very strong genetic component. A germline mutation in one of the different
differentiated NET’ signatures, corresponding to highly proliferative well
susceptibility genes identified so far explains about 40% of all cases. Genetic
differentiated neuroendocrine neoplasms with an aggressive behavior. The
testing is recommended in every affected patient and next-generation sequencing
molecular tools now available will clearly help to refine the classification of
(NGS) is the ideal technology to screen the high number of PPGL susceptibility
aggressive, high grade neuroendocrine malignancies, but their clinical and
genes (1). The interpretation of genetic variants identified by NGS can be guided
therapeutic impact remains to be evaluated. As for low grade neuroendocrine
by the clinical presentation as well as by the secretory phenotype and by the
malignancies, the main interest of molecular profiling will probably be prognostic
immunohistochemical analysis of tumors (2). The diagnosis of an inherited form
and predictive.
drives clinical management and tumor surveillance of the patient and relatives (1).
DOI: 10.1530/endoabs.49.S17.3
While whole-exome sequencing studies showed that PPGL is characterized by a
low mutation rate of 0.3 mutations per megabase similar to other neural crest-
derived tumors, the first integrative genomic analysis of a large collection of 202
PPGL, carried out by the French COMETE network, demonstrated that mutation
status in PPGL susceptibility genes is strongly correlated with multi-omics data
and revealed the crucial role of predisposing mutations as being the main drivers
Hyperandrogenism: Challenges in Clinical Management
of PPGL (3). PPGL subtypes can be defined by a set of unique genomic alterations
S18.1
that represent different molecular entities. Transcriptomic studies identified two
Hyperandrogenic states: pitfalls in diagnostic approach
main molecular pathways, activating either the hypoxic pathway (cluster C1) or
Michel Pugeat
the MAPkinase/mTOR signalling (cluster C2). This comprehensive analysis
France.
illustrated the functional interdependence between genomic and epigenomic
dysregulations. Indeed, DNA methylation profiling uncovered a hypermethylator
phenotype specific to the tumors related to a mutation in one of the PPGL
Measuring total testosterone level is the first line approach to assess androgen
susceptibility genes encoding for a protein of the tricarboxylic cycle. Besides, we
excess in women. Most laboratories in Europe use direct testosterone
demonstrated that succinate is acting as an oncometabolite, inhibiting
immunoassay without prior extraction. In the near future, liquid chromatography
2-oxoglutarate-dependent dioxygenases, such as HIF prolyl-hydroxylases and
coupled with tandem mass spectrometry (LC-MS/MS) will be commonly used for
histone/DNA demethylases, explaining noradrenergic secretory and metastatic
measuring testosterone, providing the best accuracy with low limit of detection. In
phenotypes of PPGL classified in cluster 1A (4). A recently published novel
all cases, testosterone norms must be standardized for normal premenopausal
comprehensive multi-platform analysis of
173
PPGLs led by TCGA has
women values. Where testosterone is twice the upper limit of normal, it is
confirmed the COMETE data and identified recurrent fusions genes by RNA
recommended that DHEAS assay be performed. DHEAS is primarily of adrenal
sequencing. Altogether those data suggested new therapeutic targets for patients
origin in women. Thus, a DHEAS level of over 600 mg/dl indicates a diagnosis of
with a metastatic PPGL as well as novel diagnostic and prognostic biomarkers.
androgen-secreting adrenal carcinoma (often associated with hypercorticism). In
New ‘omics’-based tests for PPGL are likely to be transferred from research
this case, abdominal scan must be performed rapidly. Where testosterone is just
laboratories to clinical practice in order to give the access to a precise molecular
above the normal upper limit, the most likely diagnosis is polycystic ovary
classification of every PPGL, after surgery, to practicing clinicians with the goal
syndrome (PCOS). However, screening should be performed for the nonclassic
of establishing a personalized medical management.
form of 21-hydroxylase deficiency (assay of 17OH-progesterone) and depending
References
on the clinical setting, Cushing disease must be ruled. Normal testosterone levels
1. Favier, Nat Rev Endocrinol, 2015.
in patients with clear clinical symptoms of hyperandrogenism must be interpreted
2. Toledo, Nat Rev Endocrinol, 2017.
with care. Indeed, T circulates in the blood tightly bound to sex-hormone binding-
3. Castro-Vega, Nat Commun, 2015.
globulin (SHBG). Low SHBG is typically observed in overweight PCOS patients,
4. Letouzé, Cancer Cell, 2013.
in association to inflammatory state and metabolic syndrome, and contributes to
5. Fishbein, Cancer Cell, 2017.
lower total testosterone by increasing its clearance from the blood. Therefore, it is
DOI: 10.1530/endoabs.49.S17.2
recommended, to measure SHBG for correct interpretation of total testosterone by
calculating free testosterone index, awaiting direct free-T assay that is still not
available. D4-androstenedione
(A) has been studied comparatively with
testosterone, and dissociations exist, with isolated elevation of A but no elevation
of testosterone, particularly in the incident of reduced SHBG. In unusual
circumstances, dexamethasone test to suppress androgens arising from a
S17.3
functional adrenal source and gonadotropin-releasing hormone (GnRH) agonist
Will genomics help to finally classify NET’s?
in identifying ovarian androgen secreting tumor and hyperthecosis, could be
Jean Yves Scoazec
helpful. All these pitfalls should not discourage endocrinologist to challenge the
diagnosis of hyperandrogenic states. Decision trees for evaluating the origin of
France.
androgen excess will be suggested and discussed during the session.
DOI: 10.1530/endoabs.49.S18.1
The genetic landscape of neuroendocrine tumors
(NETs) is being rapidly
uncovered. It has long been known that, like other endocrine tumors, NETs might
occur in the context of familial predisposition syndromes, involving genes like
MEN1, VHL, TSC1/TSC2, NF1 and CDKN1B. Recently, several seminal papers
have described the main molecular abnormalities underlying sporadic or
apparently sporadic NETs. The results confirm that:
(a) well differentiated
S18.2
NETs from various sites are genetically distinct; (b) well differentiated and poorly
Metabolic perspectives for the non-classical CAH (NCAH)
differentiated neuroendocrine neoplasms are genetically distinct and likely
Fahrettin Kelestimur
correspond to different entities. Pancreatic and lung well differentiated NETs are
Turkey.
mainly associated with abnormalities in genes encoding proteins involved in
chromatin regulation and telomere control (such as MEN1, DAXX and ATRX
in pancreatic NETs, MEN1 again and a number of genes of the SWI/SNF pathway
Congenital adrenal hyperplasia (CAH) is one of the most common autosomal
in lung NETs); in addition, recent results have revealed the occurence of fusion
recessive inherited endocrine diseases and is characterized by complete or partial
transcripts involving EWSR in pancreatic NETs, uncovering a new perspective in
impairment of adrenal steroidogenesis.
21-hydroxylase deficiency and
11b-
the molecular mechanisms underlying pancreatic and perhaps other NETs. In
hydroxylase deficiency account for 90% and 6-8% of cases of CAH, respectively.
contrast, in well differentiated small intestinal NETs, the molecular landscape
NCAH is the mild form of CAH and occurs in approximately 0.1-0.2% in the
appears to be heterogeneous, with a high frequency of chromosomal changes and
general population. The worldwide prevalence of NCAH among hyperandrogenic
a wide spectrum of mutations involving various signalling pathways (mTOR,
women is approximately 4.0%. Adrenal androgen secretion and its response to
SMAD). Taken together, these results suggest that in well differentiated NETs,
ACTH is increased in these cases. Patients with NCAH generally present with
several oncogenic mechanisms might be involved: epigenetic dysregulations due
manifestations due to high androgen levels including hirsutism, acne and
to chromosomal and genomic instability, alterations in intracellular signalling
alopecia. Ovulatory and menstrual dysfunction are seen in more than 30-50% of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
patients with NCAH. Polycystic ovarian morphology is recorded in at least 25%
demonstrated a good outcome in more than 1,300 patients with biopsy-proven
of the patients. The data regarding insulin resistance, diabetes, obesity and
mPTC who were not submitted to TX. Thus, since only a minority of mPTC
abdominal visceral adiposity in NCAH patients is scarce. Chronic androgen
progress to a clinically overt disease, it is critical to re-evaluate the current
excess around puberty may favor abdominal visceral adiposity, insulin resistance
management strategy that indiscriminately recommends thyroid surgery that is,
and its metabolic consequences. Hyperinsulinemia and insulin insensitivity
although infrequently, burdened by complications. We retrospectively evaluated
associated with high androgen levels were reported in untreated newly diagnosed
clinical data of 293 consecutive patients with mPTC, surgically treated at our
patients with NCAH. Chronic glucocorticoid administration in a limited number
Department. After 6 years of follow-up no patient had evidence of structural
of patients may also favor metabolic abnormalities. The frequency of type 2
disease. This prompted us to obtain the approval by the ethical committee to offer
diabetes was reported to be increased in NCAH patients. It seems that NCAH is
patients an active surveillance instead of immediate surgery, when they had an
associated with increased cardiovascular and metabolic morbidity. Therefore,
intrathyroid nodule with a Thy4 or a Thy5 cytology, less than 1.3 cm of diameter,
screening metabolic abnormalities may be required in patients with NCAH.
with no evidence at US of extrathyroid extension and cervical lymphnodes
DOI: 10.1530/endoabs.49.S18.2
suspicious for metastasis. Out of 163 patients who choose active surveillance, 97
(59.5%) did not satisfied the inclusion criteria and 66 (40.5%) were enrolled in the
protocol. With a median follow-up of 12 months (6-28) only 3/66 (4.5%) were
addressed to surgery for the appearance of neck metastatic lymphnodes or an
enlargement of the nodule. 7/66 (10.6%) patients withdrew from the study. In
conclusion, the results of prospective studies will provide more precise data to
S18.3
build up a patient tailored approach for the management of mPTC.
Hyperandrogenism and cardiometabolic risk
DOI: 10.1530/endoabs.49.S19.1
Marija Pfeifer
Slovenia.
Hyperandrogenism is the main characteristic of PCOS therefore hyperandrogen-
ism in women is best addressed when studying this highly prevalent syndrome.
S19.2
Besides the clinical features of oligomenorrhea, hirsutism and infertility, PCOS
When and how should we perform extensive surgery?
patients are often insulin resistant (IR), obese, they have arterial hypertension,
Electron Kebebew
dyslipidemia, an increased pro-thrombotic state, impaired glucose tolerance or
USA.
frank type 2 diabetes (T2D). The prevalence of metabolic syndrome is doubled as
compared to non-PCOS population. Obesity, particularly of visceral origin, plays
a crucial role in both the development and maintenance of PCOS and significantly
Thyroid cancer is one of the most rapidly increasing cancer diagnoses worldwide.
influences the severity of cardiovascular risk profile. At least 30% of women with
Thyroid cancers exhibit the full range of cancer behavior from the relatively
PCOS are obese, and in some series, up to 75% are obese. About 50-60% of
indolent occult papillary thyroid cancer to the uniformly aggressive and lethal
women with PCOS have central body fat distribution. Metabolic disease in PCOS
undifferentiated thyroid cancers. Surgical resection is the principal treatment for
should be considered as a continuous variable, with metabolic dysfunction
thyroid cancer and there are several important areas of controversy in the surgical
worsening with severity of androgen excess. Increasing androgen burden is
management of thyroid cancer. Some of these controversies have arisen due to the
associated with an adverse metabolic phenotype. Androstenedione (A) has been
increasing incidence of thyroid cancer, the variable biologic behavior of low-risk
shown to be in better correlation with IR than testosterone (T) in PCOS women.
differentiated thyroid cancer, and because of the improved detection of
Recent data suggest that biochemical androgen excess poses a higher risk of liver
persistent/recurrent disease. International Surgical and Medical Societies and
disease, IR, and subclinical atherosclerosis in PCOS compared with those women
Association have proposed guidelines to the surgical management of thyroid
with anovulation and polycystic ovaries alone. Serum A is a more sensitive
cancer and the level of evidence for these guidelines will be reviewed. Three
indicator of PCOS-related androgen excess than serum total T concentrations.
critical areas in the surgical management of differentiated thyroid cancer remain
Concurrent measurement of both A and T discovers a PCOS cohort that appears to
controversial: the extent of thyroidectomy for differentiated thyroid cancer, need
be at the highest metabolic risk. The analysis of 2543 pre- and perimenopausal
for prophylactic central neck lymph node dissection in patients with papillary
women in their 40s originally included in the SWAN study indicated that
thyroid cancer, and the need for completion thyroidectomy in patients who
hyperandrogenemia but not oligomenorrrhoea was independently associated with
initially undergo hemithyroidectomy. A clinical, pathologic and molecular based
the risk of prevalent metabolic syndrome. High prevalence of cardiovascular risk
approach to address these three controversial areas in the surgical management of
factors in PCOS is assumed to be associated with accelerated cardiovascular
differentiated thyroid cancer will be proposed to personalize surgical manage-
disease
(CVD). However, clear data from large end point trials about
ment decisions in patients with differentiated thyroid cancer.
cardiovascular morbidity and mortality in PCOS is currently lacking. Though,
DOI: 10.1530/endoabs.49.S19.2
there is plenty of data on early occurrence of subclinical, potentially reversible
atherosclerosis in women with PCOS. Endothelial dysfunction is associated with
higher levels of androgens and with insulin resistance. This was observed even at
very early ages, and with a trend of deterioration of endothelial function from lean
to overweight and obese PCOS women. Recent systematic review has confirmed
that carotid intima-media thickness was thicker in women with PCOS in
S19.3
comparison to controls. PCOS women have a greater prevalence and extent of
Dynamic risk stratification in low-risk vs high-risk patients
coronary artery calcification, and that is independent of age and BMI.
Miguel Melo
DOI: 10.1530/endoabs.49.S18.3
Portugal.
In recent years, an increasing interest in an individualized approach for the care of
patients with differentiated thyroid cancer has occurred. The cornerstone of
individualized treatment is the existence of a proper risk stratification system that
supports physicians’ options regarding the treatment and follow-up of patients.
How to Incorporate the New Guidelines for Thyroid Cancer
Considering that the initial risk stratification systems account for only about 15-
in my Clinical Practice
20% of the variability in the outcome they are trying to predict, it is now well
S19.1
recognized that risk stratification is a dynamic process. The input of clinical,
biochemical and imaging data collected during follow-up, notably the response to
Thyroid microcarcinoma: to treat or not to treat?
the initial treatment, can dramatically change risk estimation and significantly
Paolo Vitti
improve its accuracy in predicting long-term outcomes. The use of this approach
Italy.
faces different problems in patients with low/intermediate risk and in patients
with high risk of recurrence. Regarding the low/intermediate risk group, dynamic
In the last 20 years, the incidence of thyroid cancer (TC) has more than doubled.
risk stratification was based in the assessment of response to an initial treatment
Since 50% of the increase is related to papillary microcarcinomas (mPTC,
that consisted in total thyroidectomy followed by radioiodine (RAI) treatment.
!1 cm), it appears that an increased detection, due to the wide use of neck
However, lobectomy is now considered a reasonable approach for some low risk
ultrasound (US), is the major factor driving this dramatic rise. Autoptic and
patients and the role of postsurgical RAI in the low/intermediate risk group is
histological studies after thyroidectomy (TX) show that 10 to 30% of adults
currently under debate. As a consequence, there are no well-established
harbor an undiagnosed mPTC. The disease-specific mortality of patients treated
thyroglobulin (Tg) cut-off points to define categories (e.g. excellent response,
by surgery for mPTC is !1% and loco-regional and distant recurrence rates are
biochemical incomplete response) in patients treated with lobectomy or total
2-6 and 1-2%, respectively. Furthermore, 2 Japanese prospective clinical trials
thyroidectomy without postsurgical RAI treatment. Nonetheless, different
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
thresholds for patients submitted to lobectomy or total thyroidectomy without
S20.3
RAI treatment have been included in clinical recommendations and recently
Induction of pancreatic beta-like cell neogenesis
validated in the low risk group. Apart from static Tg levels, the trend of both Tg
Patrick Collombat
and Tg-antibodies levels over time, with similar TSH values, has proven to be an
France.
effective way of assessing response to treatment. An increase of 20% seems to
accurately predict structural disease recurrence. High-risk patients require a very
individualized follow-up because most of the patients are expected to have
The recent discovery that genetically-modified a-cells can regenerate and convert
persistent disease after the initial treatment. For these patients, the initial follow-
into b-like cells in vivo holds great promise for diabetes research. However, to
up is mainly aimed at identifying those with progressive disease despite initial
eventually translate these findings to human, it is crucial to discover compounds
treatment. Nonetheless, most impact of dynamic risk stratification in this group
with similar activities. Herein, we report the identification of GABA as an inducer
occurs when an excellent response is found, precluding patients from an
of a-to-b-like cell conversion in vivo. This conversion induces a-cell replacement
unnecessary aggressive follow-up strategy. In this session, different ways of
mechanisms through the mobilization of duct-lining precursor cells that adopt an
implementing and refining dynamic risk stratification will be discussed,
a-cell identity prior to being converted into b-like cells, solely upon sustained
addressing the low, intermediate and high risk groups.
GABA exposure. Importantly, these neo-generated b-like cells are functional and
DOI: 10.1530/endoabs.49.S19.3
can repeatedly reverse chemically-induced diabetes in vivo. Similarly, the
treatment of transplanted human islets with GABA results in a loss of a-cells and
a concomitant increase in b-like cell counts, suggestive of a-to-b-like cell
conversion processes also in humans. This newly discovered GABA-induced
a-cell-mediated b-like cell neogenesis could therefore represent an unprece-
dented hope towards improved therapies for diabetes.
DOI: 10.1530/endoabs.49.S20.3
Beta Cell Replacement and Plasticity (Endorsed by
Endocrine Connections)
S20.1
Stem cells for b cell replacement in type 1 diabetes
Valeria Sordi
Italy.
Pluripotent stem cells (PSC), both embryonic and induced (iPSC), are the most
promising cell sources for replacement therapies. In particular for a disease like
type 1 diabetes (T1D), caused by the loss of a single specific cell type that does
not need to be transplanted back in its originating site to perform its function, a
stem cell-based cell replacement therapy seems to be the ideal cure. At present,
Environmental Influences on Endocrine Systems
however, a successful strategy for the use of PSC in patients with diabetes has still
S21.1
to overcome several important hurdles, including i) the development of in vitro
Lifestyle and environmental factors in metabolic diseases; endocrine
differentiation protocol for b cell generation, efficient and reproducible in
disruptors: new diabetogens?
different cell lines in different labs, ii) the possible tumorigenicity of PSC-derived
Patrick Fenichel
b cells, iii) the risk of allo- and auto-immune rejection upon transplantation into a
France.
subject with T1D and iv) the regulatory/economic issues associated to the use of
iPSC in humans, starting from production of GMP iPSC lines. At present, the
major challenge is how to avoid immune-rejection of stem cell-derived b cells. To
The prevalence of metabolic syndrome, obesity and type
2
diabetes has
overcome the risk of an alloimmune response we could (i) use autologous iPSC,
dramatically increased worldwide during the last few decades and exceeds
but personalized cell therapy has big economic and safety limits or (ii) iPSC from
World Health Organisation’s predictions. It is not possible anymore to explain
a cell bank with a limited number of highly selected cell donors with homozygous
this real pandemic only by genetic predisposition and/or by classical lifestyle
HLA types, to enable HLA matching for a majority of potential recipients. These
changes such as sedentary lifestyle or energy-dense diet. There is increasing
strategies, however, would not eliminate the recurrence of autoimmunity after a
experimental and epidemiological evidence suggesting that exposure to
new exposure to b cell antigens of the immune system of the T1D recipient. The
environmental factors such as noxy foods, dysbiosis or endocrine disrupting
only possible solution consists into trying to ‘hide’ the transplanted cells from the
chemicals (EDCs) may also contribute to the prevalence of DT2. EDCs are
immune system: we and others are exploring the possibility to achieve this goal
natural or synthetic chemical compounds, present in the everyday domestic
through i) the setup of a new immunosuppressive regimen for PSC-derived b
environment, interfering with hormonal regulation systems critical for energy
cells, able to contrast autoimmune response; ii) the microencapsulation of cells
homeostasis. Many are present in the food chain and after absorption are
into inert biomaterials, iii) the macroencapsulation of cells into specific devices
sequestred in adipose tissue. They may represent after low-doses exposure during
able to protect them from allo- and auto-immune response while allowing oxygen,
sensitive windows or via chronic exposure to cumulative doses, one aspect of the
nutrients, and insulin exchange and iv) the genetic manipulation of the cells to
genetic/environment interface, involved in the pathophysiology of DT2. In
escape immune recognition. If the limit of immune rejection is solved, a
humans, some epidemiologic reports suggested a strong link between exposure to
successful translation to the clinical practice of stem cell therapy for diabetes will
some persistent EDCs
(pesticides, polychorinated biphenyls, bisphenol A,
be closer.
phthalates, dioxins, polycyclic aromatic hydrocarbons) and DT2, especially
DOI: 10.1530/endoabs.49.S20.1
after acute and accidental releases of EDCs (Seveso plant explosion, Vietnam war
veterans). Other cross-sectional studies around the world reported suggestive to
strong association between diabetes and obesity and EDCs exposure, especially
for persistent organic pollutants, which should be considered as insulin-resistance
risk factors. In rodents, exposure to bisphenol A is responsible for modifications
of insulin synthesis and secretion in pancreatic beta cells but also for
modifications of insulin signaling in liver, skeletal muscle and adipose tissue,
which both lead to insulin-resistanc. In vivo and in vitro experimental studies have
shown that EDCs may act through nuclear receptors (ERs, AhR, PPARg, ERRg)
involved in metabolic control and are able to induce in specific windows of
exposure
(fetal, perinatal, pre-pubertal periods) epigenetic changes
(DNA
S20.2
methylation, histone modifications, miRNA dysregulation) programming later
obesity, insulin resistance, and/or b cell failure. It is still necessary to better
New Strategies for beta cell replacement
understand the involved molecular mechanisms, to develop additional human
Stefan Bornstein
prospective, longitudinal case/control epidemiological studies, and to identify
Germany.
early biomarkers of exposure, in order to improve assessment of chronic exposure
to mixture of EEDs in order to determine the real implication of EEDs in DT2
Abstract unavailable.
highly susceptible patients.
DOI: 10.1530/endoabs.49.S21.1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S21.2
Rare Bone Diseases (Endorsed by the European Journal of
Evidence on reproductive disorders through endocrine disruption
Endocrinology)
in-utero
S22.1
Jorma Toppari
Finland.
Approach for clinicians
Maria-Luisa Brandi
Italy.
Differentiation of male reproductive system is guided by testicular hormones and
growth factors secreted during fetal development under gonadotropin control.
Disruption of testicular hormone production or action leads to gonadal dysgenesis
Rare skeletal metabolic diseases comprise a group of diseases commonly
and maldevelopment of external genitalia. Cryptorchidism and hypospadias are
associated with severe clinical consequences. In recent years, the description of
the most common birth defects in boys, and both conditions can arise as a
the clinical phenotypes and radiographic features of several genetic bone disorders
consequence of anti-androgenic disturbance during development. Both of them
was paralleled by the discovery of key molecular pathways involved in the
are also associated with poor semen quality and testicular cancer, suggestion
regulation of bone and mineral metabolism. Including this information in the
similar pathogenetic pathways. Animal experiments show robust evidence that
description and classification of rare skeletal diseases may improve the recognition
inhibition of androgen synthesis or action causes abnormalities in testicular and
and management of affected patients. In a recent effort to recognize the rare skeletal
genital development. Chemicals with different mechanisms of action towards
diseases based on their metabolic pathogenesis 116 OMIM phenotypes with 86
declined androgen activity work in an additive fashion. Therefore even small
affected genes related to bone and mineral homeostasis were recognized. The
diseases were divided into four major groups, namely, disorders due to altered
amounts of anti-androgens can add a critical dose to the total anti-androgenic
osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix
load. While this is well documented in experimental animals, there is limited
proteins; disorders due to altered bone microenvironmental regulators; and
evidence on human harm. This is due to challenges in epidemiology to
disorders due to deranged calciotropic hormonal activity. This publication
demonstrate causal relationships, albeit there are many examples of associations
provides the first comprehensive taxonomy of rare metabolic skeletal diseases
of chemical exposures with reproductive disorders.
based on deranged metabolic activity. This classification will help in the
DOI: 10.1530/endoabs.49.S21.2
development of common and shared diagnostic and therapeutic pathways for
these patients and also in the creation of international registries of rare skeletal
diseases, the first step for the development of genetic tests based on next generation
sequencing and for performing large intervention trials to assess efficacy of orphan
drugs. For their metabolic nature, the interest of endocrinologists towards this
disorders is very high. The clinical management of these diseases from a metabolic
point of view will be illustrated during the presentation.
DOI: 10.1530/endoabs.49.S22.1
S22.2
S21.3
Osteogenesis imperfecta & Ehlers-Danlos Syndrome
Euthyroid: towards a euthyroid Europe
Anna Maria Formenti
Henry Volzke
Italy.
Germany.
Abstract unavailable.
Despite the fact that iodine deficiency (ID) can easily be prevented by iodine
fortification of table salt, industrial salt and cattle food, Europe belongs to the
worst regions in terms of access to iodized salt and is seriously iodine deficient,
resulting in the perpetuation of the single most important, preventable cause of
brain damage. Up to an estimated 360 million European citizens are exposed to
ID, which is not only due to variable iodine provision, it is also rooted in
significant heterogeneity of prevention and monitoring activities, leading to
S22.3
inappropriate interventions, health inequalities and increased disease burden with
Fibrous dysplasia of bone/McCune-Albright syndrome
substantial impact on health-care costs. A major concern remains the large
Roland Chapurlat
number of pregnant women exposed to ID, which results in a measurable decrease
France.
in cognitive potential of their children. The effects of ID in total cause significant,
preventable costs in health-care systems of affected regions. More than
30
countries contribute to the EUthyroid consortium, which is funded by the EC
Fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS) is due to a
Horizon2020 programme. The overall aims of EUthyroid are to evaluate IDD
somatic activating GNAS mutation. Patients may be asymptomatic in monostotic
prevention programmes in European countries, to initiate capacity building for
forms, which represent two thirds of cases. In those forms, the diagnosis is often
integrated activities in Europe. Coordinated measures at national and EU level are
incidental. But these monostotic FD may also be revealed by bone pain, bone
a long-term goal, which will be worked towards by targeted communication
deformity or fracture. The diagnosis is generally made in childhood or in young
activities of project results. EUthyroid has established a meta-platform for
adults. Polyostotic FD is often more severe, with a higher incidence of fragility
collaborative data collection and use. National and regional registry data are
fracture. It is also commonly associated with renal phosphate wasting. About 5%
collected to gain an overview over prevalent and incident thyroid diseases and
of patients with FD also suffer from endocrine complications, including
treatments in European nations. In parallel, EUthyroid improves the data quality
precocious peripheral puberty, growth hormone excess and hyperthyroidism.
of ID monitoring studies by providing infrastructures for training and
These endocrine conditions have to be treated as early as possible. For example,
standardization of interviews, laboratory measurements and thyroid ultrasound.
the precocious puberty generally responds well to an aromatase inhibitor,
All data will be used to provide a European map of iodine status and subclinical
letrozole. Bisphosphonates have been used to treat bone pain and reduce bone
disorders and to relate the iodine status of populations to thyroid-related outcomes
turnover for more than two decades with satisfactory outcomes in most patients.
for the evaluation of ID prevention programmes. In addition, thyroglobulin, a
This treatment can often be tapered after 2-3 years. Preventive surgery is often
novel and promising biomarker for the iodine status will be evaluated using
advised in children to avoid fracture and deformity of lower limbs. This kind of
biomaterials collected in ID monitoring studies and three mother-child cohorts
approach is also warranted in adults. A multidisciplinary management is
from regions with different iodine status. The latter cohorts will investigate the
necessary, involving specialists of bone diseases, endocrinologists, orthopedic
important association between the iodine status in pregnant women and the
surgeons, and sometimes cranio-facial surgeons along with neurosurgeons, both
neurocognitive function in their children. Combining findings from all studies,
in children and adults. New therapies e.g., denosumab and tocilizumab are
health-economic analyses will be conducted to investigate benefits and harms as
currently being studied to improve bone pain in those patients who do not
well as cost-effectiveness of IDD prevention. Potential barriers against
adequately respond to bisphosphonates. An international collaboration is
harmonized IDD prevention and monitoring programmes will be explored by
currently developing a framework that would be applicable around the world to
collecting information from national and European ministries.
improve the care of this rare disease, in particular to avoid delays in treatment.
DOI: 10.1530/endoabs.49.S21.3
DOI: 10.1530/endoabs.49.S22.3
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Endo Oncology: Prolactin, GH and Metabolic Hormones in
Conclusions
We hypothesize that GH leads to a pro-neoplastic environment and that high
Oncology Pathogenesis (Endorsed by
intracellular GH is a component of the field change enabling colon mucosal
Endocrine Connections)
proliferation. GH-mediated senescence evasion may explain why GH deficiency
S23.1
is protective for cancer.
Prolactin regulation of prostate stem cells: potential implications in
DOI: 10.1530/endoabs.49.S23.2
prostate cancer
Vincent Goffin
France.
Prostate stem cells have been proposed to participate in prostate cancer initiation.
Furthermore, based on their androgen-independence, they are suspected to trigger
prostate cancer recurrence when the tumor is no longer responsive to anti-
androgens. Therefore better understanding the regulation of this particular cell
pool may have important therapeutic relevance. In the human prostate, expression
of prolactin (PRL) and activation of its major downstream signaling effector
S23.3
Stat5, have been correlated to prostate cancer progression and relapse. To
Is reducing insulin-resistance relevant to prevent cancer?
understand these effects, we use the probasin (Pb)-PRL transgenic mouse model
Michael Pollak
which involves prostate-specific expression of PRL. Pb-PRL mice recapitulate
Canada.
many pre-neoplastic features of the human prostate including focal areas of
epithelial dysplasia, prostate intra-epithelial neoplasia and moderate inflam-
Abstract unavailable.
mation (‘reactive stroma’), together with hypertrophy and ductal dilatation of all
prostate lobes. Using various cell lineage-specific markers coupled to
immunohistochemistry and cell sorting (FACS), we showed some years ago
that the p63C basal/stem cell compartment (which contains ‘tumor-initiating’
cells) was highly enriched in Pb-PRL prostate tumors (Rouet et al, PNAS 2010).
Subsequent studies revealed enrichment of another cell population that we
discovered and named ‘LSCmed’ based on its FACS profile (Sackmann Sala et al,
Am. J. Pathol 2014). LSCmed are luminal progenitors that exhibit stem-like
properties in vitro (prostasphere assay, gland formation in transplantation assays)
and importantly, resistance to androgen deprivation in vivo. Transcriptomic
profiling showed that LSCmed is a distinct cell entity that differs from the well-
known basal and luminal cell populations and that can be identified using a
Obesity: Pharmacological Solutions
specific gene expression signature. LSCmed are rare in the normal prostate and
their amplification in Pb-PRL prostate tumors more likely results from paracrine
S24.1
signals downstream of PRLR/Stat5 signaling than from a direct PRL effect.
MSH analogs
Strikingly LSCmed represent the major cell component of aggressive, castration-
Peter Kuhnen
resistant prostate tumors driven by Pten loss, both before and after castration. This
Germany.
is particularly relevant since loss of PTEN is frequently observed in the human
prostate oncogenome. In summary, LSCmed represent a newly-identified
The leptin-melanocortin signaling pathway plays a pivotal role in the regulation
prostatic cell population that is a strong candidate for mediating cell resistance
of body weight within the hypothalamus. Leptin, secreted by the adipose tissue,
to androgen-deprivation therapy. Ongoing studies aim to elucidate the
activates the leptin receptor at the arcuate nucleus, which in turn leads to the
mechanisms that that regulate these luminal progenitors and to identify
production of proopiomelanocortin (POMC) derived peptides as melanocyte
LSCmed(-like) cells in the human prostate.
stimulating hormone
(MSH). MSH activates the melanocortin
4
receptor
DOI: 10.1530/endoabs.49.S23.1
(MC4R), regulating thereby satiety and energy expenditure. Mutations within
this pathway are leading to severe early onset obesity based on severe
hyperphagia. After the discovery of MSH, different approaches have been
made to generate MC4R agonists. Unfortunately, most of the studies were not
successful either due to ineffectiveness of the drug to reduce body-weight or due
to severe side-effects as e.g. increased blood pressure. However, recently the
S23.2
development of new MC4R agonists as setmelanotide (RM-493), which is leading
Is GH a cancer growth factor?
to severe weight loss in POMC deficient patients, has open new perspectives for
Shlomo Melmed
the treatment of monogenic obesity forms. Future studies will elucidate whether
USA.
this new compounds will be of advantage and a new treatment option for obesity
in these rare diseases.
DOI: 10.1530/endoabs.49.S24.1
Acromegaly is associated with increased soft tissue neoplasms, while GH
deficient patients are protected from cancer development. Both environmental
and age-related signals lead to cellular senescence and cell cycle dysregulation.
We have shown that DNA damage-induced cellular senescence increases GH by
inducing p53. GH, in turn, suppresses tumor suppressor proteins in both pituitary
and nonpituitary cells.These observations led us to propose that intracellular
epithelial GH in the mucosal microenvironment may enable neoplastic growth.
Mechanisms underlying pro-neoplastic GH actions include: knockdown or
suppressing either GH or GHR mRNA induces p53; GH suppresses p53 by
S24.2
inhibiting PTEN,a p53 acetylator, which protects p53 from ubiquitination, and
The future drugs to come
up-regulates TRIM29, which also destabilizes p53. Thus, p53 ubiquitination and
Gema Fruhbeck
altered acetylation underlie suppression of p53 mediated by GH. GH also induces
Spain.
mTOR, EMT transcription factors and enhanced cell motility. In vivo epithelial
p53 is markedly induced in GH-deficient Prop1K/K, and in GH receptor deficient
GHRK/K mice, and in mutant GH receptor (Laron syndrome) fibroblasts. In
A complex interaction between environmental and genetic/epigenetic factors is
nutlin-treated mice with DNA damage, GH is induced in colon epithelial cells.
driving the escalating obesity and diabetes epidemics together with a multitude of
Doubly mutant Prop1K/K (GH-deficient) and ApcminC/K (develop intestinal
associated comorbidities. In the past decades the role of gastrointestinal signals in
tumors) mice exhibit high colon p53 and markedly decreased intestinal tumor
energy homeostasis and glucose control has made tangible progress mainly due to
number and size compared to single mutant APC minC/K mice.GHR blockade
the findings derived from bariatric/metabolic surgery. In particular, incretin-based
induced by pegvisomant treatment of acromegaly patients leads to increased
approaches in relation with glucagon-like peptide 1 and amylin have fostered the
colon mucosal p53 and its transcriptional target p21. Overexpressing intracellular
emergence of new treatment avenues. Interestingly, one of the most challenging
GH, or re-introducing WT GHR to mutant human fibroblasts, suppresses p53
obstacles in obesity treatment is maintaining a lower body weight after weight
thereby evading cellular senescence.
loss. It can be argued that weight loss and its maintenance may be uncoupled
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
biological processes that require different pharmacological approaches. Thus, the
S25.2
reduction in metabolic rate triggered by a high calorie-restriction-induced weight
HPA axis, insulin resistance and adipocytokines in the
loss, contributes to powerful counter-regulatory
‘homeostatic’ mechanisms
fetal-maternal unit
leading to weight regain. Therefore, innovative strategies aimed at effectively
George Mastorakos
minimizing these compensatory adaptations with combinations of drugs (combos)
Greece.
using different mechanisms of action may prove useful. Consequently, targeting
of food hedonics in combination with the archetypical anorectic and thermogenic
pathways will probably provide unparalleled pharmacological efficacy to combat
‘Stress’ is defined as a state of disharmony or threatened homeostasis. Pregnancy
obesity and prevent weight regain. Glucagon has reemerged in weight loss
is a transient period of relative hypercortisolism. Chronic or acute stressors
polypharmacy relevantly complementing thermogenic agents. Fibroblast growth
influence maternal and fetal Hypothalamus-Pituitary-Adrenal Axes (HPA) during
factors (FGFs) are undoubtedly among a plethora of newly identified metabolic
pregnancy. Insulin sensitivity is a feature of normal pregnancy, possibly reflecting
macromolecules. Evidence that brown adipose tissue exists in adult humans and is
an adaptive phenomenon aiming at diverting maternal glucose towards fetal
activated after cold exposure has opened the interest in the potential browning of
needs. We investigated the effect of maternal stress into maternal insulin
adipose tissue and the quantitative contribution of BAT induction/activation
sensitivity during pregnancy by employing state-trait anxiety inventory (STAI)
towards energy expenditure in obesity. Novel insights that facilitate the design of
trait and state questionnaires for stress assessment and we found that in normal
refined polypharmacy that relevantly targets food hedonics at the same time as
pregnant women, enhanced long-term stress is associated with decreased insulin
stimulates energy expenditure without severe off-target effects that are currently
sensitivity. Both long- and short- term stress are associated with enhanced
frequently linked to behavioral pharmacology are being pursued.
maternal HPA axis and increased placental CRH secretion. Furthermore the
DOI: 10.1530/endoabs.49.S24.2
decrease in insulin sensitivity during pregnancy is paralleled by the progressive
increase of maternal adipose tissue deposition. Throughout pregnancy maternal
adipose tissue is metabolically active, producing adipocytokines involved in the
process of insulin resistance. Visfatin concentrations in the
1st trimester
positively predict insulin sensitivity during the 2nd trimester. Body fat mass
during 1st trimester of pregnancy is negatively associated with insulin sensitivity
during the 2nd trimester and should be kept under control. Furthermore, first
trimester maternal BMI and serum visfatin seem to be strongly associated with
fetal insulin secretion and final birth weight, respectively, suggesting a role of
early-pregnancy maternal adipose tissue in the pregnancy metabolic environment.
S24.3
Interestingly, during pregnancy, maternal GLP1
might be involved in
US experience update
mechanisms that compensate for the pregnancy-related increase in glycemia
Mike Lean
and insulin resistance, suggesting a role of this peptide in maternal metabolism
UK.
and weight and fetal growth. In conclusion, both maternal adipose tissue and
stress-induced HPA activation influence directly and/or indirectly the develop-
Abstract unavailable.
ment of insulin resistance during pregnancy.
DOI: 10.1530/endoabs.49.S25.2
HPA Axis Regulation During a Woman’s Life: Impact
on Metabolic Outcomes
S25.1
HPA axis regulation during a woman’s life: impact on metabolic
S25.3
outcomes
11b-hydroxysteroid dehydrogenase activity, androgen excess, and
Svetozar Damjanovic
metabolic outcomes in woman
Serbia.
Jeremy Tomlinson
UK.
Aging in both men and women is linked with a decline in diurnal variations in
cortisol secretion. Cortisol secretion is increased during circadian nadir and
Steroid hormones have potent metabolic effects. Glucocorticoid excess is
possibly in total through the day. Reduced suppressibility of cortisol after
characterized by central adiposity, insulin resistance, type
2 diabetes and
dexamethasone (DEX) administration and increased ACTH secretion with aging
increased cardiovascular risk. Whilst endogenous glucocorticoid excess is rare,
are well documented. It appears that aging associates with the decrease in cortisol
local tissue-specific availability of glucocorticoid is controlled by a series of
negative feedback efficacy on HPA axis due to underexpression of miner-
enzymes that are, at a pre-receptor level, able to regulate cortisol’s ability to bind
alocorticoid receptors (MRs) and imbalance of MRs to glucocorticoid receptors
and activate the glucocorticoid receptor. 11b-hydroxysteroid dehydrogenase type
(GRs) in hippocampus (HC). Chronically elevated glucocorticoids (GCs) in mice,
1
(11b-HSD1) converts inactive cortisone to active cortisol, and therefore
but not in the other species, lead to neuronal cell loss in the HC. In contrast to
amplifies local glucocorticoid action. It is highly expressed in key metabolic
these results, an age-related decline in peripheral cortisol values from 30 to 60
target tissues including liver, fat and muscle and is dysregulated in metabolic
years of age within the obese subjects has been observed. This may be explained
disease including polycystic ovarian syndrome. It has been a target for therapeutic
by emotional eating which reduce HPA axis activity by CRF suppression. No
intervention and selective
11b-HSD1 inhibitors provide modest metabolic
such correlation was found in healthy individuals with normal body-mass-index
improvements in patients with type 2 diabetes. In parallel, the A-ring reductases,
(BMI). It seems that ‘healthy’ aging does not lead to enhanced HPA axis activity
(5a- and 5b-reductase), inactivate glucocorticoids, but importantly, the isoforms
and peripheral cortisol levels rather decline with aging. Parental regulation of
of 5a-reductase convert testosterone to the more potent androgen, dihydrotes-
hippocampal GR expression as well as the priming effect of high GC
tosterone. 5a-reductase activity is increased in patients with PCOS and may
concentrations on the future responses to stressors imprint life history through
contribute significantly to the androgen excess observed in these patients and fuel
epigenetic changes within HC. Additionally, men and women tend to react
their adverse metabolic phenotype. In addition, adipose tissue is able to generate
differently with stress-both psychologically and biologically. Clinical signi-
androgens through the activity of 17b-hydroxysteroid dehydrogenase type 5
ficance of reduced adrenal androgen production (DHEA and DHEAS) with aging
(AKR1C3), and activity and expression are increased in patients with obesity and
is not well established. Aldosterone secretion appears to be slightly reduced in
PCOS. In vitro data suggest that AKR1C3 may drive lipid accumulation locally
elderly whereas sympathetic tone vary from organ to organ. Altogether aging
within adipocytes through enhanced androgen generation. In conclusion, pre-
associated changes in HPA activity only in a part depends on genetic background.
receptor steroid hormone metabolism has a powerful role to play in the regulation
Individual differences in stress reactivity might be important risk factor for
of metabolic phenotype in patients with PCOS and offers significant potential as a
gender-specific health problems in men and women.
target for therapeutic intervention.
DOI: 10.1530/endoabs.49.S25.1
DOI: 10.1530/endoabs.49.S25.3
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Tissue Specific Defects in Thyroid Hormone Action
Methods
We conduct a world-wide prospective interventional trial in which about 45
S26.1
AHDS patients receive 1 year Triac treatment. The primary end-point is the
Mouse models to study tissue specific hypothyroidism
reduction of serum T3 levels, and secondary end-points include normalization of
Heike Heuer
heart rate (HR), improvement of body weight (BW) and serum parameters that
Germany.
reflect TH action in peripheral tissues. Neuro(psycho)logical functioning is
assessed before and after 1 year of Triac treatment.
Results
Thyroid hormone (TH) actions and metabolism are intracellular events that
Currently,
41 patients (age:
1-66 years) have been enrolled (median (IQR)
require the transport of TH across the plasma membrane in target cells.
follow-up time: 8 (3-12) months) of whom 18 have completed 1 year of follow-
Consequently, impaired uptake of TH can lead to tissue- specific TH deprivation
up. Triac treatment effectively suppressed serum TSH levels (2.3 (1.6-3.9) to 0.9
independent of the TH concentrations in the circulation. A prominent example for
(0.2-1.9) mU/l; P!0.001), resulting in a strong reduction of T3 levels (5.0 (3.9-
such a scenario represents the Allan-Herndon-Dudley syndrome (AHDS). This
6.5) to
1.7
(1.4-2.2) nmol/l; P!0.001). Importantly, BMI, serum HDL
syndrome is caused by inactivating mutations in the X-linked Slc16a2 gene
cholesterol, creatinine and CK levels significantly increased, whereas basal
encoding the monocarboxylate transporter MCT8, a highly specific TH
heart rate and serum SHBG levels significantly decreased.
transporter widely expressed in CNS and peripheral tissues. Patients with
Discussion
inactive MCT8
display severe neurological symptoms and signs of brain
Triac treatment effectively normalizes serum T3 levels. This interim analysis
hypothyroidism despite highly elevated serum T3 concentrations. Likewise, Mct8
suggests that Triac treatment has beneficial effects on the peripheral phenotype of
ko mice exhibit abnormal TH serum values together with complex tissue-specific
AHDS, which will be further substantiated upon completion of the follow-up
changes in the TH status ranging from hypothyroidism (brain, pituitary) to
period by the other participants.
hyperthyroidism (liver, kidney, skeletal muscle). In order to define the tissue-
specific function of Mct8 we recently started to generate mouse mutants that lack
DOI: 10.1530/endoabs.49.S26.3
Mct8 in defined cell types only. In my presentation, I will report on our studies
demonstrating pronounced cell-specific alterations in the TH status upon deletion
of Mct8 at the blood-brain barrier (BBB), in hypothalamic tanycytes as well as in
thyrocytes while absence of Mct8 in forebrain neurons or hepatocytes did not
compromise proper tissue-specific TH action. Overall, our data clearly underscore
the importance of Mct8 and other TH transporters in mediating TH transport
thereby influencing tissue-specific TH homeostasis.
Vitamin D Beyond Bone (Endorsed by
DOI: 10.1530/endoabs.49.S26.1
Endocrine Connections)
S27.1
Heart & Vessels
Klaus Witte
UK.
S26.2
Syndromes of decreased sensitivity to thyroid hormone
Vitamin D is a recognised important factor in bone health but in recent years is
Nadia Schoenmakers
receiving much attention for its role in multiple other systems. The enthusiasm
UK.
with which it is embraced as an elixir vitae especially in cancer, cardiovascular
disease and neurodegenerative diseases is overwhelming and matched only by the
skepticism from other quarters, since solid evidence is largely lacking. I will
Disorders of thyroid hormone action are classified broadly, to encompass
review the pleiotropic effects of vitamin D and how they may be of relevance to
conditions with defective cellular uptake, metabolism or nuclear action of thyroid
the specific syndrome represented by chronic heart failure and the evidence
hormones. Genomic thyroid hormone action is mediated via receptor subtypes
generated to date by, amongst others, the VINDICATE program at Leeds.
(TRalpha, TRbeta) with differing tissue distributions. TRbeta-mediated Resist-
DOI: 10.1530/endoabs.49.S27.1
ance to Thyroid Hormone (RTH) is characterised by elevated thyroid hormones,
raised metabolic rate and cardiac hyperthyroidism but hepatic resistance
(dyslipidaemia, steatosis). In contrast, TRalpha1-mediated RTH patients exhibit
growth retardation, skeletal dysplasia and constipation together with reduced
metabolic rate and cardiac hypothyroidism, with near-normal thyroid hormone
levels. The contrasting phenotypes of TRalpha1
and beta- mediated RTH
S27.2
exemplify the differing importance of receptor subtypes in tissues, providing a
rational basis for receptor-specific drug development. Mutations in SECISBP2
Fertility
and TRU-TCA1-1 cause a multisystem disorder of defective selenoprotein
Elisabeth Lerchbaum
synthesis, with features attributable both to tissue-specific selenoprotein
Austria.
deficiencies (e.g. male infertility, muscular dystrophy) and raised cellular reactive
oxygen species due to lack of antioxidant selenoenzymes (e.g. photosensitivity,
Accumulating evidence from animal and human studies suggests that vitamin D is
increased adipose mass and function). Additionally, patients have a characteristic
involved in many functions of the reproductive system in both genders. In women,
biochemical signature resulting from impaired conversion of T4
to T3 via
vitamin D status has been associated with in vitro fertilization (IVF) outcome,
selenium-containing deiodinases. This presentation will describe clinical features
features of polycystic ovarian syndrome (PCOS), endometriosis, and sex hormone
of these conditions, which increase our understanding of thyroid hormone action
steroidogenesis. In detail, cross-sectional data suggest a regulatory role of vitamin
and inform potential future therapeutic developments.
D in PCOS-related aspects such as ovulatory dysfunction, insulin resistance as
DOI: 10.1530/endoabs.49.S26.2
well as hyperandrogenism. Moreover, results from randomized controlled trials
(RCTs) suggest that vitamin D supplementation may be beneficial for follicular
development and menstrual cycle regulation in PCOS women. Although several
data converge towards a beneficial effect of vitamin D supplementation in
metabolic disturbances in women with PCOS, this remains to be demonstrated in
S26.3
high-quality RCTs. Regarding assisted reproductive techniques, recent studies
suggest that vitamin D supplementation might be beneficial for couples
Restoring TH action in patients with transporter defects: the triac trial
undergoing IVF. In men, vitamin D status has been associated with semen
Stefan Groeneweg
quality and sperm count, motility and morphology as well as with androgen levels
The Netherlands.
in both fertile and infertile men. Further, there is evidence for a favourable effect
of vitamin D supplementation on semen quality, fertility outcomes as well as on
Mutations in the thyroid hormone (TH) transporter MCT8 result in the Allan-
testosterone concentrations. In summary, vitamin D deficiency may be a risk
Herndon-Dudley syndrome
(AHDS), which is characterized by severe
factor for adverse fertility outcomes, there is, however, insufficient evidence to
intellectual and motor disability and high serum T3 levels inducing thyrotoxicity
establish causality. High quality RCTs are needed to further evaluate the effects of
in peripheral organs. At present, no effective treatment is available. Preclinical
vitamin D supplementation on fertility and sex hormone steroidogenesis in
studies suggest that the T3 analogue Triac is a promising candidate to i) normalize
women as well as in men.
serum T3 levels and thus alleviate the thyrotoxicosis and ii) restore TH signaling
DOI: 10.1530/endoabs.49.S27.2
in the brain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
S27.3
that it was responsible for the strong bonds between mother and child but in the
recent years it was investigated in relation to other types of pair bonding, the
Muscles
development of monogamous relations, and even the relation between different
Roger Bouillon
species like between humans and dogs. It’s role in sexual orgasm was also
Belgium.
recognized. Its secretion can be influenced by a hug or a simple conversation
when feelings of trust are present. Indeed, Oxytocin could be responsible for
The vitamin D endocrine system (D-endo) is essential for calcium and bone
social behaviour as it facilitates the development of trust and empathy between
homeostasis. The vitamin D receptor, VDR, is ubiquitously expressed and about
individuals, strengthening relationships. This neuropeptide seems to facilitate
3% of the mouse or human genome is regulated by D-endo. VDR knock-out mice
security in human relations thus being supportive of positive social interactions.
show impaired striated muscle maturation and selective VDR deficiency in heart
For all of these discoveries it became known as the love hormone. However other
muscle cause cardiomyopathy. Muscle weakness may be severe in patients with
roles have also been attributed to Oxytocin: decreasing levels of stress, fear and
severe chronic renal failure combined with vitamin D deficiency or in subjects
pain, and also a sort of selective influence on memory (allowing the individual to
with congenital CYP27B1 deficiency. Muscle strength and function may be
keep some memories while eliminating others). The therapeutically potential of
impaired in elderly vitamin D deficient elderly subjects and result in increased
oxytocin has already started to be studied in diseases like autism spectrum
risks of falls. The final proof of causality is hotly debated but meta-analyses of
disorder, schizophrenia and depression. Lab tools like measurements of oxytocin
supplementation studies suggest a modest reduction in falls in elderly subjects
in plasma, brain imaging (f-MRI/PET) and genetic/epigenetic assays bring new
with severe vitamin D deficiency. All cells of the immune system express VDR. A
opportunities to explore the oxytocin pathway and will continue to help us to
large number of immune-related genes are coherently controlled by 1,25(OH)2D.
understand how to live a healthy life in a love ambience.
The native immune system is stimulated by 1,25(OH)2D. A low vitamin D status
DOI: 10.1530/endoabs.49.S28.2
is associated with an increased risk for all types of infections. Human intervention
studies however are equivocal. The acquired immune system is suppressed by
D-endo. In animal models vitamin D deficiency leads to increased sensitivity to
autoimmune diseases such as inflammatory bowel disease or autoimmune
diabetes after exposure to predisposing factors. In man, epidemiological studies
confirm such associations, but intervention studies till now fail to show preventive
S28.3
effects. The antiproliferative effect of 1,25(OH)2D on cancer cells has been
Kisspeptin and neurokinin B - novel reproductive hormones with
confirmed in most cells with inhibition of the cell cycle. VDR deficient mice are
therapeutic potential
more prone to cancer when exposed to predisposing factors. The association
Waljit Dhillo
between a low vitamin D status and colon cancer is fairly consistent in several
UK.
meta-analyses. A few RCTs however have so far not confirmed beneficial effects
on caner. In conclusion, serum 25OHD levels above 20 ng/ml may convey some
global health benefits beyond bone but ongoing studies will allow confirming or
Kisspeptin and neurokinin B are 2 novel key hypothalamic hormones which are
correcting this conclusion.
vital in normal reproductive function. Inactivating mutations for the gene or the
DOI: 10.1530/endoabs.49.S27.3
receptor for either of these peptides will cause a failure of puberty due to
hypogonadtotrophic hypogondaism. In this talk I will present evidence to suggest
that kisspeptin is important in sexual and emotional processing in humans (1). In
addition I will present evidence which suggests that NK3R (the receptor for NKB
in humans) is important as a mediator of menopausal flushing and this has
potentially practice changing therapeutic potential (2).
Sleep, Love and Reproduction (Endorsed by
References
Endocrine Connections)
1. Comninos AN, et al. Kisspeptin modulates sexual and emotional brain
S28.1
articles/view/89519
Candidate mechanisms underlying the association between poor sleep
2. Comninos AN, et al. Neurokinin 3 receptor antagonism as a novel treatment for
and obesity
menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled
Christian Benedict
trial. Lancet online on
3rd April
2017
Sweden.
6736(17)30823-1
DOI: 10.1530/endoabs.49.S28.3
An increasing proportion of people living in our 24/7 culture complain about
insomnia symptoms, i.e., they experience problems to fall and/or stay asleep. As
demonstrated by epidemiological studies, chronic sleep loss is correlated with
weight gain. To investigate whether sleep loss would alter energy metabolism in
favour of weight gain, my lab therefore performed a series of sleep loss
Novel Predictors of Diabetes
experiments in metabolically healthy normal-weight subjects. These studies
S29.1
demonstrated that acute sleep loss alters circulating levels of appetite-modulatory
metabolites (e.g. higher levels of the hunger-promoting hormone ghrelin), impairs
Novel predictors of type 1 diabetes
the ability to control food impulses, and increases metabolic efficiency. In the
Mikae Knip
setting of chronically insufficient sleep, such behavioral and metabolic effects
Finland.
may predispose normal-weight individuals to gain weight.
DOI: 10.1530/endoabs.49.S28.1
Islet autoantibodies are strong predictors of type 1 diabetes (T1D), as positivity
for multiple, i.e.is two or more, autoantibodies is associated with a risk of around
70% of progression to clinical disease over the next 10 years. Autoantibodies do
not, however, predict when T1D will present clinically. We have assessed the
utility of signs of dysglycemia for the prediction of the time of disease
S28.2
manifestation and observed that an increase in HbA1c of 10% over 3-12 months
provides a 50% likelihood of disease presentation within 1.1 year after the
Oxytocin: from biology to love
observed increase. When the HbA1c value was 5.9% (41 mmol/mol) in two
Susana Guerreiro
consecutive samples, the median time to diagnosis was 0.9 years. The median
Portugal.
time to diagnosis after the detection of impaired glucose tolerance on OGTT was
0.7
years. After the detection of an increased random plasma glucose
Oxytocin was discovered by Henry Dale in 1906 and synthesized in the early 50’s
(R7.8 mmol/l) the median time to diagnosis was
1.0
years. The omics
by Vincent du Vigneaud and coworkers. It is secreted by axonal terminals in the
technologies have raised the issue, whether there is a possibility to identify
neurohypophysis emanating from the neurosecretory neurons of the supraoptic
high risk individuals before the appearance of the first autoantibodies. We have
and paraventricular nuclei of the hypothalamus. This hormone similarly to others
looked at markers generated by transcriptomics. We observed that genes and
is secreted in a pulsatile way and, classically, in relation to labor
(uterine
pathways related to innate immunity functions, such as the type 1 interferon (IFN)
contractility), lactation and to the maternal behaviour. After the initial
response, were active, and IFN response factors were identified as central
identification of its role in labor induction and lactation it became clear that
mediators of the IFN-related transcriptional changes. In a proteomics study we
Oxytocin plays other very important roles in human life namely in the creation of
found that when including the total observation time from birth to diagnosis we
bonds which gave this hormone the title of social hormone. First it became clear
were able to classify the participants into disease progressors and non-progressors
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
with a success rate of 91%. The classifica-tion was based on the combination of the
novel clinical relevance attributed to steroids previously deemed irrelevant and
relative levels of APOC4 (decreased) and afamin (AFAM, increased). Lipidomics
successful implementation of new anti-cancer treatments. Prostate cancer is a
and metabolomics analyses showed that individuals who developed T1D had
prime example of the latter with the recent confirmation that castration-resistant
reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth,
disease is still androgen-dependent and susceptible to hormonal manipulation
reduced levels of triglycerides and antioxidant ether phospholipids throughout the
with next generation steroidogenic enzyme inhibitors and anti-androgens. In
follow up, and increased levels of proinflammatory lysoPCs several months before
advanced stages of prostate cancer hormonal treatment leads to complex and
seroconversion to autoantibody positivity. The appearance of insulin and glutamic
incompletely understood changes in circulating steroid hormones levels. CYP17
acid decarboxylase autoantibodies was preceded by diminished ketoleucine and
inhibitors like abiraterone acetate lead to accumulation of mineralocorticoid
elevated glutamic acid. Another study focusing on the lipidome/metabolome in
precursors and progesterone metabolites. This ensues a steroid flux into the
cord blood revealed that those children, who progressed quickly to clinical T1D,
alternative pathway to 5a-dihydrotestosterone (DHT) with intermediates such as
were characterized by a distinct cord blood lipidomic profile that includes reduced
allopregnanolone and androstanediol. Our data in parental and abiraterone-
major choline containing phospholipids, including sphingomyelins and phospha-
resistant prostate cancer cells show a functional block at the level of CYP17 in
tidylcholines. Risk children, who progress to clinical T1D are characterized by a
prostate cancer cells, preventing de novo steroid synthesis and local activation of
decreased microbial diversity, an increased abundance of potentially pathogenic
CYP17 precursors. However, accumulation of other steroid hormones intratu-
bacteria and a reduced functional gene content in their intestinal microbiome.
morally could affect nuclear receptor activation. Concurrently, interaction with
These changes, can however, not be seen before seroconversion to autoantibody
supplemented glucocorticoids leads to a complex interaction between wild type,
positivity. To summarize, metabolic markers help in the estimation of time to
mutant and splice variants of nuclear receptors and DNA regulatory elements.
diagnosis in prediabetic individuals. The potential predictive markers generated by
Further research into pre-receptor regulation of steroid hormones combined with
omics technologies have to be validated.
innovative genome-wide receptor-DNA binding analyses will pave the way
DOI: 10.1530/endoabs.49.S29.1
towards comprehensive understanding of their effects. In turn, this could secure
efficient targeting of the detrimental sequelae of steroid hormones in prostate
cancer and other endocrine diseases.
DOI: 10.1530/endoabs.49.S30.1
S29.2
Clinical and genetic indicators for diabetes prediction
Valeriya Lyssenko
Denmark.
S30.2
Clinical relevance of steroid precursors in adrenocortical tumors
Vasileios Chortis
Worldwide diabetes epidemic leads to exponential increase in incidence and
prevalence of associated co-morbidities and mortality. During the last 10 years we
have devoted to investigate how clinical and genetic biomarkers can be used to
facilitate prediction of these life-threatening hazards. Accumulating evidence
Adrenal incidentalomas represent an increasingly common diagnostic problem
from our large prospective studies indicate that decline in insulin secretion
facing clinical Endocrinologists. Swift and accurate differentiation of benign from
adjusted for the degree of insulin sensitivity is the key factor contributing to overt
malignant disease is essential, but the diagnostic performance of current imaging
type 2 diabetes. Furthermore, genetic data indicate that risk alleles in genetic loci
modalities is sub-optimal and often leads to ill-advised management decisions.
for type 2 diabetes influenced changes in pancreatic beta-cell function over time,
Urinary steroid profiling by modern mass spectrometry-based techniques can
while having no effect on changes in body mass index. Presently, genetic
provide a comprehensive profile of steroidogenesis, quantifying both precursor
information has insufficient power to predict common type 2 diabetes. However,
molecules and end products. Adrenocortical carcinomas display a premature
our follow-up studies on variants in TCF7L2, MTNR1B, GIPR, GRB10 genes
pattern of steroidogenesis, dominated by precursor hormone synthesis, which can
unravelled multiple and pleiotropic mechanisms of genetic loci which
be captured in the urinary profile. Emerging evidence highlights the unique
significantly contributed to our understanding of pathogenesis of type 2 diabetes
diagnostic opportunities presented by this feature. The combination of high-
including effects on insular-incretin axis (GIP/GLP-1 and glucagon) and hepatic
sensitivity biochemical analysis and computational data processing is expected to
glucose production in the liver. We and others have also reported
transform the management of adrenal tumours, from the diagnostics of adrenal
a-hydroxybutyrate, linoleoyl glycerophosphocholine, and copeptin as novel
incidentalomas to the post-operative surveillance of adrenocortical carcinomas.
biomarkers to be associated with increased risk of type 2 diabetes. However, these
DOI: 10.1530/endoabs.49.S30.2
new biomarkers require a systematic evaluation and validation across different
studies and populations before their actual diagnostic and prognostic value is
confirmed.
DOI: 10.1530/endoabs.49.S29.2
S30.3
Glucocorticoid production in primary aldosteronism - from
mechanisms to clinical implications
Felix Beuschlein
Germany.
S29.3
Novel predictors of diabetes - NAFLD, diabetes and CVD
Enzo Bonora
Adrenal aldosterone excess is the most common cause of secondary hypertension
Italy.
and is associated with increased cardiovascular morbidity and mortality.
However, adverse metabolic risk in primary aldosteronism extends beyond
hypertension, with increased rates of insulin resistance, type 2 diabetes, and
Abstract unavailable.
osteoporosis, which cannot be easily explained by aldosterone excess but would
rather be associated with oversecretion of glucocorticoids. Over the last years,
exome sequencing has provided new insights into the genetic set-up of adrenal
adenomas highlighting the concept of calcium dependent signalling being the
main driver for aldosterone secretion while the cAMP/PKA pathway can be
considered of particular importance for cortisol production. In rare examples
somatic mutations in genes involved in cAMP signalling could be identified.
Moving Away from Old-fashioned Steroidogenesis:
However, in the majority of cases the contribution of glucocorticoid oversecretion
What Are the Clinical Implications?
in patients with primary aldosteronism has remained uncertain. Recently, we have
S30.1
performed mass spectrometry-based steroid metabolome profiling in 24-h urines
from consecutively recruited patients with primary aldosteronism. Comparisons
Clinical relevance of alternative synthesis of androgens
were made with healthy controls, patients with endocrine inactive adrenal
Hans Hofland
adenoma, and patients with mild subclinical and clinically overt adrenal cortisol
The Netherlands.
excess. Based on these measurements, patients with primary aldosteronism had
significantly increased cortisol and total glucocorticoid metabolite excretion, only
Recent years have seen many exciting developments in the field of
exceeded by glucocorticoid output in patients with clinically overt adrenal
steroidogenesis. These include improved diagnostics through mass spectrometry,
Cushing syndrome. Several surrogate parameters of metabolic risk correlated
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
significantly with glucocorticoid but not mineralocorticoid output. We analysed
GS1.3
the expression of cortisol-producing CYP11B1
and aldosterone-producing
Adult aspects of turner syndrome
CYP11B2 enzymes in adrenal adenoma tissue from patients with primary
Janielle Alfen-van der Velden
aldosteronism, employing immunohistochemistry with digital image analysis.
Intra-tumoral expression of CYP11B1 correlated significantly with glucocorti-
In this session, the adult aspects of Turner syndrome are addressed following the
coid excretion, whereas CYP11B2 expression correlated with aldosterone output.
new Clinical Practice Guidelines for Turner syndrome. The presentation includes
Unilateral adrenalectomy for adenoma removal resolved both mineralocorticoid
both theoretical backgrounds and practical recommendations. Fertility preser-
and glucocorticoid excess. Postoperative evidence of adrenal insufficiency was
vation is discussed and the results of our GRADE evaluation according to the
found in roughly one third of tested patients. These data show that glucocorticoid
outcome of oocyte donation is presented. New insights in health surveillance for
co-secretion is a prevalent feature in primary aldosteronism and significantly
co-morbidities are highlighted. Practical tools for transition from pediatric to
contributes to associated metabolic risk. Mineralocorticoid receptor antagonist
adult care are provided. In addition, a toolbox for neuropsychological and
therapy alone may not be sufficient to counteract adverse metabolic risk in
psychological assessment of women with Turner syndrome is presented and
medically treated patients with primary aldosteronism.
possible options for intervention are discussed.
DOI: 10.1530/endoabs.49.S30.3
DOI: 10.1530/endoabs.49.GS1.3
Guided Session 1
GS1.4
Cardiovascular health issues in turner syndrome
GS1.1
Philippe Backeljauw
New international clinical practice guidelines for the care of girls and
women with turner syndrome
Individuals with Turner syndrome (TS) have an increased risk for congenital and
Claus H Gravholt
acquired cardiovascular disease (23-50%). This results in increased morbidity
Denmark.
and mortality throughout the TS lifespan. There is an increased prevalence of
bicuspid aortic valve malformation, coarctatio of the aorta, elongation of the
transverse aortic arch, and partial anomalous venous return. In addition, TS
Turner syndrome (TS) affects 25-50 per 100 000 females and can involve
females may develop aortopathy that may result in clinically significant aortic
multiple organs through all stages of life, necessitating a multidisciplinary
dilatation, which occasionally leads to dissection or rupture. Other cardiovascular
approach to care. Previous guidelines have highlighted this, but numerous
conditions such as hypertension, coronary heart disease, and cerebrovascular
important advances have been noted since their publication. These advances
disease (stroke) further reduce the lifespan of TS individuals. Because of this high
cover all specialty fields involved in the care of girls and women with TS. This
prevalence of cardiovascular disease, any care provider should have some
new international guideline is based on an international effort that started with
familiarity with the non-invasive cardiac imaging techniques required for
exploratory meetings in 2014 in both Europe and the USA, and culminated with a
diagnosis and management. Imaging modalities include transthoracic echocar-
Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this
diography and cardiac magnetic resonance imaging. Echocardiography is useful
meeting, five groups each addressed important areas in TS care: i) diagnostic and
in the diagnosis of a bicuspid aortic valve and other congenital heart diseases, and
genetic issues, ii) growth and development during childhood and adolescence, iii)
can be used for surveillance of aortic dilatation. Some abnormalities, such as
congenital and acquired cardiovascular disease, iv) transition and adult care, and
elongation of the transverse aortic arch and partially anomalous pulmonary
5) other comorbidities and neurocognitive issues. These groups produced
venous return, are not as readily ascertained by ultrasound however, and cardiac
proposals for the new guidelines. Additionally, four pertinent questions were
magnetic resonance imaging is now commonly used as a screening and
submitted for formal GRADE
(Grading of Recommendations, Assessment,
surveillance tool, especially in adult TS patients. The newly developed clinical
Development and Evaluation) evaluation with a separate systematic review of the
care guidelines for girls and women with TS include very specific recommen-
literature. These four questions related to the efficacy and most optimal treatment
dations on which aortic dimensions may warrant consideration for close
of short stature, infertility, hypertension, and hormonal replacement therapy.
monitoring and possible operative intervention. They also provide guidance in
These guidelines were initiated and developed by the European Society of
decision-making regarding participation in various sports disciplines, and greatly
Endocrinology (ESE) in Europe, and by the Pediatric Endocrine Society (PES) in
clarify when more frequent cardiovascular health monitoring may be beneficial. It
USA, with important contributions from the European Society of Human
is important that both pediatric and adult endocrinologists, as well as reproductive
Reproduction and Embryology
(ESHRE), the Endocrine Society
(ES), the
endocrinologists, are familiar with the updated recommendations for cardiovas-
European Society for Cardiology (ESC), the American Heart Association (AHA),
cular health management in TS, in order to coordinate care with the cardiologists
and the European Society for Pediatric Endocrinology (ESPE). Several delegates
and to facilitate over health maintenance of girls and women with TS.
from other societies also participated. Advocacy groups appointed representatives
DOI: 10.1530/endoabs.49.GS1.4
who participated in pre-meeting discussions and in the consensus meeting. Here,
we will present the most important new advances in the care of Turner syndrome.
DOI: 10.1530/endoabs.49.GS1.1
GS1.5
Abstract unavailable.
GS1.2
Growth and puberty induction
Theo Sas
The Netherlands.
In July
2016, an International Turner Syndrome Meeting was organized in
Cincinnati, Ohio, USA. Today, an updated document concerning the Clinical
Practice Guidelines for the Care of Girls and Women with Turner Syndrome is
finalized. This document gives the summary of the evidence and expert opinions
GS1.6
about several aspects of the treatment and follow-up of individuals with Turner
syndrome. It will be published soon. In this presentation, the main conclusions
and recommendations about growth and induction of puberty will be reported and
discussed.
Abstract unavailable.
DOI: 10.1530/endoabs.49.GS1.2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Guided Session 2
GS2.4
GS2.1
Aggressive pituitary tumours
Stephen Petersen
Aggressive pituitary tumours
Denmark.
Olaf Dekkers
The Netherlands.
Abstract unavailable.
Abstract unavailable.
GS2.5
GS2.2
Aggressive pituitary tumours
Aggressive pituitary tumours
Anthony Heaney
Ann Mc Cormack
USA.
Australia.
Abstract unavailable.
Abstract unavailable.
GS2.3
GS2.6
Aggressive pituitary tumours
Aggressive pituitary tumours
Vera Popovic
Jacqueline Trouillas
Slovakia.
France.
Abstract unavailable.
Abstract unavailable.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
New Scientific Approaches
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
NSA1
NSA4
Identifying molecular signatures for cancer patient stratification via
CRISPR/cas9 cas9-generated mouse models of resistance to thyroid
metabolomics and integrative bioinformatics
hormone due to THRA mutations
Hector Keun
Frederic Flamant
UK.
France.
Altered metabolism in tumor cells is required for rapid proliferation but also can
Resistance to thyroid hormone due to THRA mutations (RTHa) is a recently
influence other phenotypes that affect clinical outcomes such as metastasis and
discovered genetic disease with high variability in its clinical presentation. This
sensitivity to chemotherapy. Integration of metabolome and transcriptome data
variability may result from the fact that patients bear different types of mutations,
for the NCI-60
panel of cancer cells lines allowed us to identify ecto-50 -
which may impact in different ways the functionality of thyroid hormone receptor
nucleotidase
(NT5E or CD73) and miRNA-22 as a major determinants of
a1 (TRa1). Our aim was to understand the relationship between specific
metabolic phenotypes in cancer cells. NT5E expression and associated
THRA mutations and symptoms, using mouse models. CRISPR/Cas9 genome
metabolome variations were also correlated with sensitivity to several
editing was used to generate five new models of RTHa, the human genetic disease
chemotherapeutics including platinum-based treatment. We observed that
caused by mutations in THRA. Like human patients, the mutant mice displayed a
tumor NT5E levels were prognostic for outcomes in ovarian cancer and were
hypothyroid-like phenotype, with altered post-natal development. Phenotype
elevated after treatment with platinum, supporting the translational relevance of
severity varied over a broad range between models, mainly depending on the
our findings. The cancer-associated and cardioprotective miR-22 was shown to
ability of the mutant receptor to interact with the NcoR transcription corepressor
repress fatty acid synthesis and elongation in tumour cells by targeting ATP
in the presence of thyroid hormone. These data illustrate the outstanding
citrate lyase and fatty acid elongase 6, as well as impairing mitochondrial one-
possibilities offered by CRISPR/Cas9 genome editing which allows to rapidly
carbon metabolism by suppression of methylene tetrahydrofolate dehydrogen-
produce mouse models of human genetic disease, and even to model individual
ase/cyclohydrolase (MTHFD2). Importantly, a beneficial effect of miR-22 on
sporadic cases of the disease.
clinical outcomes in breast cancer was shown to depend on the expression levels
DOI: 10.1530/endoabs.49.NSA4
of the identified target genes, demonstrating the relevance of miRNA/mRNA
interactions to disease progression in vivo. These studies illustrate one route
towards patient stratification based the rational combination of different types of
molecular biomarkers for metabolic processes.
DOI: 10.1530/endoabs.49.NSA1
NSA5.1
Methodical tools for the structural elucidation of G-protein coupled
receptors
Patrick Scheerer
NSA2
Germany.
Exosome profiling: potential in cancer diagnosis and stratification
Juan Falcon-Perez
Spain.
In my short methodological talk, I will present why we need a detailed structural
description of membrane proteins such as the TSH receptors (TSHR) of the
endocrine system and how can we succeed to get three-dimensional structures.
In the last decade, cell-secreted extracellular vesicles (EVs) have been isolated
The talk includes a methodical toolbox of protein-production or -stabilization and
from most of the fluids of the body. There are many different types of EVs that
advanced structural biology techniques like protein X-ray crystallography and
include different subpopulations of exosomes, microvesicles and apoptotic bodies,
cryo-electron microscopy for selected examples.
all of them varying in size, composition and intracellular origin. Many laboratories
DOI: 10.1530/endoabs.49.NSA5.1
around the world have shown that its composition of lipids, proteins, messenger
and micro RNAs is cell-type specific, and subject to changes in pathological
scenarios, consequently these vesicles are being actively studied as a source to
identify disease biomarkers. Metabolic syndrome is a clinical condition affecting
up to 25% of all adults worldwide. It influences many cellular systems including
adipose tissue, macrophages and hepatocytes compromising most of the time the
NSA5.2
hepatic function that is essential for homeostasis of the organism. Apart of
Small molecule agonists and antagonists as potential new therapeutics
metabolic syndrome, liver injury ranging from mild infection to life-threatening
targeting the TSH receptor
liver failure constitute by itself a serious worldwide health issue. Consequently, a
Susanne Neumann
major goal in liver pathology is the identification of molecular markers for its early
USA.
detection, i.e. before clinical manifestations are produced. In this context, by
applying metabolomics, proteomics and transcriptomics technologies as well as
specific biochemical tools, our group is studying the physiological role of
Thyroid-stimulating hormone (TSH, thyrotropin) is an activator of the TSH
extracellular vesicles in the hepatic function in normal and pathological conditions
receptor (TSHR) in the hypothalamic-pituitary-thyroid axis leading to biosyn-
to identify novel low-invasive markers for liver injury. During last years, our group
thesis and secretion of thyroid hormones. We have developed an orally available
has demonstrated that hepatocytes are able to secrete exosomes-like vesicles
small molecule, allosteric TSHR agonist, E2, for follow up diagnosis of patients
enriched in metabolic enzymes. Now, we are currently achieving a thorough
with thyroid cancer. This ligand could replace recombinant human TSH (rhTSH,
qualitative and quantitative analysis by proteomics, transcriptomics and
Thyrogen) which is currently used in the clinic. In a mouse model, oral
metabolomics of extracellular vesicles secreted by hepatocytes obtained from
administration of E2 is as efficacious as intraperitoneal injections of rhTSH.
experimental models of drug-induced liver injury and metabolic syndrome. Our
Therefore, E2 represents a next step in the pre-clinical development of an oral
work provides a repertoire of low invasive candidate markers to evaluate hepatic
drug to stimulate radioiodine uptake and/or serum thyroglobulin levels in patients
function in a low invasive manner. Furthermore, our results also support a
with thyroid cancer. Graves’ disease (GD) is caused by persistent, unregulated
physiological role of hepatic exosomes in different patho-physiological processes.
stimulation of thyroid cells by thyroid-stimulating antibodies
(TSAbs) that
activate the TSHR. We identified the first small molecule TSHR antagonist
DOI: 10.1530/endoabs.49.NSA2
(ANTAG3) which inhibits TSH- and TSAb-stimulated signaling. ANTAG3 is
selective for TSHR because it does not inhibit activation of LH or FSH receptors,
the receptors with the highest homology to TSHR within the seven
transmembrane domain in which ANTAG3 binds, and it inhibits TSHR activation
in the thyroid gland of mice in vivo. These findings suggested that ANTAG3
NSA3
could be able to inhibit TSHR signaling in extra-thyroidal tissues that express
Genomic approaches on epigenetics
TSHRs including orbital fibroblasts, which play a role in the pathogenesis of
Salvatore Oliviero
Graves’ ophthalmopathy (GO), a disease of the eye that is associated with GD.
Italy.
None of the treatment regimens for GD and GO used today are directed at the
pathogenesis of these diseases. In an ideal case the same drug would treat
Graves’ hyperthyroidism and GO. ANTAG3, directly acting at the TSHR,
Abstract unavailable.
reduced TSH- and TSAb-stimulated hyaluronan
(HA) production, a major
component of GO, by Graves’ orbital fibroblasts. Crosstalk between the TSHR
and the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) initiated by
activation of TSHR may play a prominent role in the development GO. We have
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
shown that TSHR activation alone is sufficient to stimulate HA secretion, through
nuclear DNA methylation is a well stablished feature, very little attention has
both IGF-1R-dependent and -independent pathways. ANTAG3 inhibited both
been devoted to mitochondrial epigenetics. Obesity is often associated with a state
IGF-1R-dependent and -independent pathways at all doses of the monoclonal
of mild chronic inflammation characterized by an abnormal production of
stimulating antibody M22; whereas IGF-1R antagonist linsitinib
(a small
proinflammatory and prooxidant mediators. This proinflammatory condition has
molecule kinase inhibitor) and 1H7 (inhibitory antibody) lost efficacy at high
been linked to a mitochondrial dysfuncion. In fact, an energy restriction therapy
M22 doses. We propose that combination therapy targeting TSHR and IGF-1R
devised to lose weight induces an increase in the intracellular ATP content and
may be an effective treatment strategy, especially for GO. We suggest that small
mitochondrial-related gene expression, concomitantly with a decrease oxidative
molecule TSHR antagonists are leads for the development of orally active drugs
stress and inflammatory markers. Mitochondrial dysfunction and the increment of
to treat patients with Graves’ hyperthyroidism and GO.
mitochondrial Reactive Oxygen Species
(ROS) production are important
DOI: 10.1530/endoabs.49.NSA5.2
benchmarks of the aging and metabolic disturbances development. Therefore,
the mitochondrial dysfunction might be critically involved in the pathogenesis of
obesity. However, the molecular mechanisms leading to mitochondrial
dysfunction in metabolic diseases are still unknown. In this context,
mitochondrial epigenetics is a novel mechanism to understand the pathobiology
of diseases with a mitochondrial dysfunction involvement. Epigenetic regulation
NSA6
of mtDNA has received increasing attention in the last years due to its implication
Mitochondrial epigenetics in obesity and its co-diseases
in clinically relevant disease. Variations in mtDNA methylation were associated
Ana Belén Crujeiras
with exposure to pollutants and Nonalcoholic fatty liver disease (NAFLD) and
were proposed to have a role in mitochondrial gene expression regulation.
The biological regulatory system through which the organism responds to
mtDNA methylation was reported to be induced by hyperglycaemia in retinal
environmental pressures is mediated by epigenetic modifications of the genome
endothelial cells and to negatively regulate mitochondrial gene expression.
without altering the DNA sequence. Among the epigenetic processes, DNA
Moreover, mitochondrial epigenetic can modulate nuclear DNA and nuclear
methylation is perhaps the best understood epigenetic adaption and most common
DNA epigenetic may affect mtDNA. Hence, abnormal mtDNA methylation is
DNA modification. This mechanism plays an important role in regulating the
attracting increasing attention as potential biomarker and might have therapeutic
gene expression of many biological processes and has wide-ranging effects on
potential for metabolic diseases management.
health. Aberrant epigenetic regulation has been described in many human
diseases. Concretely, there is growing body of evidence that shows a relevant role
DOI: 10.1530/endoabs.49.NSA6
of epigenetic marks with obesity and its co-disease susceptibility. However, while
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Debates
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Is There a Role for Medical Therapy for Non- Functioning
Incidentally Discovered Nonfunctioning Pancreatic NETs:
Pituitary Adenomas?
Surgery or Not? (Endorsed by the European Journal of
D1.1
Endocrinology)
Is there a role for medical therapy for non- functioning pituitary
D2.1
adenomas? - FOR
Incidentally discovered nonfunctioning pancreatic NETs: Surgery or
Yona Greenman
not? - FOR
Israel.
Ulrich Knigge
Denmark.
In this debate I will make an overview of outcomes of NFPA patients with post-
operative remnants, who were treated conservatively after surgery. In view of the
Pancreatic incidentalomas are defined as asymptomatic pancreatic lesions,
high rates of tumor progression with consequent need for repeated surgery and
discovered incidentally by imaging for an unrelated indication. A significant
radiation therapy, we propose the use of dopamine agonists in these patients.
proportion of these tumors may be malignant or have a malignant potential. As the
Recent data showing that preventive treatment with dopamine agonists
use of improved cross sectional imaging increases incidentalomas are becoming
significantly reduces the rate of tumor progression and the need for radiation
more common. In the ENETS guidelines it is proposed that selected patients with
therapy or additional surgical interventions will be reviewed.
incidentally found sporadic, asymptomatic, non-functioning
(NF) pancreatic
DOI: 10.1530/endoabs.49.D1.1
neuroendocrine neoplasms (pNEN) less than 2 cm in size may be followed with
repeated imaging instead of resected. However, this conclusion is based on
limited data as only few and retrospective studies with a heterogeneous design
have investigated the safety of active surveillance. Only few patients had
histological or cytological diagnosis and the Ki67 proliferation index, which is the
most powerful prognostic marker in NF pNEN, was only determined in 10% of
the patients. Up to 20% (in a single study 50%) of the patients had significant
tumor growth although regional lymph node metastases developed in few
patients. In a recent study, 38% of pNEN !2 cm displayed malignant features.
Hence, it cannot be predicted which patients will progress during observation.
Accordingly, active surveillance is a doubtful approach and resection should be
offered patients with small NF pNEN, if not contraindicated by age, severe
co-morbidity and poor performance status. Surgical procedures for small NF
pNEN are safe when performed in high-volume centers. In contrast, in MEN-1
D1.2
patients NF pNEN % 2 cm are generally indolent tumors with low malignant
features and surgical treatment is rarely indicated.
Is there a role for medical therapy for non- functioning pituitary
adenomas? - AGAINST
DOI: 10.1530/endoabs.49.D2.1
Stylianos Tsagarakis
Greece.
Non-functioning pituitary adenomas
(NFPA) are the second most common
variant of pituitary tumors. They are presented by compression symptoms,
hypopituitarism and in rec as incidental findings during brain imaging. When
symptomatic, primary therapy for NFPAs is surgery most commonly by the trans-
D2.2
sphenoidal (TSS) approach. Medical therapy is not generally recommended in
Incidentally discovered nonfunctioning pancreatic NETs: Surgery or
this setting, particularly when immediate decompression of the optic chiasm is
not? - AGAINST
needed. Despite the debulking efficacy of TSS, in many occasions only partial
Reza Kiamanesh
tumor resection is achieved. Recurrence rates are high in partially resected
France.
tumors. Although less frequently, even completely resected tumors may also
recur. Therefore, there is a need for post-surgical surveillance and intervention in
Abstract Unavailable.
order to prevent recurrence. The current practice in most centers is to follow-up
the pituitary lesion by MRI-imaging and offer additional therapy, usually in the
form of radiotherapy (RT), in case of recurrence. RT, either conventional or
stereotactic, is effective in controlling further tumor growth but its use is
compromised by significant side effects. Based on findings that many NFPAs
demonstrate expression of dopamine and somatostatin receptors, medical therapy
with dopamine agonists (DA) and somatostatin analogues (SSA) have been used
after surgery in order to prevent recurrence. So far, DAs have been more widely
tested showing some promise in several small-scale case series. In a recent larger
Drug Holiday in Osteoporosis (Endorsed by the European
study, introduction of DA immediately after surgery led to a lower number of
Journal of Endocrinology)
recurrences compared to a control group that did not receive DA therapy.
However, since not all patients will recur, such a strategy exposes a substantial
D3.1
number of patients to unnecessary long-term DA therapy. Unfortunately there are
Drug holiday in osteoporosis - FOR
no robust predictors for tumor recurrence. In fact, the best predictor of tumor
Bente Langdahl
growth is growth itself. However, DA therapy was less effective when introduced
Denmark.
later in patients that already demonstrated a tendency for tumor regrowth.
Surprisingly the beneficial effect of DA therapy does not correlate with dopamine
Abstract Unavailable.
receptor expression. This finding raises concerns about the pathophysiological
background of the observed DA benefit. Moreover, there are no solid data on hard
end points e.g. prevention of visual fields defects and avoidance of second
surgery. Although early initiation of treatment may be preferable, dosage and
duration of treatment are largely empirical. The need for higher doses and long
treatment periods raises some safety concerns. Definitely a well-designed
randomized control trial will resolve many of these issues. However, the lack
D3.2
of industrial interest and the long time-length required to obtain valid data, limits
Drug holiday in osteoporosis - AGAINST
the feasibility of such a perspective. To summarize, the promise of most
Dennis Black
medications is limited by imprecisions regarding the final outcome and
USA.
uncertainties on dosing and duration of preventive therapy. So far, effective
medications have rendered prolactinomas and acromegaly well manageable
disorders. For NFPAs such a possibility still remains elusive.
Abstract Unavailable.
DOI: 10.1530/endoabs.49.D1.2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Is Cardiovascular Risk Increased in Women with PCOS?
D5.2
D4.1
Should we still ablate all patients undergoing total thyroidectomy for
thyroid cancer? - AGAINST
Is cardiovascular risk increased in women with PCOS? - FOR
Sophie Leboulleux
Harpal Randeva
France.
UK.
Regarding the debate about whether we should still ablate all patients undergoing
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder
total thyroidectomy, the answer is no. Most thyroid cancer patients have an
amongst women of reproductive age and is associated with various cardiometa-
excellent prognosis with a normal life expectancy and among them most of them
bolic perturbations, in addition to chronic anovulation and factors related to
have a low risk of recurrence. The absence of ablation in patients with thyroid
androgen excess. Indeed androgen excess has been associated with increased
cancer of 1 centimeter or less (pT1a) is already widely applied, so, we are used not
cardiovascular risk in women; serum testosterone correlates with indices of
to ablate all thyroid cancer patients treated with total thyroidectomy. The
subclinical atherosclerosis and cardiovascular disease (CVD). Moreover, women
question, indeed, is whether the group of patients not undergoing systemic
with PCOS, as compared with age- and body mass index-matched women without
ablation can be extended beyond pT1aN0/x patients. The selection of patients to
the syndrome, appear to have a higher risk of insulin resistance, hyperinsulinemia,
be spared from ablation can indeed be based on pathology examination, on
glucose intolerance, dyslipidemia, and an increased prothrombotic state, possibly
tumour size, on lymph node involvement and since some of these patients are now
resulting in a higher rate of type 2 diabetes mellitus, fatty liver disease, subclinical
recognized as low risk patients. The selection can also be based on postoperative
atherosclerosis, vascular dysfunction, and potentially cardiovascular disease and
thyroglobulin level because of its excellent negative predictive, whether
mortality. Obesity, an independent risk factor for CVD, is also more prevalent in
measured after TSH stimulation or measured under levothyroxine treatment
PCOS women as compared to age-matched controls, and is aggravated by
with ultrasensitive method, and on neck ultrasonography. However, prospective
androgen excess and has an detrimental android pattern of distribution. Further
randomized trials are needed in order to answer this question of ablation. This will
alterations in PCOS include an increased prevalence of sleep apnoea, as well as
allow reinforcing the strength of recommendation that can be done.
various changes in the secretion and/or function of adipokines and adipose tissue-
derived pro-inflammatory factors, all of them with direct or indirect influences on
DOI: 10.1530/endoabs.49.D5.2
the complex signaling network that regulates metabolism, insulin sensitivity, and
energy homeostasis. The literature is full of conflicting data and this is partly due
to the definition(s) used to identify women with PCOS and also the phenotypic
variability of PCOS, which in itself generates significant influence on the
cardiometabolic risks.
DOI: 10.1530/endoabs.49.D4.1
Is It Time for Initial Combination in Type 2 Diabetes?
D6.1
Is it time for initial combination in type 2 diabetes? - FOR
D4.2
Stefano Del Prato
Is cardiovascular risk increased in women with PCOS? - AGAINST
Italy.
Enrico Carmina
Italy.
Abstract Unavailable.
Young women with PCOS presents a severe risk of developing type II diabetes,
cardiovascular diseases, chronic liver disease and endometrial cancer. However,
in term of events, there is proven evidence only for type II diabetes and for
endometrial cancer. In particular, it is still unclear whether CV events are
increased in women with PCOS. Completely different data have been published
and the quality of many studies is relatively low. Some recent evidence suggests a
larger number of cardiovascular events (4 fold) in young population with PCOS.
However, studies at this age present an inherent difficulty linked to the low
D6.2
number of CV events in young population. In addition, these data are based on
Is it time for initial combination in type 2 diabetes? - AGAINST
hospitalized population and this approach may have some biases because it may
Didac Mauricio
exclude the less affected population. In our large follow up of unselected PCOS
Spain.
patients, no increase of CV events was noted. In aged PCOS patients the data are
also contrasting with some studies showing a slight increase of CV diseases and
others reporting normal prevalence of CV events. Large follow up studies are
missing and are urgently needed to solve this important issue. However, it is clear
2
Type
diabetes mellitus is a heterogeneous disease with multiple
that the number of events in aged women, who had PCOS during their
pathophysiological pathways contributing to hyperglycemia, and also
reproductive age, is much lower than that expected on the basis of risk calculation
resulting in a variable clinical picture. Thus, individualization of
during young adult age. The mechanisms of the discrepancy between CV risk and
hypoglycemic therapy is a mainstay of current clinical guidelines. Several
late events in PCOS are unclear but a progressive normalization of CV risk during
factors should be considered for a given treatment choice. These include the
late reproductive age may have a main role.
characteristics related to a given medication (efficacy, hypoglycemia, effect
DOI: 10.1530/endoabs.49.D4.2
on weight, other safety issues, the mechanism of action), and other factors,
like costs related to each treatment, convenience for the patient, etc. Initial
combination therapy may be considered as a suitable choice for some
patients/circumstances. However, the evidence favoring this combinatory
initial option has not been clearly established. Different issues concerning
the convenience of using either initial combination therapy vs sequential
Should We Still Ablate all Patients Undergoing Total
addition of hypoglycemic drugs will be addressed during the discussion. The
Thyroidectomy for Thyroid Cancer?
following aspects will be dealt with: long term efficacy of combination
therapy vs sequential titration/addition of hypoglycemic agents; durability;
D5.1
overall cost and cost-effectiveness; safety issues, including hypoglycemia
Should we still ablate all patients undergoing total thyroidectomy for
and weight changes; advantages/disadvantages in terms of treatment
thyroid cancer? - FOR
adherence; effects on patient-oriented outcomes, including long-term
Markus Luster
morbidity and mortality; effect on clinical inertia; what is the best
Germany.
combination of hypoglycemic agents; individualization vs combination for
every patient. To conclude, the question about the implementation of initial
Abstract Unavailable.
combination therapy as a strategy in usual clinical practice is still open.
DOI: 10.1530/endoabs.49.D6.2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Meet The Expert Sessions
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
MTE1
MTE3
How to manage diabetes in the elderly?
Hormone-secreting adrenal tumours in pregnancy
Leocadio Rodriguez-Manas
Catherine Williamson
Spain.
UK.
The prevalence of diabetes and glucose intolerance is close to 50% in people older
Hormone-secreting adrenal tumours are rare occurrences in women or
than 65. At the same time, near 50% of people with type 2 diabetes are R 65 years
reproductive age. The commonest is phaeochromocytoma, followed by primary
old. But being these figures relevant enough to raise a special consideration about
aldosteronism and Cushing’s syndrome. The shared maternal phenotypic feature
how to manage diabetes in this population, there are other reasons supporting the
of these tumours in marked hypertension. They may be difficult to diagnose as
need of that a special consideration. These other needs are not quantitative but
many of the clinical features are mimicked by pregnancy, e.g. flushing, weight
qualitative ones, making older people with diabetes a particular group of patents
gain, palpitations. Furthermore hypertensive disease occurs in approximately 5%
with different characteristics, different aims and, as a consequence, different
of pregnant women. However, there are specific clinical features associated with
management compared to adult non-older patients with type 2 patient and, of
each tumour type that aid diagnosis; the hypertension in phaeochromocytoma may
course, younger patients with both type 1 and type 2 diabetes. These differences
be paroxysmal; primary aldosteronism is often accompanied by hypokalaemia and
range from differences in the pathophysiology of diabetes, that although
the striae in Cushing’s syndrome are usually more purple and marked than in
stemming from insulin resistance have a different origin of this insulin resistance,
normal pregnancy. It is important to know the normal ranges for the specific
to the mechanisms underlying the development of vascular and other
endocrine tests used to diagnose each hormone-producing tumour, and once a
complications of diabetes, the impact of the disease in the several classical target
diagnosis has been made a multidisciplinary team should be involved with clinical
organs (in people older than 80 diabetes does not increase the risk of blindness),
management. This should include endocrinologists with an understanding of
the clinical manifestations of the disease, the diagnostic approach or the general
gestational disease, obstetricians, specialist anaesthetists, midwives and neonatol-
management of the patient. Among all of those, and some others, differences,
ogists. Individualised decisions should be made with regard to treatment with
perhaps the most relevant is the focus on function. While in younger populations,
surgery or drugs. All hormone-secreting adrenal tumours are associated with
the focus is usually centered in preventing or treating vascular disease (both
increased rates of adverse pregnancy outcome, including preterm labour and
micro- and macroangiopathy) and other complications of diabetes, when people is
stillbirth. This talk will summarise current knowledge about the management of
older the main focus is to avoid, delay or, if possible, reverse functional (both
these rare, and potentially life-threatening tumours in pregnant women and will
physical and cognitive) impairment. It is quite clear that diabetes increases less
consider the merits of prospective population cohorts to improve our understanding
significantly the risk of death in this population, reaching relative risks as low as
of the optimal management strategies to improve maternal and offspring outcomes.
1.2 in people older than 80 years. old. However, diabetes is one of the chronic
DOI: 10.1530/endoabs.49.MTE3
diseases increasing the risk of mobility disability, dependency for instrumental or
basic activities of daily living, falls and cognitive impairment/dementia in more
than twice. In addition, the role of functional status in conditioning the prognosis
(both functional and vital, plus other outcomes like hospitalization) is increasingly
higher as patient is getting older, substituting the classical role of the
MTE4
comorbidities (both those related and those non-related to diabetes). Finally, the
functional impact of the disease is also the main factor explaining the costs of
Treatment of congenital hypothyroidism
the disease, reaching figures of
78% of the costs. As a consequence, the
Heiko Krude
management of diabetes in older people should be based in functional status as the
Germany.
main factor in the decision-making process, but also as the main therapeutic
target. This change in the focus is crucial to get the best benefits when facing older
Treatment for congenital hypothyroidism (CH), based on thyroid extracts, was
people with diabetes.
introduced more than 100 years ago and resulted in a compelling improvement of
DOI: 10.1530/endoabs.49.MTE1
impaired growth, obesity, depression and severe delay of motor development.
However, severe mental retardation remained despite treatment. It was only after
the implementation of neonatal screening for CH in 1970s that intellectual
outcomes improved to an average normal IQ. However, whether complete
normalization of cognitive outcome is possible remains controversial, since some
studies have found significant gaps compared to control populations including
healthy siblings. Furthermore, there is some evidence that quality of life (QoL)
scores are lower compared to the general population. To further improve the
outcome, higher starting doses of more than 10 mg/kg and commencement of
treatment within the first two weeks of life were recommended. The most recent
outcome study from New Zealand, reporting patients treated according to a
MTE2
regimen consistent with these recommendations, documented IQ at age 10 years
Diagnosis and management of GH deficiency - from childhood to
that was no longer different from sibling control subjects. Nevertheless treatment
adulthood
with higher starting doses has raised concerns regarding adverse effects of
Jens Jorgensen
supraphysiological T4 levels, with studies in rodents and patients with neonatal
Denmark.
hyperthyroidism suggesting abnormal CNS development. In addition, it has been
repeatedly shown that the recommended high LT4 dose of O10 mg/kg results in
fT4 levels in newborns and infants with CH that exceed the reference ranges in
Pituitary dwarfism has been known for many decades, originally as a component
this age group. However, after decades of neonatal screening and recent confusion
of organic panhypopituitarism. GH for clinical use was purified by Maurice
about an “unfavourable” outcome with a high dose LT4 treatment, we now
Raben from human cadaveric pituitaries and tested for the first time and with
provide strong evidence -based on a recent IQoutcome study- that the present
success in 1957 in a patient with childhood onset disease. Moreover, pivotal short
recommendations of a high initial dose above 10 mg/kg is necessary, efficient and
term studies on the metabolic effects were performed in both healthy and
safe to achieve optimal cognitive development in all CH patients including those
hypopituitary adults. The concomitant introduction of imunnoassays for GH led
who are severely affected.
to the introduction of GH stim tests and recognition of isolated and idiopathic
GHD. But the scarcity of GH for clinical use was a major limitation until the
DOI: 10.1530/endoabs.49.MTE4
1980s when biosynthetic GH became available. This opened the possibility of
novel indications including GHD in adults (GHDA). The two first placebo-
controlled studies in 1989 reported positive effects in both childhood- and adult-
onset GHDA in terms of body composition and exercise capacity. This has since
been corroborated in numerous trials, and it is also documented that
MTE5
discontinuation of GH in the transition from child to adulthood is unfavorable.
Modern spectrum of bone turnover markers - are they clinically useful?
Finally, there is indirect evidence to suggest that GH replacement in adults may
Richard Eastell
reduce mortality and does not associate with increased cancer risk. Still, GH
UK.
therapy in adults is by no means a fountain of youth, and there is no evidence to
suggest that it is of any meaningful use in either normal or frail aging. This MTE
will discuss this exiting journey from a personal point of view.
Bone turnover markers reflect the work of the osteoblast and the osteoclast. They
DOI: 10.1530/endoabs.49.MTE2
can be measured in blood or urine and allow for an inexpensive and non-invasive
way to study bone metabolism. They have been evaluated for their use in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
predicting risk of fracture, accelerated bone loss or the presence of secondary
the thyroid. Additionally, patients can take b blockers for symptomatic relief.
osteoporosis, but for all these uses they are not yet established. They are useful in
Although all three options are effective, no treatment is ideal and thus indicated in
monitoring the response to treatment of osteoporosis, especially with drugs such
all patients with GD. Selection of therapy depends on multiple considerations,
as oral bisphosphonates. One study focused on the clinical utility of modern
including: patient’s age, severity of thyrotoxicosis, presence of goiter,
spectrum of bone turnover markers for monitoring oral bisphosphonate therapy
orbitopathy, pregnancy, comorbidities. The treatment selection must also take
(alendronate, ibandronate, risedronate) in women with postmenopausal osteo-
into account the patient’s preference. Before deciding on a treatment plan, the
porosis. The study concluded that two approaches could be used to identify
treating physician and patient should discuss each of the treatment options,
response, namely a change beyond the least significant change or a change to
including the logistics, local availability, advantages, disadvantages, potential
below the mean value of bone turnover in healthy young women (1). This
side effects and costs.
approach identified about 90% of women from the study as responding by 12
DOI: 10.1530/endoabs.49.MTE7
weeks on treatment. The International Osteoporosis Foundation and European
Calcified Tissue Society proposed that a bone marker measurement made after 12
weeks was a good way to identify patients who are not adhering to therapy, as
non-adherence is the commonest reason for non-response (2). The meet-the-
expert session will examine the evidence for the use of bone turnover markers in
treatment monitoring and give case examples of this approach in practice.
MTE8
References
How best to manage neuroendocrine tumours? - Towards a new
1. Naylor KE, Jacques RM, Paggiosi M, Gossiel F, Peel NF, McCloskey EV,
algorithm
Walsh JS, & Eastell R. Response of bone turnover markers to three oral
Alicja Hubalewska-Dydejczyk
bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.
Poland.
Osteoporosis International 2016 27 21-31.
2. Diez-Perez A, Naylor KE, Abrahamsen B, Agnusdei D, Brandi ML, Cooper C,
During the last couple of years an essential increase of newly diagnosed NENs has
Dennison E, Eriksen EF, Gold DT, Guan˜abens N, et al. Recommendations for the
been observed, however it should be underlined that many cases represent new
screening of adherence to oral bisphosphonates. Osteoporosis International 2017
challenges for the medical staff. Development of personalized approach to NEN
28 767-774.
patients on the basis of knowledge rapidly coming from genetic/molecular
DOI: 10.1530/endoabs.49.MTE5
research, improvement of biochemical/imaging diagnostic methods and
availability of more efficient therapeutic options, means that existing guidelines
are still being changed. However, the questions: ‘what of the future hold for
NEN?’ and ‘how will future achievements influence the new algorithm?’ remain
open. In the majority of patients the overall prognosis depends on the grade (G)
MTE6
and stage (TNM) of the tumour. Recently proposed classification of NENs divides
How best to utilise technology in diabetes?
additionally G3 NENs into NET G3a and G3b neuroendocrine cancers. Ki-67 is
Hans DeVries
currently the main prognostic index which drives the management of all NENs,
The Netherlands.
nevertheless it should be stressed that very often patient outcomes are difficult to
foresee and the lack of response to therapeutic treatment regiments remains
unpredictable so the identification of other prognostic factors would be of great
More and more devices are becoming available for people with diabetes. Should
help and it would make diagnostic and therapeutic decisions more appropriate. At
you advise your patients to use a pedometer? How can insulin pumps be of help?
present chromogranin A, urinary 5-HIAA and tumour specific hormones in
An insulin pump is the best way to accommodate the changing insulin needs over
secreting NENs are widely used as biomarkers. One should bear in mind that
the 24 hours of the day and gives one the opportunity to temporarily stop insulin
surgery is the only possible curative method in NENs however, half of the patients
administration in case of unanticipated exercise, which is impossible when using
have metastases at presentation and unknown primary focus can also be
injection therapy. Trials have mainly been done in Type 1 diabetes, but a recent
challenging. Therefore, the development of fast and accurate imaging procedures
trial also shows beneficial effects in a selected group of people with Type 2
(endoscopies, USG, CT/MRI and the implementation of the different radiolabelled
diabetes. The evidence for Continuous Glucose Monitors Continuous has recently
compounds targeting various membrane/intracellular receptors/metabolic
been brought to higher level, both for insulin pump and injection therapy users.
pathways (PET/SPECT-CT/MRI) is necessary. Antiproliferative therapy with
Both a lower HbA1c and less severe hypoglycemia have now convincingly been
SSA, TKI, PRRT and cytotoxic therapy should be given rather as sequential
shown in people with Type 1 diabetes. The role of continuous glucose monitoring
monotherapy than a combination one. Based on clinical cases of patients with
in diabetic pregnancy on the other hand is unclear. The newest kid on the block is
NENs in different locations and at a different stage of the disease the different
Flash Glucose Monitoring, for which the evidence is mixed and scarce, but it does
diagnostic/therapeutic options will be discussed during the Meeting.
herald the end of finger pricks. And how are we going to implement the holy grail
of diabetes technology, the artificial pancreas or closed loop? A first generation
DOI: 10.1530/endoabs.49.MTE8
closed loop is now on the market in the US, EU to follow early 2018. What can it
do and what not? Together we will cover a number of the above questions in an
interactive way.
DOI: 10.1530/endoabs.49.MTE6
MTE9
Sarcopenia - why should we care?
Franz Jakob
MTE7
When and which treatment to use in Graves disease?
Tomasz Bednarczuk
Abstract Unavailable.
Poland.
Graves’ disease (GD) is a heterogeneous autoimmune disorder affecting, with
varying degrees of severity, the thyroid, eyes and skin. GD is the most common
cause of hyperthyroidism. The incidence peaks between 30 and 50 years of age,
but people may be affected at any age. Hyperthyroidism is caused by
autoantibodies stimulating the TSH receptor on thyroid cells. The severity of
thyrotoxicosis in GD is variable and the response to anti-thyroid drugs is difficult
MTE10
to predict. Graves’ orbitopathy
(GO) is the most common and serious
Contraception in women with obesity, metabolic syndrome and diabetes
extrathyroidal manifestation of GD, significantly impairing the quality of life of
Phillippe Bouchard
affected patients. Clinically apparent orbitopathy occurs in 25%-50% of patients.
France.
Pretibial myxedema and acropachy are much less common, occurring in less than
2% of patients. The reasons for this variation in the clinical presentation of GD are
Abstract Unavailable.
largely unclear. There are three treatment options for Graves’ hyperthyroidism:
(1) blocking of hormone synthesis by antithyroid drugs (ATD), (2) destruction of
the thyroid by radioactive iodine (RAI) and (3) partial or total surgical ablation of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
MTE11
been approved for advanced thyroid cancers either from follicular or
parafollicular origin. A judicious use of different treatment modalities in
Drug induced osteoporosis
advanced thyroid carcinoma may improve patients’ outcome and prolong
Gherardo Mazziotti
survival. Illustrative cases of some advanced thyroid cancer patients will be
Italy.
presented and discussed in this MTE session.
DOI: 10.1530/endoabs.49.MTE14
Abstract Unavailable.
MTE15
Gaucher disease: interdisciplinary management
Milan Patakov
MTE12
Serbia.
A modern approach for treatment PCOS
Hector Escobar-Morreale
Gaucher disease (GD) is a rare, genetic, autosomal recessive lysosomal storage
Spain.
disease with multi-system manifestations caused by a deficiency of the lysosomal
enzyme glucocerebrosidase, which leads to an accumulation of its substrate
glucosylceramide (glucocerebroside) in macrophages of various tissues with an
Abstract Unavailable.
inflammatory response and a release of cytokines. In general population its
incidence is approximately 1/40 000 to 1/60 000, rising to 1/800 in Ashkenazi
Jews. Clinical features comprise cytopenias, splenomegaly, hepatomegaly, and
bone lesions. Non-neuronopathic type-1
Gaucher disease, which affects the
majority of patients (90% in Europe and USA), is characterized by visceral
effects, whereas neuronopathic types 2 and 3 are dominantly associated with
neurological impairment. The diagnosis of GD can be confirmed by the deficient
MTE13
acid glucocerebrosidase activity in peripheral blood leukocytes. Patients with
What can new insulins provide for management of diabetes?
type 1 GD, and even carriers of one gene mutation have predisposition to develop
Jean François Gautier
Parkinson’s disease, and there is increased risk of some neoplasia in GD patients.
France.
Disease-specific treatment of type
1
GD consists of intravenous enzyme
replacement therapy (ERT) with one of the available enzymes (imiglucerase,
velaglucerase, or taliglucerase) or oraly administered substrate reduction therapy
The major abnormality in type 1 diabetes is insulin deficiency. Type 2 diabetes is
(SRT) with inhibitors of glucosylceramide biosynthesis (miglustat or eliglustat).
also characterized by an insulin secretory defect so that many patients are on
Currently there is no treatment for type 2 disease which is lethal early in the life.
insulin therapy. Methods of replacing insulin have improved throughout the
decades, but there are still limiting factors that prevent the achievement of a better
DOI: 10.1530/endoabs.49.MTE15
HbA1c levels such as hypoglycaemic events and glycaemic variability, weight
gain and fatty liver. Additionally, most patients wish to do less insulin injections
and less blood glucose self-monitoring! New insulins and newer delivery systems
are being developed that can improve some of the limitations of current insulins
or make the delivery of insulins more acceptable for some patients. Extending the
MTE16
duration of action of basal insulins (glargine U300, Insulin degludec, PEGylated
New treatment approaches in dyslipidemia
insulin Lispro) may have advantages in reducing risk of hypoglycemia (and
Luis Masana
especially nocturnal hypoglycemia) and weight gain. PEGylated insulin Lispro is
no more in development for safety reasons (high triglycerides and liver enzymes)
The introduction of PCSK9 inhibitors has changed the paradigm of dyslipidemia
and there is still no head-to-head comparison between glargine 300 U/ml and
treatment. These monoclonal antibodies produce an incremental LDL reduction
degludec. Shortening the peak of fast-acting insulins in order to mimic the
of about 60% add-on current therapy. Achieving LDL concentrations below
physiological first phase insulin secretion (bioD-090, rHuPH20, Ultra-fast-acting
40 mg/dl is usual. The recent publication on the effect of very low LDL
insulin aspart, BioChaperone lyspro) may also have advantages. However, peer-
concentrations on atherosclerotic plaque burden
(Glagov study) and on
reviewed evidence to date remains scarce. Biosimilars are developed to minimize
cardiovascular outcomes (Fourier and Spire) show the impact of this therapy in
insulin cost but do not bring something new for the patients. Combination of new
cardiovascular prevention. In the other hand these treatments seem to be pretty
long acting insulins with a short acting insulin or with a GLP-1 analogue are
safe. Ebbinhouse study has demonstrated no impact on neurocognitive function.
available in some countries. These combinations reduce the number of injections.
Price of therapy is the main limiting factors and several scientific societies have
Different delivery systems may make insulin more acceptable to patients.
issued recommendation for use. The aim of this meeting is discussing about the
Whether these innovations permit a better glycemic control will be discussed.
new approaches of dyslipidemia therapy.
Lastly, we will see whether ‘smart’ insulin, that is glucose-responsive insulin, the
DOI: 10.1530/endoabs.49.MTE16
Holy Grail promise, will be available in the next future.
DOI: 10.1530/endoabs.49.MTE13
MTNE1
A paediatric perspective of endocrine late complications following
MTE14
childhood cancer
Thyroid carcinoma: complicated cases
Tanya Urquhart
Valeriano Leite
UK.
Portugal.
Dramatic improvements in cancer survival over the past four decades means that
Thyroid neoplasias show a wide range of biological behaviours from indolent to
greater than 80% of children diagnosed with cancer can expect to survive for
highly aggressive, invasive and metastatic cancers. The great majority of thyroid
more than five years. For some cancers, such as acute lymphoblastic leukaemia
carcinomas are successfully treated with surgery, radioactive iodine and TSH
and Hodgkin’s disease, cure rates exceed 90%. Currently, there are over 26000
suppressive therapy. However, a subset of tumors can behave aggressively, with
young adults living in the UK,
600 000 across France, Italy, Switzerland,
distant metastasis and/or local invasion. These patients have a poor prognosis and
Netherlands and the Nordic countries and 363 000 in the US, who are survivors of
a shorter survival, remaining a challenging task in treatment options. Cytotoxic
childhood cancer (CCS). A late effect (LE) is the term used to describe any
chemotherapy has only limited effect, without clear evidence that benefit
physical, psychological or social consequence of the disease itself or the disease
outweighs risk of toxicity. Radiotherapy is an option for surgically unresectable
treatment. The consequence of cytotoxic effects on maturing tissues may only
neck recurrences and for bone and brain metastases. Recently, interest rose on
become apparent many years following completion of treatment and with
tyrosine kinase inhibitors (TKI) and, currently, there are several TKIs that have
subsequent development, hence the term LE. Treatment for childhood cancer
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
usually involves chemotherapy, radiotherapy
(including radiosurgery) and
MTBS1
surgery. These treatments can occur in isolation or in any combination, and can
Unravelling the role of transient receptor potential channels in
affect almost any system in the body. The most common effect of these treatments
endocrine regulation and metabolism
is on growth, endocrine function, fertility, neuropsychology and the cardiac
Thomas Gudermann
systems. Two-thirds of childhood cancer survivors will experience at least one LE
Germany.
and the endocrine system is commonly involved. Another third of patients will
develop two or more LE which may be severe or life threatening. Therefore this
session will explore the endocrinopathies associated with the treatment for cancer
Abstract Unavailable.
in childhood using case studies to provide examples from practice. Knowledge of
oncology and endocrinology are paramount for nurse specialists working with this
patient cohort to ensure accurate education for young people about their past
treatment and its implications for their future health. Transition will also be
considered as these young people grow, develop and require continuing care from
adult healthcare professionals.
MTBS2
DOI: 10.1530/endoabs.49.MTNE1
Regulation and dysregulation of appetite and satiety
Patricia Iozzo
Italy.
The modulation of appetite, satiation and food intake stems from the interplay of
central mechanisms of homeostasis, hedonism and cognitive control, receiving
and integrating information on energy balance and feeding status of the body from
peripheral organs, including dietary and gut-related signals. Obesity is a
phenotype, likely resulting from the dysregulation of one or more of the above
mechanisms. Different mechanisms may prevail in different people, though
leading to a similar phenotype. The recognition of such diversity would offer
opportunities for personalized treatment. This lecture will present data from a
study conducted in well characterized overweight women, undergoing brain
imaging of glucose metabolism to detect cerebral reactions to sensory food
stimuli. The study suggests that women with food addictive behavior have a
specific pattern of activation, which implicates cognitive control and diet-related
factors (hormones, substrates, and possibly microbiota) in their food seeking
MTNE2
behavior. This hypothesis is supported by the characterization of feeding behavior
Providing nursing care for the adult patient with endocrine late effects
and brain and brown adipose tissue (BAT) metabolism in mice models of
of cancer treatment
neurodegenerative disease and/or high-fat feeding, also in combination with
Cecilia Follin
intranasal insulin therapy. In order to better define the sequence of events linking
Sweden.
brain function and feeding behavior, studies in the offspring of obese mothers are
addressed, since maternal obesity represents a preventable condition, in which the
factors above are affected since early life in the offspring. Results in humans, and
Survival rates of childhood cancer have improved markedly and today more than
animal models will be presented. Cumulatively, our studies suggest that a
80% of those diagnosed with a pediatric malignancy will become
5-year
hypermetabolic brain, deriving from metabolic disturbances or high-fat dietary
survivors. Nevertheless, survivors exposed to cranial radiotherapy (CRT) are at
exposure may be an early detrimental factor, and a hypometabolic brain reflecting
particularly high risk for long-term morbidity, such as endocrine insufficiencies,
neuronal loss may enhance food intake, but also BAT browning. Substrates,
metabolic complications and cardiovascular morbidity. Deficiencies of one or
hormones and gut microbes can promote a vicious cycle.
more anterior pituitary hormones have been described following therapeutic CRT
for primary brain tumours, nasopharyngeal tumours, and following prophylactic
DOI: 10.1530/endoabs.49.MTBS2
CRT for childhood acute lymphoblastic leukemia
(ALL). Studies have
consistently shown a strong correlation between the total radiation dose and the
development of pituitary deficits. Further, age at treatment and also time since
treatment has strong implications on pituitary hormone deficiencies. Studies have
shown that childhood cancer survivors
(CCS) need information regarding
psychosocial support and social advocacy. Thus, the challenge is to guide the
MTBS3
survivors through the potential late complications and offer care designed to meet
MicroRNAs and the regulation of glucose and lipid metabolism
their specific needs in order to optimise their quality of life. Information about late
Markus Stoffel
complications is essential in order to achieve an independent life and to engage in
Switzerland.
healthy behaviour, such as regular physical activity. Thus, having a holistic
approach, tailored to their specific needs is crucial for their future well-being and
quality of life.
Abstract Unavailable.
DOI: 10.1530/endoabs.49.MTNE2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Nurse Sessions
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
N1.1
as envisioned future directions. At the conclusion of this session participants will
be able to:
Clinical practice overlap and seamless care - diagnosis and
† describe the interrelationship between hypogonadism and MetS/T2DM
management of hypothyroidism in patients with diabetes mellitus
† identify those patients who warrant screening for androgen deficiency
Elena Shelestova
† recognize barriers to providing integrated care for these patients
Today diabetes (DM) is one of the largest global health emergencies. Each year a
† examine how their nursing care for these patients may be improved
large number people live with this condition. Currently there are more than 422
DOI: 10.1530/endoabs.49.N1.2
mln people with DM worldwide. DM is one of the major public health problems
in Georgia. Number of people with DM is on the rise, though no exact statistical
data for Georgia exist. Diabetes Atlas (International Diabetes Federation, 2015)
gives diabetes prevalence for Georgia of 7.9%, though these data are extrapolated
from other countries. On the other hand, hypothyroidism (HOT) is believed to be
a common health issue worldwide. The prevalence of HOT in the developed
world is about 4-5%, and the prevalence of subclinical HOT is about 4-15%.
N1.3
Both HOT and subclinical HOT are thought to be risk factors for T2DM
Clinical practice overlap and seamless care - challenges in the
development. In our patients approximately 30% of women and 15% of men have
management of patients with Cushing’s syndrome and diabetes
both conditions. Prevalence of both conditions increases with the age of the
Mies Kerstens
patients (age 35-74 years, prevalence range 7-5%).
The Netherlands.
Materials and methods
Herein, 2 clinical cases (coexisting T2DM and HOT) are discussed. Both patients
(pt) were diagnosed and are managed at the National Centre for Diabetes
This lecture focuses on, a patient with Cushing’s syndrome cased by bilateral
Research. Case #1 - pt. E.G., 49 years old, female. T2DM since 2008, HOT -
adrenal hyperplasia. After adrenal surgery, there are major challenges in the care
since 2015. Pt. was treated with oral hypoglycaemic agents (OHAs) - SU and
for this patient, that will be addressed: challenges in medical treatment (cortisol
Metformin (Met), in 2017 pt. was transferred to DPP-4 and Met. DM control is
withdrawal and change of medication in hypertension en diabetes mellitus) as
satisfactory. In 2015 pt addressed the Centre with typical signs and symptoms -
well as challenges in coaching (misconceptions in diabetes mellitus treatment,
weight gain, dyspeptic symptoms, cognitive impairment, constipation. Ultra-
fears, educational needs with respect to hypercortisolisme and hypocortisolisme,
sound examination was performed and thyroid hormones (TSH, F4, anti-TPO)
withdrawal complains).
were tested. L-thyroxine therapy was initiated (50 mg, then elevated to 100 mg).
DOI: 10.1530/endoabs.49.N1.3
Since treatment initiation pt. condition is satisfactory, clinical and laboratory tests
have improved. Pt is control every 3 months. Prescribed treatment is continued,
Case # - pt. K.N., 65 years old, female, HOT and goiter with thyroid nodules (no
biopsy performed) were diagnosed in 2010. Treatment with L-thyroxine was
initiated. No follow-up was carried out though the drug (50 mg) was used
regularly. In 2017 pt. came to our Centre for the 1-st time. Ultrasound of the
thyroid gland and hormone tests was performed that revealed thyroid nodules
(TSH was within the n range). Nodule biopsy was carried out, colloid goiter was
N1.4
diagnosed. Pt had following DM risk factors - family history of DM, obesity,
Clinical practice overlap and seamless care - at risk of two endocrine
arterial hypertension, HOT. Thus, she was screened for DM. HbA1c was 7.0%
emergencies: the patient with type 1 diabetes and Addison’s disease
indicating to T2DM. Met. (500 mg) was initiate. Treatment with L-thyroxine at
Sofia Sjoberg
selected dose is continued. Diet and physical activity recommendations were
Sweden.
selected individually. At present both pts are regularly followed-up (every 3
months). Doses and treatment are adjusted based on the results achieved.
Patients diagnosed with Addison’s disease and diabetes mellitus type1, has a rare
Conclusion
combination of two autoimmune conditions. Two diagnosis that requires a great
Combination of the conditions is globally widely spread, it needs serious
deal of self-care. Patients have a potential risk to induce endocrine emergencies
attention, knowledge and experience to manage. Proper management permits pts
such as diabetic hypoglycemia, adrenal crisis and diabetic ketoacidosis. The lack
to live long and productive life and avoid complications caused by the conditions.
of lifesaving hormones can put the patient in potential life threatening situations.
DOI: 10.1530/endoabs.49.N1.1
I’ll share my experience in meeting these patients. Brief physiology how the lack
of hormones affects the glucose metabolism and what aid the patient need to
handle the two disorders in daily life.
DOI: 10.1530/endoabs.49.N1.4
N1.2
Clinical practice overlap and seamless care - links between
hypogonadism, the metabolic syndrome and type 2 diabetes
N2.1
Andrew Dwyer
Nurses professional development and networking session - obstructive
Switzerland.
sleep apnea and comorbidities in patients with pituitary adenomas
Christine Yedinak
USA.
There is a bi-directional relationship between hypogonadism and type 2 diabetes
and the metabolic syndrome (T2DM/MetS). Studies show that up to 50% of men
with MetS/T2DM have testosterone deficiency. Moreover, both hypogonadism
Short sleep duration and insomnia have been linked to higher risk of
and MetS confer increased health risk for morbidity and mortality. Men with
cardiovascular disease and CVD related mortality. Likewise, obstructive sleep
MetS are twice as likely to develop cardiovascular disease and have a fivefold
apnea has been shown to confer a higher cardiovascular risk and is reported to be
higher risk for developing T2DM. Notably, the inverse relationship between
associated with 52-70% of acute myocardial infarctions and strokes. Hyperten-
testosterone and MetS is consistently observed across racial and ethnic groups.
sion (HTN), diabetes (DM), weight gain, sleepiness, fatigue and depression have
Therefore, in the setting of ever increasing obesity rates, the relationship between
all been correlated with obstructive sleep apnea (OSA). Patients with pituitary
the reproductive endocrine axis and metabolism warrants renewed attention.
adenomas (PA), particularly those with Cushing’s disease and acromegaly, often
Using a case-based approach, this presentation will provide an overview of the
present with reported sleep dysfunction, fatigue and metabolic risk factors,
pathophysiologic basis for the relationship between hypogonadism and
diabetes, hypertension and cardiovascular disease and depression. The prevalence
MetS/T2DM. Male patients may be trapped in the vicious cycle of
of sleep apnea in patients with pituitary hypersecretion at diagnosis has not been
hypogonadism-obesity-insulin resistance. We will review an evidence-based
clearly quantified in patients as it may not be recognized and may go undiagnosed
approach to the patient including the appropriate evaluation and treatment based
at the time of presentation. Additionally, the correlation with diabetes and other
on existing guidelines and recommendations. This presentation will have a
cardiovascular risk factors is not clear in these disorders. There is little data
particular focus on the role of the endocrine nurse in managing patients who
regarding the impact of treatment and disease remission on both OSA and
present with this confluence of endocrine disorders. Current challenges in the field
persistent risk factors. The aim of this presentation is to explore the prevalence
will be highlighted and we will touch on some yet unanswered questions as well
and correlation between sleep disturbance (SD), depression, BMI, HTN, diabetes
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Mellitus (DM), pituitary deficiencies (PD), tumor size, diagnosis and risk of OSA
N3.1
for patients with PA pre and post treatment remission. Data from one institution
Update on diet and lifestyle throughout lifespan to improve health -
will be presented.
prevalance and treatment of vitamin D deficieny in children
DOI: 10.1530/endoabs.49.N2.1
Pauline Musson
UK.
A number of factors have been associated with the apparent increase in children
with vitamin D deficiency (VDD) in developed countries: increased awareness,
N2.2
increased migration, children living with chronic illness or disabilities, effects of
Nurses professional development and networking session - utilising the
medication (e.g. glucocorticoids, anticonvulsants), use of sunscreen, changes in
competence framework to develop the role of endocrine nurses in
lifestyles and a rise in childhood obesity. The clinical features of VDD vary with
adrenal insufficiency
age and degree of deficiency and importantly, calcium deficiency is now
Janina Kirchner
recognized as a key factor in symptomatic VDD. At presentation, children may be
Germany.
asymptomatic or, have musculoskeletal pain; and in severe cases hypocalcaemic
seizures, rickets and life threatening cardiomyopathy may occur. Evaluation of
children should include careful assessment of dietary intake, previous medical
The competence of endocrine nurse in the treatment of adrenal insufficiency (AI)
history, medication review
(including use of complementary alternative
is defined by the competence framework. Here is distinguished into Competent,
medicines), growth and puberty, and systemic enquiry of symptoms suggestive
proficient and expert. In these points, the nurse’s knowledge is presented and
of malabsorption. Biochemical investigations are merited in symptomatic cases
gives a good overview of already acquired knowledge and things to be learned.
and there are important rare diagnoses that should be considered when
With the acquired knowledge the endocrine nurse is intended to treat, train and
interpreting results. There are a variety of treatment regimens for VDD. Typically
support patients with AI as far as possible. Due to differences in the health
treatment is with cholecalciferol, administered in daily, weekly, monthly or 12
systems of the countries in Europe, not all approaches are possible. Here the
weekly doses. Oral doses are considered as effective as intramuscular injections in
example of Germany is shown how patients with AI are provided with a national
children with normal intestinal absorption. Potential side effects from treatment
training program and the competence framework is also applied.
should be communicated to the family and are rare. Calcium supplements should
DOI: 10.1530/endoabs.49.N2.2
be considered in those with inadequate dietary intake. The family should be made
aware of the reasons for intervening, the differences between treatment versus
supplement doses of vitamin D, and how to optimize diet and adverse lifestyle
factors. Some licensed products are not palatable for children and achieving
adherence can be challenging. Poor medicine adherence may be further
N2.3
aggravated by confusion regarding the doses required and inconsistent
information given to families by health care professionals. I will review the
Nurses professional development and networking session - hybrid
contemporary multidisciplinary approach to the child presenting with vitamin D
training of nurses in/for the endocrinology; train the trainer with help
deficiency with illustrative clinical cases.
of e-learning modules
Johan Beun
DOI: 10.1530/endoabs.49.N3.1
The Netherlands.
Adrenal insufficiency is a rare adrenal disorder that can be made more
complicated by an adrenal crisis even to a life-threatening situation. An adrenal
crisis occurs when the body has a shortage of the hormone cortisol. If the patient
does not receive the correct treatment an adrenal crisis can be fatal. This can be
N3.2
avoided by correctly and carefully following the ‘stress instructions’ (also known
Update on diet and lifestyle throughout lifespan to improve health -
as
‘sick day rules’). A significant percentage of patients have insufficient
sexual hormones and bone, a close link throughout lifespan
knowledge of these stress instructions or are not able to put them into practice
Georgios Papadakis
themselves. In addition, it has become evident that the stress instructions vary
Switzerland.
between the different hospitals. For that reason, AdrenalNET has drawn up
uniform stress instructions. These form part of the Quality of Care Standard for
Adrenal Disorders, which sets out quality criteria
(as applicable in the
Bone health is increasingly recognized as a crucial factor for quality of life.
Netherlands) for the care of patients with adrenal insufficiency. One important
Osteoporosis, defined as bone impairment leading to an increased risk of fracture,
quality criterion for the proper care of patients with adrenal insufficiency is that
is an important source of morbidity and even mortality in later life. Both male and
the hospital must have a nurse who has successfully completed this training
female achieve the peak bone mass at around the age of 25 years. This peak is
course.
significantly lower in case of puberty and/or growth disorders, thus increasing the
Objective
risk of osteoporosis later in life.
The objective of this training course is to offer nurses the essential theoretical and
Discussion
practical knowledge that they need if they are to provide adrenal patients with
Our Reproductive Division of Endocrinology in Lausanne University Hospital
optimum care and instruct them how to apply the stress instructions for
specializes in Congenital Hypogonadotropic Hypogonadism (CHH), a disorder
themselves. Indirectly, this will also help to promote the principle of
characterized by absent puberty and infertility due to complete or partial
co-management when patients with adrenal insufficiency find themselves in
deficiency of GnRH, the hypothalamic hormone that initiates the reproductive
stressful situations. We are, in fact, training the trainers first via e-learning
cascade. When CHH is accompanied by anosmia, it is called Kallmann syndrome
modules (4!) later one day at the university incl. a test at the end.
(KS). In our cohort of KS and CHH patients, there is an important decrease of
DOI: 10.1530/endoabs.49.N2.3
bone density, which is more significant when the disease was diagnosed late in
life, resulting in long periods without hormonal replacement. On the contrary, as
our clinical cases illustrate, when diagnosis of these rare disorders is performed
promptly and adequate treatment is followed, the patients maintain a near-normal
bone density and avoid fractures later in life. In a different approach to the relation
between bone and sexual hormones, using data from the OsteoLaus population-
N2.4
based study, a large cohort of post-menopausal women, we recently showed that
Nurses professional development and networking session - developing a
menopausal hormone treatment (MHT) is associated with enhanced bone density
European position statement for endocrine nurses providing care for
and structure. Interestingly, the bone benefit seems to persist for at least 2 years
patients with adrenal insufficiency
after its withdrawal. These results corroborate other studies outlining that in
Sofia Llahana
young postmenopausal women aged 50 to 60 years old the ratio benefit/risk is
UK.
clearly in favor of the benefits in terms of bone health, cardiovascular outcomes
and even mortality. We should reconsider MHT for recently postmenopausal
women with menopausal symptoms such as hot flushes and/or increased risk of
Abstract unavailable.
fractures. In new unpublished data, we detected that MHT users have significantly
lower visceral fat mass, an important element with potential bone and systemic
implications.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
lifestyle, pharmacological therapy, and patient education. Changes to the patient’s
Sexual hormone deficiency throughout lifespan severely impairs bone quantity
diet and lifestyle typically involve: optimizing calcium and vitamin D intake and
and quality leading to bone fragility. Increased awareness of the link between
exercise levels, cessation of smoking and reducing alcohol consumption.
bone and gonadal function is mandatory among endocrine physicians and nurses
Pharmacological therapies used to treat osteoporosis by reducing the fracture
in order to promote early diagnosis and avoid lack of treatment. The risk of bone
risk include bisphosphonates or the RANK ligand inhibitor denosumab. Nurses
morbidity later in life can be an important argument to increase patient’s
have an important role in educating patients about fracture risk, the benefits of
adherence to therapy.
lifestyle modifications for maintaining bone health and the treatment options
DOI: 10.1530/endoabs.49.N3.2
available, including side effects and the importance of adherence. In the current
Dutch osteoporosis guidelines, it is recommended that hospitals appoint a
specialised fracture nurse for the organisation and coordination of osteoporosis
care. These specialised nurses provide care relating to case finding, risk
evaluation, prevention, diagnosis, treatment and follow up. Each of these steps
is essential and an insufficient implementation can result in suboptimal fracture
N3.3
prevention. Their main area of expertise is the recognition of risk factors. These
Update on diet and lifestyle throughout lifespan to improve health -
risk factors can be related to the bone itself, a fall or the patient’s lifestyle. Some
osteoporosis and prevention of fractures: nurses can a play key role
of these factors can be influenced, some cannot. Patients need to have a good
Marsha Van Ooswaard
understanding of their diagnosis and fracture risk to make informed choices with
The Netherlands
regard to pharmacological treatment and/or lifestyle change.
DOI: 10.1530/endoabs.49.N3.3
Treatment of osteoporosis is all about prevention of fractures. It relies on a
combination of approaches, including adjustments to the patient’s diet and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Oral Communications
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Adrenal - Basic & Clinical
EZH2 in the control of stress progenitors homeostasis through WT1 and GATA4
and adrenal cortex zonation, which rely on a novel interaction between EZH2 and
OC1.1
PKA signalling pathway.
High resolution tissue mass spectrometry imaging: a new tool for
DOI: 10.1530/endoabs.49.OC1.2
identification of prognostic markers in adrenocortical carcinoma
Thomas Kunzke1, Na Sun1, Silviu Sbiera2,3, Vanessa Wild3,
Michaela Aichler1, Cristina Ronchi2, Nicolas Schlegel2,
Andreas Rosenwald3, Martin Fassnacht2,3, Axel Walch1 &
Matthias Kroiss2,3
1Helmholtz-Center Munich, Munich, Germany;2University Hospital
OC1.3
Wurzburg, Wurzburg, Germany;3University of Wurzburg, Wurzburg,
Steroid metabolomics for accurate and rapid diagnosis of inborn
Germany.
steroidogenic disorders
Elizabeth Baranowski1,2, Kerstin Bunte3,4, Cedric H L Shackleton1,
Angela E Taylor1,2, Beverley A Hughes1, Michael Biehl3, Peter Tino1,4,
Adrenocortical carcinoma (ACC) is an orphan tumor entity the pathogenesis of
Tulay Guran5 & Wiebke Arlt1,2
which is poorly understood. In advanced tumour stages, prognosis is unfavorable,
1Institute of Metabolism and Systems Research, University of Birmingham,
but biomarkers for early diagnosis are lacking. MALDI-Mass Spectrometry
Birmingham, UK;2Centre for Endocrinology, Diabetes and Metabolism,
Imaging (MALDI-MSI) enables semi-quantitative detection of a broad spectrum
Birmingham Health Partners, Birmingham, UK;3Johann Bernoulli Institute
of analytes including endogenous cell metabolites in tissue sections. MALDI-MSI
for Mathematics and Computer Science, University of Groningen,
was used as a discovery approach to analyse tissue specimens of 72 ACC patients
Groningen, The Netherlands;4School of Computer Science, University of
in FFPE tissue arranged in tissue microarrays to identify pathways of
Birmingham, Birmingham, UK;5Department of Pediatric Endocrinology
pathophysiological relevance and histologic markers related to patient prognosis.
and Diabetes, Marmara University, Istanbul, Turkey.
We focused on steroid hormones and their metabolites which might also serve as
tumour-derived blood biomarkers in the future. 3843 individual endogenous m/z
species were obtained of which five were identified as known components of
Background
steroid hormone synthesis and metabolism. 2/5 steroid hormone metabolites
Urinary steroid metabolite profiling is an accurate reflection of adrenal and
showed differential abundance between ACC samples. Their low abundance in 5
gonadal steroid output and metabolism in peripheral target cells of steroid action.
and 6 of the 72 ACC samples was associated with poor overall survival in Kaplan-
Measurement of steroid metabolite excretion by gas chromatography--mass
Meier analyses (Log rank PZ0.0030 and 0.0045, respectively). Based on the type
spectrometry
(GC-MS) is considered reference standard for biochemical
of the steroid hormone modification present, mass spectra were screened for
diagnosis of steroidogenic disorders. However, performance of GC-MS analysis
related m/z species. An unusual steroid hormone metabolite (M) was identified
and interpretation of the resulting data requires significant expertise and age- and
and validated by tandem mass spectrometry. After multivariable adjustment for
sex-specific reference ranges. Here we developed novel computational
age, tumor stage and sex by using the Cox proportional hazards model, presence
approaches for rapid interpretation of GC-MS data for diagnosis of inborn
of M was associated with poor overall survival (HR 4.54, 95%CI 1.56-13.22;
steroidogenic disorders
PZ0.0056). By using immunohistochemistry we analysed protein expression of
Methods
two related enzymes which was correlated with metabolites abundance. In
We analysed the urinary steroid metabolome by GC-MS in 829 healthy controls
conclusion, we demonstrated the utility of MALDI-MSI in detecting and
(302 neonates and infants, 167 children and 360 adults) and 118 untreated patients
identifying small molecule markers in FFPE tissue samples of ACC. A limited
with genetically confirmed inborn disorders
(21-hydroxylase deficiency,
number of compounds related to steroidogenesis with strong prognostic value
17-hydroxylase deficiency, POR deficiency,
11b-hydroxylase deficiency,
could be detected. One steroid hormone metabolite and related enzymes were of
3b-HSD2 deficiency, 17b-HSD3 deficiency, 5a-reductase type 2 deficiency,
outstanding prognostic value. The potential of these metabolites as blood
cytochrome b5 deficiency). We calculated age-related normative values for
biomarkers remains to be investigated.
established metabolite ratios representing distinct enzymatic functions. We
DOI: 10.1530/endoabs.49.OC1.1
developed a novel interpretable machine learning technique, Angle Learning
Vector Quantisation (ALVQ), which looks at all possible metabolite ratios,
computationally reduces these to the most relevant for discrimination, and
differentiates disease states by comparison to a representative prototype. The
method runs independent of sex and age information, units of measurement and
method of urine collection.
OC1.2
Results
EZH2: a master regulator of adrenal cortex homeostasis and zonation
Conventional biochemical ratios had
100% sensitivity but only very poor
Mickael Mathieu1, Coralie Drelon2, Houda Tabbal1, Stéphanie Rodriguez1,
specificity. By contrast, ALVQ predicted ‘affected urine’ vs ‘healthy urine’ with
Amandine Septier1, Annabel Berthon3, David Sainte-Catherine1,
100% sensitivity and 97% specificity. For our three most prevalent conditions
David Breault4 & Antoine Martinez1
(PORD, SRD5A2 and CYP21A2), the specific condition was identified correctly
1Laboratoire GReD, Clermont-Ferrand, France;2Albert Einstein College of
in 96% of cases.
Medicine, Bronx, New York, USA;3National Institutes of Health, Bethesda,
Conclusion
Maryland, USA;4Harvard Stem Cell Institute, Boston, Massachusetts, USA.
We developed a novel Steroid Metabolomics approach to automatically diagnose
inborn steroidogenic disorders with very high sensitivity and specificity, superior
to current methods, and with high potential for implementation in routine clinical
In adult mice the adrenal cortex is divided, in two distinct functional zones,
care.
outermost zona glomerulosa
(ZG) and innermost zona fasciculata
(ZF),
encapsulated by a thin layer of mesenchymal cells (capsule). The adrenal cortex
DOI: 10.1530/endoabs.49.OC1.3
undergoes constant centripetal cell renewal, reliying on recruitment of
progenitors located within an outer cortex niche. Progenitors initially differentiate
as ZG cells and undergo lineage conversion to ZF as they move within the cortex.
This relies on a subtle balance and trans-inhibition between WNT and PKA
signalling pathways. Epigenetic histone modifiers are prototypical factors that
OC1.4
play essential roles from embryonic development to carcinogenesis. We have
The epidemiology of pheochromocytoma: increasing incidence and
recently shown that the histone methyl-transferase EZH2 is overexpressed in
changing clinical presentation. A population-based retrospective study
adrenal cortex carcinomas where is it associated with poor prognosis and tumour
1977-2015
aggressiveness. In order to understand EZH2 function in adrenal physiology, we
Andreas Ladefoged Ebbehoj1,2, Esben Sondergaard1, Christian Trolle1,
have developed a mouse model of EZH2 inactivation relying on a floxed allele of
Kirstine Stochholm1 & Per Logstrup Poulsen1
EZH2 and the Sf1:Cre driver (EZH2KO). Our analyses show adrenal hypoplasia
1Department of Endocrinology and Internal Medicine, Aarhus University
and primary corticosterone insufficiency, associated with expansion of ZG at the
Hospital, Aarhus, Denmark;2Department of Clinical Medicine, Aarhus
expense of ZF and aberrant mixed ZG/ZF differentiation. Consistent with the role
University, Aarhus, Denmark.
of PKA and WNT signalling in establishment and maintenance of zonation, WNT
pathway is increased whereas PKA activity is decreased in EZH2KO adrenals. In
addition to zonation defects, EZH2KO present abnormal accumulation of ‘stress
Pheochromocytoma is a rare disease but frequently poses a diagnostic dilemma
progenitors’. Recruitment of these particular progenitors is under control of WT1
due to the unspecific symptoms and its potentially life-threatening nature. There is
and GATA4. Our in vivo ChIP and expression data show that these two
a perception of an increase in the incidence of pheocromocytomas in recent years,
transcription factors are direct targets of the inhibitory action of EZH2 in the
but no data on time trends exist. We obtained data from The Danish National
adrenal. Altogether, these data suggest completely unanticipated functions of
Registry of Patients, The Danish Registry of Causes of Death, and The National
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Pathology Registry for all persons registered with pheochromocytoma in 1977-
1Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil;2Postgraduation
2015. Health records were reviewed to validate the diagnosis for all patients in the
Program in Medical Sciences: Endocrinology, Faculdade de Medicina,
Northern and Central Regions of Denmark (population 1.75 million). Incidence
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;3Instituto
rates were calculated using Poisson regression and time trends were analysed with
da Crianc¸a com Diabetes, Porto Alegre, Brazil;4Institute of Informatics,
year as a continuous explanatory variable. As incidence increased significantly in
Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
2007-2015, we compared the clinical characteristics of patients diagnosed in this
time interval with patients diagnosed in 1977-2006 in a secondary analysis using
the Wilcoxon-Mann-Whitney test. We identified
183
confirmed cases of
Context
pheochromocytoma. A significant increasing trend (P!0.001) was observed in
Since the exact cause of type 1 diabetes mellitus (T1DM) remains unclear, the
incidence rates from 2.06 (CI95% 1.68-2.49) per million person-years 1977-
detection of novel biomarkers is necessary to complement the information
obtained from the presence of autoantibodies together with genetic and
2006
to
4.65
(CI95% 3.72-5.82)
2007-2015. In
1977-2006
paroxysmal
environmental risk factors. MicroRNAs (miRNAs) are a class of small noncoding
symptoms and secondary hypertension were the primary causes leading to the
RNA molecules that negatively regulate gene expression. Changes in their
diagnosis (34 and 21%, respectively), while incidentalomas were the leading
expression were described in several pathological conditions, including
cause of diagnosis 2007-2015 (57%). Patients diagnosed 2007-2015 were older
autoimmune diseases. Circulating miRNAs are attractive biomarker candidates
(P!0.001), less symptomatic (PZ0.003) and had smaller tumours (PZ0.033),
as they can be easily collected, are stable under different storage conditions and
compared to 1977-2006. No changes were observed in duration of symptoms or
can be measured using specific assays.
level of catecholamines. The incidence of pheochromocytoma has increased
Objective
significantly in recent years, presumably due to increased use of imaging studies.
To investigate a miRNA expression profile in plasma from patients with T1DM
It is unlikely that earlier diagnosis or lead-time bias accounts for the increasing
and nondiabetic controls and suggest their targets using bioinformatics analysis.
incidence since patients are getting older. Therefore, these incidentaloma patients
Design
appear to represent a new group of pheochromocytomas not previously
Expressions of 48 miRNAs were investigated in the plasma from 33 T1DM
diagnosed. Whether surgical treatment provides a health benefit in this group
patients and 26 age-and-gender-matched controls using Stem-loop RT-PreAmp
remains unknown.
Real-time PCR and TaqMan Low Density Array cards (Thermo Scientific Inc).
DOI: 10.1530/endoabs.49.OC1.4
Five dysregulated miRNAs were chosen for validation using RT-qPCR in an
independent sample (27 T1DM patients and 14 age-and-gender-matched controls).
Results
Nine miRNAs were differentially expressed between controls and T1DM patients
with !5 years of diagnosis: 1 miRNA was downregulated (has-miR-146a-5p)
OC1.5
while 8 miRNAs were upregulated (hsa-miR-101-3p, hsa-miR-103a-3p, hsa-miR-
Diagnostic accuracy of three confirmatory tests for primary
1275, hsa-miR-146a-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-200a-3p,
aldosteronism: a prospective study and systematic review
hsa-miR-210-5p and hsa-miR-21-5p) in patients with
!5 years of T1DM
Qifu Li, Ying Song, Shumin Yang & Aipin Zhang
diagnosis compared to controls. In contrast, no differences were detected between
Department of Endocrinology, Chongqing, China.
controls and T1DM patients with O5 years of diagnosis. Bioinformatics analysis
evidenced that hsa-miR-103a-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-
200a-3p and hsa-miR-210-3p participate in pathways associated with T1DM
Background
pathogenesis, such as apoptosis, insulin and immune system.
Confirmatory tests, including saline infusion test (SIT), captopril challenge test
Conclusions
(CCT) and fludrocortisone suppression test
(FST) are commonly used for
Our data demonstrate that 9 miRNAs are differentially expressed in T1DM
diagnosis of primary aldosteronism (PA). Each test has its advantages and
patients in the first years of the diagnosis. Our study also provided novel
disadvantages, but which one should be preferentially performed is controversial.
information about biological pathways implicated in T1DM. Ongoing studies will
We aimed to evaluate the diagnostic accuracy of three tests in a prospective study.
further explore the role of these miRNAs as possible novel biomarkers for T1DM
Methods
prediction.
Five hundred and thirty-one hypertensive patients with high risk of PA were
DOI: 10.1530/endoabs.49.OC2.1
enrolled. Plasma aldosterone-renin ratio
(ARR) was used for screening.
Hypertensive patients tested positive at PA screening
(ARRR3.7 ng/dl per
mIU/ml), one in every three consecutive patient tested negative (ARR!3.7 ng/dl
per mIU/ml) and patients who tested negative but PA was strongly suspected
proceeded to three confirmatory tests. Area under receiver operator characteristics
curve (AUC), sensitivity and specificity were calculated. A systematic review and
meta-analysis of relevant studies were performed to place our results in context.
OC2.2
Findings
Finally,
132
patients diagnosed as PA and
104
diagnosed as essential
Effectiveness of complex therapy in patients with comorbidity
hypertension completed three tests. AUC of CCT, SIT and FST were 0.97
of type 2 diabetes and essential hypertension depending on genetic
(95% CI 0.95-0.99), 0.97 (0.95-0.99) and 0.98 (0.97-0.99), respectively, when
polymorphism PPARg2
post-test plasma aldosterone concentration (PAC) was used to confirm PA. But
Anna Shalimova, Oleksandr Bilovol & Lesya Bobronnikova
AUC of CCT significantly decreased to 0.76 (0.69-0.82) if PAC suppression ratio
Kharkiv National Medical University, Kharkiv, Ukraine.
was used to confirm PA. When PAC cutoffs of SIT and FST was set at 8 ng/dl, and
CCT at 11 ng/dl, the sensitivity were 87.9%, 93.2%, 92.4% and specificity were
The aim
93.3%, 90.4%, 90.4% respectively. No significant difference of synthetic AUC,
To evaluate effectiveness of complex therapy in patients with comorbidity of type
pooled sensitivity or specificity between SIT and CCT was found in the meta-
2
diabetes
(DM2) and essential hypertension
(EH) depending on genetic
analysis. Only one study of FST fulfilling the criteria of the systematic review was
polymorphism peroxisome proliferator-activating receptor-g2 (PPARg2). Before
included, reporting a sensitivity of 0.87 and a specificity of 0.95.
and after 3 months of treatment we examined 145 patients with EH stage II, grade
Interpretation
and DM2 moderate, subcompensated aged 45-60 years: group 1 (71 patients)
CCT, SIT and FST has comparable diagnostic accuracy. Based on their pros and
received standart therapy
(telmisartan, indapamide, metformin, gliclazide,
cons, it is reasonable to recommend CCT as the first choice to confirm PA in
atorvastatin, acetylsalicylic acid) and group 2 (74 patients) additionally received
clinical practice. When interpreting the results of CCT, PAC post-CCT is
a-lipoic acid (a-LA). Both groups were matched for age, sex, EH stage and grade,
recommended.
the degree of compensation DM2. Methods: biochemical blood analysis,
DOI: 10.1530/endoabs.49.OC1.5
echocardiography evaluation of mitral diastolic blood flow and tissue Doppler
spectral modes, reactive hyperemia, color Doppler mapping, enzyme immu-
noassay. We conducted genotyping of Pro12Ala polymorphism of PPARg2.
Results
Patients with genotype Pro/Pro of PPARg2 had significantly higher levels of total
cholesterol, LDL, proinflammatory cytokines (TNF-a and IL-6), the values of
Diabetes Prediction and Complications
intima-media thickness and significantly lower degree of endothelium-dependent
OC2.1
vasodilatation as compared to genotype Pro12Ala/Ala12Ala. After standart
microRNA expression profile in plasma from patients with type 1
therapy in patients with EH and concomitant DM2 (in all PPARg2 genotypes)
diabetes: a case-control study and bioinformatics analysis
metabolic and hemodynamic parameters were improved. More pronounced
Tais Silveira Assmann1,2, Mariana Recamonde-Mendoza4, Marcia Punales3,
dynamics was in patients with genotype Pro12Ala/Ala12Ala. Additional
Balduino Tschiedel3, Luis Henrique Canani1,2 & Daisy Crispim1,2
appointment of a-LA impacted more to vascular remodeling and levels of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
proinflammatory cytokines as compared to standard therapy. Decrease HbA1c
A total of 53 patients met the criteria for inclusion. They were randomly assigned
and triglyceride levels in patients with additional appointment of a-LA was
to receive multiprobiotic
‘Symbiter’
(concentrated biomass of
14 probiotic
significantly more pronounced as compared to standard therapy only in genotype
bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium)
Pro12Ala/Ala12Ala.
or placebo for 8-weeks administered as a sachet formulation in double-blind
Conclusions
treatment. The primary main outcome was the change HOMA-IR (homeostasis
Effectiveness of complex therapy in comorbidity of DM2 and EH depends on
model assessment-estimated insulin resistance) which calculated using Matthews
PPARg2 genotype. Dynamics of metabolic and hemodynamic parameters was
et al.’s equation. Secondary outcomes were the changes in glycemic control-
more pronounced in additional appointment of a-LA, especially in genotype
related parameters, anthropomorphic variables and cytokines (TNF-a, IL-1b,
Pro12Ala/Ala12Ala.
IL-6, IL-8, INF-g) levels. ANCOVA was used to assess the difference between
DOI: 10.1530/endoabs.49.OC2.2
groups.
Results
Supplementation with alive multiprobiotic for 8 weeks was associated with
significant reduction of HOMA-IR from 6.85G0.76 to 5.13G0.49 (PZ0.047),
but remained static in the placebo group (7.24G0.74 to 7.95G1.01; PZ0.573).
With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09%
(PZ0.383) and 0.24% (PZ0.068) respectively in placebo and probiotics groups.
However, in probiotic responders (nZ22, patient with decrease in HOMA-IR)
OC2.3
after supplementation a significant reduction in HbA1c by 0.39% (PZ0.022) as
GLP-1 based multi-agonists-induced signaling includes profound TRP
compared to non-responders was observed. In addition, from markers of chronic
channel involvement in insulin secretion
systemic inflammatory state only TNF-a (15.8%, P!0.001), and IL-1b (14.4%,
Noushafarin Khajavi1, Brian Finan2, Oliver Kluth3,4, Stefan Mergler5,
PZ0.001) and IL-6 (22.1%, PZ0.027) changes significantly after treatment with
Timo Muller2, Gunnar Kleinau1, Annette Schurmann3,4, Matthias
probiotics.
H Tschop2, Richard DiMarchi6, Heiko Krude1 & Heike Biebermann1
Conclusion
1Institute for Experimental Pediatric Endocrinology, Charite, University-
Probiotic therapies modestly improved insulin resistance in patients with type 2
Medicine Berlin, Berlin, Germany;2Institute for Diabetes and Obesity,
diabetes. Modulation of the gut microbiota represents a new treatment for
Helmholtz Center Munich, German Research Center for Environmental
diabetes and should be tested in larger studies.
Health (GmbH) and Technical University Munich, Munich, Germany;
DOI: 10.1530/endoabs.49.OC2.4
3Department of Experimental Diabetology, German Institute of Human
Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;4German Center for
Diabetes Research, Neuherberg, Germany;5Department of Ophthalmology,
Charite, University-Medicine Berlin, Berlin, Germany;6Department of
Chemistry, Indiana University, Bloomington, Indiana, USA.
Promiscuous multi-agonists that simultaneously activate two or three key
receptors (incretin- and/or glucagon receptor) were recently shown to improve
OC2.5
glycemic control in mice. Here we investigated the underlying mechanisms of
Urinary peptidomics for the detection of diabetic kidney disease
multi-agonists to enhance insulin secretion in murine islets and human pancreatic
Leticia A Brondani, Ariana A Soares, Angelica D’Allagnol,
b-cells. These mixed agonists display a greater potency in cAMP signaling as
Joíza L Camargo, Karina Monteiro & Sandra P Silveiro
compared to the native incretins. However, pharmacological blockade of cAMP
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
signaling only partially inhibited the increases in insulin secretion. Therefore,
additional mechanisms independent from Gs signaling-coupled Ca2C influx
appear to mediate insulin secretion. Here, we showed multi-agonists evoked
Background
significant increases in Ca2C influx through activation of both voltage-dependent
Diabetic kidney disease (DKD) is the main cause of end-stage renal disease It is
Ca2C channels (VDCCs) and transient receptor potential channels (TRPs). These
defined by glomerular filtration rate
(GFR) impairment and/or presence of
responses were more rapid and larger after multi-agonist stimulation than those
increased urinary albumin excretion (UAE). However, these parameters are
after mono-agonists. Pharmacological blockade of TRP channels suppressed
nonspecific and somewhat delayed manifestations of renal damage. Thus, earlier
Ca2C transients induced by multi-agonists to a greater degree than exposure to
DKD new biomarkers are strongly warranted.
VDCC blocker. TRP blockers also blunted cAMP accumulation and abolished
Objective
increases in whole-cell currents that are evoked with multi-agonists. These
To investigate the urinary peptidomics profile of type 2 diabetes mellitus (DM)
observations argue for a direct TRP channel activation by ligand-engaged incretin
patients with different stages of DKD.
receptors. Collectively, direct activation of adenylyl cyclase through GPCR/
Methods
channel constellations and concomitant rapid Ca2C influx likely contribute to the
Casual urine samples were collected from 66 type 2 DM patients matched by age,
increases in insulin secretion induced by multi-agonists.
gender and time of diabetes duration. Urine natural occurring peptides were
DOI: 10.1530/endoabs.49.OC2.3
purified by ultrafiltration under denaturing conditions and analyzed by
LC-MS/MS. UAE was assessed by immunoturbidimetry and GFR was estimated
by CKD-EPI equation. Kruskall-wallis, Mann-Whitney and c2 tests were
performed when appropriate; Perseus software was used to perform hierarchical
clustering of significantly up- and down-regulated proteins.
Results
Type 2 DM patients (mean ageZK61.5G9.7 years; malesZ47.1%) were
stratified by the levels of albuminuria (normal (nZ27), moderately increased (MI,
OC2.4
nZ18) and severely increased (SI, nZ21)). A total of 116 urinary proteins were
Effect of alive probiotic on insulin resistance in type 2 diabetes patients:
detected by LC/-MS/MS. A distinct proteomic profile was identified in patients
randomized clinical trial
with SI albuminuria, represented by
11 proteins. When GFR values were
Nazarii Kobyliak1, Kateryna Kondratiuk1, Dmytro Kyriienko2 &
analyzed, we observed that 13 urinary proteins differed significantly in the
Galyna Mykhalchyshyn1
9 patients with GFR !60 ml/min per 1.73 m2 when compared to 57 patients with
1Bogomolets National Medical University, Kyiv, Ukraine;2Kyiv City
GFR R60 ml/min per 1.73 m2. Among the most remarkably different urinary
Endocrinology Center, Kyiv, Ukraine.
protein profile, alpha-1 type I collagen was around 10% less expressed in SI
patients, while alpha-1 antitrypsin, plasma protease C1 inhibitor and apolipopro-
Background
tein-1 were wtwofold increased in these patients.
Probiotics have beneficial effect on obesity related disorders in animal models.
Conclusions
Despite a large number of animal data, randomized placebo-controlled trials
LC-MS/MS analysis revealed that at least 11 urinary proteins were differentially
(RCT) concluded that probiotics have a moderate effect on glycemic control-
expressed in type 2 DM patients according to DKD severity. This study confirms
related parameters. However, effect of probiotics on insulin resistance are
the previously described findings in other populations and also detected novel
inconsistent.
proteins commonly altered in patients with GFR impairment and increased
Aim
albuminuria.
In a double-blind single center RCT, effect of alive multistrain probiotic vs
DOI: 10.1530/endoabs.49.OC2.5
placebo on insulin resistance in type 2 diabetes patient were assessed.
Methods
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Receptors & Signalling
P!0.01) in Lxra/b DKO. Androgen biosynthesis genes (Cyp17a1, Hsd3b2,
Hsd17b3), triglyceride synthesis (Acsl, Acot7) as well as genes involved in
OC3.1
sphingolipid metabolism were altered correlating with lipidomic data.
Epigenetic regulation of aldosterone synthase gene, CYP11B2 by
Discussion
potassium
Our integrative approach using lipidomic analysis with mRNA transcript studies
Yoshiyu Takeda, Masashi Demura, Takashi Yoneda, Yoshimichi Takeda,
provides novel data, implicating LXRs in pathways such as sphingolipid
Mitsuhiro Kometani, Seigo Konishi & Toshitaka Sawamura
metabolism, critical for successful spermatogenesis.
Kanazawa University, Kanazawa, Japan.
DOI: 10.1530/endoabs.49.OC3.2
Purpose
We found the hypomethylation status of CYP11B2 gene in the aldosterone-
producing adenomas compared with normal adrenal glands or non-functioning
adrenal adenomas and reported that the methylation of promoter region of this
gene influenced the mRNA expression in the adrenal cells. Angiotensin II or
OC3.3
potassium regulates CYP11B2 gene expression in the adrenal cells. In order to
AKR1C3-mediated adipose androgen generation drives lipotoxicity in
clarify the acute effect of potassium on the methylation status of CYP11B2 gene,
polycystic ovary syndrome
Human adrenal cells rats were treated with potassium and the methylation status
Michael O’Reilly1, Punith Kempegowda1, Mark Walsh3, Angela Taylor1,
of CYP11B2 gene in the adrenal cells was examined.
Konstantinos Manolopoulos1, William Allwood1, Robert Semple4,
Methods
Daniel Hebenstreit3, Warwick Dunn1, Jeremy Tomlinson2 & Wiebke Arlt1
H295R cells were treated with potassium for 28 days. The gene expression of
1University of Birmingham, Birmingham, UK;2University of Oxford,
CYP11B2 was measured by real time quantitative PCR in the adrenal cells. ChiP
Oxford, UK;3University of Warwick, Coventry, UK;4University of
assay and methylation activity were measured. Isolated DNAs from adrenal cells
Cambridge, Cambridge, UK.
were treated with bisulfite and amplified using primers specific for the human
CYP11B2 promoter regions.
Polycystic ovary syndrome (PCOS) is prevalent metabolic disorder in women,
Results
associated with androgen excess and insulin resistance. These two major features
CYP11B2 mRNA levels were increased from 4th day to 7th day by the treatment
are closely correlated, but the direction of causality remains unclear.
with potassium. The methylation ratio was decreased from
4th day. The
Aldoketoreductase type
1C3 (AKR1C3) converts the androgen precursor
expression of CREB1 and NR4A1 were increased from 4th day. The methylation
androstenendione to testosterone (T), and is highly expressed in subcutaneous
activity was increased from 7th day. The chromatin accessibility was increased
(SC) adipose tissue. We hypothesised that adipose tissue represents an important
from 4th day to 7th day
site linking androgen activation and metabolic dysfunction in PCOS. We
Conclusions
undertook metabolic phenotyping in 10 PCOS women and 10 age- and BMI-
Aldosterone biosynthesis may be reversibly regulated by the epigenetic
matched controls. Participants underwent an oral challenge with the androgen
mechanism.
precursor DHEA, alongside adipose tissue microdialysis, with measurement of
DOI: 10.1530/endoabs.49.OC3.1
metabolic markers and adipose androgens in microdialysate fluid. Non-targeted
serum metabolome analysis was performed before and after androgen exposure.
SC adipose tissue biopsies were collected for RNA-sequencing. Complementary
in vitro experiments in primary SC adipocytes and a preadipocyte cell line were
performed to examine the effects of insulin and androgens on AKR1C3
expression and de novo lipogenesis, respectively. PCOS women had higher
adipose T (P!0.0006) and dihydrotestosterone (DHT, PZ0.01) than controls as
OC3.2
measured by liquid chromatography-tandem mass spectrometry. Non-targeted
Elucidating the role of Liver X receptors (LXRs) in the testis using lipid
serum metabolomics and adipose microdialysis revealed pro-lipogenic effects of
systems biology
androgens at baseline and after DHEA in PCOS. AKR1C3 mRNA expression was
Sheba Jarvis1, Lee Gethings2, Raffaella Gadaleta3,1, Lord Robert Winston1,
increased in PCOS SC adipose tissue
(PZ0.04). Transcriptional profiling
Catherine Williamson4 & Charlotte Bevan1
revealed dysregulation of mitochondrial and inflammatory pathways in PCOS SC
1Department of Surgery and Cancer, Imperial College London, Hammer-
adipose tissue. In vitro studies showed that insulin upregulates adipose AKR1C3
smith Hospital, London, UK;2Waters Corporation, Wilmslow, UK;
expression and activity, and androgens enhance adipose de novo lipogenesis.
Pharmacological inhibition of AKR1C3
decreased adipose tissue androgen
3Dipartimento Interdisciplinare di Medicina, University of Bari, Bari, Italy;
generation and androgen-mediated de novo lipogenesis. Complementary in vivo
4Womens Health Clinical Academic Group, Kings College London, Guys
and in vitro studies highlight that AKR1C3-mediated intra-adipose androgen
Campus, London, UK.
activation drives lipotoxicity and adverse metabolic risk in PCOS, fuelling a
vicious circle of androgen generation and insulin resistance. Selective inhibition
Introduction
of AKR1C3 holds promise as a novel therapeutic approach in PCOS.
The importance of the liver-X receptors (LXRs) in the maintenance of cholesterol
DOI: 10.1530/endoabs.49.OC3.3
homeostasis within the testis has yet to be fully characterised. By 7 months of age,
Lxra/b double knockout male mouse (Lxra/b DKO) develops sterility with
aberrations in testosterone production and lipid homeostasis. However, the
underlying testicular LXR-regulated pathways are not well understood.
Aim
The aim of this study was to further understand the importance of LXRs in the
OC3.4
testis by investigating disruption of candidate genes and networks of cellular
Treatment with thyroid hormone metabolite 3,5-T2 alters cholesterol
lipids and steroid metabolites in Lxra/b DKO mice.
and sex steroid metabolism in mouse liver
Methods
Julika Lietzow1, Janine Golchert2, Georg Homuth2, Wenke Jonas3,
We used RNA-seq and quantitative mass spectrometry to study whole testicular
Claes Ohlsson4, Andreas Landin4, Matti Poutanen5 & Josef Kohrle1
tissues from 6-month old Lxra/b DKO mice alongside age-matched littermate
1Institute of Experimental Endocrinology, Charité Universitatsmedizin
controls. cDNA libraries were prepared followed by sequencing using NextSeq-
Berlin, Berlin, Germany;2Interfaculty Institute for Genetics and Functional
500. Lipid extracts from mouse testis were prepared for LC-MS analysis using
Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald,
SONAR acquisition, based on an m/z isolation range of the quadrupole. Results
Germany;3Department of Experimental Diabetology, German Institute of
were analysed using LipidMaps and Progenesis QI for normalized quantitation.
Human Nutrition, Nuthetal, Germany;4Institute of Medicine,
Results
The Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden;
Histological assessment of testicular tissues from Lxra/b DKO mice confirmed
5Department of Physiology, Institute of Biomedicine, University of Turku,
abnormal seminiferous tubules, germ-cell loss and lipid deposition. Quantitative
Turku, Finland.
lipidomic analysis confirmed statistically significant differences in
53 lipid
species including triglycerides and cholesterol esters (notably 20:4 cholesteryl
ester) in the Lxra/b DKO mice. Sphingolipid species (e.g. ceramide t18:0/20:0)
Recent findings revealed
3,5-diiodo-L-thyronine
(3,5-T2) as a metabolically
were also altered. The retrieved curated targets were mapped onto KEGG
active iodothyronine affecting hepatic energy and lipid metabolism. Therefore,
pathway analysis, identifying key changes in steroid hormone biosynthesis and
3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of
sphingomyelin metabolism. RNA-seq analysis revealed
1161
differentially
obesity and its hepatic aftermath. So far only limited data exists relating to the
expressed genes (log2 fold change in gene expression of K3.49 to C2.17,
effects of 3,5-T2 on metabolism in euthyroid mammals maintained on high-fat
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
diet from the day of weaning onwards. Therefore, we performed a study in which
Furthermore, unbiased GMLVQ analysis of the urinary steroid metabolome
20-week old diet-induced obese male mice in comparison to lean animals
appears robust in differentiating healthy controls from cirrhosis and warrants
received either 3,5-T2 (2.5 mg/g body weight) or saline over a four-week period.
further exploration as a novel non-invasive biomarker tool to assess the severity
To identify new target genes and signaling mechanisms of 3,5-T2 which are
of NAFLD.
distinct from established hepatic T3
action we performed microarray-based
DOI: 10.1530/endoabs.49.OC3.5
transcriptome analyses of liver tissue. The transcriptome as well as qPCR data
demonstrated higher hepatic expression of genes involved in cholesterol
biosynthesis (e.g. Sqle 4.8-fold, Cyp51 2.8-fold, Hsd17b7 1.8-fold) and bile
acid formation (Cyp7a1 2.0-fold, Cyp39a1 2.9-fold) in obese but not in lean mice
treated with
3,5-T2. In contrast to the elevation of hepatic cholesterol
biosynthesis, serum cholesterol concentration was reduced by up to 57% with
Thyroid Disease 1
3,5-T2
administration. In addition,
3,5-T2
modulated expression of genes
OC4.1
important for sex steroid biosynthesis and inactivation (e.g. Cyp17a1 3.5-fold,
Hypothyroidism in pregnancy is associated with twin pregnancies and
Hsd17b6 -7.8-fold). GC MS/MS analysis of the hepatic sex steroid hormone
with adverse obstetric outcome: Analysis of 142,277 deliveries data
profile indicated higher progesterone and androstenedione content in livers of
from a single center
obese mice treated with 3,5-T2, whereas no such changes were observed in
Orit Barenholz-Goultschin1,2, Rivka Farkash1,2, Arnon Samueloff1,2 &
3,5-T2-treated lean mice. These results suggest a diet-dependent role of 3,5-T2 in
Gabriel Munter1,2
modulating local cholesterol as well as sex steroid biosynthesis and androgen
1Shaare Zedek Medical Center, Jerusalem, Israel;2Hebrew University,
homeostasis in mouse liver. Such actions of thyroid hormone metabolites have
Jerusalem, Israel.
not been reported elsewhere up to date and might help to explain liver-targeting
effects of T3-receptor beta-selective ligands.
DOI: 10.1530/endoabs.49.OC3.4
Introduction
Many studies have examined maternal and fetal complication rates in treated and
untreated overt and subclinical hypothyroidism. Maternal hypothyroidism may
adversely affect the development of the fetal pituitary-thyroid axis. It has also
been reported to be closely related to adverse pregnancy outcome.
Aim
To study the prevalence and outcome of hypothyroidism in pregnancy during the
OC3.5
last decade in a high volume obstetric center in Jerusalem.
Accurate staging of non-alcoholic fatty liver disease through analysis of
Methods
the urinary steroid metabolome
A retrospective study of the obstetric database between August
2005 and
Ahmad Moolla1, Amin Amin2, Beverly Hughes2, Wiebke Arlt2,
December 2015 in Shaare Zedek Medical Center, Jerusalem.
Zaki Hassan-Smith2, Lorna Gilligan2, Matt Armstrong3, Philip Newsome3,
Results
Tahir Shah3, Luc Van Gaal4, An Verrijken4, Sven Francque4, Jane Grove5,
During the study period there were 142,277 deliveries of singleton or twin
Neil Guha5, Guruprasad Aithal5, Ellie Barnes6, Michael Biehl7 &
pregnancies (1.9% twin deliveries). The medical files of 4042 (2.8%) deliveries
Jeremy Tomlinson1
(group A) included a diagnosis of maternal hypothyroidism. Women giving birth
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of
with the diagnosis of hypothyroidism were older (31.1G6 years 28.8G5.6 y.
Oxford, Oxford, UK;2Centre for Endocrinology, Diabetes & Metabolism,
P!0.0001). Gestational diabetes was more prevalent (7.3% vs 3.3%, P!0.0001)
University of Birmingham, Birmingham, UK;3Centre for Liver Research,
in group A as were hypertensive disorders (3.7% vs 2.3%, P!0.0001). Higher
University of Birmingham, Birmingham, UK;4University of Antwerp,
rate of assisted reproduction techniques were used in group A (8.5% vs 3.7%,
Antwerp, Belgium;5NIHR Nottingham Digestive Diseases Biomedical
P!0.0001). Although not previously reported, the incidence of twin pregnancies
Research Unit, Nottingham University Hospitals NHS Trust and University
was higher in group A (3.8% vs 1.8% P!0.0001) and this association remained
of Nottingham, Nottingham, UK;6Translational Gastroenterology Unit,
significant in a multivariate analysis with IVF as a co-variate
(OR 1.43
University of Oxford, Oxford, UK;7University of Groningen, Groningen,
95%CI[1.20-1.71], P!0.001). Obstetric complications including preterm
The Netherlands.
deliveries
(7.8% vs 5.2%, PO0.0001), cesarean sections (20.6% vs 11.4%,
PO0.0001), any obstetric hemorrhage and prolonged hospitalization were more
frequent in group A. The incidence of adverse neonatal outcome including low
Introduction
birth weight (7.3% vs 5.4%, PO0.0001) and NICU admission (5.1% vs 3.6%,
Non-alcoholic fatty liver disease
(NAFLD) is associated with dysregulated
PO0.0001) was higher in group A but there was no difference in fetal
glucocorticoid metabolism. Advanced stages of NAFLD are associated with
macrosomia and apgar scores.
adverse outcome and current strategies to stage disease severity are still reliant
Conclusions
upon liver biopsy. We have previously described changes to enzymatic pathways
In this large database, hypothyroidism is associated with adverse obstetric
that regulate cortisol bioavailability; 11b-hydroxysteroid dehydrogenase type-1
outcome. This is the first study to describe a higher incidence of hypothyroidism
(11b-HSD1) regenerates cortisol from inactive cortisone, and A-ring reductases,
in twin pregnancies. TSH screening should be considered in twin pregnancies.
5a- and
5b-reductase
(5aR/5bR), inactivate cortisol to tetrahydrocortisol
DOI: 10.1530/endoabs.49.OC4.1
metabolites (THF/5aTHF). Changes to these pathways are apparent across the
NAFLD spectrum (simple steatosis, steatohepatitis
(NASH), fibrosis and
cirrhosis). Here we have further validated these observations in a large cohort
of patients with NAFLD and compared these to healthy controls and to patients
with alcoholic cirrhosis.
Methods
OC4.2
Using gas chromatography / mass spectrometry, we analysed steroid metabolites
Inducible thyrocyte-specific Gs alpha-deficient mice as a novel model
in spot urine samples (corrected for creatinine) in patients with biopsy proven
for hypothyroidism
NASH (nZ65), NAFLD cirrhosis (nZ51), alcoholic cirrhosis (nZ48) and in
Konrad Patyra1, Holger Jaeschke1, Henriette Undeutsch1, Christoffer Lof1,
healthy controls (nZ58). Additionally, we used machine learning-based analysis
Suvi Ruohonen1, Meeri Jannari1, Min Chen2, Lee S. Weinstein2,
to investigate changes across 32 steroid metabolites.
Ralf Paschke3, Jorma Toppari1 & Jukka Kero1
Results
1Institute of Biomedicine, Turku, Finland;2Metabolic Diseases Branch,
Cortisol regeneration
(11b-HSD1 activity: THFC5aTHF/THE ratio), was
National Institute of Diabetes, Digestive and Kidney Diseases, National
significantly increased in NAFLD cirrhosis (PZ0.0004), and alcoholic cirrhosis
Institutes of Health, Bethesda, MD, USA;3Division of Endocrinology and
(P!0.0001), compared to controls. Cortisol inactivation
(A-ring reductase
Metabolism, Departments of Medicine and Oncology and Arnie Charbon-
activity: THF/5aTHF ratio) was significantly reduced in NAFLD cirrhosis
neau Cancer Institute, Cummings School of Medicine, University of
compared to controls (PZ0.0004), but not between controls and alcoholic
Calgary, Calgary, Canada.
cirrhosis (PO0.99) nor NASH (PZ0.332). Machine learning-based analysis by
generalised matrix-learning vector quantisation (GMLVQ) achieved excellent
separation of control and NASH groups (AUC-ROCZ0.87). Furthermore, there
The thyroid gland produces thyroid hormones, which are essential regulators of
was near perfect separation of controls from NAFLD cirrhosis (AUC-ROCZ
growth, development and metabolism of the body and is mainly regulated by the
0.99) and controls from alcoholic cirrhosis (AUC-ROCZ0.98).
thyroid stimulating hormone (TSH)/TSH receptor (TSHR) interplay. The TSHR
Conclusion
couples to all four G protein families in vitro but only for the Gs and Gq signaling
This data is consistent with our previous findings that identified differentially
cascade a role has been identified in vivo. To gain further insights into the
regulated steroid metabolic pathways across the spectrum of NAFLD.
complex signaling networks mediated by G proteins in the thyroid, we generated
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
a thyrocyte-specific tamoxifen-inducible Gs deficient mouse line (iTGsKO). Mice
Whereas G-protein coupled receptors (GPCRs) have long been believed to signal
were injected with tamoxifen at P28 and phenotypic characterization was carried
via cyclic AMP (cAMP) exclusively at the cell surface, our group has shown that
out by performing thyroid function tests at different ages. iTGsKO mice showed
GPCRs also stimulate cAMP production from the cell interior once internalized
hypothyroidism at P56, four weeks after induction with tamoxifen. Furthermore, a
together with their ligands. This phenomenon, which we originally described for
decrease in thyroid weight and an increased pituitary weight support the
the thyroid stimulating hormone receptor (TSHR) in thyroid follicles, has now
conclusion of hypothyroidism in these mice. Morphometric analysis of the
also been shown for several other GPCRs. However, the involved subcellular
thyroid histology of iTGsKO mice with an age of 6 months (P168) showed that
compartment(s) and the mechanisms linking signalling by internalized GPCRs to
the thyrocyte layers between adjacent follicles and the follicle areas were
downstream biological effects are largely unknown. The aim of this study was to
significantly reduced when compared with controls. Interestingly, despite of an
follow the trafficking of internalized TSHRs and involved signalling proteins in
identical thyroid hormone status we observed a clear sex difference. In iTGsKO
living primary thyroid cells by highly inclined thin illumination
(HILO)
males, the body weight was significantly decreased at P70 when compared with
microscopy as well as to monitor cAMP production and protein kinase A
control males but no weight difference was seen in females over the investigated
(PKA) activation by real-time fluorescence resonance energy transfer (FRET)
time period of 6 months (P168). The lower body weight in iTGsKO males was
microscopy. Importantly, using a biosensor nanobody that is specific for the
associated with reduced fat mass. In summary, we show that iTGsKO mice are a
active Gs-protein, we were able to directly demonstrate that the internalized
useful tool for understanding the role of G-protein signaling in the thyroid as well
TSHR activates an endogenous pool of Gs-protein located on membranes of the
as investigating the metabolic consequences in hypothyroidism.
Trans Golgi Network (TGN). Direct monitoring of PKA activation with a Golgi-
DOI: 10.1530/endoabs.49.OC4.2
localized FRET sensor (AKAR2) showed a delayed PKA activation (approx.
10 min) after TSH stimulation, which is compatible with the time required for
TSH/TSHR complexes to reach the Golgi/TGN. Moreover, our results also
indicate that Gs-protein mediated signalling by internalized receptors at the TGN
and the resulting PKA activation at a critical position near the nucleus are
required for the efficient induction of CREB phosphorylation and gene
OC4.3
transcription. These findings provide a mechanism to explain the biological
A novel variant in the SERPINA7 gene causing partial TBG deficiency
relevance of GPCR signalling at intracellular sites, which might help explaining
in a women and two male siblings: molecular and protein structural
the pathogenesis of endocrine disorders such as Graves’ disease and might pave
analysis
the way to innovative pharmacological therapies.
Cristiane Lima1, Andressa Maciel1, Sarah Caixeta Cardoso1,
DOI: 10.1530/endoabs.49.OC4.4
Matheus Andrade1, Vinicius Cunha1, Lucas Bleicher2, Juliana mazzeu3
& Adriana Lofrano-Porto1
1University of Brasília, Faculty of Health Sciences, Molecular Pharma-
cology Laboratory, Brasilia, DF, Brazil;2Federal University of Minas
Gerais, Department of Bichemistry and Imunology, Belo Horizonte, MG,
Brazil;3Univeristy of Brasilia, Faculty of Medicine, Medical Genetics
OC4.5
Laboratory, Brasilia, DF, Brazil.
Levothyroxine replacement therapy: once treatment is started, should it
last indefinitely?
Sarantis Livadas1, Christina Bothou1, Ioannis Androulakis1,
Background
Anastasios Boniakos1, Nicholas Angelopoulos1 & Leonidas Duntas2
Thyroxine-binding globulin (TBG) is the major human thyroid hormone transport
1Endocrine Unit, Metropolitan Hospital, Athens, Greece;2Unit of
protein. It is encoded by the SERPINA7 gene, located on the long arm of the X
Endocrinology, Diabetes and Metabolism, Evgenideion Hospital, University
chromosome (Xq22.2). Inherited TBG abnormalities result in complete (TBG-
of Athens, Athens, Greece.
CD) or partial (TBG-PD) TBG deficiency. We performed a comprehensive
molecular analysis of the SERPINA7 gene in a Brazilian family with TBG-PD.
Methods
Background
Genomic DNA was extracted from the female proband, her father, dizygotic twin
Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once
sister and two brothers, and the coding region of the SERPINA7 gene was
started, about 90% of patients continue LT4 treatment long-term.
sequenced. The proband’s X-chromosome inactivation pattern was evaluated by
Aim of the study
methylation analysis using the human androgen receptor (AR) gene, located next
To evaluate the necessity of long-term thyroxine supplementation and to
to SERPINA7 (Xq11.2). Structural analysis of the Serpin protein family was
determine the prognostic factors that could identify which patients may
performed using PFSTATS, and was also used to map equivalent positions in all
discontinue LT4 treatment.
human homologs. Molecular modeling was done as described by Feyfant et al.
Design and methods
Results and Discussion
LT4 replacement therapy was paused for at least six weeks in all patients
A novel missense mutation in the SERPINA7 gene (p.R35W; c.163COT) was
consecutively visiting our department, excluding those who have a definite need
found in heterozygosity in the proband and in hemizygosity in her brothers.
for L-thyroxine use (replacement after total thyroidectomy), those on thyroid-
They presented low serum levels of total T4, total T3 and TBG, compatible with
altering medication, women wishing to conceive and those who gave birth last
TBG-PD. The proband expressed an X-chromosome inactivation ratio of 20:80.
year. 231 individuals were assessed (84% females), aged 48 years (SDZ16.5),
The substitution of an arginine by a tryptophan is predicted to disrupt the protein
who were categorized into the following categories: a) unknown reason for
surface and main electrostatic interactions. The conservation and correlation
thyroxine supplementation (nZ62), b) presence of thyroid nodules (nZ90),
patterns showed that tryptophans are extremely rare (0.1%) in this position, and
normal TSH before thyroxine administration (nZ44), over 10 years’ use (nZ10),
there is no significant (P!10-10) pairwise.
therapy initiated post-pregnancy (nZ20). Thyroid function was evaluated before
Conclusion
and after the thyroxine pause. A value of TSH R4.5 IU/ml post treatment
We report a new variant of the SERPINA7 gene associated with TBG-PD in three
discontinuation was considered as ‘relapse’ and LT4 was reinstituted in those
siblings. The proband’s X-chromosome inactivation pattern may have accounted
individuals. The potential prognostic factors analyzed were family history of
for the rare phenotypic expression in a heterozygous woman. The hydrophobic
thyroid dysfunction, sex, age, dose per BMI and dose per kg, thyroid volume,
nature of the mutant is predicted to create an apolar patch at the protein surface,
thyroid ultrasound characteristics, positivity of thyroid autoantibodies, basal TSH
which would be significantly exposed to the solvent, and result in protein
values and reason for the initial treatment indication.
aggregation and/or misfolding with consequent thyroxin transport defect.
Results
DOI: 10.1530/endoabs.49.OC4.3
25.54% (83% females) of the studied subjects relapsed. Of the above-described
factors, only diffuse inhomogeneous echogenicity was tentatively identified as the
only predictive factor for relapse (71% vs 57%, P:001). The age (47.27G15.45 vs
48.17G16.98 years, P:0.72), the positivity of TPOAb (69%% vs 54%, P:0.064)
and basal TSH values (1.51G0.96 US. 1.57G0.84, P:0,81) did not differ
significantly among the two groups.
OC4.4
Conclusions
The TSH receptor reaches the trans-Golgi network to induce PKA
One out of four individuals evaluated required thyroxine treatment. The need for
activation and trigger gene transcription
a patient-centered approach regarding L-thyroxine supplementation and for a
Amod Godbole1,2, Sandra Lyga1,2, Martina Leo1,2 & Davide Calebiro1,2
thorough review of patient history was evident.
1Institute of Pharmacology and Toxicology, University of Wurzburg,
DOI: 10.1530/endoabs.49.OC4.5
Wurzburg, Germany;2Bio-Imaging Center/Rudolf Virchow Center,
University of Wurzburg, Wurzburg, Germany.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Cardiovascular Endocrinology
Materials and methods
Visceral and subcutaneous adipose tissues were obtained from 97 non-diabetic
OC5.1
subjects (41 non-obese, 18 obese, and 38 morbid obese), who underwent open
Polarized epithelial cells release exosomes loaded with miRNAs capable
abdominal surgery with minimal impact on dietary intake. Intake of hydrogenated
of interacting with HSD11B2 and MR genes
and non-hydrogenated vegetable oils and butter was collected using a valid and
Eric Barros1, David Ortiz1, Carmen Campino1, Carolina Valdivia1,
reliable food frequency questionnaire. The gene expressions of PPAR-gamma in
Alejandra Tapia-Castillo1,2, Jaime Lizama1, Fidel Allende1, Sandra Solari1,
visceral and subcutaneous adipose tissue were assessed by Real-Time PCR.
José Vicente Gonzalez1, Alejandro Martínez-Aguayo1, Andrea Vecchiola1,
Findings
Gabriela Repetto1,2, Marlene Aglony1, Rene Baudrand1, Carlos
After adjustment for total energy intake and age, visceral adipose tissue PPAR-
F Salomon1,3, Carlos E Fardella1 & Cristian Carvajal1
gamma gene expression was correlated with total fat and oil intake (bZK0.531,
1Pontificia Universidad Católica de Chile, Santiago, Chile;2Universidad del
PZ0.014) in total population. Among non-obese subjects, visceral adipose tissue
Desarrollo, Santiago, Chile;3University of Queensland, Brisbane, Australia.
PPAR-gamma gene expression was correlated with non-hydrogenated oil
(bZ0.621, PZ0.017). PPAR-gamma gene expression in subcutaneous adipose
tissue was correlated with non-hydrogenated oil (bZ0.481, PZ0.026) among
obese subjects. Moreover, among morbid obese subjects we found significant
Arterial hypertension is a major health problem affecting 1.13 billion people
correlations between visceral adipose tissue PPAR-gamma expression and total
worldwide, of which 10% could be due to endocrine pathologies related
fat and oil intake (bZ0.417, PZ0.020).
to the mineralocorticoid receptor
(MR) (i.e. primary aldosteronism,
Conclusions
11b-hydroxysteroid dehydrogenase type 2 enzyme (HSD11B2) deficiency).
Expression of adipose tissue PPAR-gamma mRNA negatively correlates with
The MR pathway is expressed mainly in placenta, kidney and colon
total fat and oil intake mostly in visceral fat. In addition, non-hydrogenated oil
epithelial cells. Current research highlights potential epigenetic regulatory
positively correlates with PPAR-gamma expression.
mechanisms for the MR pathway. Here, specific miRNAs are being studied
as epigenetic regulators, either present in cells or exosomes (nanovesicles of
DOI: 10.1530/endoabs.49.OC5.2
40-150 nm diameter) carrying miRNA, RNA, lipids and proteins. Those
miRNAs could dynamically influence the onset and progression of the
mineralocorticoid arterial hypertension (AH).
Aim
To isolate exosomes from polarized epithelial cells and to identify in their cargo
miRNAs affecting HSD11B2 and MR gene expression.
Methods
OC5.3
The bioinformatic tool mirWalk2.0 was used to determine miRNAs capable to
interact with HSD11B2 and MR RNAs. The cell line derived from colon epithelia
Cardio metabolic assessment of lamin A/C mutation carriers according
(Caco-2) cells was cultured and polarized in Transwells. MR pathway genes and
to R482 or Non-R482 mutation
miRNAs targeting the MR and HDS11B2 were measured by qPCR. Exosomes
Maxime Kwapich1, Kenza Benomar1, Stéphanie Espiart1, Eric Van Belle2,
from apical and basolateral culture medium were isolated at 24 h of incubation in
Pascal Pigny3, Gisèle Bonne4, Corinne Vigouroux5,6, Dominique Lacroix2
basal conditions, quantified with NanoSight-NS300 and their specific miRNA
& Marie-Christine Vantyghem1,7
content was determined.
1Service d’Endocrinologie et Métabolisme, Hôpital C Huriez Centre
Results
Hospitalo-universitaire de Lille, 1 rue Polonovski, 59 037 Lille Cedex,
We identified bioinformatically that miRNA 135b, 644a and miRNA 488, 1205
France;2Service de Cardiologie, Institut Cœur-poumon, Centre Hospitalo-
could interact with the MR and HSD11B2, respectively. Caco-2 cells polarize
universitaire de Lille, 1 rue Polonovski, 59 037 Lille Cedex, France;
after
21
days of culture
(trans-epithelial resistance
(TEER):
114.18 cm2),
3Service de Biochimie et Biologie Moléculaire, Centre de Biologie-
expressing polarization genes (SLC11A2, SLGT1, ALPI), genes associated to
Pathologie, Centre Hospitalo-universitaire de Lille, 1 rue Polonovski,
MR pathway (NR3C2, HSD11B2, SCNN1A, SLC12A2, SGK1, ATP1A1) and
59 037 Lille Cedex, France; 4Sorbonne Universités, UPMC Univ Paris 06,
pre-miRNAs (135b,
644a,
488,
1205). We identified that Caco-2
release
INSERM UMRS974, CNRS FRE3617, Center for Research in Myology,
21!109G0.69!109 (apical) and 4.1!109G0.0029!109 (basolateral) extra-
Institut de Myologie, G.H. Pitié Salpêtrière, F-75651 Paris Cedex 13,
cellular vesicles per ml of which a 36.8 and 38.5% are exosomes with a modal
France;5Saint-Antoine Research Center, Institute of Cardiometabolism and
range in 124-125 nm diameter respectively. Preliminary results show expression
Nutrition, INSERM UMR, Pierre-and-Marie Curie University, Université
of miRNA 135b, 644a, 488 and 1205 in apical and basolateral exosomes.
Paris, Sorbonne Universités, Paris, France;6Departments of Molecular
Conclusion
Biology and Endocrinology, Assistance Publique-Hopitaux de Paris,
Caco-2 cells release five-times more exosomes in the apical than basolateral side,
Hôpital Saint-Antoine, Paris, France;7Equipe INSERM 1190 Prise en
both carrying miRNAs that could interact HSD11B2 and MR gene.
charge translationnelle du diabète Institut EGID (European Genomic
Institute for Diabetes), Lille, France.
DOI: 10.1530/endoabs.49.OC5.1
Background
Lamin A/C mutations show heterogeneous phenotypes expanding from
cardiopathies to lipodystrophies. LMNA-related heart disease has recently been
shown to be associated with a high incidence of phenotypic progression and
OC5.2
adverse arrhythmic and non-arrhythmic events. Anticipatory planning to prevent
sudden death has been recommended in a multicentric cardiologic recruitment.
Association of PPAR gamma gene expression with dietary intake of fat
Nevertheless the specific cardiac prognosis of R482-LMNA mutated patients, the
and oil among non-diabetic subjects
hot-spot for partial lipodystrophic syndromes, has not been well studied.
Emad Yuzbashian1,2, Maryam Zarkesh3, Golaleh Asghari1,
Objectives
Azita Zadeh-Vakili3, Behnaz Mahmoodi1, Mehdi Hedayati3,
To compare the cardio-metabolic complications of R482-LMNA mutated
Parvin Mirmiran1 & Alireza Khalaj4
patients, and carriers of other LMNA mutations.
1Nutrition and Endocrine Research Center, Research Institute for Endocrine
Methods
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
This retrospective study included 29 R482-LMNA mutated patients and 29
2Student Research Committee, Biochemistry of Nutrition Research Center,
carriers of another lamin A/C mutation (non-R482 group) followed at a single
School of Medicine, Mashhad University of Medical Sciences, Mashhad,
university hospital for a median of
5.5 years. The cardiac and metabolic
Iran;3Cellular and Molecular Endocrine Research Center, Research
phenotypes were compared between the two groups.
Institute for Endocrine Sciences, Shahid Beheshti University of Medical
Results
Sciences, Tehran, Iran;4Obesity Treatment Center, Department of Surgery,
The non-R482 carriers showed more electrocardiographic anomalies and wore
Shahed University, Tehran, Iran.
more cardiac devices than the R482-carriers (P!0.001). The ultrasound cardiac
examinations of non-R482 patients showed a higher frequency of left auricular
Background and Objective
dilatations
(P!0.05) and a lower mean left ventricular ejection fraction
Several animal studies showed the expression of peroxisome proliferator
(P!0.01) than in R482-carriers. A family history of medical devices
activated receptor-gamma (PPAR gamma) in adipocytes among rats fed with
(P!0.001) or sudden death (P!0.01) was more frequent in non-R482 than in
high-fat diet was higher than those fed with normal diet. However, there are no
R482-carriers. The prevalence of diabetes (P!0.01) and hypertriglyceridemia
human studies to support this. The objective of the present study was to
(P!0.05) and coronaropathy was higher in R482 than in non-R482 carriers.
investigate the association between the PPAR gamma expression in adipose tissue
The R482 carriers had a lower leptin (P!0.01) and BMI (P!0.05) level than the
and intake of hydrogenated and non-hydrogenated vegetable oils and butter.
non-R482.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
1INSERM 1185, Le Kremlin Bicetre, France;2Service d’endocrinologie
The non-R482 presented more arrhythmias than the R482-carriers, who were
pédiatrique, hôpital Robert Debré, APHP, Paris, France;3INSERM UMR-S
twice more often diabetic with more coronaropathies. The frequency of diabetes
938, Paris, France;4Prem Up foundation, Paris, France.
reached, however 40% in non-R482 mutations. The follow-up of laminopathies
should be adjusted to the genotype. Arrythmias, especially associated to diabetes
or medical device family history should lead to LMNA genetic testing.
Sex differences have been demonstrated in various biological processes such
DOI: 10.1530/endoabs.49.OC5.3
as arterial blood pressure. However, the potential sex dimorphism of the
renin-angiotensin-aldosterone system and, by extension, the mineralocorti-
coid receptor (MR) signaling pathway, major regulators of blood pressure,
has only been poorly studied, notably in the kidney. Basal systolic blood
pressure (SBP) and heart rate (HR) were measured in adult male and female
mice. Renal gene expression studies of major players of MR signaling were
performed at different developmental stages in male and female mice using
OC5.4
RT-qPCR, and were compared to that of the same genes in the lung, another
Food history characterization of Portuguese centenarians, nutritional
mineralocorticoid epithelial target tissue. The potential role of sex hormones
biomarkers and cardiovascular risk: case control study
in the regulation of these genes was also investigated in differentiated
Alda Pereira da Silva1,2, Catarina Chaves3, Andreia Matos1,5, Angela Gil1,5,
KC3AC1 renal cells. Additionally, renal expression of the
11bHSD2
Carolina Santos1,5, Ana Valente4, Manuel Bicho1,5 & João Gorja˜o Clara2
protein, a regulator of mineralocorticoid specificity, was measured by
1Genetics Laboratory, Environmental Health Institute - ISAMB, Faculty of
immunoblotting and its activity was indirectly assessed in the plasma using
Medicine, University of Lisbon, Lisbon, Portugal;2Geriatric Universitary
LC-MSMS method. SBP (91.7 G1.1 vs 99.2 G1.0 mmHg, P!0.0001) and
Unit of Faculty of Medicine, University of Lisbon, Lisbon, Portugal;
HR (662 G3 vs 687 G 4 bpm, P!0.0001) were significantly lower in
3Centro Hospitalar de Lisboa Central, Lisbon, Portugal;4Department of
females compared to males. This was accompanied by a sex and tissue-
Nutritional Science, Atlantica University, Barcarena, Portugal;5Instituto de
specific expression of MR signaling pathway from fetal stage (E18) to
Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal.
adulthood, most notably for GR (Nr3c1) and Gilz renal mRNA expression
which was twofold-lower in adult females mice compared to males
(P!0.01). Moreover, 11bHSD2 mRNA and protein expression was found
Introduction
significantly increased in females (P!0.05), with a statistically different
Eating habits may contribute to longevity. Consumption of red meat, source of
ratio of corticosterone/dehydrocorticosterone between both sexes
saturated fatty acids and cholesterol may be associated with increased risks of
(PZ0.012). Finally, the implication of sex hormones in this sex-specific
diabetes, cardiovascular disease (CVD), and mortality risk.
expression profile was confirmed in vitro, most notably for Gilz mRNA
Methods
expression. We demonstrate a tissue-specific, sex-dependent and develop-
We studied 521 subjects, both genders, 253 centenarians (CENT) (100.26G1.98
mentally-regulated pattern of expression of MR signaling that could have
age) and 268 controls (67.51G3.25 age), both low (LCR) and high cardiovascular
important implications in physiology and pathology, particularly in the
risk
(HCR), calculated based on QRISKw2-2016. Anthropometric and body
development of essential hypertension in men.
composition analysis were evaluated by bioimpedance. The abdominal obesity
DOI: 10.1530/endoabs.49.OC5.5
(cm), BMI (kg/m2) and the cut-off for fat mass (FM) by gender, defined according
WHO. Sarcopenia defined by muscle-mass index cut-off%16.7 kg/m2. Statistical
methods were chi-square test, ANOVA and binary logistic regression.
Results
There were differences in the distribution of food frequency history between
centenarians and controls concerning food groups except oilseeds. The daily
intake of red meat, adjusted for age and gender, was a protective factor for
sarcopenia (ORZ0.25, CI 95%Z0.096-0.670, PZ0.006), but contributes for FM
Diabetes therapy and complications
excess (ORZ4.946, CI 95%Z1.471-16.626, PZ0.01), overweight and obesity
OC6.1
(ORZ4.804, CI 95%Z1.666-13.851, PZ0.004). Only 2% of the centenarians
A passe-PAR2 for b-cell regeneration and protection
reported this eating habit unlike the 64.3% of the HCR group. The frequency
Ron Piran1 & Fred Levine2
history of red meat intake was associated with higher cardiovascular risk
1Bar Ilan University’s Faculty of Medicine, Safed, Israel;2Sanford
(c2Z239,807; dfZ8, P!0.0001), as well as canned food intake (c2Z225.321;
Children’s Health Research Center, Sanford Burnham Prebys Medical
dfZ8, P!0.0001). Basal metabolism (Kcal) was lower in centenarians and
Discovery Institute, La Jolla, California, USA.
higher in HCR group
(CENTZ1176.78G201.98; LCRZ1356.54G170.65;
HCRZ1561.33G267.85; P!0.0001), in the same way as BMI (CENTZ
21,06G3.68; LCRZ28.49G4.69; HCRZ29.56G5.26; P!0.0001), waist
circumference (CENTZ85.29G10.83; LCRZ96.02G11.71; HCRZ104.50G
Cell and tissue damage, particularly to pancreatic b-cells, is an essential
11.84; P!0.0001) and hip-waist ratio (CENTZ0.88G0.07; LCRZ0.92G0.08;
characteristic of diabetes mellitus, triggered by autoimmune destruction of
HCRZ1.01G0.08; P!0.0001).
b-cells in type-1
(T1D) and by obesity associated factors or insulin
Conclusions
resistance in type 2. Thus, stimulating b-cell regeneration has long been a
Centenarians have different food history than the control population. Frequent
most important goal of diabetes research. Recently, we have shown that
consumption of red meat may contribute to obesity and increased cardiovascular
pancreatic injury consisting of acinar cell inflammation and b-cell
risk, since the hemic iron of red meat may catalyze oxidations leading to disease
destruction led to islet cell transdifferentiation. In this work, we report
processes. The low frequency of this consumption, observed in centenarians,
that the molecular mechanism for this process requires the activation of the
although associated with sarcopenia, may be one of the keys to longevity.
protease-activated receptor-2 (PAR2), a G-protein-coupled receptor. PAR2
DOI: 10.1530/endoabs.49.OC5.4
modulation was sufficient to induce islet cell transdifferentiation in the
b-cells ablated animals as PAR2 Knock out mice and mice injected with
PAR2 pharmacological activator showed that it was necessary and sufficient
for the induction of islet cell transdifferentiation in the settings of b-cell
ablation. PAR2 expression was modified in an islet cell type-specific manner
in murine and human T1D. In addition to transdifferentiation, PAR2
OC5.5
regulated b-cell apoptosis in caerulein-mediated pancreatitis, demonstrating
Sex dimorphism of renal corticosteroid signaling during development
that PAR2
was required for b-cell survival and protection during
and long term consequence on blood pressure
inflammation.
Laurence Dumeige1, Caroline Storey1,2, Lyvianne Decourtye3,
DOI: 10.1530/endoabs.49.OC6.1
Mélanie Nehlich1,4, Christophe Lhadj1,4, Say Viengchareun1,
Laurent Kappeler3, Marc Lombès1 & Laetitia Martinerie1,2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
OC6.2
differentially methylated CpG regions near the promoters. Five genes,
Insulin-mimetic effects of short-term Rapamycin in type 1 diabetic
considered most likely biologically relevant to have impact in diabetes were
patients prior islet transplantation
those involved in processing of energy molecules, differentiation and
Federica Ermetici1, Silvia Briganti1, Stefano Benedini1,2, Roberto Codella2,
formation of adipocytes and exhibiting GTF-ase activities. Eighteen regions
Paola Maffi3, Rossana Caldara3, Antonio Secchi3, Lorenzo Piemonti3,
included genes with known specific functions that are not directly linkable to
Rodolfo Alejandro4, Camillo Ricordi4 & Livio Luzi1,2
influencing diabetic phenotype. Finally 12 genes where either pseudogenes
1Endocrinology and Metabolism, IRCCS Policlinico San Donato,
or had unknown function. In conclusion this is the first study that shows
San Donato Milanese, Italy;2Department of Biomedical Sciences for
influence of metformin in altering DNA methylation in humans and
Health, Università degli Studi di Milano, Milano, Italy;3Department of
identified markers may prove to be valuable biomarkers for the under-
Internal Medicine, Transplant Medicine Unit, San Raffaele Scientific
standing of the molecular basis of metformin action and may lead to the
identification of new drug targets.
Institute, Milano, Italy;4Diabetes Research Institute, University of Miami
Miller School of Medicine, Miami, Florida, USA.
DOI: 10.1530/endoabs.49.OC6.3
It has been suggested that the selective m-TOR inhibitor, Rapamycin, has
been improved the success pancreatic islet allotransplantation (ITx) in type
1 diabetic patients (T1DM). Forty-one ITx were studied. Thirteen T1DM in
OC6.4
poor glycemic control underwent a 45-days Rapamycin before ITx followed
Copeptin and its association to cardiovascular dysfunction in type 2
by standard Edmonton Protocol (EP, group 1, Milan), and they were
diabetes
compared to 28 T1DM patients undergoing EP (group 2, Miami). Outcome
Simona Ioana Chisalita1, Lee Ti Chong2, Fredrik Nystrom1,
measures were daily insulin requirement (DIR), HbA1c, C-peptide and the
Carl Johan Ostgren3 & Toste Länne4
SUITO index of beta-cell function before and 1 year after ITx. Four patients
1Department of Endocrinology and Department of Medicine and Health
from group 1 underwent euglycemic-hyperinsulinemic clamp with 6,6-d2-
Sciences, Linkoping University, Linkoping, Sweden;2Department of
glucose infusion before and after ITx. We found a significant reduction in
Emergency and Department of Medicine and Health Sciences, Linkoping
DIR after Rapamycin pre-treatment (K8G6 U/day, meanGS.D., P!0.001).
University, Linkoping, Sweden;3Department of Medical and Health
Nine patients from group 1 fulfilled follow-up. One year after ITx, DIR
Sciences (IMH)/Division of Community, Linkoping, Sweden;4Department
significantly decreased
(K37G15 U/day, P!0.001) and six patients
of Thoracic and Vascular Surgery, and Department of Medicine and Health
became insulin independent. We observed greater DIR reduction in group
Sciences, Linkoping University, Linkoping, Sweden.
1 as compared to group 2 at 1-year follow-up (K37G15 vs K19G
13 U/day, PZ0.005), which remained significant after adjusting for gender,
Background
age, glucose and baseline HbA1c (beta coefficient of multivariate regression
We aim to test whether plasma copeptin (copeptin), the C-terminal fragment of
analysisGS.E. 18.2G5.9, PZ0.006). In patients from group 1, HbA1c
vasopressin, has predictive value of cardiovascular events in patients with type 2
significantly decreased 1 year after ITx (K2.1G1.4%, PZ0.002), while
diabetes without previous cardiovascular disease who were treated in primary
C-peptide (C1.5G0.9, PZ0.002), and SUITO index increased (C57.4G
care.
39.7, PZ0.016). We did not observe differences in change between group 1
Methods
and 2 as far as HbA1c, C-peptide and SUITO index are concerned before
We measured copeptin in 697 patients who participated in the epidemiological
and after ITx. Hepatic glucose production during the insulin clamp
study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes - a
decreased after Rapamycin pre-treatment
(K1.1G1.1 mg/kg per min,
Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737)
PZ0.04) and after ITx (K1.6G0.6 mg/kg per min, PZ0.015), while no
and who did not have previously known myocardial infarction or stroke. The
changes in peripheral glucose disposal were observed during Rapamycin
outcome variable was a composite endpoint consisting of cardiovascular
treatment. In conclusion, Rapamycin contributes to improve metabolic
mortality, hospitalization for myocardial infarction and hospitalization for stroke.
control also enhancing hepatic insulin sensitivity after ITx. Rapamycin
Results
pre-treatment may improve ITx success rate by reduction of pre-transplant
During a median follow-up time of almost 7 years, the unadjusted HR per each
DIR and increase of hepatic insulin sensitivity.
increment of Copeptin by 1 pmol/l was 3.5 (95% CI 1.7-7.1, P!0.001) for the
DOI: 10.1530/endoabs.49.OC6.2
primary endpoint. Following adjustments for age, sex, HbA1c, arterial stiffness
(PWW) as well as atherosclerosis plaque the adjusted hazard ratio was 2.4 (95%
CI 1.1-5.2, PZ0.03).
Conclusions
In primary preventive patients with type 2 diabetes treated in primary care,
copeptin predicted a composite outcome of incident cardiovascular events
OC6.3
independently of age, sex, HbA1c, arterial stiffness as well as atherosclerosis
Alterations in DNA methylation from peripheral blood cells in humans
plaque.
threated with metformin
DOI: 10.1530/endoabs.49.OC6.4
Janis Klovins1, Ilze Elbere1, Raitis Peculis1, Ineta Kalnina1,
Linda Zaharenko1, Ilze Konrade3 & Valdis Pirags1,2
1Latvian Biomedical Research and Study Centre, Riga, Latvia;2Department
of Endocrinology, Pauls Stradins Clinical University Hospital, Riga, Latvia,
3Riga Stradins University, Riga, Latvia.
OC6.5
Activation of the Renin-Angiotensin II-Aldosterone-System leads to
increases in extracellular protein disulfide isomerase: role in insulin
Metformin is a biguanide class agent widely used as a first-line treatment
resistance
for type
2 diabetes, however the detailed mode of action and exact
Ricardo Perez-Fuentes4, Patricia Pulido1,4, Joshua Cazares1,2,
pharmacodynamics has not been clarified. Moreover there is no studies in
Yaritza Inostroza-Nieves1, Enrique Torres-Rasgado1,4, Akira Nishiyama3,
humans displaying the effect of metformin on DNA methylation. We
Alicia Rivera1, Rudy Ortiz2 & Jose Romero1
therefore performed a clinical study involving twelve healthy nondiabetic
1Division of Endocrinology, Diabetes and Hypertension, Department of
individuals who were subjected to the
1
week of metformin
(2!
Medicine, Brigham and Women’s Hospital, and Harvard Medical School,
850 mg/day) treatment. Peripheral blood for DNA isolation was drawn at
Boston, Massachusetts, USA;2Department of Molecular and Cellular
three time points during metformin treatment: i) right before metformin
Biology, University of California, Merced, California, USA;3Department of
treatment, ii) 10 hours after the first metformin dose and iii) after a week-
Pharmacology, Kagawa Medical University, Kagawa 761-0793, Japan;
long metformin administration. DNA methylation was estimated using
4Universidad Autonoma de Puebla/Instituto Mexicano Seguro Social,
genome-wide Illumina Infinium HumanMethylation450 BeadChip (Illu-
Puebla, Mexico.
mina), which allows interrogation of 485 512 CpG dinucleotides. Analysis
global methylation data displayed predominance of demethylated CpGs
over the methylated as the result of metformin treatment. In order to identify
differentially methylated gene promoter regions we filtered all CpGs located
Insulin resistance and type II diabetes (T2D) are associated with activation
in
2000 pb proximity of the transcription start site and having median
of the Renin-Angiotensin-Aldosterone-System
(RAAS) in part via
methylation change across all samples larger than 3% with Bonferroni
regulation of its principal effector molecule, Angiotensin II
(AngII).
corrected P values. This stringent approach resulted total in 35 genes with
Endothelial cell activation leads to, among other factors, increased
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
extracellular protein disulfide isomerase (PDI), a multifunctional protein
OC7.2
that is critical to thrombus formation and regulation of reactive oxygen
Targeted molecular markers derived from genomic classification for
species. However, the effects of RAAS on PDI are unknown. We studied the
adrenocortical cancer prognostication
in vitro effects of AngII on EA.hy926 human endothelial cells and measured
Anne Jouinot1,2, Guillaume Assié1,3, Martin Fassnacht4,5, Rossella Libé1,3,
PDI activity. Our results show that AngII
(10 nM), dose- and time-
Bertrand Dousset6, Silviu Sbiera Cristina Ronchi4, Matthias Kroiss5,
dependently, increased PDI activity (P!0.05, nZ6); an event that was
Esther Korpershoek7, Ronald De Krijger7,8, Jens Waldmann9,
blocked by pre-incubation with 0.5 mM losartan, an AngII Type I receptor
Marcus Quinkler10, Antoine Tabarin11, Olivier Chabre12,
antagonist (ARB). Western blot analyses showed increased PDI following
Michaela Luconi13, Massimo Mannelli13, Lionel Groussin1,3, Eric Baudin14,
AngII that was likewise reduced by losartan. In normal in Sprague-Dawley
Laurence Amar15, Felix Beuschlein16 & Jérôme Bertherat1,3
rats, we studied the in vivo effects of exogenous AngII infusion and observed
1Institut Cochin, INSERM U1016, CNRS UMR8104, Paris Descartes
significant increases in plasma PDI levels (P!0.05, nO5) that were blunted
University, Paris, France;2Medical Oncology, Assistance Publique
by ARB treatment. We then studied the obese Otsuka Long Evans
Hôpitaux de Paris, Hôpital Cochin, Paris, France;3Department of
Tokushima Fatty (OLETF) (nZ6/group) rats, a model of naturally increased
Endocrinology, Assistance Publique Hôpitaux de Paris, Hôpital Cochin,
AngII and RAAS-mediated insulin resistance and hypertension. Our results
Paris, France;4Endocrinology and Diabetes Unit, University Hospital,
show that OLETF rats had increased insulin resistance and greater
University of Wurzburg, Wurzburg, Germany;5Comprehensive Cancer
circulating PDI activity than lean control rats (P!0.05) and was reduced
Center Mainfranken, University of Wurzburg, Wurzburg, Germany;
by ARB treatment to baseline levels (P!0.05). To assess the clinical
6Department of Digestive and Endocrine Surgery, Assistance Publique
relevance of our findings, we measured circulating PDI in subjects with and
Hôpitaux de Paris, Hôpital Cochin, Paris, France;7Department of
without T2D. PDI activity correlated with measures of insulin resistance in
Pathology, Erasmus MC University Medical Center, Rotterdam,
our cohort (HOMA2-IR, Spearman PZ0.496, P!0.001, nZ134) and was
The Netherlands;8Department of Pathology, Reinier de Graaf Hospital,
significantly greater in T2D patients than healthy controls (P!0.01, nZ56
Delft, The Netherlands;9Department of Surgery, University Hospital
vs 78, respectively). Our data in human and animal models suggest that
Giessen and Marburg, Marburg, Germany;10Department of Medicine,
RAAS activation represents a novel mechanism for PDI secretion. Thus we
Charite University, Berlin, Germany;11Department of Endocrinology,
posit that PDI may contribute to the deleterious effects of RAAS-mediated
Diabetes and Metabolic Diseases, University Hospital of Bordeaux,
vascular disease.
Bordeaux, France;12Department of Endocrinology, University Hospital of
DOI: 10.1530/endoabs.49.OC6.5
Grenoble, Grenoble, France;13Department of Experimental and Clinical
Biomedical Sciences, University of Florence, Florence, Italy;14Department
of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy,
Villejuif, France;15Hypertension Unit, Hôpital Européen Georges Pompi-
dou, Assistance Publique-Hôpitaux de Paris, Paris, France;16Medizinische
Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen,
Munchen, Germany.
Cardiovascular endocrinology
Background
OC7.1
Adrenocortical cancer
(ACC) is an aggressive tumour with heterogeneous
prognosis. Recently integrated genomics reported distinct genomic alterations:
Estrogens enhance gonadectomy-induced adrenocortical tumor
transcriptome “C1A” (high expression of proliferation/cell cycle-related genes)
progression in mice
vs “C1B”, “CIMP” (CpG islands hypermethylation) vs “non-CIMP”, chromo-
Marcin Chrusciel1,2, Milena Doroszko1, Meike Jakobi1, Michal Brouze1,
some alterations “Noisy” (numerous and anarchic alterations) vs “Chromosomal”
Donata Ponikwicka-Tyszko3, Piotr Bernaczyk4, Slawomir Anisimowicz5,
(extended patterns of loss of heterozygosity) and “Quiet” (limited alterations),
Slawomir Wolczynski2,3, Jorma Toppari1,6, Ilpo Huhtaniemi1,7 &
and recurrent somatic mutations in 20 genes. These alterations converge into a
Nafis Rahman1,2
single three-groups classification, correlating with outcome. The aim was to
1Department of Physiology, University of Turku, Turku, Finland;
develop and validate targeted molecular markers reflecting these genomic groups.
2Department of Reproduction and Gynecological Endocrinology, Medical
Patients and methods
University of Bialystok, Bialystok, Poland;3Institute of Animal Repro-
Two hundred and forty five ACC were included from 21 ENSAT (European
duction and Food Research, Polish Academy of Sciences, Olsztyn, Poland;
network for the Study of Adrenal Tumors) centers. Tumor RNA was assessed
4Department of Pathology, Medical University of Bialystok, Bialystok,
by RT-qPCR for BUB1B-PINK1 expression (nZ135). Tumor DNA was studied
Poland;5Center of Gynecology and Reproductive Endocrinology Artemida,
by SNP array for chromosomal alterations (nZ238), targeted NGS for mutations
Bialystok, Poland;6Department of Pediatrics, Turku University Hospital,
of 20 driver genes (nZ251), and MS-MLPA for CpG islands methylation of
Turku, Finland;7Institute of Reproductive and Developmental Biology,
four genes -PAX5, GSTP1, PYCARD, PAX6- (nZ221).
Imperial College London, London, UK.
Results
Gene expression levels identified “C1A”, “C1B” and “undetermined” ACC in 50,
Prepubertally gonadectomized (GDX) wild-type DBA/2J mice develop adreno-
38 and 12% of cases respectively. Methylation assay identified “CIMP” and “non
cortical neoplasms presenting with small spindle-shaped non steroidogenic
CIMP” ACC in 44 and 56% of cases respectively. Chromosomal alteration
A-cells and large lipid-laden, steroidogenic and mitotically active B-cells.
profiles identified “chromosomal”, “noisy” and “quiet” ACC in 55, 32 and 13%
Neoplastic B-cells overexpress estrogen receptor a (ERa, Ers1) and b (ERb,
of cases respectively. Recurrent mutations or deletions were found in ZNFR3,
Ers2), aromatase (CYP19a1) and produce sex-steroids, resembling gonadal rest
CDKN2A, TP53 and CTNNB1 in 21, 17, 15 and 11% of cases respectively, in
tissue. To test the role of estrogen-ER system in adrenocortical tumor progression,
agreement with previous exome studies. All molecular statuses were available for
GDX 12 months-old DBA/2J females were treated with selective estrogen
107 tumors. 87/107 (81%) concordantly recapitulated the 3 main ACC subgroups
receptor modulator tamoxifen (TMX, 0.4 mg/kg/24 h) and aromatase inhibitor
previously identified by genomic classifications: 37 were “C1A/CIMP”, 18 were
letrozole
(LET, 2 mg/kg/24 h) for 21 days. Both TMX and LET treatments
“C1A/non-CIMP”, and 32 were “C1B/non-CIMP”. Death events occurred in
significantly reduced the adrenal weights, with stronger effect of the latter. Both
34/37, 7/18 and 1/32 patients respectively (Fisher exact P!10-15).
treatments decreased the expression of proliferation marker MKI67 and induced
Conclusion
apoptosis predominantly in the tumorous B-cells. TMX and LET treatments
Targeted molecular measures can recapitulate the genomic classification of ACC,
decreased plasma estradiol (E2) levels significantly decreasing sensitivity of the
giving original and useful prognostication information for patient management.
negative feedback on luteinizing hormone
(LH) secretion. Gene expression
DOI: 10.1530/endoabs.49.OC7.2
profiling showed that TMX and LET downregulated gonadal-like markers Ers2,
LH receptor (Lhcgr) and transcription factor Gata4, but upregulated a negative
regulator of steroidogenesis Nr0b1. Additionally, LET significantly decreased
expression of Esr1, Cyp19a1 and Cyp17a1. Control GDX mouse uteri displayed
endometrial hyperplasia without cellular atypia. TMX- and LET-treated mice
OC7.3
uteri were significantly smaller and showed cystically dilated endometrial glands
and signs of mild chronic inflammation. In summary, we showed that adrenal
High Total 68Ga-DOTATATE-Avid Tumor Volume (TV) is associated
estrogens promote progression of GDX-induced adrenocortical tumors. Our
with low progression-free survival and high disease-specific mortality
findings also support the rationale for TMX- and LET-based therapeutic strategies
rate in patients with neuroendocrine tumors
in treating ERs-positive/estrogen responsive adrenocortical carcinomas in human.
Amit Tirosh1,2, Georgios Z. Papadakis1,3, Corina Millo1,
Samira M. Sadowski4, Peter Herscovitch1, Karel Pacak1, Stephen J. Marx1,
DOI: 10.1530/endoabs.49.OC7.1
Lily Yang5, Pavel Nockel5, Jasmine Shell5, Patience Green5,
Xavier M. Keutgen6, Dhaval Patel5, Naris Nilubol5 & Electron Kebebew5
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
National Institutes of Health, Bethesda, MD, USA;2Sackler Faculty of
expression levels. These effects were totally abolished in QGP-1 cells lacking
Medicine, Tel Aviv University, Tel Aviv, Israel;3Institute of Computer
AIP. In conclusion, metformin acts as anticancer agent in P-NET cells, its activity
Science (ICS), Foundation for Research and Technology Hellas (FORTH),
is mediated by AIP and its interacting proteins, HSP70, AHR and Zac1. These
Crete, Greece;4Endocrine and Thoracic Surgery, University Hospitals of
findings provide a novel insight into the antitumorigenic mechanism of
Geneva, Geneva, Switzerland;5Endocrine Oncology Branch, National
metformin.
Cancer Institute, National Institutes of Health, Bethesda, MD, USA;
DOI: 10.1530/endoabs.49.OC7.4
6Department of Surgery, Rush University Medical Center, Chicago, IL,
USA.
Background
Patients with neuroendocrine tumors (NETs) have divergent survival, even when
OC7.5
having the same site of primary tumor, and tumor stage and grade. 68Gallium
Regulation of steroid receptor signalling by tumor suppressor INPP4B
(68Ga)-DOTATATE positron emission tomography
(PET)/computed
Manqi Zhang1, Egla Suarez1, Lubov Nathanson2, Michael Ittmann3,
tomography (CT) is a sensitive imaging modality for detecting NETs. The
Nancy Weigel2 & Irina Agoulnik1,3
purpose of this study was to determine whether 68Ga-DOTATATE PET/CT
1Florida International University, Miami, FL, USA;2Nova Southeastern
imaging has any prognostic utility in patients with NETs.
University, Ft. Lauderdale, FL, USA;3Baylor College of Medicine,
Methods
Houston, TX, USA.
One hundred and eighty-four patients with NETs were enrolled in a prospective
study of 68Ga-DOTATATE PET/CT imaging and comprehensive biochemical
analysis. Total
68Ga-DOTATATE-Avid Tumor Volume (68Ga-DOTATATE
Androgen receptor
(AR) signaling is the main driver for prostate cancer
TV) was measured in all participants. The primary outcome measures were
progression and androgen ablation is the treatment of choice for tumors that
progression-free survival (PFS) and disease-specific mortality (DSM). PFS and
spread beyond the prostate. Efficient at first, androgen ablation fails due in part to
DSM rates were compared according to 68Ga-DOTATATE TV quartiles of the
altered cell signaling and expression of AR spice variants. Cell signaling in
current cohort. Then, specific 68Ga-DOTATATE TV cut-offs were set using a
prostate cancer is regulated by dual specificity phosphatases and tumor
receiver operating characteristic (ROC) curve analysis, and the risks for DSM and
suppressors INPP4B and PTEN that are lost with prostate cancer progression.
PFS were validated with Kaplan-Meyer and Cox regression analyses.
Loss of PTEN destabilizes AR and alters AR transcriptional output. We
Results
investigated how loss of INPP4B affects AR signaling. We have previously
Patients were followed for a median of 18 months (range 4-35 months). 68Ga-
shown that AR induces expression of INPP4B in prostate cancer. Intriguingly, AR
DOTATATE TV quartiles had inverse correlation with PFS (PZ0.001) and
splice variant AR-V7, which also contributes to ADT resistance, was unable to
survival rates
(PZ0.002). Using cut-offs derived from ROC curve analysis,
induce INPP4B expression. We performed microarray analysis of changes in gene
68Ga-DOTATATE TV R7.0 was associated with a lower PFS (HRZ2.0,
expression caused by INPP4B knockdown. Gene expression clustering and GSEA
PZ0.03), and 68Ga-DOTATATE TV R35.8 ml was associated with increased
analysis revealed that the INPP4B loss significantly altered AR transcriptional
(HRZ10.7) disease-specific mortality in multivariate analysis (PZ0.03), as well
activity. Using immunofluorescent labeling with 3D rendering we determined that
as in subgroup analysis of patients with pancreatic NETs.
INPP4B localizes to cellular and endoplasmic membranes. We and others have
Conclusions
shown that INPP4B suppresses PI3K/Akt and PKC pathways. We show that
We show for the first time the prognostic utility of 68Ga-DOTATATE TV in a
INPP4B specifically inhibits PKCz and bII in multiple prostate cancer cells. The
large cohort of patients with NETs, enabling clinicians to determine the need for
analysis of PI3K, Akt and PKC specific inhibitors, LY294002, AZD5363, and
intervention using this non-invasive tool.
BIM-I, showed that Akt and PKC signaling did contribute to the changes in AR
signaling. We investigated INPP4B functions in prostates of Inpp4bK/K mice.
DOI: 10.1530/endoabs.49.OC7.3
AR expression in mouse prostate was not affected by the loss of INPP4B.
Remarkably, expression of several direct AR target genes like Msmb, Apof, and
Nkx3.1 was significantly reduced in Inpp4bK/K prostates. We compared Akt and
PKC signaling in the anterior (AP), dorsal/lateral (DLP) and ventral (VP) prostate
lobes of the wild-type and Inpp4bK/K mice. Loss of INPP4B increased Akt
signaling in DLP and VP and PKC z and b II pathways in AP and DLP. We
determined that levels of PTEN protein were unchanged in Inpp4bK/K mouse
OC7.4
prostates suggesting that Akt signaling was elevated exclusively due to Inpp4b
A novel insight into the anticancer mechanism of metformin in
loss. Taken together, full length AR, but not AR-V7 induce INPP4B expression.
Pancreatic Neuroendocrine Tumor cells
INPP4B reciprocally modulates AR transcriptional activity without altering AR
Eleonora Vitali1, Sara Piccinini1, Ilena Boemi1, Alberto Tresoldi1,
protein level in both normal prostate and prostate cancer cells and suppresses
Alessandro Zerbi2, Carlo Carnaghi3, Anna Spada4 & Andrea Lania1,5
Akt and PKCz and b II signaling and the suppression is required for optimal AR
1Laboratory of Cellular and Molecular Endocrinology, IRCCS Humanitas
transcriptional activity.
Research Hospital, Rozzano, Italy;2Pancreas Surgery Unit, IRCCS
DOI: 10.1530/endoabs.49.OC7.5
Humanitas Research Hospital, Rozzano, Italy;3Oncology Unit, IRCCS
Humanitas Research Hospital, Rozzano, Italy;4Endocrinology and
Diabetology Unit, IRCCS Ospedale Maggiore Policlinico, Milano, Italy;
5Department of Biomedical Sciences, Humanitas University, Rozzano,
Italy.
Neuroendocrinology
Metformin (1.1-dimethylbiguanide hydrochloride), a widely used antidiabetic
OC8.1
drug, has been reported to display potent anticancer properties in various types
Elucidating the molecular mechanisms underlying AIP dependent
of cancers, including neuroendocrine tumors. Recently, a potential synergistic
tumorigenesis
activity between metformin and octreotide (SSA) in Pancreatic Neuroendocrine
Eva-Maria Bogner1, Adrian F. Daly2, Albert Beckers2, Michael J. Atkinson3
Tumors (P-NETs) has been proposed. AIP (aryl hydrocarbon receptor-interacting
& Natalia S. Pellegata1
protein) acts as tumor suppressor gene in neuroendocrine tumors at pituitary level
1Institute for Diabetes and Cancer, Helmholtz Center Munich, Munich,
and it is up-regulated by SSA. We investigated the effects of metformin on
Germany;2Department of Endocrinology, Centre Hospitalier Universitaire
P-NETs cell proliferation, apoptosis and colony formation, the potential
de Liège, University of Liège, Liège, Belgium;3Institute for Radiation
synergistic effect between metformin and octreotide and the possible role of
Biology, Helmholtz Center Munich, Munich, Germany.
AIP pathway in mediating these effects. We found that in QGP-1 cells metformin
significantly inhibited cell proliferation
(K37G2% P!0.001 vs basal at
10 mM). We showed no additive effect between Metformin and Octreotide on
Pituitary adenomas (PAs) are benign neoplasms that comprise 10-20% of all
P-NETs cell proliferation. Moreover, metformin incubation reduced colony
intracranial tumors. Mutations in the aryl hydrocarbon receptor interacting
formation, cells amount after 7 days (K66G6% P!0.001 vs basal) and it
protein (AIP) have been identified to cause a small subset of hereditary PAs. To
promoted apoptosis (C150G8% P!0.05 vs basal). As expected, octreotide
study the mechanisms of tumor formation in patients with AIP-mutated PAs we
induced AIP up-regulation (C60G11% P!0.05 vs basal), and surprisingly, AIP
conducted a miRNA array analysis comparing AIP-mutated PAs with AIP-wild
expression levels were also increased by metformin (C90G13% P!0.05 vs
type PAs. We found a novel and specific set of miRNAs differentially expressed
basal). In addition, AIP silencing abolished the antiproliferative and proapoptotic
between the two groups of PAs. We selected several candidate miRNAs and
effects of metformin, confirming its involvement in mediating metformin effects.
validated them in the patient tissues. To characterize the candidate miRNAs
Interestingly, metformin decreased HSP70 expression, increased Zac1 and AhR
in vitro and clarify their role in AIP dependent tumorigenesis we performed
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
functional studies using mouse embryonic fibroblasts (MEFs) derived from Aip
1Section of Specialized Endocrinology, Department of Endocrinology, Oslo
knockout (AIP-KO) mice and a rat somatotroph tumor cell line (GH3). In the
University Hospital, Oslo, Norway;2University of Southern Denmark,
AIP-KO MEFs we saw that transfection of mutant AIP altered the expression of
Odense, Denmark;3Department of Medical Genetics, Oslo University
two of the candidate miRNAs according to the changes observed in the miRNA
Hospital, Oslo, Norway;4Faculty of Medicine, University of Oslo, Oslo,
array. Additionally, cell viability and cell migration were increased after
Norway;5Research Institute for Internal Medicine, Oslo University
transfection of mutant AIP. Since deregulation of cAMP levels is a common
Hospital, Oslo, Norway;6Latvian Biomedical Research and Study Centre,
feature of PAs we also checked cAMP levels upon transfection of mutant AIP. We
Riga, Latvia;7Department of Endocrinology and Metabolism, Odense
could observe that mutant AIP increased cAMP levels in AIP-KO MEFs.
University Hospital, Odense, Denmark.
Overexpression of the candidate miRNAs in GH3 cells increased cell migration
and cAMP levels while apoptosis was decreased. To further clarify the role of the
Background
selected miRNAs in tumor development we identified their predicted targets and
Non-functioning pituitary adenomas (NFPAs) necessitate prolonged clinical,
focused on those involved in cAMP signalling. We plan to validate the role of
biochemical and radiological observation, constituting a significant burden in
these predicted targets in PAs in the future. In conclusion, we identified novel
terms of medical resources and societal costs. Reliable biomarkers associated
miRNAs in AIP-mutated PAs and were able to show that these miRNAs promote
with aggressiveness and recurrence of NFPAs are lacking. As the growth of tumor
a tumor-like behaviour in several functional assays in AIP-KO MEFs and GH3
remnants is highly variable, molecular markers that can predict growth potential
somatotroph cells.
and tumor behavior are necessary.
DOI: 10.1530/endoabs.49.OC8.1
Aim
To identify target genes in fast- and slow- growing NFPAs estimated by
postoperative initial tumor volume doubling time (TVDT), and to find reliable
biomarkers predicting the growth potential of the remnant tumor, focusing on the
specific role of epithelial-mesenchymal transition (EMT) process.
Material and methods
RNA sequencing was performed in gonadotroph NFPAs with short TVDT
OC8.2
(median
!30.05 months, fast group, nZ4) and long TVDT
(median
Knocking down/out the prokineticin pathway during zebrafish
O30.05 months, slow group, nZ4). Data was analyzed by tophat2
and
development results in the GnRH neurons axons misguiding
cufflinks/cummeRbund pipeline. Furthermore, genes
(nZ40) were selected
Ivan Bassi1, Federica Marelli1, Valeria Vezzoli2, Luca Persani1,2,
based on significance, fold of change and pathway analysis for validation with
Yoav Gothilf3 & Marco Bonomi1,2
RT-qPCR in a larger cohort of gonadotroph NFPAs (nZ20, 13 male).
1Laboratory of Experimental Endocrinology, Istituto Auxologico Italiano
Results
IRCCS, Milan, Italy;2Department of Clinical Sciences and Community
RNA sequencing identified 350 genes significantly differentially expressed,
Health, University of Milan, Milan, Italy;3Department of Neurobiology,
between the two groups (285 genes up- and 65 down- regulated in the fast group,
The George S. Wise Faculty of Life Sciences and Sagol School of
P adjusted !0.05). Of the 40 genes chosen for further validation by RT-qPCR, 11
Neuroscience, Tel-Aviv, Israel.
showed significant correlations with TVDT (K0.669%RRK0.466, P!0.05).
These were six genes involved in EMT (PCDH18, SPAG9, SKIL, MTDH,
HOOK1 and CNOT6L), and also UNC5D, EMCN, MYO1B, GPM6A and
Studies conducted using knockout mouse model revealed that defects of PROKR2
PRKACB.
affect the correct ontogeny of GnRH neurons and, by consequence, neuroendo-
Conclusions
crine control of reproduction. Nevertheless its exact role during these processes
Fast- and slow- growing NFPAs show different gene expression profiles. Genes
and in the pathogenesis of congenital hypogonadotropic hypogonadism (CHH)
known as related to EMT have higher expression in fast-growing tumors,
remains elusive due to the phenotypic differences observed between mouse and
suggesting a pathogenic role in tumor growth. The identified genes and their
human. Zebrafish (ZF) has emerged in the last ten years as a reliable model
products could represent useful markers for predicting tumor aggressiveness and
organism for studying the GnRH neuronal development and the neuroendo-
recurrence, and may be potential targets for drug therapy.
crinology of reproduction. Previous results obtained in our lab identified two well-
DOI: 10.1530/endoabs.49.OC8.3
conserved loci in the ZF genome, on chr1 and chr13, respectively named prokr1a
and prokr1b. Whole mount in situ hybridization
(WISH) and qRT-PCR
experiments conducted at different developmental stages of ZF revealed distinct
patterns of expression for prok-receptors suggesting prokr1b as the potential
candidate involved in the GnRH-secreting neurons migration process from
olfactory placode to their final hypothalamic destination. To verify these
OC8.4
indications and better elucidate the function of both prokineticins receptors we
Cerebrovascular stroke incidence in GH-treated adults: experience
recently conducted knockdown experiments using morpholino oligonucleotides
from KIMS (Pfizer International Metabolic Database)
sequences. Our results display an alteration of the GnRH fibers network
Cecilia Camacho-Hubner1, Jose Cara1 & Anders Mattsson2
architecture at 48 hours post fertilization (hpf) after downregulation of prokr1b
1Endocrine Care, Pfizer Inc, New York, NY, USA;2Endocrine Care, Pfizer
that appeared misguided and reduced in numbers especially at level of pallium
Health AB, Sollentuna, Sweden.
commissure and optic chiasm. Moreover, we also generated in ZF the prokr1b
knockout model and our preliminary data are confirming the knockdown model
observations. On the contrary, the downregulation of prokr1a does not affect
Background and aim
GnRH fibers architecture. Taken together these results confirm the role of prokr1b
Patients with GH deficiency (GHD) have increased risk of cerebrovascular
during GnRH neurons migration establishing it as the ZF orthologous of human
events. The aim of this study was to evaluate the rate and factors associated with
PROKR2. A deeper characterization of ZF prokr1b KO model could provide new
the occurrence of stroke, a major cause of death and disability, in adults with
information regarding the early establishment of the forebrain GnRH system, the
GHD.
factors controlling this complex developmental event, and its functional
Patients and methods
significance.
Data from 15,188 GHD patients treated with GH replacement therapy (GHRT)
This work was supported by funds from University of Milan (Dotazione per
enrolled in KIMS were analyzed. Stroke incidence rates were compared to rates
attività istituzionali—Linea 2 azione B Piano di Sviluppo di Ateneo) and IRCCS
from the Oxford Vascular Study (Lancet_2004; 363:1925-33) by standardized
Istituto Auxologico Italiano (Ricerca Corrente Funds: 05C202 and GONAFISH).
incidence ratios (SIRs). Age at first radiotherapy (RT) corrected for attained age
Funds: 05C202 and GONAFISH).
and sex, was analyzed with Poisson regression.
Results
DOI: 10.1530/endoabs.49.OC8.2
Causes of GHD comprised pituitary adenoma 42.9%, craniopharyngioma 10.8%
and idiopathic GHD 15.6%. Mean age at KIMS entry was 43.7 (range 17-75)
years. Mean GH dose was 0.42 mg/day and number of patient treatment-years
was 81,086. Mean age at first radiotherapy (RT) was 34.5 (range 3-72) yrs. First-
ever stroke was reported in 155/7667 (M) and 123/7521 (F) patients. The crude
OC8.3
incidence was 377 (M) and 308 (F) per 100,000 patient- years and overall SIR was
RNA sequencing and RT-qPCR identify different gene expression
2.51
(95% CI: 2.22-2.82). SIR ranged between causes of GHD from 1.02 (0.41-
profiles in fast- vs. slow-growing non-functioning pituitary adenomas
2.1) in patients with Idiopathic GHD and unexposed to RT to 19.3 (11.6-30.1) in
Camilla Maria Falch1,2, Arvind Y.M. Sundaram3, Kristin Astrid
patients with GHD secondary to a malignant cranial tumor. RT was reported in
Berland Øystese1,4, Kjersti Ringvoll Normann1,4, Ivars Silamikelis6,
3866 patients and 146 reported a stroke (SIR: 3.96; 3.35-4.66). Rates were
Marianne Andersen7, Jens Bollerslev1,4 & Nicoleta Cristina Olarescu1,5
increased in all ages at first exposure (P!0.01), especially in younger patients
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(RRZ2.2 (1.05-4.63) for !18 vs R18 years of age). Among 11,322 patients
the highest prevalence of elevated BP (60%), elevated glucose (22.7%), waist
who did not receive RT, 132 cases were reported, SIR 1.78 (1.49-2.11).
circumference (33.4%) and TG (30.2%), low HDL-cholesterol (26.5%), and MetS
Conclusion
(27.7%). In women, the lowest FT4 quartile was only associated with elevated TG
GHD patients have a significantly increased rate of strokes with considerable
(11.2%), waist circumference (47.4%), and MetS (13.8%). In contrast, higher FT3
variability between causes of GHD. Rates were positively associated with RT in
levels were associated only with low HDL-cholesterol in both sexes, and with a
all studied ages, with younger patients at first RT showing a higher risk.
higher percentage of participants with R3 MetS components (21.6% in men,
DOI: 10.1530/endoabs.49.OC8.4
12.4% in women).
Conclusions
Levels of FT4, but not FT3, were inversely associated with all components of the
metabolic syndrome in men, and with elevated TG, waist, and overall MetS in
women.
DOI: 10.1530/endoabs.49.OC9.1
OC8.5
Ephrin-B2 is required for pituitary development
Fernando Jimenez, Angelica Gualtieri, Valeria Scagliotti &
Carles Gaston-Massuet
WHRI, Queen Mary University of London, London, UK.
OC9.2
Effect of restoration of euthyroidism in patients with hypothyroidism on
The pituitary progenitors are responsible for generating a fully functional
cold induced thermogenesis
endocrine organ during embryonic development. They also preserve potency, to
Claudia Maushart, Rahel Loeliger, Cemile Bathelt, Nina Hutter,
maintain the homoeostasis in the adult pituitary, being able to respond to
Mirjam Christ-Crain & Matthias Betz
endocrine challenges, such as pregnancy or obesity. But the main players of this
Department of Endocrinology, Diabetes and Metabolism, University
complex process remain elusive. Eph-Ephrins have been implicated in an
Hospital Basel, Basel, Switzerland.
increasing number of physiological functions such as axon-guidance, eye field
segregation from neural plate, tissue boundary formation, cell migration,
angiogenesis and more recently stem cell maintenance and differentiation in the
Background
colon and mammary gland. However, the EprhinB:EphB signalling pathway in
Thyroid hormones have been shown to be necessary for proper function of brown
hypothalamic-pituitary function is not known. Using a transgenic line that
adipose tissue (BAT) and cold induced thermogenesis (CIT) in rodent models. In
expresses GFP under the EphrinB2 (Efnb2) genetic locus we observed that cells
humans hyperthyroidism has been demonstrated to activate BAT and increase
expressing Efnb2 are localised in the pituitary progenitor of the anterior pituitary.
thermogenesis. However, the data on CIT in humans in the hypothyroid vs. the
We found Efnb2 co-expressed with known PPSCs markers Sox2/Sox9 during
euthyroid state are limited and conflicting.
embryogenesis and this expression continues in adulthood, suggesting a role in
Methods
adult pituitary homoeostasis. Conditional genetic removal of Efnb2
in the
This was a prospective observational study. We recruited 40 patients presenting
undifferentiated precursor using a Cre-pituitary line, results in significant pituitary
to a University hospital out-patient endocrine clinic with subclinical or overt
abnormalities, comprising multiple bifurcations hyperplasia of the anterior
hypothyroidism, and in whom thyroid hormone replacement was planned.
pituitary gland. These data suggest for the first time, that Efnb2 is a critical
Currently, 24 patients completed the study. Thermogenesis was measured by
regulator of pituitary development and could have an effect on hypothalamic-
indirect calorimetry during warm conditions and after a mild cold stimulus of
pituitary body endocrine regulations. Interestingly a proportion of Efnb2 Knock-
90 min, both during the hypothyroid state and after at least 3 months of sufficient
out animals exhibit features of congenital hypopituitarism, such as dwarfism and
thyroid hormone replacement. CIT was determined as the difference between
eye abnormalities suggesting that, in this physiological context, Efnb2 could be a
resting energy expenditure (REE) during cold (REEcold) and warm (REEwarm)
candidate gene for rare unknown conditions such Septo-Optic Dysplasia.
conditions. Additionally, skin temperature was measured using wireless probes in
DOI: 10.1530/endoabs.49.OC8.5
one-minute intervals in the supraclavicular region adjacent to the major human
BAT depot. The primary endpoint was CIT in the hypothyroid vs euthyroid state.
Data were analysed by non-parametric tests and are given as meanGS.D.
Results
CIT increased from 73(G103) kcal/d during the hypothyroid state (CIThypo) to
160
(G143) kcal/d in the euthyroid state (CITeu), PZ0.0007. REEwarm was
Thyroid Disease 2
1324
(G120) kcal/d during hypothyroidism and rose slightly to 1395(G140)
kcal/d, PZ0.0137. REEcold rose profoundly from
1396(G157) kcal/d to
OC9.1
1555(G178) kcal/d, PZ0.0001. While the inter-individual variability of CIT
Thyroid function and metabolic syndrome: results from the population-
was large, the correlation between CIThypo and CITeu was moderate, rZ0.657,
based LifeLines Cohort study
PZ0.001. The change in supraclavicular skin temperature during cold exposure
Bruce Wolffenbuttel, Hanneke Wouters, Sandra Slagter,
correlated with CIT in the euthyroid
(rZ0.389, PZ0.067), but not in the
Robert van Waateringe, Jana van Vliet-Ostaptchouk, Thera Links &
hypothyroid state (rZ0.041, PZ0.853).
Melanie van der Klauw
Conclusion
University of Medical Center Groningen, Groningen, The Netherlands.
Cold induced thermogenesis is blunted in hypothyroid patients and increases
markedly after restoration of euthyroidism. The difference in CIT is larger than
the difference in resting energy expenditure during warm conditions.
Background
DOI: 10.1530/endoabs.49.OC9.2
The metabolic syndrome (MetS) is a combination of unfavourable health factors
including abdominal obesity, dyslipidaemia, hypertension and impaired fasting
glucose. Several small-scale studies have reported a relationship between thyroid
function and some MetS components or suggested that serum FT3 levels within
the normal range were independently associated with insulin resistance. We
assessed how thyroid function relates to the prevalence of MetS in a large
OC9.3
population-based study.
How much of the genetic predisposition to Hashimoto’s thyroiditis can
Methods
be explained by genes commonly associated with the disease?
Data of 26,719 western European participants aged 18-80 years from the Dutch
Anna Skalniak1,2, Agata Jabrocka-Hybel1,2, Jakub Piętkowski2,
LifeLines Cohort study, all with normal TSH, FT4
and FT3
levels
Renata Turek-Jabrocka1,2, Dorota Pach1,2, Agnieszka Ludwig-Gałęzowska3,
(electrochemiluminescent immunoassay, Roche Modular E170
Analyzer),
Julita Machlowska3, Przemysław Kapusta3, Paweł Wołkow3 &
were available. MetS was defined with the revised NCEP ATP III criteria. We
Alicja Hubalewska-Dydejczyk1,2
calculated prevalence of all MetS components according to FT4
and FT3
1Chair and Department of Endocrinology, Jagiellonian University Medical
quartiles.
College, Krakow, Poland;2Endocrinology Department, University Hospital
Results
in Krakow, Krakow, Poland;3Center for Medical Genomics OMICRON,
At similar TSH levels and age (mean 45 yrs), men had significantly higher levels
Jagiellonian University Medical College, Krakow, Poland.
of FT4, FT3, blood pressure
(BP), heart rate, total and LDL-cholesterol,
triglycerides
(TG), and creatinine, but lower HDL-cholesterol compared to
women (all P!0.001). In total, 9.1% of women and 10.2% of men were treated
Background
with BP-lowering agents. In men, lower FT4 levels were associated with higher
Hashimoto’s thyroiditis (HT) is a common autoimmune disorder of the thyroid
prevalence of all MetS components. The lowest FT4 quartile was associated with
(AITD) which affects about 1-2% of the European population. The disease often
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
clusters in families, which is why many attempts have been undertaken to find the
Conclusions
genetic background that would underly the predisposition to HT. In contrast to
Thyroid dysfunction during the use of PD-1/PD-L1 blockade and its severity
another AITD - Graves’ disease, results of genetic analyses have been ambiguous
predict its favorable disease outcome in NSCLC patients. Therefore, regular
and have failed to find a major genetic locus that would be essential for HT
measurement of thyroid hormone levels during the use of PD-1/PD-L1 blockade
development.
could be the good biomarker of immune monitoring.
Aim
DOI: 10.1530/endoabs.49.OC9.4
To assess the joined impact of disease loci associated in the literature with HT
predisposition.
Methods
One hundred and forty seven HT fully-symptomatic patients and 147 healthy
controls (matched for age, gender, incomes, education, marital status and place of
descent), unrelated to each other, were genotyped for
40
polymorphisms
(Illumina GoldenGate, custom panel), which were located in genes most often
tested in literature for association with AITD, or typed out by genome-wide
association studies. All polymorphisms were confirmed to be in Hardy-Weinberg
equilibrium in the control group (PO0.05). Variations in the HLA-DRB1 gene
were analyzed by Sanger sequencing. A genetic model for HT predisposition was
OC9.5
obtained with use of stepwise logistic regression. Biostatistical analyses were
Selenium supplementation in the management of thyroid autoimmunity
performed with the programs Statistica v12, Plink v1.9, and GCTA v1.02.
during pregnancy: results of the ‘Serena Study’ a randomized,
Results
double-blind, placebo-controlled trial
The model which best explained the predisposition to HT contained seven
Carla Di Dato1, Giovanna Mantovani2, Costanzo Moretti3, Ermanno Greco4,
polymorphisms in the genes PTPN22, IFIH1, CTLA4, RGS6, TNMD, NOX1, and
Marco Bonomi5, Antongiulio Faggiano6, Stefania Di Sante1,
the promoter region of FAM155A. The model was able to classify correctly 67%
Vincenzo Giannetta1, Luisa Petrone7, Angela Fumarola1,
of all cases, similarly for both groups. Such a model explained only 5.12% of the
Annamaria Colao8, Andrea Lenzi1, Andrea M. Isidori1 & Elisa Giannetta1
between-group variance. This value is in agreement with a model published lately
1Department of Experimental Medicine - Sapienza University of Rome,
for another autoimmune disorder.
Rome, Italy;2Endocrine Unit, Department of Clinical Sciences and
Discussion
Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
Our data confirm that there seem to be no genes that are per se crucial for HT
Policlinico, University of Milan, Milan, Italy;3Unit of Endocrinology,
development. Future analyses on HT predisposition should focus on the joined
Section of Reproductive Endocrinology, Department of Systems’ Medicine,
influence of many polymorphisms in different genetic regions.
University of Rome Tor Vergata, Rome, Italy;4Centre for Reproductive
DOI: 10.1530/endoabs.49.OC9.3
Medicine, European Hospital, Rome, Italy;5Department of Clinical
Sciences and Community Health, University of Milan, Milan, Italy;
6
Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la
Cura dei Tumori-IRCCS, Fondazione G. Pascale”, Naples, Italy;
7
Endocrinology Unit, Careggi Hospital and University of Florence,
Florence, Italy;8Endocrinology Unit, Department of Clinical Medicine and
Surgery, University of Naples Federico II, Naples, Italy.
Autoimmune thyroiditis and related complications represent a growing concern
during pregnancy. Selenium is frequently present in nutraceuticals recommended
OC9.4
for thyroiditis and pregnancy, given its advocated role in immunity, fertility and
Thyroid dysfunction during the use of PD-1/PD-L1 blockade predicts its
thyroid function. However, most evidences come from non-controlled studies.
therapeutic response in the patients with advanced non-small cell lung
Materials and Methods
cancer
We designed a multicenter, randomized, double-blind, placebo-controlled trial
Hye In Kim1, Tae Hyuk Kim1, Hye Won Jang2, Young Nam Kim1,
(Serena Study: NCT01465867) to evaluate the effects of L-selenomethionine (Se)
Hosu Kim1, So Young Park1, Sun Wook Kim1 & Jae Hoon Chung1
supplementation on antibodies title in euthyroid women with positive anti-thyroid
1Samsung Medical Center, Seoul, Republic of Korea;2Sungkyunkwan
antibodies that are pregnant or undergoing in-vitro fertilization. Secondary
University School of Medicine, Seoul, Republic of Korea.
outcomes included: implantation rates, pregnancy rate, delivery, obstetrical, fetal
and neonatal complications. Ten endocrinology and gynecology Italian referral
centers participated. The study was promoted and supported by EnGioI Club
Background
(Italian Young Endocrinology).
PD-1/PD-L1 blockade is one of the promising drugs in the treatment of advanced
Results
non-small cell lung cancer (NSCLC). and predicting drug effect is important due
56 women were randomly assigned to placebo (PLB) or Se 83 mcg/die. Thyroid
to unique pattern of response. Immune-related adverse event (IRAE) might be
hormones, TgAb, TPOAb, selenium concentration were measured during
associated with favorable clinical outcome. Thyroiditis is the most common IRAE
pregnancy and after labor (months 38 to 68). All analysis were centralized. Of
which can be easily detected with the measurement of thyroid hormone levels.
the enrolled women,
45
(80.3%) were pregnant and
11
(19.6%) embryo
However, the relationship between thyroid dysfunction during the use of
transferred. A significant reduction of TgAb was observed in Se-treated women
PD-1/PD-L1
blockade and its therapeutic response has not been well
after labor: treatment effect dZ108.67 (95%CI:K1.3, 218.6; PZ0.03). The
demonstrated in advanced NSCLC patients.
change in antibodies was paralleled by a significant increase in selenium serum
Methods
concentration measured already at
36G2 weeks:
(PLB:K11G23.76,
A total 53 patients with stage IV NSCLC treated with PD-1/PD-L1 blockade were
Se:C30.5G17.63; treatment effect dZ35.57 95% CI:14.9, 62.3; PZ0.004)
enrolled. Patients were categorized into thyroid dysfunction and euthyroid group.
and confirmed after labor: treatment effect dZ17.56
(95% CI: 3.9,
31.2;
Overall survival (OS) and progression free survival (PFS) of two groups were
PZ0.014). Post-labor rebound in antibodies’ title of PLB treated, as compared to
compared. Hazard ratio (HR) adjusting patients, tumor, and drug factors were
Se-treated women was paralleled by a trend toward TSH rise (PLB:C3.96G
analyzed using Cox proportional hazard model. Response rate (RR) and durable
12.56 vs Se: C1.69G6.00). Safety analysis showed no discontinuation in the
RR were assessed according to thyroid dysfunction and its severity.
Se-treated subjects. Two miscarriage occurred in PLB vs 0 in Se-treated. No
Results
differences were found in fetal and maternal complications. The pregnancy rate
OS (mean 148.5G82.6 vs 82.0G65.1, log-rank PZ0.003) and PFS (143.2G88.2
after embryo transfer was 3/5 (60%) in Se-treated vs 1/6 (16.6%) in PLB.
vs
68.0G50.0, log-rank PZ0.001) were significantly longer in the thyroid
Conclusion
dysfunction group. After adjustment for age, sex, smoking status, tumor stage,
SERENA Study demonstrated a beneficial effect on the title of TgAb with a safety
and drug type, adjusted HR (95% CI) for overall death and progression disease
profile. Larger studies are needed to confirm the trends observed on post-partum
were 0.08 (0.01-0.65) and 0.29 (0.12-0.69) compared with euthyroid group. RR
thyroiditis recurrence and hypothyroidism, miscarriage and pregnancy rate in
(36.0 vs 10.7%, PZ0.028) and durable RR (28.0 vs 0%, PZ0.003) were more
in vitro-fertilization.
frequent in the thyroid dysfunction group. Severity of thyroid dysfunction was
DOI: 10.1530/endoabs.49.OC9.5
also associated with RR (P for trend Z0.018) and durable RR (P for trend Z
0.001).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Bone & Calcium Homeostasis
were collected form clinical records. TBS was calculated by reevaluating the
already existing BMD images. Patients were classified into two different groups
OC10.1
according to their treatment: 1) 13 patients who underwent surgery, in whom TBS
Treatment of 711 patients with hypoparathyroidism: a retrospective
was evaluated before surgery (B-S) and one year after surgery (A-S), and 2) 10
study in 3 German endocrine centres
patients who received standard medical treatment, in whom TBS was evaluated
Martin Grussendorf1, Bettina Stamm2, Niklas Stamm3,4 &
with a time-lapse of 1 year. Basal age, body mass index (BMI), serum calcium,
Heide Siggelkow4,5
vitamin 25-OH-D levels and T-Scores were not significantly different between the
1Endocrine Centre, Stuttgart, Germany;2MVZ Endokrinologikum, Saar-
two groups. Only PTH levels (82 vs 110 pg/ml, PZ0.04) presented differences.
brucken, Germany;3Endocrinology and Metabolism, University Medicine,
We observed a significant improvement of TBS one year after surgery in the first
Mainz, Germany;4Clinic of Gastroenterology and Gastrointestinal
group (1.244G 0.11 vs 1.311G0.1 PZ0.08). A subtle deterioration on TBS was
Oncology, University Medical Center, Gottingen, Germany;5MVZ
observed one year after standard treatment in the second group (1,249G0.06 vs
Endokrinologikum, Gottingen, Germany.
1.223G0.07 PZ0.124). Overall, surgical patients experienced a TBS increase
5.8% whilst a decrease of K2.04% was observed in the second group (PZ0.02).
In the multivariate correlation analysis, the percentage of variance in TBS was
Care of patients (pts.) with hypoparathyroidism (HypoPT) is a challenge, because
negatively correlated with the level of PTH and calcium at the moment of the
pts. are usually not treated with the absent hormone, but with several forms of
second BMD (0.04 and 0.03 respectively). Bone microarchitecture, measured by
vitamine D. We retrospectively evaluated the data of pts. with HypoPT in three
TBS, improves after surgery in patients with PHH and has shown to be sensitive
endocrine centres in Germany.
to changes developed during only one year time-lapse in bone. This parameter is a
Methods
promising tool in the evaluation of bone status in PHH.
Records of 711 pts. with HypoPT (Centre 1 (C1): nZ381, C2: nZ253, C3:
nZ77) were reviewed (female: 592, male: 119). The following data under
DOI: 10.1530/endoabs.49.OC10.2
treatment (time range 2-199 months) were evaluated: medication, Calcium (Ca) -
values, tingling sensations (paresthesia), and cramps.
Results
Of these 711 pts. 29 had idiopathic HypoPT, 10 HypoPT after parathyroidectomy,
669 after thyroid operation (Tx): subtotal Tx: 471, HemiTx: 12, totalTx: 186 pts.
Age of pts. at first visit (V1): 49.85 years (mean), time between Tx and V1: 76.85
months (mean, range 0-733 months). Mean values of Ca (mmol/l), PO4 (mg/dl)
OC10.3
in serum, Ca in urine (Ca U; mmol/24 h); % of patients with paresthesia (par.) and
High prevalence of radiological vertebral fractures in patients with
cramps under different therapies (mean daily dose in brackets) as follows:
differentiated thyroid carcinoma undergoing L-thyroxine
TSH-suppressive therapy
Anna Maria Formenti1, Gherardo Mazziotti2, Stefano Frara3,
Filippo Maffezzoni1, Mauro Doga3, Francesco Bertagna4, Roberto Maroldi5,
Medication
Ca
PO4
Ca U par. % cramps %
Maurizio Memo1, Raffaele Giubbini4 & Andrea Giustina3
1
Department of Molecular and Translational Medicine, University of
Calcium (1462 mg/d)
2.08
1.49
1.67
90
63
Brescia, Brescia, Italy;2Department of Internal Medicine, Mantua Hospital,
Vitamine D
2.12
1.46
2.88
51
43
Mantua, Italy;3Chair of Endocrinology, Vita-Salute San Raffaele
(11,442 U/d),
University, Milan, Italy;4Chair of Nuclear Medicine, University of Brescia,
Ca (1245)
Brescia, Italy;5Chair of Radiology, University of Brescia, Brescia, Italy.
1-Alphacalcidol
2.19
1.26
2.65
32
26
(2.41 ug/d), Ca (1321)
1-Alphac.(1.26),
2.19
1.44
2.65
38
38
Thyroid hormones play a central role in the regulation of bone turnover and
Vit.D (15,949),Ca
thyrotoxicosis is an established cause of secondary osteoporosis. Increased
(1005)
prevalence of reduced bone mineral density (BMD) has been reported even in
Calcitriol (0.64 ug/d),
2.19
1.43
2.52
57
35
patients with subclinical thyrotoxicosis such as those with differentiated thyroid
Ca (1354)
carcinoma undergoing long-term L-thyroxine (L-T4) TSH-suppressive therapy.
Calcitr.(0.60),
2.18
1.34
3.27
48
31
Morphometric vertebral fractures (VFs) are an early and clinically crucial marker
Vit.D (9845), Ca (1133)
of bone fragility but they have never been investigated so far in this setting. In this
Tachysterin (0.73 mg/d)
2.29
1.35
2.52
36
34
cross-sectional study, we evaluated the VF prevalence
(DXA quantitative
Tachysterin (0.77),
2.22
1.43
2.75
67
48
morphometry) and BMD (DXA Hologic 4500 W, at lumbar spine, total hip and
Ca (1292)
femoral neck) in 53 consecutive patients with differentiated thyroid carcinoma
(two males, 51 females; median age 61 years, range: 42-82; 45 with papillary
carcinoma and eight with follicular carcinoma; median duration of therapy
Conclusion
5 years, range: 1-45) and 75 control subjects (72 females and three males; median
As expected monotherapy with high doses of calcium was not sufficient. The
age 62 years, range: 42-83) with normal thyroid function attending an outpatient
combination of 1-Alphacalcidol and Calcium was the best regimen for treating
bone clinic. VFs were significantly more prevalent in patients with thyroid
HypoPT and improving complaints. Further correlations between different
carcinoma as compared to the control subjects (30.2 vs 9.3%; PZ0.002) without
treatment regimen and parameters of renal and bone metabolism will be
significant (PZ0.21) differences in BMD at either skeletal sites. BMD was not
calculated.
significantly different between fractured and non-fractured TSH suppressed
patients at either skeletal site. Prevalence of VFs was not significantly (PZ0.29)
DOI: 10.1530/endoabs.49.OC10.1
different among patients with normal BMD (11.1%), osteopenia (39.1%) and
osteoporosis (28.6%). In patients under TSH-suppressive therapy, VFs were
significantly associated with age (OR 1.1, C.I.95% 1.01-1.12; PZ0.03) but not
with duration of L-T4 therapy (OR 1.03; C.I.95% 0.96-1.11; PZ0.34). This is the
first study showing high prevalence of VFs in patients with thyroid carcinoma
OC10.2
undergoing L-T4 TSH-suppressive therapy likely due to an impairment in bone
Evaluation of bone quality, measured by trabecular bone score (TBS) in
quality. Vertebral morphometry should be performed at baseline and during
patients with primary hyperparathyroidism (PHH) with and without
follow-up of TSH-suppressed patients to assess their skeletal health.
surgery
DOI: 10.1530/endoabs.49.OC10.3
Isabel Huguet, Miguel Sampedro-Nú
˜ez, Jose Luis Mun˜ oz De Nova,
Ana Ramos-Levi, Sandra Campos, Eugenio Escolano & Mónica Marazuela
Hospital La Princesa, Madrid, Spain.
Evaluation of bone quality represents a challenge since the analysis by bone
OC10.4
mineral density (BMD), provides useful but incomplete information. New tools
The effect of denosumab or bisphosphonates in women with severe
are arising, and amog them, TBS is emerging as a new surrogate marker of bone
postmenopausal osteoporosis after completion of teriparatide treatment
texture and microarchitecture which may be useful to potentially evaluate the risk
Tomaz Kocjan1, Antonela Sabati Rajic1, Mojca Jensterle Sever1,
of bone fracture and can be obtained from already existing BMD scans.
Gaj Vidmar2, Barbara Ostanek3, Janja Marc3, Nina Orehek3 &
Retrospective study of 23 patients with PHH. Clinical, analytical and BMD data
Marija Pfeifer1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
University Medical Centre Ljubljana, Ljubljana, Slovenia;2University
identified a novel Ga11
mutation, Phe220Ser, causing FHH2, and have
Rehabilitation Institute, Ljubljana, Slovenia;3Faculty of Pharmacy,
demonstrated the importance of the hydrophobic Phe220 residue, which forms
University of Ljubljana, Ljubljana, Slovenia.
part of a cluster, for G-protein signaling via PLC-Ca2Ci and ERK/MAPK
pathways.
DOI: 10.1530/endoabs.49.OC10.5
The ideal antiresorptive agent to preserve or further increase bone mineral density
(BMD) following teriparatide treatment is not known. We aimed to compare
BMD changes after one year of therapy with denosumab or bisphosphonates in
osteoporotic patients who had completed treatment with teriparatide. We
retrospectively analyzed 140 women (age 74 years, 26 years from menopause,
BMI 27 kg/m2 on average) with severe postmenopausal osteoporosis who had
been treated between 2006 and 2014 with teriparatide for 18-24 months at our
outpatient clinic. After stopping teriparatide, they continued with a bispho-
Obesity
sphonate
(alendronate, risedronate, ibandronate or zoledronic acid) or with
OC11.1
denosumab in standard doses per physician’s and/or patient’s preference. All
Role of Extracellular vesicles in the crosstalk between adipocytes and
patients were prescribed with vitamin D3 1000 IU daily and were instructed to
pancreatic beta-cells
ingest 1200 mg of calcium daily. BMD was measured at lumbar spine (LS), total
Iacopo Gesmundo1, Eleonora Gargantini1, Enrica Favaro2,
hip (TH) and femoral neck (FN) by DXA when teriparatide was stopped and after
Lorenzo Piemonti3, Giovanni Camussi2 & Riccarda Granata1
12 months of further treatment. The data were analyzed using multiple linear
1Division of Endocrinology, Diabetology and Metabolism, Department of
regression to adjust the comparison between groups for age, BMD, 25-hydroxy-
Medical Sciences, University of Torino, Torino, Italy;2Department of
vitamin D, serum urate, procollagen type 1 N-terminal propeptide (P1NP) at
Medical Sciences, Torino, Italy;3San Raffaele Diabetes Research Institute,
baseline and BMD gain on teriparatide. Seventy patients continued treatment with
IRCCS San Raffaele Scientific Institute, Milano, Italy.
a bisphosphonate and 70 received denosumab. The results indicate a lower BMD
increase (especially at LS) in patients on bisphosphonates when compared to
denosumab; a lower BMD increase at FN and LS in patients who had a larger
Obesity is characterized by insulin resistance and pancreatic b-cell dysfunction;
BMD increase on teriparatide (i.e. regression to the mean); a lower BMD increase
moreover, secretion of adipokines from adipocytes may affect metabolic
at FN and a higher BMD increase at LS in patients with higher baseline P1NP; and
functions in several tissues, including pancreatic b-cells. Extracellular vesicles
a higher BMD increase at FN in patients with higher baseline serum urate. Twelve
(EVs), released by cells as exosomes or shedding vesicles, play a key role in cell-
months after stopping teriparatide, sequential osteoporosis treatment with
to-cell communication, modifying the phenotype and function of recipient cells
denosumab yields higher additional BMD gain as compared to a bisphosphonate.
by delivering proteins, RNAs and microRNAs. The crosstalk between adipocytes
The effect is more pronounced at LS.
and b-cells in the regulation of glucose and lipid metabolism is still unclear. We
DOI: 10.1530/endoabs.49.OC10.4
hypothesized that EVs derived from adipocytes are able to influence the survival
and function of b-cells in pathophysiological conditions. In this study, the role of
EVs released by murine 3T3-L1 adipocytes was evaluated on cell viability and
proliferation, apoptosis and function of rat INS-1E b-cells and human pancreatic
islets. INS-1E b-cells and human pancreatic islets were treated for
24 and
72 hours, respectively, with EVs in either presence or absence of CKs or palmitic
acid and high glucose (P/G). Our results show that EVs derived from untreated
adipocytes promote cell survival and proliferation, inhibit apoptosis in b-cells and
OC10.5
pancreatic islets treated with CKs and P/G, and stimulate glucose-induced insulin
Ga11-Phe220Ser loss-of-function mutation causes familial
secretion. Conversely, EVs derived from adipocytes treated with CKs enhanced
hypocalciuric hypercalcemia type-2 (FHH2) by disrupting a
the detrimental effects of CKs and P/G. These results suggest a functional
hydrophobic cluster critical for G-protein signaling
crosstalk between adipose tissue and b-cells/pancreatic islets. Furthermore, the
Caroline M. Gorvin1, Treena Cranston2, Fadil M. Hannan1,3, Helena Valta4,
protective effects of EVs derived from adipocytes on survival and function of
Outi Makitie4, Camilla Schalin-Jantti5 & Rajesh V. Thakker1
b-cells exposed to stress, such as inflammatory CKs or glucolipotoxicity, suggest
1Academic Endocrine Unit, Radcliffe Department of Medicine, Oxford
possible therapeutic implications in pathological conditions like diabetes and
Centre for Diabetes, Endocrinology and Metabolism, University of Oxford,
obesity.
Oxford, UK;2Oxford Molecular Genetics Laboratory, Churchill Hospital,
Oxford, UK;3Institute of Ageing and Chronic Disease, University of
DOI: 10.1530/endoabs.49.OC11.1
Liverpool, Liverpool, UK;4Children’s Hospital, University of Helsinki and
Helsinki University Hospital, Helsinki, Finland;5Division of Endo-
crinology, Abdominal Center, University of Helsinki, Helsinki, Finland.
Mutations of the calcium-sensing receptor (CaSR), G-protein alpha-11 subunit
(Ga11), and adaptor protein-2
sigma subunit
(AP2s) resulting in a loss-
OC11.2
of-function, cause familial hypocalciuric hypercalcemia types 1-3 (FHH1-3),
Three year prospective study in morbidly obese patients between
respectively. We investigated a family with FHH
(four affected and two
longitudinal gastrectomy and gastric bypass based on a composite
unaffected members) for CaSR, Ga11 and AP2s mutations, and identified a
outcome combining weight loss efficacy and surgery related
heterozygous Ga11 missense mutation, Phe220Ser, which is predicted to disrupt
complications (PHRC SLEEVE K060213 / IDRCB2007-A00373-50)
a cluster of hydrophobic residues that are important for G-protein/G-protein
Jean Marc Catheline1, Marinos Fysekidis2, Yasmina Bendacha1,
coupled receptor interactions. Ga11, which acts downstream of the CaSR,
Najib Bdeoui1, Vidhya Raghavan3, Sophie Gérard3, Jean Jacques Portal3,
activates phospholipase C (PLC) leading to two predominant signal outputs:
Rami Dbouk1, Jean Michel Fabre4, Gilles Fourtanier5, Jean Gugenheim6,
intracellular calcium (Ca2Ci) release; and activation of the extracellular-signal
Noël Huten7, Maxime Sodji8, Simon Msika9, Michel Scotté10, Eric Vicaut3
regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. We
& Regis Cohen1
assessed the effects of the Ga11 mutation on signalling by expressing Ga11-wild-
1Centre coordinateur du PHRC, Centre Hospitalier de Saint-Denis, Saint-
type Phe220, and three Ga11-mutants: Ser220, detected in the FHH2 kindred; and
Denis, France;2CHU Bobigny, Bobigny, France;3Unité de Recherche
engineered mutants, Ala220
(a hydrophobic residue); and, Glu220
(a non-
Clinique Lariboisière-St Louis Hôpital Fernand Widal, Paris, France;4CHU
hydrophobic residue), in HEK293
cells stably expressing CaSR. Ca2Ci
de Montpellier, Montpellier, France;5CHU Toulouse, Toulouse, France;
responses to extracellular calcium
(Ca2Ce) were assessed using a Fluo-4
6CHU Nice, Nice, France;7CHU Tours, Tours, France;8Clinique
fluorescent assay and an NFAT-response element-containing luciferase reporter
Emailleurs, Limoge, France;9Hôpital Louis Mourier « APHP », Colombes,
that measures Ca2Ci-induced gene expression; and MAPK responses assessed
France;10CHU Rouen, Rouen, France.
using a phospho-ERK (pERK) AlphaScreen assay and a serum-response element
(SRE)-containing luciferase reporter that measures ERK-induced gene
expression. Mutation of Phe220 to the non-hydrophobic Ser220 and Glu220
Since its first description in 2000, Longitudinal Gastrectomy (LG) has become the
residues, but not the hydrophobic residue, Ala220, significantly impaired Ga11
first surgical procedure in the treatment of morbid obesity in the world, exceeding
signalling via PLC-Ca2Ci and ERK/MAPK pathways. Thus, Ser220 and Glu220,
in numbers Gastric Bypass
(GB). GB is considered to have better results
when compared to wild-type (Phe220) and Ala220 led to: a rightward shift of the
regarding long-term weight loss and improvement in co-morbidities. We aimed to
dose-response curves of Ca2Ci responses to Ca2Ce with increased mean half-
demonstrate that LG is non inferior to GB for a composite end point that included
maximal concentration (EC50) values; reductions in NFAT reporter responses;
more than 50% excess weight loss from the baseline and surgery related
impaired pERK responses; and reductions in SRE reporter activity. Thus, we have
complications after a mean follow-up of 36 months. This is a prospective study in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
morbidly obese patients that tested a two hypotheses composite outcome: the first
Weight loss induced with diet and exercise decreases hepatic steatosis and
hypothesis was that after 36 months LG was non-inferior to GB regarding EWL
inflammation, but requires greater efforts to sustain compared to medication. We
(the predefined margin of non-inferiority was G15%), and the second hypothesis
therefore aimed to compare the effects of liraglutide, a glucagon-like peptide-1
was the presence of significant difference in post-operative morbidity and
agonist which induces weight loss, on hepatic steatosis and inflammation in obese
mortality. From February 2008 to March 2015 we included 277 patients (91 GB
Asian adults with NAFLD with intensive lifestyle modification.
vs 186 LG). The mean age was 41.1 years, 19.2% had a previous bariatric
Methods
operation,
85.9% were women and the average pre-intervention BMI was
22
abdominally obese Asian
(mean BMI
33.6G3.9 kg/m2, mean waist
45.3 kg/m2. At baseline there were no significant differences between the GB and
circumference WC
108.5G10.6 cm) non-diabetic normotensive adults with
LG for age, sex and BMI. The % of patients with EWL O 50% was at 18 months
NAFLD, as diagnosed by a hepatologist based on elevated serum alanine
for 82.1% (GB) vs 84.5% (LG), and 79.1 vs. 79.5% respectively at 36 months.
transaminase (ALT) and aspartate transaminase (AST) levels and liver fat fraction
The estimated difference in EWL was [K10.5% to 9.8%], confirming the non-
O5% using magnetic resonance imaging (MRI) in the absence of other causes of
inferiority of LG compared to BP. Finally there was a significant less morbidity
hepatic steatosis and transaminitis, were randomized to supervised dieting
and mortality for the LG group (GB vs LG, 12.1 vs. 4.8%, one death for LG,
(restriction by 400 kcal/day) plus moderate-intensity exercise (200 minutes/week)
PZ0.01). This is the first prospective study demonstrating that LG is not inferior
to induce R5% weight loss (DE group, nZ11) or liraglutide 3 mg daily (LI
to GB for an estimated
10% difference in EWL but with less surgical
group, nZ11) for 26 weeks. Insulin resistance was estimated by homeostasis
complications. These results reinforce the choice of LG as surgical procedure
model assessment (HOMA-IR) and liver shear stiffness with MRI elastography.
for obesity.
Results
DOI: 10.1530/endoabs.49.OC11.2
At 26 weeks, both DE and LI groups had significant (P!0.01) and similar
reductions in weight (K3.1G2.9 vs K3.6G2.4 kg), WC (K4.4G3.2 vs K5.7G
3.9 cm), liver fat (K9.5G13.8 vs K7.7G7.3%), liver stiffness (K0.22G0.20 vs
K0.32G0.25 kPa), ALT (K42G34 vs K43G39 U/l), AST (K21G16 vs
K26G25 U/l) and HOMA-IR (K2.87G2.67 vs K3.12G2.40).
Conclusion
Once-daily liraglutide is as effective as intensive lifestyle modification for
decreasing hepatic steatosis, inflammation and stiffness in obese Asian adults
with NAFLD.
OC11.3
DOI: 10.1530/endoabs.49.OC11.4
Interleukin-1 antagonism decreases cortisol levels in obese individuals
Sandrine Urwyler1, Philipp Schutz2, Fahim Ebrahimi1, Marc Y. Donath1 &
Mirjam Christ-Crain1
1University Hospital Basel, Basel, Switzerland;2Kantonsspital Aarau,
Aarau, Switzerland.
Background
Increased cortisol levels in obesity may contribute to the associated metabolic
syndrome. In obesity, the activated innate immune system leads to increased
interleukin (IL)-1b, which is known to stimulate the release of adrenocortico-
OC11.5
tropin hormone
(ACTH). We therefore hypothesised that in obesity IL-1
Differentiating constitutional thinness from anorexia nervosa in
antagonism would result in downregulation of the hypothalamo-pituitary-adrenal
DSM 5 era
(HPA) axis, leading to decreased cortisol levels.
Bruno Estour1,2, Nesrine Marouani1, Torrance Sigaud2,3, Francois Lang2,3,
Methods
Eric Fakra2,3, Aurelie Diamonde2, Bogdan Galusca1,2 & Natacha Germain1,2
In this prospective intervention study we included 73 patients with obesity (BMI
1Endocrinology Department, University Hospital of Saint Etienne,
O30 kg/m2) and at least one additional feature of the metabolic syndrome.
Saint Etienne, France;2EA 7423, Jean Monnet University of Saint Etienne,
The primary endpoint was change in morning cortisol from baseline to after
Saint Etienne, France;3Psychiatry Department, University Hospital of Saint
the administration of the IL-1 receptor antagonist (anakinra/Kineretw, total dose
Etienne, Saint Etienne, France.
3!100 mg). Secondary endpoints were effects on salivary cortisol and ACTH.
Results
Introduction
Median morning serum cortisol levels (nmol/l) decreased significantly after IL-1-
antagonism (from baseline 452 to 423, absolute difference K38.7, 95%CI K64 to
Constitutional thinness (CT) is an underweight state characterized by normal
menstruations and no change in feeding behaviour. Thinness is the only
K13.4, PZ0.0019). Similar effects were found for salivary cortisol levels (K2.8,
resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea in
95%CI K4.4 to K1.3, PZ0.0007), ACTH levels (K2.2, 95%CI K4.2 to K0.1,
the new DSM 5 definition of AN might lead to misdiagnosis between these two
PZ0.038), systolic blood pressure (K5.2, 95%CI K8.5 to K1.8, PZ0.0006) and
populations. The objective of this study was to compare CT, AN and Control
heart rate (K2.9, 95%CI K4.7 to K1.0, PZ0.0029).
subjects in terms of biological, anthropometric, and psychological markers in
Conclusion
order to better distinguish AN from CT subjects.
IL-1 antagonism in obese individuals with features of the metabolic syndrome
Patients and method
leads to a decrease in serum cortisol, salivary cortisol and ACTH-levels along
This retrospective study conducted from 2000 to 2015 included three groups of
with a reduction in systolic blood pressure and heart rate. IL-1 antagonism could
young women: fifty-six CT, forty restrictive-type AN and fifty-four control
thus be a novel treatment option to improve cortisol levels and associated
subjects were included in the study. Basal evaluation was made in all groups with
comorbidities in obesity.
any intervention. Body composition, nutritional markers, pituitary hormones,
DOI: 10.1530/endoabs.49.OC11.3
bone markers and psychological scores were evaluated in three groups. For every
markers, a receiver Operator Characteristics (ROC) curve was calculated to
evaluate the accuracy of differentiation between AN and CT groups.
Results
For the majority of the studied parameters, CT subjects were similar to controls
but dramatically different from AN subjects. According to ROC data, while
psychological scores were unsuccessful to differentiate AN from CT, except for
OC11.4
DEBQ Restrained Eating item, free-T3 and Leptin were strong tools for AN and
Comparing effects of weight loss by liraglutide with intensive lifestyle
CT distinction as they displayed high sensitivities and specificities with low P
modification on hepatic steatosis, inflammation and stiffness, and insulin
values (!0.0001).
resistance in obese Asians with non-alcoholic fatty liver disease
Conclusions
(NAFLD)
Taking AN and CT distinction as a major objective, the exclusive use of
Joan Khoo, Ngai-Moh Law, John Hsiang, Jessica Tan & Tiing-Leong Ang
psychological criteria is not sufficient and should be completed by at least a free
Changi General Hospital, Singapore, Singapore.
T3 determination, which is a cheap and an accessible laboratory testing for
general practitioners. The final goal is to avoid social stigmatization and excessive
useless therapies for CT women.
Background and Aims
DOI: 10.1530/endoabs.49.OC11.5
Non-alcoholic fatty liver disease (NAFLD), a leading cause of cirrhosis and liver
cancer, is increasing worldwide due to rising obesity rates, particularly in Asia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Pituitary Clinical
Design
Cohort study based on an electronic survey open for participation to ESE
OC12.1
members Dec 2015-Nov 2016.
T2-Weighted signal intensity of functional pituitary adenomas:
Results
correlation with clinicopathological findings and response to treatment
Reports on 167 patients, 40 pituitary carcinomas, and 127 aggressive pituitary
Sema Ciftci Dogansen1, Seher Tanrikulu1, Gulsah Yenidunya Yalin1,
tumours were obtained. Median age at diagnosis was 43 (range 4-79) years. 59%
Sakin Tekin1, Nihan Nizam1, Bilge Bilgic2 & Sema Yarman1
of tumours were clinically functioning at presentation, and the most frequent were
1Division of Endocrinology and Metabolism, Department of Internal
corticotroph tumours. TMZ was the first line chemotherapy in 157 patients. At the
Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul,
end of TMZ treatment (mean 9.92 cycles) radiological evaluation showed
Turkey;2Department of Pathology, Istanbul Faculty of Medicine, Istanbul
complete response in 6%, partial response in 31%, stable disease in 33% and
University, Istanbul, Turkey.
progressive disease in
30%. Progression occurred more often in pituitary
carcinomas (40%) than in aggressive adenomas (26%), PZ0.05. Clinically silent
tumours showed less regression compared with secreting tumours, 17 vs 45%,
Purpose
PZ0.01 (overall c2 test). Median follow-up after TMZ treatment was 21 months.
Somatotrophinomas have been shown to demonstrate T2-weighted signal
Of patients with complete response, partial response and stable disease 22, 34 and
intensity (WSI) on MRI that is correlated with clinicopathological findings and
40% respectively showed progression during further follow-up. Twenty five
response to treatment. Therefore, we aimed to investigate these correlations in
patients received a second course of TMZ, 3 had a partial response. Overall
functional pituitary adenomas, including prolactinoma and corticotrophinoma.
mortality was 33%, and highest in patients with progression after TMZ treatment
Material and Methods
(54%).
Patients with somatotrophinoma (nZ87), prolactinoma (nZ78) and cortico-
Conclusion
trophinoma (nZ33) were involved in this study. The initial T2-WSI findings
TMZ was accompanied by tumour regression in 37% of patients, documenting its
(grouped into hypo-, iso- and hyperintense) were compared with hormon levels,
value in the management of these aggressive tumours. The high recurrence rate
tumor diameter, granulation patterns and treatment response.
following TMZ cessation highlights the need to identify additional effective
Results
therapies.
While most of somatotrophinomas were hypointense, most of prolactinomas and
corticotrophinomas were hyperintense. Tumor diameter was significantly larger
DOI: 10.1530/endoabs.49.OC12.2
in hyperintense somatotrophinomas than in hypointense group (PZ0.007), but
the tumor diameter in the isointense group did not show any difference when
compared to the others. IGF-1% ULN (upper limit of normal) was higher in
hypointense somatotrophinomas than the other two groups (PZ0.02). Sparsely
granulation pattern in hyperintense somatotrophinomas and densely granulation
pattern in hypointense somatotrophinomas are more frequent
(PZ0.035),
whereas the granulation pattern distribution in isointense group did not differ
from the other two groups. The hormonal response to somatostatin analogs (SSA)
treatment (percentage of IGF-1 reduction) was higher in the hypointense group
OC12.3
than in the other two groups (PZ0.04). The tumor diameter was smaller in the
hyperintense prolactinomas than in the other groups (PZ0.039), but the basal
Recombinant Growth Hormone added to physical therapy in
PRL levels were not different between the groups. The response to dopamine
GH-deficient adults with complete (ASIA A) Spine Injury
agonist (DA) treatment of iso- and hyperintense prolactinomas is much better than
(EudraCT 2011-005377-23)
the hypointense group (P!0.001). Tumor diameter was larger in hyperintense
Guillem Cuatrecasas1, Hatice Kumru2,3, M8Josep Coves1, Ioana Patrascioiu1
corticotrophinomas than the other two groups (PZ0.012), but there was no
& Josep Vidal2,3
difference between the baseline cortisol and ACTH levels of the groups. Sparsely
1Department of Endocrinology, Hospital Quiron-Teknon, Barcelona, Spain;
granulation pattern was higher in hyperintense corticotrophinomas and densely
2Fundación Institut Guttmann, Badalona, Spain;3Institut Universitari de
granulation patern in hypointense corticotrophinomas
(PZ0.029), whereas
Neurorehabilitació (UAB), Badalona, Spain.
granulation pattern distribution in isointense group was not different from the
other two groups. There was no difference between the groups in terms of
Introduction
remissions and recurrences.
Although in-vitro models suggest GH-induced differentiation, migration and
Conclusion
survival of astrocytes and oligodendrocytes, no studies had been published
Hyperintense somatotrophinomas support literature knowledge with increased
in-vivo. We want to evaluate the efficacy and safety of GH associated with
tumor diameter, sparsely granulation pattern and less responsiveness to SSA
physical therapy compared to placebo in patients with complete spine injury (SI)
treatment. The response to DA treatment of iso- and hyperintense prolactinomas
and associated GH deficiency (GHD).
is much better, but there was no difference between the groups in terms of
Methods
remissions and recurrences in corticortophinomas. Our results in prolactinomas
Eighteen Patients with complete SI were screened for GHD (glucagon test). 12
and corticotrophinomas should be supported by further studies.
severe
(GH!3 ng/ml) or partial (!10 ng/ml) GHD were randomized in a
DOI: 10.1530/endoabs.49.OC12.1
double-blind placebo-controlled study. Motor and sensory ASIA scale, SCIM-III
(spinal cord injury independence measure), Ashworth (spasticity), Neuropathic
Pain Scale and Quantitative Sensory tests were assessed. Patients received
subcutaneous injections of placebo or GH (Nutropinw) 6 days/week IGF1-
adjusted, in addition to intensive physical therapy 2 h/day, for 6 months. Both
groups were similar according to age, sex, BMI, waist circumference.
Results
Significant (PZ0.05) improvement was observed in SCIM-III score at 3 months:
55.6
(14.4 S.D.) vs 74 (2.8 S.D.) and 6 months: 55.4 (14.2 S.D.) vs 73.5 (2.1 S.D.),
OC12.2
comparing GH-treated group with placebo. A significant improvement in the
electrical perception threshold from the 1st up to the 5th metamera below the SI
Use of temozolomide in a large cohort of patients with aggressive
site was observed on both sides after 6 months of treatment in the GH, but not in
pituitary tumours and pituitary carcinomas: Results from a European
the placebo group. These differences were observed intra-individually (PZ0.04
Society of Endocrinology (ESE) survey
Friedman’s test) and between groups (5th left level (PZ0.023) and 5th right level
Ann McCormack, Olaf M Dekkers, Stephan Petersenn, Vera Popovic,
Jacqueline Trouillas, Gerald Raverot & Pia Burman
(PZ0.031), mixed linear model). No correlations with IGF1 were observed. No
1Garvan Institute, Darlinghurst, Australia;2Leiden University Medical
GH-related adverse events were reported.
Centre, Leiden, The Netherlands;3ENDOC Center for Endocrine Tumors,
Conclusions
Hamburg, Germany;4Medical Faculty, University Belgrade, Belgrade,
Not studied so far, GHD seems very prevalent in SI. This is the first trial with
Serbia;5Faculté de Médecine Lyon-Est, Lyon, France;6Universite de Lyon,
complete SI and concomitant GHD. GH added to intense physical rehabilitation
Lyon, France;7Medical Faculty, University of Lund, Malmo, Sweden.
improved functional parameters (SCIM) and changes in sensory quantification
up to 5 levels below SI. Larger studies should be performed to confirm a GH
beneficial effect on sensitive pathways in SI.
Objective
DOI: 10.1530/endoabs.49.OC12.3
To collect clinical and treatment outcome data in a large patient cohort, and
specifically to report experience with temozolomide (TMZ).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
OC12.4
2.79, C.I. 95%1.03-7.61; PZ004). By contrast, no significant differences in
incident VFs were found between patients receiving PegV and those treated with
Subclinical cardiovascular system dysfunction in the patients with
SRLs alone, either when disease was persistently active (58.3% vs 60.0; PZ0.94)
Cushing’s disease
or when disease was controlled by treatment (20.0 vs 27.0%; PZ0.67). In
Przemyslaw Witek1, Beata Uzieblo-Zyczkowska2, Pawel Krzesinski2,
conclusion, this longitudinal study showed that PegV and SRLs had comparable
Agnieszka Jurek2, Grzegorz Zielinski3, Andrzej Skrobowski3 &
effects on VF risk in acromegaly. Biochemical control as well as early diagnosis
Grzegorz Gielerak3
of the disease are the main endpoints for fracture prevention in acromegaly.
1Department of Endocrinology and Isotope Therapy, Military Institute of
Medicine, Warsaw, Poland;2Department of Cardiology and Internal
DOI: 10.1530/endoabs.49.OC12.5
Medicine, Military Institute of Medicine, Warsaw, Poland;3Department of
Neurosurgery, Military Institute of Medicine, Warsaw, Poland.
Background
Hypercortisolism in Cushing’s disease (CD) is associated with high cardiovas-
Reproduction & Endocrine Disruption
cular risk. Hemodynamic disturbances, especially excessive vasoconstriction and
elevated blood pressure
(BP), may contribute to accelerated myocardial
OC13.1
remodeling. Early identification of subclinical left ventricular (LV) dysfunction
may be crucial for optimizing treatment and reducing mortality in patients
with CD.
Abstract withdrawn.
Purpose
The aim of this study was to assess the hemodynamic function of cardiovascular
system in three groups of patients: 1/ with CD (CD), 2/ with essential arterial
hypertension (AH) and healthy volunteers (HV).
Methods
In 171 subjects (CD - 22, AH - 114, HV - 35), without any symptoms of heart
failure, the echocardiographic assessment of LV systolic and diastolic function
and non-invasive hemodynamic assessment by impedance cardiography (ICG)
were performed. Statistical comparison included separate analysis for women and
men.
Results
CD revealed good BP control
(82% below 140/90 mmHg). However, in
OC13.2
comparison to AH and HV they presented: 1) significantly lower LV contractility
Thyroid peroxidase antibodies do not predict outcome in 900 women
expressed by global longitudinal strain (GLS: K17.7% vs K19.2 vs K20.0;
with recurrent pregnancy loss
PZ0.004); 2) higher prevalence of LV diastolic function (45.0% vs 14.2% vs
Sofie Bliddal1, Henriette Svarre Nielsen2, Aase Krogh-Rasmussen1,
0.0%; P!0.00001); 3) lower impedance indices of LV performance: stroke index
Astrid Marie Kolte2, Ole Bjarne Christiansen2, Claus Henrik Nielsen3
(SI: 39.8 vs 52.2 vs 49.9 ml/m2; P!0.00001) cardiac index (CI: 2.86 vs 3.54 vs
& Ulla Feldt-Rasmussen1
3.27 l/min/m2; P!0.0001) and 4) higher afterload: systemic vascular resistance
1Department of Medical Endocrinology, Copenhagen University Hospital
index (SVRI: 2560 vs 1901 vs 1907 dyn*s*m2/cm5; P!0.0001). Men with CD
(Rigshospitalet), Copenhagen, Denmark;2Recurrent Pregnancy Loss Unit,
distinguished with lower CI (P!0.00001) and SVRI (P!0.0001), as though
Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark;
worse LV diastolic function
(e‘: PZ0.0002; GLS: PZ0.052). In women
3Institute of Inflammatory Research, Copenhagen University Hospital
hypercortisolism was more related to impaired LV systolic function
(GLS:
(Rigshospitalet), Copenhagen, Denmark.
PZ0.010; e‘: NS).
Conclusions
Introduction
Cushing’s disease, even with well-controlled BP, is associated with LV systolic
Thyroid autoimmunity has been associated with pregnancy loss. A possible
and diastolic dysfunction and pronounced vasoconstriction which individual
mechanism is an overactive maternal immune system leading to rejection of the
presentation depends on sex. These hemodynamic alterations can be detected by
fetal allograft. In women with recurrent pregnancy losses (RPL), we investigated
modern non-invasive diagnostic tools and became potential therapeutic
the association of thyroid peroxidase antibodies (TPOAbs) with number of losses
objectives.
and outcome of first pregnancy after referral.
DOI: 10.1530/endoabs.49.OC12.4
Methods
Prospective study of women with RPL
(R3) followed at the RPL Unit,
Copenhagen University Hospital, from 2011 to 2016. Upon first visit, all women
were screened for TSH
(Roche Modular E170
electrochemiluminescense
immunoassays) and TPOAbs (automated Kryptor immunoflourescent assay).
OC12.5
TPOAb-positivity O60 kU/l. We performed test for trends by chi-square or
Effects of pegvisomant and somatostatin receptor ligands on risk of
independent t-tests as appropriate, and adjusted regression analyses with
vertebral fractures in patients with Acromegaly
covariates: maternal age, TSH (logtransformed), number of losses, immunother-
Sabrina Chiloiro1, Gherardo Mazziotti3, Antonella Giampietro1, Anna
apy, thyroxine replacement therapy. The National Data Protection Agency
Maria Formenti2, Antonio Bianchi1, Marilda Mormando1,
approved the project.
Alfredo Pontecorvi1, Andrea Giustina4 & Laura De Marinis1
Results
1Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;
We included 5219 pregnancies (76.6% spontaneous) in 900 women; 119 (13.2%)
2Department of Molecular and Translational Medicine, University of
women were TPOAb-positive. TPOAb-positivity was neither associated with
Brescia, Brescia, Italy;3Department of Internal Medicine, Mantua Hospital,
number of losses (PZ0.87, aOR 0.004 (-0.3-0.3), PZ0.98), nor number of
Mantua, Italy;4Chair of Endocrinology, Vita-Salute San Raffaele
pregnancies (PZ0.62, aOR 1.02 (0.92-1-11) PZ0.76). Among TPOAb-positive
University, Milan, Italy.
women, TPOAb-concentration was not associated with number of losses (BZ
0.75
(-0.12-0.27), PZ0.45). In women with a registered first pregnancy after
referral, TPOAb-positivity (72 of 557 (12.9%)) was not associated with live birth
Acromegalic osteopathy is an emerging complication of chronic GH excess
rate (54.4 vs 60.6%, PZ0.35, aOR 0.78 (0.42-1.43) PZ0.38). However, live birth
characterized by increase in bone turnover, deterioration in bone microarchi-
rate was significantly associated with total number of losses (aOR 0.53 (0.45-
tecture and high risk of vertebral fractures (VFs). Medical therapies may exert
0.61) PZ0.000). TSH-levels were positively associated with TPOAb-positivity
direct effects on peripheral targets leading to improvement of clinical outcomes
(PZ0.00), but not with any investigated outcome. Immunoglobulin therapy or
regardless of biochemical control of acromegaly. In this longitudinal study, we
thyroxine replacement did not alter results.
compared the effects pegvisomant (PegV) and somatostatin receptor ligands
Conclusion
(SRLs) on VF risk in 80 acromegaly patients (47 females, 33 males; mean age 53
In a large cohort of women with RPL, we found no association between TPOAbs
years, range 24-86 years) who were prospectively evaluated by quantitative
and pregnancy outcome. TSH-levels were significantly increased in TPOAb-
vertebral x-ray morphometric approach. During the 30 month study period, 39
positive women and screening according to guidelines should be performed.
patients (48.8%) were treated with PegV, 33 (41.2%) with SRLs and 8 (10%)
However, if RPL is caused by an immunological reaction, thyroid autoimmunity
showed a controlled disease after neurosurgery. At follow-up, 23 patients (28.8%)
does not seem to be a sensitive marker hereof.
experienced incident VFs which were significantly correlated with persistently
DOI: 10.1530/endoabs.49.OC13.2
active disease (OR .49, C.I.95% 1.75-17.22; PZ0.003) and preexisting VFs (OR
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
OC13.3
parameters showed worsening MMP in diabetic patients (P!0.05). Patients with
DM2 showed a significant decrease in the degree of sperm vitality and increased
Sertoli cell expressed hydroxysteroid (17beta) dehydrogenase 1 is
spermatozoa in late apoptosis vs Controls and of the DNA fragmentation
required for male fertility
compared to the other two groups (P!0.05). Moreover, patients with DM1 had a
Janne Hakkarainen1, Heli Jokela1, Fuping Zhang1, Noora Kotaja1,
lower progressive motility when the disease duration was O10 years vs the other
Petra Sipila1 & Matti Poutanen1,2
two groups, and lower MMP after 5 years of disease (P!0.05). The degree of PL
1Department of Physiology and Turku Center for Disease Modeling,
was higher in DM2 patients compared to the other two groups (P!0.05), while
Institute of Biomedicine, University of Turku, Turku, Finland;2Institute of
the concentrations of mitochondrial superoxide were greater in DM2 patients
Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg,
compared to DM1 and control group (P!0.05). The ultrasound data showed that
Sweden.
the diameter of the epididymal head and tail after ejaculation were greater in
patients with DM1 long term than those of short duration compared to controls
(P!0.05). Testosterone levels were lower in DM2 patients vs controls (P!0.05).
Hydroxysteroid (17beta) dehydrogenase 1 (Hsd17b1) is a steroidogenic enzyme
Conclusion
catalyzing the conversion of estrone (E1) to estradiol (E2), and androstenedione
Patients with DM1 have low ejaculate volume for an altered epididymal emptying
(A-dione) to testosterone (T). We have shown that the deletion of Hsd17b1 gene
and a mitochondrial damage that anticipates the later decline of sperm motility.
in mice resulted in the failure of ovarian estrogen production and subfertility. In
DM2 is instead characterized by an inflammatory condition with increased
this study, we clarified the role of Hsd17b1 in male reproduction. The data
leukocyte and oxidative stress and elevated levels of sperm DNA fragmentation
revealed that in mice Hsd17b1 mRNA is highly expressed in the Sertoli cells at
and decreased sperm vitality.
the fetal age. The Sertoli cell function is critical for normal spermatogenesis, and
DOI: 10.1530/endoabs.49.OC13.4
their action is dependent on the pituitary gonadotropins and testosterone. The
breeding tests revealed that the Hsd17b1 knockout male mice (HSD17B1KO)
were infertile. Because the Hsd17b1 is part of the steroid synthesis machinery, we
analyzed the in vivo biomarkers for androgen action, while no changes were
observed in fetal masculinization or in onset of puberty. Furthermore, the weights
of androgen-dependent tissues in HSD17B1KO were neither affected. Also, the
serum gonadotropin levels and the steroid concentrations in the testis, were close
to normal in the HSD17B1KO males, with minor changes in the E1/E2 and
A-dione/T ratios. Interestingly, several steroidogenic genes, Hsd17b3, Star,
Cyp11a1 and Hsd3b1, were significantly upregulated in HSD17B1KO testes,
suggesting a functional compensation due to the lack of Hsd17b1 activity.
Although no marked changes were observed in the hormonal environment,
OC13.5
histological analysis of HSD17B1KO testis revealed defects in the organization of
Urinary cadmium excretion is associated with increased synthesis of
differentiating germ cells in the seminiferous epithelium, and major defects in the
haploid germ cell differentiation, particularly in the head shaping of elongating
cortico- and sex steroids in a family-based Swiss population study
spermatids. Consequently, the epididymal sperm count was dramatically reduced
Murielle Bochud1, Judith Jenny-Burri2, Menno Pruijm3, Belen Ponte4,
in the HSD17B1KO males, and the remaining spermatozoa were morphologically
Idris Guessous1, Georg Ehret5, Dusan Petrovic1, Vincent Dudler2,
abnormal. These results revealed a novel role for Hsd17b1 in the control of
Max Haldimann2, Geneviève Escher7, Bernhard Dick7, Markus Mohaupt7,
spermatogenesis and male fertility, and suggest that Hsd17b1 is required for a
Fred Paccaud1, Michel Burnier3, Antoinette Péchère-Bertschi6,
proper function of Sertoli cells.
Pierre-Yves Martin4, Bruno Vogt7 & Daniel Ackermann7
1Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzer-
DOI: 10.1530/endoabs.49.OC13.3
land;2Federal Food Safety and Veterinary Office, Bern, Switzerland;
3Service of Nephrology, Lausanne, Switzerland;4Service of Nephrology,
Geneva, Switzerland;5Cardiology, Department of Specialities of Internal
Medicine, Geneva, Switzerland;6Endocrinology, Department of Special-
ities of Internal Medicine, Geneva, Switzerland;7University Clinic for
Nephrology and Hypertension, Bern, Switzerland.
Background
Cadmium (Cd) is considered as a human carcinogen. A potential intermediate
OC13.4
mechanism could be hormone-related by disturbing steroidogenesis in gonads and
Diabetes mellitus: a new cause of male infertility
adrenal glands. We tested whether urinary Cd excretion, as a marker of long-term
Rosita Angela Condorelli, Sandro La Vignera, Rossella Cannarella,
exposure, is associated with the urinary steroid profile in the general adult
Laura Maria Mongioì & Aldo Eugenio Calogero
population.
Unit of Andrology and Endocrinology, Department of Clinical and
Methods and Findings
Experimental Medicine, Catania, Sicily, Italy.
The Swiss Kidney Project on Genes in Hypertension (SKIPOGH) is a multicentric
family-based population study with a response rate of 25.6%. We measured 24-h
Introduction
urinary excretions of Cd and steroid hormone metabolites by gas chromatography
Diabetes mellitus (DM) may cause male infertility acting with pre-testicular,
and mass spectrometry in 1000 participants (473 men, 527 women), with separate
testicular and post-testicular mechanism.
day and night collections. Mixed linear models were used to analyse the
Aim
associations of each steroid metabolite with Cd excretion.
To evaluate the presence of male infertility and the mechanisms of sperm damage
Cd and testosterone excretions were positively associated in men (b[SE, P]:
in diabetic patients in childbearing age.
1.378[0.242,
!0.00001] and
1.440[0.333,
0.00002] for day and night,
Patients and methods
respectively), but not in women (0.333[0.257, 0.2] and 0.674[0.361, 0.06]).
Thirty-four patients with DM1, 55 with DM2 and 100 healthy fertile men
There was a strong positive association of the urinary excretion of Cd and cortisol
(controls) were enrolled. Diabetic patients were further divided into three groups
(0.475[0.157,
0.0025] and
0.877[0.194,
0.00001], for day and
0.875[0.253,
based on their glycometabolic status and illness duration. Conventional and
0.00053] and 1.183[0.277, 0.00002] for night, respectively). Cd excretion was not
biofunctional sperm parameters were evaluated by standard semen analysis
associated with the excretion of tetrahydroaldosterone, the major metabolite of
and flow cytometry. This latter included sperm DNA fragmentation, vitality, early
aldosterone, but with other mineralocorticoid metabolites (P!0.01 in men and
and late apoptosis, chromatin condensation, mitochondrial membrane potential
women). Further adjustment revealed an independent effect between the synthesis
(MMP), leukocyte subpopulations, lipid peroxidation (PL) and sperm mito-
of sex hormones and corticosteroids and an interdependent effect of Cd on gluco-
chondrial superoxide. In addition, all patients and controls underwent testicular
and mineralcorticoid synthesis.
ultrasound sca and serum LH and testosterone measurements.
Conclusions
Results
Our findings provide evidence for a global stimulating effect of low-dose Cd
Diabetic patients had lower sperm concentration, progressive motility and
exposure on sex and corticosteroid synthesis in the general adult population.
morphology vs controls (P!0.05). The ejaculate volume is significantly lower in
Further studies are needed to explore the health consequences of chronic low-dose
patients with DM1 vs controls (P!0.05). Leukocyte concentrations were higher
exposure to Cd on selected diseases such as steroid-sensitive cancers or metabolic
in patients with DM2 (P!0.05), showing a statistically significant reduction in
disorders.
the percentage of T helper cells and an increase of the suppressor T lymphocytes
DOI: 10.1530/endoabs.49.OC13.5
compared to controls
(P!0.05). The analysis of the biofunctional sperm
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Thyroid Cancer
with advanced tumor stage in thyroid cancer. Therefore, we hypothesize that
HO-1 may represent a potential target for cancer therapy. HO-1 inhibitors
OC14.1
have been clinically used in patients with hyperbilirubinemia and hereditary
Anti-Mullerian hormone (AMH) in pre-menopausal females after
porphyria. In the present study, thyroid cancer cells were treated with two
ablative radioiodine (RAI) treatment for differentiated thyroid cancer
different classes of HO-1
inhibitors: metalloporphyrin and imidazole-
(DTC): single-center study
dioxolane compound. We found that treatment with HO-1
inhibitors
Miranda Mittica1, Paola Comite2, Claudia Campana1, Stefano Gay1,
suppressed cell growth, colony formation, cell migration, and invasion of
Michele Mussap2 & Massimo Giusti1
thyroid cancer cells in a dose-dependent manner. Cell cycle analysis by flow
1UO Clinica Endocrinologica, Azienda Ospedaliera Universitaria San
cytometry revealed that growth arrest in the G0/G1 phase. However, there
Martino - IST, Genoa, Italy;2UO Laboratorio Analisi, Azienda Ospedaliera
was no synergistic effect of HO-1
inhibitors in combination with
Universitaria San Martino - IST, Genoa, Italy.
doxorubicin or sorafenib. Our results suggest a modest susceptibility of
thyroid cancer cells to HO-1 inhibitors. Nonetheless, HO-1 inhibition may
not act as a sensitizer to chemotherapy in thyroid cancer.
Background
It is generally reported that female fertility is not affected by high-dose RAI
DOI: 10.1530/endoabs.49.OC14.2
treatment. AMH has been considered a reliable and accurate index of ovarian
reserve. There are few data on AMH values in thyroid diseases. Recently, in DTC
women who had undergone RAI ablation treatment, Acibucu et al. (2016)
reported low AMH levels without significant impairment of fertility.
Aim
The aim of this single-center study was to evaluate AMH levels in association
with the characteristics of spontaneous menstrual cycles and the levels of
pituitary-gonadal hormones in our cohort of pre-menopausal women with a
history of low-risk DTC.
OC14.3
Subjects
From a group of 68 women, 39 who were not on oral contraceptive therapy were
TERT, BRAF and NRAS in the molecular profile of metastatic thyroid
enrolled. All hormone evaluations were performed on chemiluminescence assays.
cancer: differences between primary and distant disease
AMH, FSH, 17B-estradiol (E2) were assayed on day 2 and PRL and progesterone
Miguel Melo1,2, Adriana Gaspar da Rocha1,3, Rui Batista1,4, Joao Vinagre1,
(P) levels on day 21-24 of the same menstrual cycle. Twenty-seven women (aged
Maria Joao Martins5, Gracinda Costa6, Cristina Ribeiro2,
40G6 years) were studied 7G4 years after primary DTC treatment, which
Francisco Carrilho2, Valeriano Leite7,8, Claudia Lobo9, Jose Manuel
included at least one RAI treatment (median activity 80 mCi). As a control group,
Cameselle-Teijeiro10, Manuel Sobrinho-Simoes1,11 & Paula Soares1,12
12
female DTC patients
(aged
40G8 years) who had undergone only
1Instituto de Investigac¸ão e Inovação em Saúde (I3S), Porto, Portugal;
thyroidectomy were used.
2Department of Endocrinology - Centro Hospitalar e Universitário de
Results
Coimbra, Coimbra, Portugal,3Unidade de Saude Publica de Cantanhede,
All women were free from DTC. Pregnancy (study group 62%; control group
ACeS do Baixo Mondego, Cantanhede, Portugal;4Medical Faculty,
50%) and abortion rates (17 and 33%) were similar. TSH and f-T4 were similar in
University of Porto, Porto, Portugal;5Department of Pathology - Centro
both groups. Hyperprolactinemia was found only in one patient, while FSH
Hospitalar e Universitário de Coimbra, Coimbra, Portugal;6Department of
O30 mU/l was found in 2 (1 study, 1 control). Regular (28G2 days) menses were
Nuclear Medicine - Centro Hospitalar e Universitário de Coimbra,
reported in 33% of both groups. A high incidence of polymenorrhea was reported
Coimbra, Portugal;7Unit for Investigation of Molecular Pathobiology,
in the study group (33%), while a high incidence of oligomenorrhea was noted in
Portuguese Institute of Oncology - Lisbon Center, Lisboa, Portugal;
the control group (50%). Ovulatory cycles (PO4 ng/ml) were noted in 72 and
8Department of Endocrinology, Portuguese Institute of Oncology - Lisbon
60% of study and control women, respectively. AMH levels were found to be
Center, Lisboa, Portugal;9Department of Pathology, Portuguese Institute of
negatively correlated with age (PZ0.002), but not with E2, FSH, TSH or f-T4
Oncology - Porto Center, Porto, Portugal;10Department of Pathology,
levels. AMH levels were 2.0G0.4 ng/ml and 2.3G1.5 ng/ml in the study and
Clinical University Hospital, SERGAS, Medical Faculty, University of
control groups, respectively.
Santiago de Compostela, Santiago de Compostela, Spain;11Department of
Limitations
Pathology, Hospital S. João, Porto, Portugal;12Department of Pathology and
These data are preliminary, as data collection is still ongoing.
Oncology, Medical Faculty, University of Porto, Porto, Portugal.
Conclusions
AMH should replace FSH in the evaluation of gonadal reserve in pre-menopausal
Context
DTC women. At present, age is the only predictor of AMH levels. About one out
Little is known about the frequency of key mutations in thyroid cancer metastases
of two women with a history of DTC suffers from menstrual dysregulation, but
and its relationship with the primary tumor genotype.
infertility must be considered a low risk.
Objectives
DOI: 10.1530/endoabs.49.OC14.1
To evaluate the frequency of TERT promoter (TERTp), BRAF and NRAS
mutations in metastatic thyroid carcinomas, analyzing primary thyroid tumors,
lymph node metastases (LNM) and distant metastases.
Material and Methods
Mutation analysis was performed in 437 tissue samples from 204 patients, mainly
with papillary thyroid carcinomas (PTC) (nZ180), including 196 LNM and 56
distant metastases. All the distant metastases included corresponded to radio-
iodine-refractory metastatic tissue.
Results
We found the following mutation frequency in primary thyroid tumors, LNM and
OC14.2
distant metastases, respectively: TERTp- 15.9, 10.8, and 52.4%; BRAF (PTC-
Suppression of heme oxygenase-1 inhibits growth and invasion of
only)- 44.6, 41.7, and 23.8%; NRAS- 1.7, 1.3, and 11.9%. In the subgroup of
thyroid cancer
patients with PTC, the TERTp mutation frequency in primary tumors, LNM and
Shih-Ping Cheng1,2, Jie-Jen Lee1,2, Ming-Jen Chen1,2, Chien-Liang Liu1,2,
distant metastases was
12.9,
10.5, and
52.4%, respectively. There was a
Po-Sheng Yang1,2 & Yi-Chiung Hsu3
significant concordance between the primary tumor genotype and the
1MacKay Memorial Hospital, Taipei, Taiwan;2Mackay Medical College,
corresponding LNM, in particular for BRAF-mutated PTC. The overall
Taipei, Taiwan;3National Central University, Taoyuan City, Taiwan.
concordance between primary tumors and respective distant metastases was
low. In the group of patients with PTC, we found a high frequency of TERTp
mutations and a low frequency of BRAF mutations in distant metastases, in
comparison to the paired primary tumors.
Oxidative stress generated in the process of iodide metabolism and thyroid
Conclusions
hormone synthesis may play a role in thyroid tumorigenesis and progression
The frequency of BRAF, NRAS and TERTp mutations is similar in primary
of thyroid cancer. The transcription factor Nrf2
is the most important
tumors and matched LNM, whereas distant metastases show an enrichment in
regulator of antioxidant responses. It has been shown that Nrf2 expression is
TERTp mutations and a decrease in BRAF mutations. TERTp mutations seem to
upregulated in papillary thyroid cancer. In response to oxidative stress,
play an important role in distant metastases.
nuclear Nrf2 activates antioxidant-responsive elements and induces the
expression of stress-responsive genes, including heme oxygenase-1 (HO-1).
DOI: 10.1530/endoabs.49.OC14.3
Previously we have demonstrated that HO-1 overexpression was associated
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
OC14.4
OC14.5
Inverse relation between thyroid cancer incidence and threshold for
Dose aggressive variants of papillary thyroid carcinoma have worse
thyroid surgery: a national population-based retrospective study
clinical outcome than classical papillary carcinoma?
Brigitte Decallonne1, Van den Bruel Annick3, Elaut Nathalie1 &
Eyun Song1, Min Ji Jeon1, Hyemi Kwon1, Suyeon Park1, Hye-Seon Oh1,
De Schutter Harlinde2
Jin-Sook Ryu1, Dong Eun Song1, Eui Young Kim2, Tae Yong Kim1,
1KU Leuven, Leuven, Belgium;2Belgian Cancer Registry, Brussels,
Young Kee Shong1, Won Bae Kim1 & Won Gu Kim1
Belgium;3General Hospital Sint Jan, Bruges, Belgium.
1Asan Medical Center, Seoul, Republic of Korea;2Dongnam Institute of
Radiological & Medical Sciences Cancer Center, Busan, Republic of Korea.
Background
Background
In Belgium, lower thyroid cancer incidence - most pronounced for microcancers
Unlike excellent prognosis of classical papillary thyroid carcinoma (cPTC),
(T1a) - is present in the North compared to the South. This variation is paralleled
certain pathological subtypes of aggressive variants of PTC
(AV-PTC) are
by differences in clinical practice: in the North less thyroid surgery is performed,
considered to have poor clinical outcome. However, the evidence of unfavorable
more surgery is preceded by fine needle aspiration (FNA), and more patients with
outcome of AV-PTC is not clear because previous studies did not control other
a final cancer diagnosis (2004-2006) underwent a presurgical FNA or a lymph
confounding factors contributed to clinical outcomes.
node dissection (LND) at fist surgery.
Methods
Aim
This retrospective cohort study initially included 4339 patients with cPTC and
To study 1/ the evolution in the use of FNA and LND, and 2/ the weight of T1a
121 patients with AV-PTC including tall cell, columnar, hobnail, solid and diffuse
non-thyrotoxic thyroid glands in a recent thyroid cancer cohort.
sclerosing variants. Dynamic risk stratification
(DRS) and recurrence free
Methodology
survival
(RFS) between the two groups were compared after two-to-one
Population-based retrospective study, using data from the Belgian Cancer
individual risk factor matching by age, sex, tumor size, and initial surgical extent.
Registry
(including case-by-case study of pathology protocols) and Belgian
Outcome
Healthcare Insurance database for differentiated thyroid cancer (DTC) cases
AV-PTC was associated with larger tumor size (P!0.001) and higher rates of
diagnosed between 2009 and 2011 (nZ2659).
cervical lymph node (LN) metastasis (P!0.001) compared to cPTC. A total of
Results
121 patients with AV-PTC and 242 patients with cPTC were evaluated after
Linkage of both databases resulted in 2557 DTC cases (96%). In the North a
individual risk factor matching. There were no significant differences in the tumor
higher proportion of DTC cases underwent FNA before surgery: 62.3%[95%CI
size and cervical LN metastasis between the two groups after mating. When we
58.3;66.3] compared to 33.6%[95%CI 29.3;39.9] in the South (P!0.0001),
compared the proportion of patients according to the DRS, there was no
confirming geographical differences. A positive trend for FNA was observed in
significant difference between patients with cPTC and those with AV-PTC
the period 2004-2012, at national and regional level, especially in the South. The
(PZ0.14). There was also no significant difference in RFS (hazard ratio [HR]
execution of LND during first thyroid surgery was proportionally higher in the
1.93, 95% confidence interval [CI] 0.68-5.47, PZ0.23) between the two groups.
North
(24.3%[95%CI
20.6;28.0]) compared to the South
(15.3%[95%CI
In subgroup analysis including patients with tall cell, columnar, and hobnail
12.0;18.7], P!0.0001), without temporal trend. Finally, in the subgroup of T1a
variants of PTC, there were no significant differences in DRS (PZ0.68) and RFS
DTC cases - considered to be mainly incidental findings - the mean thyroid
(HR 2.04, 95% CI 0.56-7.41, PZ0.29) compared with matched patients with
weight was 57.7G52.1 g in the North, compared to 37.99G29.1 g in the South
cPTC.
(P!0.0001).
Conclusion
Conclusion
The clinical outcome of patients with AV-PTC was not different with those with
In the present cohort, more FNA precedes thyroid cancer diagnosis, according
cPTC when their other clinicopathological risk factors were similar. Therapeutic
to international guidelines. However, geographical differences clearly persist.
and follow-up strategies for PTC might not need to be modified according to
A lower thyroid weight is present in DTC T1a in the South. These findings
presence of AV-PTCs.
support the alignment of a higher thyroid cancer incidence with a lower threshold
DOI: 10.1530/endoabs.49.OC14.5
for thyroid surgery in case of nodular disease, strongly suggesting overdiagnosis.
DOI: 10.1530/endoabs.49.OC14.4
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Guided Posters
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Adrenal 1
these mutations in regulating aldosterone biosynthesis has been clearly
established, the mechanisms involved in proliferation and APA formation still
GP1
remain to be elucidated. The aim of our study was to identify pathways involved
PRKACA mutations in adrenal Cushing can alter substrate specificity
in adrenal cortex nodulation and APA formation.
Kerstin Bathon1,2, Isabel Weigand3, Jens T Vanselow4, Cristina L Ronchi3,5,
Transcriptomic analysis from 123 APA and 11 control adrenal and correlations of
Guido Di Dalmazi6,7, Felix Beuschlein6, Silviu Sbiera3, Andreas Schlosser4,
gene expression with genetic, morphological and functional characteristics of the
Martin Fassnacht3,5 & Davide Calebiro1,2
tumors allowed us to identify retinoic acid receptor (RAR) signalling as a central
1Institute of Pharmacology and Toxicology, University of Wurzburg,
molecular network involved in APA formation independently of the mutation status.
Wurzburg, Germany;2Bioimaging Center, University of Wurzburg,
Treatment of H295R cells with all-trans retinoic acid and 9-cis retinoic acid
Wurzburg, Germany;3Division of Endocrinology and Diabetes, Department
reduced cell viability in a time and dose dependent manner. This effect was due to
of Internal Medicine I, University Hospital, Wurzburg, Germany;4Rudolf
decreased cell proliferation and increased cell apoptosis. In contrast to the effects
Virchow Center, University of Wurzburg, Wurzburg, Germany;5Compre-
observed in vitro, 9-cis retinoic acid did not modify tumor progression in a mouse
hensive Cancer Center Mainfranken, University of Wurzburg, Wurzburg,
xenograft model.
Germany;6Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians
Investigation of the adrenal phenotype of raraK/K mice demonstrated that in
University, Munchen, Germany;7Division of Endocrinology, Department of
young (12 weeks) and old (52 weeks) raraK/K mice the characteristic cellular
Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
arrangement of the adrenal cortex was replaced by an enlarged zona glomerulosa
and a disorganized zona fasciculata. This is also associated to dilatation and
disorganisation of vessels and increased capsule thickness. Furthermore, young
Previously, we identified seven mutations in the main catalytic subunit of protein
raraK/K mice displayed lower plasma aldosterone concentration and decreased
kinase A
(PKA Ca) to be responsible for cortisol-secreting adrenocortical
expression of steroidogenic enzymes. Interestingly, this was associated with the
adenomas
(CPAs): L206R, L199_C200_insW, S213R_L212_K214insIILR,
inhibition of WNT/b-catenin pathway.
C200_GlyinsV, W197R, del244-248CE249Q, E32V. Here we performed a
Our results suggest that RAR signaling contributes to normal adrenal morphology
functional characterization of these mutants. Specifically, we evaluated the
and functional zonation through modulation of WNT/b-catenin pathway and that
association between PKA regulatory and catalytic subunits using co-immuno-
its disruption could contribute to abnormal cell proliferation in the adrenal cortex,
precipitation and PKA activity using a kemptide assay and a western blot analysis.
creating a propitious environment for the emergence of specific driver mutations in
Our results show that four mutations
(L206R, L199_C200_insW, W197R,
APA.
del244-248CE249Q) cause increased basal PKA activity. Interestingly, the
measured activity varied considerably among mutants depending on the assay
DOI: 10.1530/endoabs.49.GP2
used, suggesting changes in substrate specificity. Binding to RIa and RIIb
subunits was lost for three and two mutants respectively. One mutant (E32V)
showed no differences with the wild type. The S213R_L212_K214insIILR
mutant was associated with a loss of PKA activity, but showed a strong
accumulation in the nucleus. The C200_G201insV mutant was associated with a
GP3
loss of activity in the kemptide assay but showed normal behavior in the western
blot and nuclear translocation. For all mutants we performed an in silico analysis
Exosomal hsa-miR-483-5p and hsa-miR-101 are potential minimally
to predict the effect of the mutation on substrate specificity. The analysis
invasive biomarkers of adrenocortical carcinoma
suggested changes in substrate specificity for five mutants. Based on this, we
Pal Perge1, Henriett Butz2, Raffaele Pezzani3, Irina Bancos4, Zoltan Nagy1,
performed phosphoproteomic experiments, which directly compare the phos-
Abel Decmann1, Michaela Luconi5, Massimo Mannelli5, Edit Iren Buzas6,
phorylation of a large number of PKA substrates. The results directly
Miklos Toth1, Marco Boscaro3, Attila Patocs2,7 & Peter Igaz1
demonstrated altered substrate specificity for three mutants (L206R, del244-
12nd Department of Medicine, Semmelweis University, Budapest, Hungary;
248CE249Q, C200_G201insV). Taken together, these findings suggest that the
2Molecular Medicine Research Group, Hungarian Academy of Sciences and
PKA Ca mutations found in CPAs alter substrate specificity and that interference
Semmelweis University, Budapest, Hungary;3Endocrinology Unit,
with the formation of a stable PKA holoenzyme is probably just one of the
Department of Medicine, University of Padua, Padova, Italy;4Division of
mechanisms through which these mutations affect PKA signaling, ultimately
Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal
leading to increased cortisol production and cell proliferation. The results of the
Medicine, Mayo Clinic, Rochester, MN, USA;5Department of Experi-
phosphoproteomics analysis might lead to the identification of new PKA targets
mental and Clinical Biomedical Sciences, Endocrinology Unit, University
involved in the pathogenesis of CPAs.
of Florence, Florence, Italy;6Department of Genetics, Cell- and
Immunobiology, Semmelweis University, Budapest, Hungary;
DOI: 10.1530/endoabs.49.GP1
7‘Lendulet-2013’ Research Group, Hungarian Academy of Sciences and
Semmelweis University, Budapest, Hungary.
Background
Extracellular vesicles
(exosomes, microvesicles) shed from tumor cells
GP2
containing microRNAs can be exploited as markers of malignancy. The
Contribution of retinoic acid receptor signalling to adrenal cortex
preoperative diagnosis of adrenocortical malignancy is difficult and microRNAs
morphology and functional zonation through modulation of
have proved useful in the diagnosis of many tumors, including adrenocortical
WNT/b-catenin pathway
cancer (ACC), but there have no studies to date on extracellular vesicle associated
Rami El Zein1, Amanda J Rickard1, Golib Dzib Jose Felipe2,
microRNAs in ACC.
Benoit Samson-Couterie1, Angélique Rocha1, Marko Poglitsch3, Celso
Aim
E Gomez-Sanchez4, Laurence Amar1,5, Fabio Luiz Fernandes-Rosa1,6,
To evaluate the diagnostic potential of extracellular vesicle-associated
Norbert B Ghyselinck7, Arndt Benecke2, Enzo Lalli8,9,
(exosomal) microRNAs in human adrenocortical tumors.
Maria-Christina Zennaro1,6 & Sheerazed Boulkroun1
Methods
1INSERM, UMRS_970, Paris Cardiovascular Research Center and
The isolation of extracellular vesicles (EV) was performed either by differential
Université Paris Descartes, Sorbonne Paris Cité, Paris, France;2Centre
centrifugation/ultracentrifugation or by applying Total Exosome Isolation Kit.
National de la Recherche Scientifique (CNRS), Institut des Hautes Etudes
EV preparations were also assessed by transmission electron microscopy and flow
Scientifiques, Bures sur Yvette, France;3Attoquant Diagnostics GmbH,
cytometry. 6 adrenocortical adenomas (ACA) and 6 histologically verified ACC
Vienna, Austria;4Division of Endocrinology, G.V. (Sonny) Montgomery
samples were profiled by Taqman Human Microarray A-cards in the discovery
VA Medical Center and University of Mississippi Medical Center, Jackson,
cohort. The significantly differentially expressed microRNAs were validated in
MS 39216, USA;5Assistance Publique-Hôpitaux de Paris, Hôpital
13 ACAs and 12 ACCs by targeted quantitative real-time PCR.
Européen Georges Pompidou, Unité d’hypertension, Paris, France;
Results
6Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges
Significant overexpression of EV-associated hsa-miR-101 and hsa-miR-483-5p
Pompidou, Service de Génétique, Paris, France;7Institut de Génétique et de
was measured in ACC vs ACA samples in the microRNA profiling. We could
Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104-INSERM
confirm the overexpression of these microRNAs in the validation cohort, too.
U964, Department of Functional Genomics and Cancer, Illkirch, France;
dCThsa-miR-483-5p normalized to cel-mir-39 showed the highest area under
8Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de
curve (AUC) value (0.96), with 91.67 sensitivity and 92.33 specificity.
Recherche 7275, CNRS, Valbonne, France;9Université de Nice-Sophia
Conclusions
Antipolis, Valbonne, France.
Extracellular vesicle-associated
(exosomal) hsa-miR-483-5p might be a
promising minimally invasive biomarker in the preoperative diagnosis of ACC.
Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1 and ATP2B3 have
DOI: 10.1530/endoabs.49.GP3
been identified in aldosterone producing adenoma (APA). Although the role of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP4
NCI-H295R cells co-transfected with RIIb and Ca-WT or different Ca mutants,
only the L206R mutation led to a full degradation of RIIb and this degradation
Androgen receptor signalling is essential for regression
could not be abolished by proteasome and lysosome inhibition but, surprisingly, by
of the adrenal x-zone and regulation of the adrenal cortex
stimulating PKA signaling. Same co-transfections with RIa did not lead to its
in the male mouse
degradation. By performing RIIb co-IP experiments in the presence of Ca-WT or
Anne-Louise Gannon, Laura O’Hara, Rod Mitchell, Ian Mason & Lee Smith
Ca-L206R, followed by nanoLC-MS/MS analysis, we could identify possible
University of Edinburgh, Edinburgh, UK.
novel RIIb interaction partners mediating RIIb stability in NCI-H295R cells. In
conclusion, our data demonstrate that mutations in PKA Ca lead to post-
Introduction
transcriptional downregulation of the main regulatory subunit in CPA. In NCI-
Androgens have long been known to play an important role in health and wellbeing.
H295R cells, transfection with the L206R mutant led to full degradation of RIIb,
A range of clinical disorders in males and females can arise due to disruption to
which could not be rescued by different degradation mechanisms, suggesting
production and action of androgens. Androgen receptor (AR) is widely expressed
another mechanism that can be abrogated by stimulating PKA signaling.
throughout the adrenal cortex, yet the wider role for androgen signalling in the
LC-MS/MS revealed putative RIIb interaction partners affecting its stability in
adrenal remains underexplored due to the lack of suitable animal models.
the presence of Ca L206R only after stimulation of PKA signaling.
Methods
DOI: 10.1530/endoabs.49.GP5
An adrenal-specific androgen receptor knockout mouse model was created by
targeting GFP-Cre-GC to the mouse Cyp11a1 locus to drive Cre Recombinase
expression in steroidogenic cells. Males were then mated to C57BL/6 female
homozygous ARfl/fl mice. C57BL/6 mice were also used to investigate normal
adrenal function. Tissue was analysed through qRT-PCR and statistical analysis by
one way ANOVA. Immunohistochemistry was used to determine changes in
protein localisation.
Results
Results highlight that androgens signalling through AR is essential for the
regression of the foetal ‘X-zone’ during puberty in male mice. Loss of androgens
(through castration) or AR results in significant morphological differences in the
adrenal cortex and X-Zone cells. However, interestingly, loss of androgens or AR
impact cortex structure, gene expression and protein localisation differently.
Conclusions
We show that androgen signalling through AR is essential for removal of X-zone
GP6
cells during puberty. We also demonstrate that androgens can act independently of
AR to modulate cortex function. Additionally, the loss of androgen signalling
Involvement of ARMC5 in proliferation and cell cycle control
results in a decrease in apoptotic cells, suggesting the adrenal has become more
of human cell cultures from adrenal nodules of primary
resistant to cell death. Improper removal of cortical cells and loss of apoptosis could
macronodular adrenocortical hyperplasia (PMAH)
have serious implications for adrenal function and disease progression. The impacts
Isadora Cavalcante1, Mirian Nishi2, Maria Claudia Zerbini4,
of this are undergoing further investigation.
José Luiz Chambo3, Madson Almeida2,5, Claudimara Lotfi1 &
2,5
DOI: 10.1530/endoabs.49.GP4
Maria Candida Fragoso
1Institute of Biomedical Sciences, São Paulo, Brazil;2Laboratory de
Medical Investigation LIM 42, São Paulo, Brazil;3Department of Urology,
São Paulo, Brazil;4Department of Pathology, São Paulo, Brazil;
5
Adrenal Unit, São Paulo, Brazil.
Background
The mechanisms causing hypercortisolism in primary macronodular adrenocor-
tical hyperplasia (PMAH) are not fully clarified. The participation of ectopic
receptors and autocrine/paracrine regulation of intra-adrenal ACTH in
hyperplastic tissue have been considered. Additionally, germline ARMC5
mutations have been described as main cause of PMAH. So far, the functional
study that analyzed the role of ARMC5 used the adrenocortical carcinoma cell
GP5
line, H295R. Therefore, we propose a more suitable model in cell cultures
Protein Kinase A signaling saves regulatory subunit IIb from PRKACA
obtained from nodules of PMAH.
mutation-mediated degradation
Aim
Isabel Weigand1, Kerstin Bathon2, Cristina Ronchi1, Marthe Rizk-Rabin3,
To investigate the role of ARMC5 related to PMAH.
Guido Di Dalmazi4, Vanessa Wild5, Beatrice Rubin6, Jens T Vanselow7,
Methods
Andreas Schlosser7, Davide Calebiro2, Felix Beuschlein4,
Cell cultures obtained from nodules of 13 unrelated patients with PMAH ARMC5
Jérôme Bertherat3, Martin Fassnacht1 & Silviu Sbiera1
mutated or not were analyzed for: i) Morphological and functional character-
1Division of Endocrinology and Diabetes, University Hospital Wuerzburg,
ization; ii) ARMC5 sequencing; iii) ARMC5 silencing through shRNA in non-
Wuerzburg, Germany;2Institute of Pharmacology and Toxicology,
mutated PMAH cells for steroidogenic and proliferative functional studies;
Bioimaging Centre, University of Wuerzburg, Wuerzburg, Germany;
iv) ARMC5 overexpression through transient transfection in mutated PMAH cells
3Institut Cochin, Department of Endocrinology, Hôpital Cochin, Paris,
and viability analyses.
France;4Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians
Results
University, Munich, Germany;5Institute of Pathology, University of
i) The cell cultures demonstrating presence of steroidogenic cells, ectopic/aber-
Wuerzburg, Wuerzburg, Germany;6Department of Medicine, University of
rant receptors and functional intra-adrenal ACTH. ii) ARMC5 mutations were
Padua, Padua, Italy;7Rudolf Virchow Center for Experimental Biomedi-
located mostly in exons 1, 2 and 3, responsible for protein-protein interactions of
cine, University of Wuerzburg, Wuerzburg, Germany.
ARM repeat family; ARMC5 germline mutations identified in seven samples were
associated or not to somatic mutations or LOH. In six samples, ARMC5 mutation
Protein Kinase A (PKA) consists of two catalytic and two regulatory subunits with
was not identified; iii) ARMC5 silencing in non-mutated PMAH cell cultures
several isoforms
(Ca,b,g, RIa,IIa,Ib,IIb). In
30-40% of cortisol-producing
decreased StAR, CYP17A1, CYP11A1, NR5A1 and MC2R, increased CCNE1
adrenocortical adenomas (CPA) heterozygous activating somatic mutations in the
mRNA expression and its proliferative capacity, but without interference in cell
catalytic subunit a (Ca) of PKA have been found. Previous reports found strikingly
viability. iv) ARMC5 overexpression induced apoptosis and necrosis after 8h in
reduced levels of RIIb in CPA compared to other adrenocortical tumors. Here, we
PMAH mutated cell cultures, decreasing cell viability.
investigated the correlation between Ca mutational status, RIIb expression levels
Conclusions
and the underlying regulation mechanisms in CPA and the adrenal cell line NCI-
We confirm the role of ARMC5 as a pro-apoptotic protein and its importance in
H295R. RIIb expression was strongly reduced in Ca-mutated CPAs, especially in
the steroidogenesis related to PMAH, as previously described in H295R cells. We
tumors harboring the frequent L206R mutation (34 Ca-WT and 23 Ca-mutated
also report for the first time the involvement of ARMC5 in proliferation control
CPA) by both immunohistochemistry (mean expression: 1.5G0.7 vs 0.4G0.5,
and cell cycle regulation of PMAH cell cultures, which needs to be further
P!0.05) and WB. Similar results were observed for RIa (1.8G0.9 vs 2.6G0.6,
explored.
P!0.05) but not for the other regulatory subunits. Notably, mRNA expression of
DOI: 10.1530/endoabs.49.GP6
all subunits was unchanged in Ca-WT compared to Ca-mutated CPA. In
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP7
cut-off value for miR483-5p (0.221 ng/ml) significantly predicted overall and
recurrence-free survival. miR483-5p was the only variable that significantly
Identification of a new glucocorticoid receptor mutation underscores
predicts recurrence, but not overall survival, in a multivariate Cox analysis (HR
the substantial prevalence of genetic NR3C1 alterations in adrenal
16.2, 95%CV[1.39-188.6, P!0.026]). In addition, miR483 and 483-5p levels
hyperplasia: the French National Research Program MUTA-GR
significantly correlated with the number of circulating tumor cells in the same
Géraldine Vitellius1, Brigitte Delemer2, Philippe Caron3, Antoine Bennet3,
blood samples, independently of the timing of sampling. Analysis of an
Jerome Bouligand1,4, Anne Guiochon-Mantel1, Say Viengchareun1,
independent cohort of metastatic ACC (nZ21) revealed that miR483 negatively
Christian Dani6, Severine Trabado1,4 & Marc Lombes1,5
correlated with mitotane levels.
1Inserm UMR S 1185, Kremlin Bicetre, France;2Service d’Endocrinologie,
In conclusion, we demonstrated that miR483 and miR483-5p absolute plasma
Hopital Robert Debré, CHU de Reims, REIMS, France;3Service
levels in ACC patients are powerful molecular markers that may help to follow
d’endocrinologie, maladies métabolique et nutrition,CHU Larrey,
patients after surgery and chemotherapy, and contribute to better classify and
TOULOUSE, France;4Service de Génétique moléculaire,
predict tumor evolution.
pharmacogénétique et hormonologie, KREMLIN BICETRE, France;
5Service d’Endocrinologie et des Maladies de la Reproduction, KREMLIN
DOI: 10.1530/endoabs.49.GP8
BICETRE, France;6Université Côte d’Azur, CNRS, Inserm, iBV, NICE,
France.
Primary generalized glucocorticoid resistance is characterized by glucocorticoid
excess without any Cushing syndrome. Patients exhibit variable clinical
presentation including arterial hypertension, hirsutism or adrenal hyperplasia.
Although glucocorticoid resistance has been associated with glucocorticoid
GP9
receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been
Mortality is increased in patients with Cushing’s disease in long-term
reported so far. We have conducted a French National Research Program, referred
remission: A nation-wide study
to as MUTA-GR that aims at determining the prevalence of NR3C1 genetic
Dimitrios Chantzichristos1, Eleni Papakokkinou1, Per Dahlqvist2,
alterations in patients with adrenal masses associating by glucocorticoid
Elin Segerstedt2, Tommy Olsson2, Katarina Berinder3, Charlotte Hoybye3,
resistance. In this context, we have recently identified a novel GR stop mutation
Sophie Bensing3, Britt Edén Engstrom4, Pia Burman5, Cecilia Folin6,
in a 43-year-old man presenting with glucocorticoid resistance, bilateral adrenal
Eva Marie Erfurth6, Jeanette Wahlberg7, Bertil Ekman7, Erik Schwarcz8,
hyperplasia and biological hypercortisolism (1.5 to 3-fold increased in 24 h
Ing-Liss Bryngelsson9, Eva Andersson10, Gudmundur Johannsson1,
urinary free cortisol, negative response to dexamethasone suppression test and
Daniel S Olsson1 & Oskar Ragnarsson1
normal plasma ACTH concentrations). Alteration of GR signaling is currently
1Institute of Medicine at Sahlgrenska Academy, University of Gothenburg
validated by transient transfection assays, binding studies, subcellular trafficking,
and the Department of Endocrinology, Sahlgrenska University Hospital,
Chromatin Imunoprecipitation experiments, stability investigation, three-dimen-
Gothenburg, Sweden;2Department of Medicine, Umeå University, Umeå,
sional modeling and gene expression studies.
Sweden;3Department of Molecular Medicine and Surgery, Karolinska
More than 120 patients have been enrolled and five original GR heterozygous
Institutet, and Department of Endocrinology, Metabolism and Diabetology,
mutations (two missense and three false sense including R469X, R477S, Y478C,
Karolinska University Hospital, Stockholm, Sweden;4Department of
L672P) were discovered. Each original mutation impaired a different step of GR
Medical Sciences; Endocrinology, Diabetes and Metabolism, Uppsala
intracellular signaling. Ex vivo experiments performed on patients’ fibroblasts
University Hospital, Uppsala, Sweden;5Department of Endocrinology,
demonstrated that some mutations (R469X, R477S) led to an haploinsufficiency
Skane University Hospital, Malmo, University of Lund, Malmo, Sweden;
phenotype with a decreased response in glucocorticoid-dependent target gene
6Department of Endocrinology, Skane University Hospital, Lund, Sweden;
expression (FKBP5, SGK1).
7Department of Endocrinology and Department of Medical and Health
Interestingly, all mutated patients present with metabolic disorders (high BMI,
Sciences, Linkoping University, Linkoping, Sweden;8Department of
metabolic syndrome, .), supporting the essential role played by glucocorticoid
Internal Medicine, School of Health and Medical Sciences, Orebro
signaling in adipocyte physiology that we are currently exploring. Altogether, GR
University, Orebro, Sweden;9Department of Occupational and Environ-
mutations are not such an uncommon event given that 5% of our patients carried
mental Medicine, Orebro University Hospital, Orebro, Sweden;
NR3C1 alterations. Collectively, GR defects are not a rare cause of glucocorticoid
10Department of Occupational and Environmental Medicine, Institute of
resistance, an incidence initially minimized. We propose that genetic screening of
Medicine, Sahlgrenska Academy, University of Gothenburg and Sahl-
the NR3C1 gene should be conducted in patients with adrenal incidentalomas and
grenska University Hospital, Gothenburg, Sweden.
subclinical hypercorticism.
DOI: 10.1530/endoabs.49.GP7
Background
It is still undetermined whether patients with Cushing’s disease (CD) in remission
have an increased mortality. Most previous studies are limited by small numbers
of patients and/or short follow-up time.
Objective
To study mortality in a nation-wide cohort of patients with CD during long-term
follow-up.
GP8
Methods
Clinical and translational relevance of circulating miR483 in
Patients with ICD codes for Cushing’s syndrome and/or CD, between 1987 and
adrenocortical cancer
2013, were identified in the Swedish National Patient Registry. Medical records
Letizia Canu1, Francesca Salvianti1, Giada Poli1, Roberta Armignacco1,
of the patients were reviewed (clinical, biochemical, imaging and histopatholo-
Giulia Cantini1, Alessandra Di Franco1, Stefania Gelmini1,
gical data) to verify the diagnosis, and to determine remission status. All other
Tonino Ercolino1, Massimo Terzolo2, Gabriella Nesi1, Pamela Pinzani1,
forms of Cushing’s syndrome than CD were excluded from the study.
Massimo Mannelli1 & Michaela Luconi1
Standardized mortality ratios
(SMRs) with 95% confidence intervals were
1University of Florence, Florence, Italy;2University of Turin, San Luigi
calculated using the Swedish general population as reference.
Gonzaga Hospital, Orbassano, Turin, Italy.
Results
Out of 1252 identified patients, 502 (387 women (77%)) had a confirmed CD
Adrenocortical cancer
(ACC) is a rare aggressive malignancy, with poor
diagnosis. Of these, 411 (82%) were in biochemical remission. The meanGS.D. age
prognosis when metastaic at diagnosis. Recent ACC pan-genomics analysis
at diagnosis was 46G16 years. The median (interquartile range) follow-up time was
contributed to redefine the risk groups on molecular bases, including tumor micro
13
(6-23) years, resulting in 7165 patient-years of follow-up. Of the 502 patients, 364
RNA (miR), which can be detectable not only in the primary lesion but also in the
(73%) had been treated with pituitary surgery, 129 (26%) with radiotherapy and 102
bloodstream.
(20%) with bilateral adrenalectomy. The observed number of deaths was 133 vs 54
We develop a quantitative real-time assay for the measurement of absolute levels
expected, resulting in an overall SMR of 2.46 (95% CI 2.06-2.91). SMR in patients
in plasma samples of miR483 and its mature miR483-5p form. miR483/miR483-5p
not in remission (nZ91) was markedly increased, SMR 8.23 (95% CI 5.42-12.0).
levels were evaluated in plasma samples of 27 patients with ACC before surgery
Mortality in patients in biochemical remission was lower (P!0.0001), but increased
and at follow up, and in an independent validation cohort of 21 metastatic ACC.
compared to the general population, SMR 1.80 (95% CI 1.44-2.23).
Statistically significant difference in miR483-5p and miR483 levels of pre-surgery
Conclusion
and post-surgery samples was found between low (stage 1/2) and high (stage 3/4)
This large nation-wide study demonstrates that patients with CD have an excess mortality,
risk groups. Moreover the mean levels of both miRs were significantly higher in
irrespective of remission status. The findings emphasize the importance of curative
plasma of patients belonging to the high stage risk group compared to subjects with
treatment as well as continued active surveillance after remission has been achieved.
the benign form (ACA) and healthy subjects. ROC curves analysis of miR483-5p
DOI: 10.1530/endoabs.49.GP9
levels resulted in predicting the risk stage (accuracy 0.917G0.084). The best ROC
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP10
higher in patients with SAI than PAI. Most patients were treated with conventional
hydrocortisone, with similar mean doses administered in Germany, the Nether-
Expression of GATA transcription factors and their role in the aetiology
lands, Sweden and the UK (PAI: 24.7G8.4 mg/day, 22.2G5.7 mg/day, 21.5G
of Testicular Adrenal Rest Tumours
10.0 mg/day,
21.0G9.3 mg/day; SAI:
20.0G6.4 mg/day,
20.8G6.1 mg/day,
Manon Engels1,2, Paul Span3, Monica Marijnissen-van Zanten4, Teun van
21.6G9.4 mg/day, 18.9G5.2 mg/day). Cortisone acetate was most commonly
Herwaarden2, Christina Hulsbergen-van de Kaa4, Rod Mitchell6,
used in the Netherlands (PAI, 23%; SAI, 27%). No difference was observed in
Lee Smith6, Nike Stikkelbroeck5, Fred Sweep2 &
fludrocortisone dosing in patients with PAI between countries (0.1G0.07 mg/day,
Hedi Claahsen-van der Grinten1
0.1G0.04 mg/day,
0.1G0.05 mg/day,
0.1G0.12 mg/day). Patients with PAI
1Department of Pediatrics, Radboud University Medical Center, Nijmegen,
treated with dual-release hydrocortisone (DRHC) were treated with lower doses
The Netherlands;2Department of Laboratory Medicine, Radboud
in Germany 21.3G2.3 compared with those in Sweden 28.0G6.0 mg/day.
University Medical Center, Nijmegen, The Netherlands;3Department of
Conclusions
Radiation Oncology, Radboud University Medical Center, Nijmegen, The
The maintenance doses of hydrocortisone observed in this study are in line with
Netherlands;4Department of Pathology, Radboud University Medical
international guidelines in all four countries. The country difference in maintenance
Center, Nijmegen, The Netherlands;5Department of Internal Medicine,
doses in DRHC is consistent with data showing that mean daily doses of
Radboud University Medical Center, Nijmegen, The Netherlands;6Medical
hydrocortisone tend to be higher in Sweden than in other countries.
Research Council Centre for Reproductive Health, University of Edinburgh,
Edinburgh, UK.
DOI: 10.1530/endoabs.49.GP11
Background
Recently, GATA transcription factors have been linked to the development of
Testicular Adrenal Rest Tumours (TART), benign adrenal-like testicular tumours
that frequently occur in male patients with congenital adrenal hyperplasia (CAH).
The objective of this study is to determine GATA expression in TART and other
steroidogenic tissues, examining their discriminative potential and their possible
role in the aetiology of TART.
Methods
GATA1-6 expression was determined in TART, Leydig cell tumour (LCT), adult testis,
adult adrenal, foetal testis, and foetal adrenal tissues. In addition, GATA expression was
measured in Hs181.tes cells after induction with dibutyryl cAMP (dbcAMP).
Results
GP12
In TART, testis-like GATA4 gene expression, but higher compared to adult adrenal,
Activation of the cAMP/PKA transduction system triggers
was found. In contrast, GATA3 and GATA6 expression in TART is similar to adrenal,
abnormal expression of the serotonin signaling pathway in human
but higher compared to adult testis or LCT. GATA3 and GATA6 could discriminate
adrenocortical cells
between TART and testis (AUC of 0.982 and 0.920, respectively). ACTH is a
Julie Le Mestre1, Céline Duparc1, Zakariae Bram1, Yves Reznik2,
potential stimulator of TART differentiation in CAH. Stimulation of the Hs181.tes cell
Jérôme Bertherat3, Philippe Touraine4, Jacques Young5, Olivier Chabre6,
line with 0.1 mM dbcAMP for 4 hours increased gene expression of both GATA3 and
Constantine A. Stratakis7, Hervé Lefebvre1,8 & Estelle Louiset1
GATA6.
Conclusion
1Normandie University, UNIROUEN, INSERM, U1239, Rouen, France;
Gene expression of GATA transcription factors in TART shows both testicular and
2Department of Endocrinology-Diabetology, Caen University Hospital,
adrenal characteristics. Additionally, GATA3 and GATA6 mRNA levels can help
Caen, France;3Department of Endocrinology and Metabolic Diseases,
discriminate TART from LCT. Furthermore, we found that dbcAMP can induce
Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Paris, France;
GATA3 and GATA6 gene expression, which might indicate that ACTH can stimulate
4Department of Endocrinology and Reproductive Medicine, Assistance
testis cells to become more adrenal like and eventually TART cells. To confirm this,
Publique-Hôpitaux de Paris, Hôpital Pitié Salpêtrière, Paris, France;
we are pending on the results of stimulation experiments with dbcAMP or ACTH in
5Department of Endocrinology, Assistance Publique-Hôpitaux de Paris,
ACTH-responsive H295RA cells.
Hôpital Bicêtre, Kremlin-Bicêtre, France;6Department of Endocrinology,
CHU de Grenoble, Grenoble, France;7Section of Endocrinology and
DOI: 10.1530/endoabs.49.GP10
Genetics, PDEGEN, NICHD, Bethesda, Maryland, USA;8Department of
Endocrinology, Rouen University Hospital, Rouen, France.
In human adrenals, serotonin (5-HT), released by subcapsular mast cells,
increases aldosterone secretion through activation of type
4 serotonin
Adrenal 2
receptors (5-HT4R) but only exerts a modest control on cortisol production.
Interestingly, illicit synthesis of 5-HT in adrenocortical cells as well as
GP11
overexpression of the 5-HT4R and ectopic expression of the type 7 receptor
A country comparison of glucocorticoid replacement therapy in
(5-HT7R) have been observed in bilateral macronodular adrenal hyperplasia
patients with primary and secondary adrenal insufficiency: data from
responsible for hypercortisolism. In this study, we have investigated the
the EU-AIR
expression of the key enzyme of 5-HT synthesis tryptophan hydroxylase
Bertil Ekman1, Marcus Quinkler2, Pinggao Zhang3, Pierre Zelissen4 &
(Tph) and 5-HT4R, 5-HT6R, 5-HT7R in the adrenal samples removed from
Robert D. Murray5
patients suffering from diseases associated with activation of the
1Linkoping University, Linkoping, Sweden;2Endocrinology in Charlotten-
cAMP/PKA pathway in adrenocortical cells, such as primary pigmented
burg, Berlin, Germany;3Shire, Lexington, Kentucky, USA;4University
nodular adrenocortical disease (PPNAD), Cushing’s disease (CD), ectopic
Medical Center Utrecht, Utrecht, The Netherlands;5St James’s University
secretion of ACTH, and
21-hydroxylase deficiency
(21-OHD), in
Hospital, Leeds, UK.
comparison with normal adrenals. In PPNAD cells, we observed
upregulation of Tph together with 5-HT4R, 5-HT6R and 5-HT7R. Over-
Introduction
expression of the 5-HT signaling pathway appeared to be the consequence of
The daily maintenance dose of conventional hydrocortisone currently recommended
the activation of PKA by PRKAR1A gene mutations which cause the disease.
by international guidelines for the management of primary adrenal insufficiency
5-HT strongly stimulated cortisol production and inhibition of Tph reduced
(PAI) or secondary adrenal insufficiency (SAI) is 15K25 mg/day, in 2K3 divided
corticosteroidogenesis in cultured PPNAD cells. High expression of Tph
doses. The aim of this analysis was to investigate inter-country differences in
and 5-HTRs was also detected in adrenal tissues exposed to high plasma
glucocorticoid replacement doses in patients with PAI and SAI.
ACTH levels, including CD, 21-OHD and ectopic Cushing’s syndrome. Our
Design
results indicate that activation of the cAMP/PKA pathway in adrenocortical
EU-AIR (ClinicalTrials.gov identifier: NCT01661387) with 20 contributing centres
cells resulting either from PRKAR1A mutations or activation of the MC2R
across Germany, the Netherlands, Sweden and the UK started enrolling patients
by sustained increase in plasma ACTH levels induces an aberrant
with AI in August 2012. Baseline clinical and biochemical data from patients in the
serotonergic stimulatory loop in zona fasciculata. They also suggest that
four countries were compared. 1798 patients (626 PAI, 1172 SAI) were included in
the intraadrenal 5-HT signaling pathway may participate in the pathophy-
the current analysis of data collated until November 2016. Patients with congenital
siology of PPNAD-associated and ACTH-dependent hypercortisolisms and
adrenal hyperplasia or tertiary AI were excluded.
could represent an adaptive mechanism to increase glucocorticoid synthesis
Results
in 21-hydroxylase deficiency.
No major differences between countries were seen in disease duration, BMI, blood
DOI: 10.1530/endoabs.49.GP12
pressure or blood lipids in patients with PAI and SAI. However, BMI was generally
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP13
(aldosterone). The analytical sensitivity of this particularly novel active
PRKARIA (Carney complex gene) is a major regulator of the tight link
renin assay was 0.1 pg/ml, which was better than that of radioimmunoassay
between cell cycle phases and steroidogenesis in the adrenocortical
(2.0 pg/ml). Using Bland-Altman plots with the mass-spectrometry values,
tumor cells H295R
both bias and limits of agreement with 95% confidence interval of the
Marthe Rizk-Rabin1, Bruno Ragazzon1 & Jerôme Bertherat1,2
automated aldosterone assay were smaller than those of the radioimmuno-
1INSERM U1016, CNRS UMR8104 Paris Descartes University, Paris,
assay, indicating smaller systemic errors in the novel measurement. The
France;2Center for Rare Adrenal Diseases, Department of Endocrinology,
ratio of aldosterone-over-renin concentrations of 11.2 (ng/dl per pg/ml)
Hôpital Cochin, Paris, France.
provided
80.8% sensitivity and
94.9% specificity as a cut-off for
differentiating primary aldosteronism from essential hypertension. This
novel measurement is expected to be a clinically reliable alternative for
conventional radioimmunoassay and to provide better throughput and cost-
The cyclic AMP/PKA signalling cascade is involved in the pathogenesis of
effectiveness in diagnosis of hyperaldosteronism from larger numbers of
cortisol-secreting adrenocortical tumors
(ACT). Defects in cell cycle
hypertensive patients in clinical settings.
checkpoints play a major role in oncogenesis. The PKA regulatory subunits
DOI: 10.1530/endoabs.49.GP14
PRKARIA and PRKARIIb are involved in cell survival and steroidogenesis
in the adrenocortical carcinoma H295R cell line. We have previously shown
that their inactivation enhances the accumulation of cells in the G2 phase
and activates PKA and MAPkinases pathways.
This study investigates the correlation between the cell cycle phases and the
adrenal steroid secretion, as well as their control by PKA.
Methods
Using pharmacologic drugs, H295R cells were synchronized at specific cell cycle
check point (G1 phase), (S phase) and (G2 phase). The cell cycle distribution
(Cytometry), the expression of cyclins, PKA subunits, cell signalling pathways,
StAR and steroidogenic enzymes were analysed. The effect of PKA activation
GP15
either by the different PKA subunits, or cAMP, PKA inactivation by H89 and PKI
Integrated genomic and phenomic analysis reveals key molecular
along the cell cycle synchronization were studied.
pathways of aldosterone producing adenoma
Results
Fabio Fernandes-Rosa1,2, Sheerazed Boulkroun1, Felipe Golib Dzib3,
Cells synchronized at G2 phase increased the expression of the steroidogenic
Georgios Daniil1, Laurence Amar1,4, Bastien Rance5,
enzymes and steroid secretion. Arresting H295R in G1 phase decreased the
Benoit Samson-Couterie1, Xavier Jeunemaitre1,2, Tchao Meatchi1,6,
steroidogenic enzymes expression and cortisol secretion. PKA subunits
Arndt Benecke7,8, Tim Strom9,10 & Maria-Christina Zennaro1,2
distribution and PKA activity modulation were cell cycle dependent. PKA
1INSERM, UMRS_970, Paris Cardiovascular Research Center, Université
activation by PRKARIA inactivation counteracted specifically the decrease of
Paris Descartes, Sorbonne Paris Cité, Paris, France;2Assistance Publique-
steroidogenesis in cells arrested in G1 phase: StAR/luc reporter gene activity and
Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de
cell progression in G2
phase were stimulated. PRKARIIb inactivation and
Génétique, Paris, France;3Institut des Hautes Etudes Scientifiques, Bures
PRKACA overexpression or cAMP increased the StAR/luc reporter gene activity,
sur Yvette, France;4Assistance Publique-Hôpitaux de Paris, Hôpital
independently of the cell cycle check point arrest. The H89 and PKI differentially
Européen Georges Pompidou, Unité Hypertension artérielle, Paris, France;
reduced StAR/luc reporter gene activity, and both reversed the cell cycle in the G2
5Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges
arrested cells.
Pompidou, Département d’Informatique Hospitalière, Paris, France;
Conclusion
6Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges
Inactivation of the Carney complex gene stimulates steroidogensis in the low
Pompidou, Service d’Anatomie Pathologique, Paris, France;7Université
steroidogenic G1 phase arrested cells. This study shows a link between the cell
Pierre et Marie Curie, Paris, France;8CNRS UMR 7224, Paris, France;
cycle check points and the regulation of steroidogenesis, in which the PRKARIA
9Institute of Human Genetics, Helmholtz Zentrum Munchen, Neuherberg,
subunit is a key regulator of both cell cycle and steroidogenesis.
Germany;10Institute of Human Genetics, Technische Universitat Munchen,
DOI: 10.1530/endoabs.49.GP13
Munich, Germany.
Primary aldosteronism is the most common form of secondary hypertension.
Somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D have been
described in 50% of aldosterone producing adenomas (APA). To identify
genetic alterations in new genes, we performed whole exome sequencing in
GP14
23 patients with APA negative for recurrent mutations in known driver
genes. A low number of somatic variations were identified per patient,
Simultaneous assays of aldosterone and renin concentrations in just ten
ranging from 1 to 22. No somatic variations were identified in two patients.
minutes could change the clinical assessment for the diagnosis of
Somatic mutations in KCNJ5 and CACNA1D were identified in 12 APA.
primary aldosteronism
These mutations were not observed or were present at very low levels on
Fumitoshi Satoh1,2, Morimoto Ryo2, Yoshikiyo Ono2, Yuta Tezuka1,2,
previous Sanger sequencing, indicating tumor heterogeneity. Two patients
Kei Omata1,2, Masahiro Nezu2, Yoshitsugu Iwakura2, Yoshuhiro Igarashi2,
harbored mutations in genes involved in the Wnt/b-catenin pathway, which
Masataka Kudo2 & Sadayoshi Ito2
represents, together with the membrane ion transporter activity, the two
1Tohoku University Graduate School of Medicine - Division of Clinical
significantly overrepresented pathways in gene ontology analysis. Sequen-
Hypertension, Endocrinology and Metabolism, Sendai, Japan;2Tohoku
cing of CTNNB1 in somatic DNA from 150 subjects with APA identified
University Hospital - Division of Nephrology, Endocrinology and Vascular
additional variants in 13 subjects, including 2 APA harboring also a KCNJ5
Medicine, Sendai, Japan.
mutation. Transcriptome data obtained from 123 APA and 11 control
adrenals did not show differences on the expression levels of Wnt4, an
activator of the Wnt/b-catenin pathway, and LEF1 and Axin2, two b-catenin
Measurement of plasma aldosterone and renin concentration, or activity, is
target genes, as a function of the mutation status. Hierarchical clustering of
useful for selecting antihypertensive agents as well as detecting
transcriptional profiles at a genome-wide scale was not associated to the
hyperaldosteronism in hypertensive patients. However, it takes several
APA mutation status, supporting a model whereby all recurrent mutations
days to get results when measured by radioimmunoassay and development
converge upon activation of calcium signaling and increased aldosterone
of more rapid assays has been long expected. We have developed
production. In addition, b-catenin activation was observed by immunohis-
chemiluminescent enzyme immunoassays enabling the simultaneous
tochemical analysis in two thirds of APA independently of CTNNB1
measurement of both aldosterone and renin concentrations in ten-minutes
mutations, suggesting the involvement of additional mechanisms promoting
by a fully automated assay using antibody-immobilized magnetic particles
cell proliferation. Using transcriptome affinity-propagation-based analysis
with quick aggregation and dispersion. We performed clinical validation of
we identified 15 different clusters of APA. These clusters are not associated
diagnostic ability of this newly developed assay-based screening of 125
with demographic or clinical data, highlighting additional molecular
patients with primary aldosteronism from
97
patients with essential
pathways underlying APA development and identifying subgroups to be
hypertension. Results of this novel assay significantly correlated with the
targeted for gene discovery.
results of radioimmunoassay (aldosterone, active renin concentration and
DOI: 10.1530/endoabs.49.GP15
renin activity) and liquid chromatography-tandem mass spectrometry
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP16
test (DST). Patients who failed to suppress to %50 nmol/l after the DST were
further examined with 48 h low dose dexamethasone suppression test (LDDST)
Cardiovascular features of autonomous cortisol secretion in patients
and 24-h urinary free cortisol collection (UFC). Patients with elevated cortisol
with adrenal incidentalomas
levels according to LDDST or UFC underwent ACTH measurements and
Emilia Sbardella1, Marianna Minnetti1, Laura Rizza1, Maria Rosaria
imaging.
Di Giorgio1, Valeria Hasenmajer1, Denise D’Aluisio2, Sergio Morelli2,
Results
Andrea Lenzi1 & Andrea M Isidori1
85
(22%) patients had elevated cortisol after DST of whom 20 (5%) failed to
1Department of Experimental Medicine, Sapienza University of Rome,
suppress after LDDST and/or had elevated UFC. No significant difference in age,
Rome, Italy;2Department of Internal Medicine and Medical Specialties,
BMI, HbA1c, T-score, Total Body Fat or blood pressure were recorded between
Sapienza University of Rome, Rome, Italy.
the two groups. Among the 20 patients with biochemical CS subsequent imaging
with either pituitary MR or abdominal CT, according to suppressed (nZ10) or
Background
unsuppressed (nZ10) ACTH levels, revealed adrenal adenoma(s) in nine cases
Possible Autonomous Cortisol Secretion (pACS) is a condition found in 1-29% of
and a pituitary macroadenoma in one case.
patients with adrenal incidentalomas. The diagnosis of pACS has been variably
Conclusion
associated with an increased risk of cardiovascular events and mortality.
i) The prevalence of hypercortisolism is high in T2D, also in unselected newly
However, dedicated studies describing the morphologic and functional cardiac
diagnosed patients, ii) Hypercortisolism was not associated with a persuasive
alterations in these patients are lacking.
phenotype, iii) The clinical implications remain uncertain but continued interest is
Aim
justified, preferably in terms of randomized intervention trials.
To compare the cardiovascular features of patients with pACS to those with
DOI: 10.1530/endoabs.49.GP17
nonfunctioning (NF) adrenal masses.
Materials and methods
Fifty-eight patients with adrenal incidentaloma without the classic signs or
symptoms of overt hypercortisolism were prospectively enrolled. Anthropo-
metric, metabolic and hormonal parameters, adrenal magnetic resonance,
echocardiography B-mode ultrasound and arterial stiffness calculated with
oscillatory method were assessed in all patients. We diagnosed patient with
pACS after
1-mg overnight dexamethasone suppression test
(1 mg-DST),
confirmed by traditional 48-h Liddle tests, if post-test serum cortisol felt between
51 and 138 nmol/l.
Results
Overall 30 patients had pACS and 28 NF adrenal masses. No differences in
gender, smoke habits, hypertension, obesity and diabetes prevalence were
observed between pACS and NF patients. Mean left ventricular (LV) mass index
was increased in the pACS compared to the NF group (112.6G29.2 vs 94.8G
31 g/m2 PZ0.032). We also detected a significantly higher prevalence of LV
hypertrophy in PACS than NF group (35.7% vs 14.3% PZ0.007). Furthermore,
there was a negative correlation between the post-dexamethasone cortisol levels
GP18
and ejection fraction (rZK0.26; PZ0.041). The assessment of arterial stiffness
Effects of two mineralocorticoid receptor antagonists on the
showed a higher pulse wave velocity in pACS compared with the NF group
morphology of the adrenal cortex
(11.3G1.4 vs 10.2G0.6 m/s; PZ0.048).
Sofia S Pereira1,2, Madalena M Costa1, Ângela Moreira1, Liliana Carvalho3,
Conclusions
Mariana Monteiro1, Gavin Vinson4 & Duarte Pignatelli2,5
Autonomous Cortisol Secretion (pACS) can lead to early cardiac and vascular
1Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical
dysfunction even in apparently asymptomatic patients. These results underline the
Research) of ICBAS, University of Porto, Porto, Portugal;2IPATIMUP/I3S,
need for further studies, including second line cardiovascular assessment, to
Porto, Portugal;3Departament of Experimental Biology, Faculdade de
correctly define the management of pACS and allow early recognition of possible
Medicina, University of Porto, Porto, Portugal;4The School of Biological
complications.
and Chemical Sciences Queen Mary University of London, London, UK;
DOI: 10.1530/endoabs.49.GP16
5Department of Endocrinology, Hospital S.Joa˜o, Porto, Portugal.
Arterial hypertension usually results from the deregulation and hyperactivity
of the renin angiotensin-aldosterone system. One of the available
therapeutic approaches for its treatment is the use of mineralocorticoid
receptor (MR) antagonists, thus blocking aldosterone action.
The aim of this study was to characterize the effects of spironolactone and
eplerenone, on the morphology of the adrenal gland of spontaneously
hypertensive (SHR) and normotensive (Wistar-Kyoto) rats.
SHR (nZ18) and Wistar-Kyoto (nZ18) rats were exposed, for 1 month, to
spironolactone (100 mg/kg per day, nZ6), eplerenone (50 mg/kg per day,
GP17
nZ6) or not exposed to either drug (nZ6) and at the end of this period their
Hypercortisolism is prevalent in newly diagnosed type 2 diabetes: a
adrenal glands were collected and we evaluated the percentage of the stained
prospective study of 384 consecutive patients
area (%SA) of CyP11B1, CyP11B2, the adrenal inner zone antibody (IZAb),
Charlotte Steffensen1, Olaf M Dekkers2,3, Johanne Lyhne1, Per L Poulsen1,
a proliferation marker
(ki-67), b-catenin and finally the percentage of
Jørgen Rungby4, Henrik T Sørensen2 & Jens Otto L Jørgensen1
cellular area occupied by lipid droplets as well as the capsular width.
1Department of Endocrinology and Internal Medicine, Aarhus University
SHR Hypertensive rats presented higher area of lipid droplets in all layers of
Hospital, Aarhus, Denmark;2Department of Clinical Epidemiology, Aarhus
the adrenal cortex, an effect that was even further increased by the exposure
University Hospital, Aarhus, Denmark;3Department of Epidemiology,
to eplerenone, in the fasciculata and reticularis zones. In the normotensive
Leiden University Hospital, Leiden, The Netherlands;4Department of
rats it was only spironolactone that elicited this effect, being significant only
Clinical Pharmacology, Aarhus University, Aarhus, Denmark.
in zona reticularis. Both drugs also increased Ki-67 expression in the
hypertensive rats, but only eplerenone increased it on normotensive rats.
Background
Finally, spironolactone decreased the capsular size but only in the
Cross-sectional studies in small and selected populations indicate a relatively high
normotensive rats. No significant differences were found for the % SA of
prevalence of incipient and/or subclinical Cushing’s syndrome (CS) in patients
CyP11B1, CyP11B2, IZAb or b-catenin.
with type 2 diabetes (T2D), which could have therapeutic implications.
In conclusion, we have found that, morphologically the adrenal glands of
Aim
normotensive and SHR only differed in number of lipid droplets. Exposure
To estimate the prevalence of CS in a large, unselected cohort of recently
to the MR antagonists had significant consequences on the capsular size,
diagnosed T2D patients.
lipidic depots and on the cellular proliferation of both normotensive and
Methods
SHR adrenal glands.
A total of 384 consecutive out - patients with T2D diagnosed after 1 January 2009
DOI: 10.1530/endoabs.49.GP18
were investigated by means of an overnight dexamethasone (1 mg) suppression
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP19
for patients who had died and those alive for each AI subset. Patients with
congenital adrenal hyperplasia or tertiary AI were excluded. 1798 patients were
Plasma cortisol and aldosterone responses to insulin tolerance test and
included (626 PAI, 1172 SAI) in the current analysis.
sodium depletion in women with non classic 21-hydroxylase deficiency
Results
caused by bi-allelic CYP21A2 mutations (NC-CAH)
To November 2016, 21 deaths had occurred (7 PAI, 14 SAI). Causes of death
Peter Kamenicky1,2, Anne Blanchard3, Antonin Lamaziere4,
were cardiovascular (nZ8), infection (nZ3), unclear (nZ3), Addisonian crisis
Bruno Donadille4, Lise Duranteau1, Sylvie Salenave1, Laurence Pietri5,
(nZ1), suicide (nZ2), renal failure, drug-induced hepatitis, cachexia and brain
Marie Laure Raffin-Sanson6, Jean-Franc¸ois Gautier7, Philippe Chanson1,2,
tumour (each nZ1). Patients who died were significantly older at enrolment than
Sophie Christin Maitre4, Veronique Tardy8, Yves Le Bouc4, Sylvie
those alive (PAI, 63.4G13.4 vs 50.0G15.8 years, PZ0.0253; SAI, 64.0G16.6 vs
Brailly-Tabard1 & Jacques Young1,2
54.3G16.2 years, PZ0.0250). Interestingly, duration of AI was shorter in
1APHP Hôpital Bicêtre, Paris, France;2University Paris Sud- Reproductive
patients with PAI who died versus alive patients (6.5G5.7 vs 16.3G13.1 years,
Endocrinology, Paris, France;3APHP Hôpital Georges Pompidou, Paris,
PZ0.0035), whereas the reverse was true for SAI (20.4G13.2 vs 13.7G11.1
France;4APHP-UPMC Hôpital Saint-Antoine, Paris, France;5Hôpital Saint
years, PZ0.0257). There were no significant differences in sex, BMI, blood
Joseph, Paris, France;6APHP Hôpital Ambroise Paré, Paris, France;7APHP
pressure, triglycerides, LDL-cholesterol, cholesterol or HbA1c between the
Hôpital Lariboisière, Paris, France;8Hôpital Nord-Hôpitaux Civils de Lyon,
deceased and alive cohorts. Patients who died were generally more likely to have
Lyon, France.
hypertension
(PAI,
85.7% vs
21.8%, PZ0.0007; SAI,
71.4% vs
33.9%,
PZ0.0076) and diabetes mellitus (PAI, 57.1% vs 14.4%, PZ0.0112; SAI,
28.6% vs 11.5%, ns) at study inclusion.
NC-CAH is diagnosed in pubertal/post-pubertal women because of
Conclusions
androgen excess however, the risk of potential adrenal insufficiency is not
This is the first study providing detailed characteristics of AI patients who died.
known, and indication of systematic glucocorticoid replacement therapy is
Hypertension and diabetes, as well as infectious diseases, appear to play a major
controversial.
role in mortality.
Aim
DOI: 10.1530/endoabs.49.GP20
To evaluate cortisol and aldosterone secretions in response to challenges tests.
Design
Prospective controlled clinical study in a tertiary referral center. 20 women with
NC-CAH (serum stimulated 17-OHP O10 ng/ml/250 mg, Synacthen) compara-
tively to matched healthy women, were included if they had not receive
glucocorticoid treatment O1 year and estrogen-based oral contraception stopped
O3 months. Each participant underwent sequentially two tests separated by a 2 to
7-days: insulin tolerance gold standard test (ITT) and a sodium depletion test (oral
40 mg furosemide under low sodium diet) to stimulate both endogenous active
renin (AR) and aldosterone. Steroid levels measured by LC-MSMS.
Adrenal 3
Results
NC-CAH had lower pic plasma cortisol concentrations during ITT than healthy
GP21
women: 17.2 mg/dl (13.1-22.8) vs 21.2 mg/dl (17.1-33.5), PZ0.0002. A peak
Is diabetes mellitus associated with catecholamine-secreting tumours
plasma cortisol above 17.0 mg/dl was obtained in all controls but only in 60%
always a secondary diabetes?
NC-CAH women. NC-CAH had higher baseline ACTH and AR levels. 24-h after
Mara Baetu1, Ana Maria Stefanescu1, Simona Jercalau1, Victor Tomulescu2,
sodium depletion, mean plasma aldosterone levels were comparable between the
Anna-Maria Tinu3 & Corin Badiu1,4
two groups, but NC-CAH women had higher (PZ0.003) stimulated AR levels
1‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;
than healthy women: 67 mUI/l (15-156) vs 39 mUI/l (6-87).
2‘Fundeni’ Clinical Institute, Bucharest, Romania;3‘N.C. Paulescu’
Conclusions
National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest,
Forty percent women with NC-CAH have subnormal glucocorticoid adrenal
Romania;4‘Carol Davila‘ University of Medicine and Pharmacy, Bucharest,
function. Their aldosterone secretion was maintained normal by increased AR
Romania.
levels. Besides androgen excess therapy, clinical management of NC-CAH
women should include assessment of their cortisol and aldosterone secretion;
systematic chronic replacement therapy is still an open question, but transient
Introduction
glucocorticoid supplementation and rehydration during periods of stress should
Hyperglycaemia occurs frequently in catecholamine-secreting tumours due to
be considered.
insulin suppression or induced insulin resistance. These changes can be reversible
DOI: 10.1530/endoabs.49.GP19
postoperatory (postOp).
Objective
Our study aims to establish the impact of surgery in patients with catecholamine-
secreting tumours upon glucose metabolism disorders, as well as the predictive
factors for postOp diabetes-free patients.
Methods
We retrospectively analysed 72 patients (46 women-26 men), mean age 48 years
(9-82), median body mass index 24.5 kg/m2 (16-36.19), 66 with pheochromo-
cytoma, 6 with paraganglioma, 3 malignant, 12 known with genetic syndromes.
We evaluated their glycaemic status preoperatory (preOp), and for 64 of them
GP20
postOp, with a median follow-up of 4.17 years. Glucose metabolism disorders
were diagnosed according to World Health Organization criteria.
Which are the factors and causes of death in patients with adrenal
Results
insufficiency? Mortality data from EU-AIR
We found preOp diabetes mellitus (DM) in 32 patients (44.44%). We identified
Marcus Quinkler1, Bertil Ekman2, Pinggao Zhang3, Pierre Zelissen4 &
significant glycaemic changes in older patients, with longer hypertensive period,
Robert D Murray5
higher frequency of metabolic syndrome, adrenal tumours rather than ectopic, and
1Endocrinology in Charlottenburg, Berlin, Germany;2Linkoping
a higher level of ChromograninA (P!0.05). PostOp, 66.6% of patients were free
University, Linkoping, Sweden;3Shire, Lexington, Kentucky, USA;
of DM, 30% of them starting from week one postOp. We found significantly more
4University Medical Center Utrecht, Utrecht, The Netherlands;
cases of remnant DM in patients with longer duration of preOp DM (PZ0.0004,
5St James’s University Hospital, Leeds, UK.
110-vs-10 months) and in those requiring insulin preOp (PZ0.005). Patients with
or without postOp DM did not differ in presence of metabolic syndrome (but all
Introduction
patients with remnant DM had metabolic syndrome), history of familial DM,
If untreated, adrenal insufficiency (AI) leads to premature death. Hospital record
tumour characteristics, clinical or laboratory findings.
data suggest mortality associated with primary (PAI) and secondary AI (SAI) to
Conclusions
be 2-3-fold higher than in the general population. Major causes of death include
Our study found that DM is associated frequently with catecholamine-secreting
cardiovascular disease, Addisonian crises, brain tumours and infections; however,
tumours and
2
thirds disappear postOp. Remnant DM suggests that DM
there is little further characterization of patients who died.
associated with catecholamine-secreting tumours is not always a secondary DM.
Design
A longer duration of preOp DM and the fact that the glycaemic control is obtained
We analysed real-world data from the European Adrenal Insufficiency Registry
with insulin upon tumour diagnosis are predictive factors for remnant DM.
(EU-AIR; NCT01661387) with centres across Germany, the Netherlands,
DOI: 10.1530/endoabs.49.GP21
Sweden and the UK. Clinical and biochemical data at enrolment were compared
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP22
SDHBZ16,7%; SDHDZ55,6%. Family history of SDHx-related PPGL was
present in 20%. Deletions in SDHB exon-1 were the most frequent genetic defect.
Epithelial to mesenchymal transition in adrenocortical tumours: focus
Complete resection was achieved in
7(33,3%) and pre-surgery vascular
on FGF-FGFR pathway and c-MET
embolization was performed in 10(47,6%) of HNPGL patients. Radiotherapy
Iuliu Sbiera1, Barbara Altieri1,2, Annette Feuchtinger3, Kerstin Hofner1,
was used in 12(40%) patients (mainly unresectable HNPGL) achieving partial
Axel Walch3, Martin Fassnacht1,4, Cristina L Ronchi1, Matthias Kroiss1,5 &
response/stabilization. 177Lu-DOTATOC or 131I-MIBG were used in 4. Overall,
Silviu Sbiera1,4
remission was observed in 33,3%, stable disease in 53% and progression in 13,3%
1Division of Endocrinology and Diabetes, University Hospital, University of
of patients. Related morbidity was observed in 66,6% of patients, and one death
Wurzburg, Wuerzburg, Germany;2Division of Endocrinology and
occurred.
Metabolic Diseases, Catholic University of the Sacred Heart, Rome, Italy;
Conclusion
3Research Unit Analytical Pathology, Helmholtz Zentrum Munchen,
SDHC and SDHD patients are prone to develop single and multiple HNPGL,
Oberschleissheim, Germany;4Comprehenssive Cancer Center Mainfran-
respectively, and SDHB patients carry increased risk of malignancy, as suggested
ken, University of Wurzburg, Wuerzburg, Germany;5Clinical Chemistry
in other studies. SDHB patients and HNPGL had the worse prognosis, the former
and Laboratory Medicine, University Hospital, University of Wurzburg,
related to malignancy, and the last to cranial nerve deficits, unresectable disease
Wuerzburg, Germany.
and multimodality interventions. Radiotherapy represented a good alternative in
unresectable HNPGL.
Ad Adrenocortical carcinoma (ACC) is an aggressive tumour and treatment
DOI: 10.1530/endoabs.49.GP23
remains unsatisfactory in advanced disease. Activation of epithelial to
mesenchymal transition (EMT) is considered causative for metastatic spread in
a variety of human cancers. Accordingly, new drugs were developed specifically
targeting EMT with a focus on hepatocyte growth factor (HGF)/HGF receptor
(c-MET) and fibroblast growth factor (FGF)/FGF receptor (FGFR) signalling.
We here asked whether EMT is relevant to ACC progression to evaluate the
GP24
therapeutic potential of small molecule drugs targeting EMT.
Increased exosomes in endogeneous Cushing syndrome
Expression of FGFR family members and c-MET was analysed in 20 normal
Gloria Aranda1, Gemma Xifra2, Jose Manuel Fernandez-Real2,
adrenal glands (NAG), 23 adrenocortical adenomas(ACA) and 27 ACC at mRNA
Guillermo Garcia-Eguren1, Gregori Casals3, Adriana Pane1, Mireia Mora1,
and protein level. Expression of FGFR1-4 was quantified in FFPE tumour tissue
Irene Halperin1 & Felicia A Hanzu1
using RNAscope mRNA in situ hybridization technique. c-MET mRNA was
1Group of Endocrine Disorders, Department of Endocrinology Hospital
quantified by qRT-PCR. In a subset of 40 samples we quantified expression of 92
Clinic Barcelona, IDIBAPS, CIBERDEM, Barcelona, Spain;2Department
different genes involved in FGF-FGFR pathway signalling.
of Endocrinology, Hospital de Girona ’Dr Josep Trueta’; IdIBGi Girona,
FGFR2 mRNA was lower in ACC compared to ACA (3.1G2.1 vs 6.5G2.3
CIBERobn, Girona, Spain;3Biochemistry and Molecular Genetics, Hospital
mRNA copies/cell, PZ0.0005) whereas FGFR1 (7.5G5.3 vs 4.5G2.9, PZ0.09)
Clinic Barcelona, Barcelona, Spain.
and FGFR4 (5.1G2.3 vs 2.6G1.3, PZ0.002) were higher in ACC. FGFR4
expression was higher in advanced vs localized ACC (6.2G1.6 vs 3.9G2.7,
Exosomes are nano-sized vesicles secreted by the cells in the exatracellular fluids
PZ0.03). Pan-FGF-FGFR pathway qRT-PCR confirmed differential FGFR
representing a novel way of intracellular communication. Exosomes secreted
expression and revealed decreased expression of FGF7, FGF17 and mitogen
from blood cells like monocytes and platetes have been reported to be checkpoints
associated protein kinases in tumours compared with NAG. In advanced ACC
involved in haemostatic and thrombotic response. Glucocorticoids are inducing a
protein kinase c PRKCA was decreased but PRKCQ increased.
profound alteration of blood cells homeostasis with atherothrombotic, bleeding
c-MET mRNA expression was significantly higher in ACC compared to ACA and
and immune response alterations. Hereby we quantified for the first time
NAG (0.03G0.05 vs 0.01G0.03 and 0.01G0.02, respectively, PZ0.02).
circulating exosomes in overt Cushing syndrome (CS) patients.
Considering median expression as a cut-off, high c-MET expression in ACC
Methods
was associated with decreased overall survival (HRZ8.8, PZ0.02).
Cross sectional study in CS patients and controls. Diagnosis of CS was performed
In conclusion, EMT appears to be relevant for adrenocortical tumourigenesis and
following ECE and Endo guidelines. Blood samples from active, drug naive CS
progression. PRKCQ may be involved in EMT signalling in advanced ACC.
patients (nZ20) and age and sex matched controls (nZ20) were obtained after
EMT-related kinases such as c-MET and FGFR4 may be suitable treatment
overnight fast. Peripheral blood cells, biochemical and hormonal parameters were
targets in advanced ACC.
analyzed using standard methods. Circulatory exosomes were quantified in plasma by a
DOI: 10.1530/endoabs.49.GP22
sandwich enzyme-linked-immuno-sorbent assay (ExoTEST) employing a monoclonal
antihuman CD9 antibody. Further exosome phenotyping and analysis is ongoing.
Results
CS patients present as compared to controls a significant increased number of
CD9 positive exosomes (2.35!1010 vs 7.74!109/100 ml; PZ0.005**). Absolute
monocytes (MN) number and 24 h urinary free cortisol (UFC) level correlates
GP23
with the number of exosomes, respectively PZ0.022* with r:0.391 for MN and
Clinical features and treatment outcomes in a group of SDHx-related
PZ0.005** with an r:0.467 for UFC.
pheochromocytoma/paraganglioma patients
Conclusion
Helder Simoes, Pedro Antunes, Ana Pinto, Sara Donato, Valeriano Leite &
Circulatory exosomes are increased in the hypercortisolemic state of Cushing
Branca Cavaco
syndrome.
Portuguese Oncology Institute, Lisbon Centre, Lisbon, Portugal.
DOI: 10.1530/endoabs.49.GP24
Introduction
Germline mutations in succinate dehydrogenase complex (SDHx) are a risk factor
for developing Pheochromocytoma (Pheo) and/or Paragangliomas (PGL) (named
together PPGL), being responsible for approximately 30% of cases. The precise
GP25
genotype-phenotype correlations and best management strategies are still uncertain.
Tumor microenvironment increases migration/invasion of murine
Objective
pheochromocytoma SDHB silenced spheroids
To characterize the clinical features and genotype-phenotype associations in a
Vanessa D’Antongiovanni1, Serena Martinelli1, Susan Richter3,4,
group of SDHx-mutated PPGL patients.
Letizia Canu1, Daniele Guasti2, Paolo Romagnoli2, Karel Pacak5,
Methods
Graeme Eisenhofer3,4, Massimo Mannelli1 & Elena Rapizzi2
Retrospective analysis of all germline SDHx-mutated PPGL cases followed in a
1Department of Experimental and Clinical Biomedical Sciences, University
reference centre.
of Florence, Florence, Italy;2Department of Experimental and Clinical
Results
Medicine, University of Florence, Florence, Italy;3Institute of Clinical
Total PPGL patients with SDHx-mutation:
30
(16
female). SDHB-related:
Chemistry & Laboratory Medicine, Dresden, Germany;4Department of
18(60%); SDHD-related: 9(30%); SDHC-related: 3(10%). Mean age at diagnosis:
Medicine III, Technische Universitat Dresden, Dresden, Germany;5Eunice
36,8G15,4 years. Median follow-up: 94,8 months. Twenty nine patients had
Kennedy Shriver National Institute of Child Health and Human
symptoms at diagnosis. Cathecholamine secretion was detected in 9(30%). Nine
Development, National Institutes of Health, Bethesda, USA.
cases (30%) were malignant. Anatomical distribution: SDHB: 9 head and neck
PGL (HNPGL), 5 Pheo and 5 thoraco-abdominal PGL (TAPGL) cases; SDHD: 9
HNPGL, 1 Pheo and 1 TAPGL cases. All SDHC were single non-metastatic
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendo-
HNPGL. Malignancy: SDHBZ44,4%; SDHDZ11,1%. Multiple PPGL:
crine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
of the 13 main susceptibility genes which include the genes encoding the four
Tumours caused by mutations in the SDH enzyme complex have a unique
subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In
tumour metabolome due to a truncated citric acid cycle. The accumulation
PHEO/PGL due to SDHB mutations up to 80% of affected patients develop
of the onco-metabolite succinate is believed to drive tumourigenesis. The
metastatic disease and no successful cure is at present available. To obtain an
aim was to investigate the role of MRI spectroscopy (H-MRS) to detect
experimental model resembling the in vivo conditions of the SDHB-mutated
in vivo succinate elevations in suspected SDH deficient tumours including
PHEO, we used multicellular tumor spheroids (3D culture) of a murine cell line
GIST, phaeochromocytoma/paraganglioma (PPGL) and pituitary adenomas
cultured alone or in co-culture with mouse primary fibroblasts, evaluating the
(PA). Suitable patients were identified based on SDH germline status,
effects of SDHB silencing and microenvironment on invasion and migration
clinical phenotype and or tumour SDHB immunonegativity. A minimum
processes. The growth of spheroids is linear with clear edges. When the spheroids
tumour size of 1.5 cm was applied. H-MRS was performed on a 3T MRI
are treated with conditioned medium of cancer-associated fibroblasts (CAFs), we
scanner and spectra with and without water suppression, was obtained.
observe an evident detachment of clusters of viable cells in the surrounding space.
Succinate when detected, was visible on the spectra at a frequency of
SDHB silenced cells show a greater migratory capability than negative control
2.4 ppm and a succinate to choline ratio of O0.1 was deemed confirmatory
(NC) cells. In particular, SDHB silenced cells invade the surrounding space
of succinate detection. H-MRS was performed on nine patients to date
moving collectively, unlike the NC spheroids where cells tend to move
including four patients with GIST, 4 with PPGL and 1 with a PA. A
individually. This difference was even more evident when spheroids were
succinate peak was detected in
7/9
patients and correlated with the
co-cultured directly with mouse primary fibroblasts. Using electronic microscopy
immunohistochemistry (IH) and or germline status in all seven cases.
on spheroids, we observed that SDHB silenced cells show swollen mitochondria
H-MRS of a PA in a patient with a germline mutation in SDHB
and, alterations of mitochondrial crests (similarly to mitochondria of patients with
demonstrated no succinate peak and this correlated with the tumour
SDHB mutations) while SDHB mutated spheroids show borders that are more
SDHB immunopositivity. H-MRS successfully detected a succinate peak in
fraying than those of NC spheroids. In conclusion, SDHB silencing strongly
a patient with a metastatic GIST and a somatic mutation in SDHC. This is
increased the invasion/migration capabilities, and these changes are more evident
the first study to investigate the use of in vivo metabolomics in SDH
in SDHB spheroids co-cultured directly with primary fibroblasts. Further studies
deficient GIST and pituitary adenomas and has proven efficacy as a non-
on these mechanisms may suggest new therapeutic targets.
invasive test for the identification of in vivo succinate peaks and detection of
DOI: 10.1530/endoabs.49.GP25
SDH deficient tumours. It may be particularly useful for the detection of
somatic SDH mutations and to clarify the role of SDH mutations in newly
identified phenotypes. Future application includes the use of in vivo
succinate detection as a biomarker for therapeutic response.
DOI: 10.1530/endoabs.49.GP27
GP26
Metformin reduces viability and proliferation of pheochromocytoma
cells in vitro
Cinthia Meireles, Francisco Neves, Luiz Simeoni & Adriana Lofrano-Porto
GP28
University of Brasilia, Brasilia, Brazil.
A PRKACB somatic mutation in a cortisol producing adenoma: a new
example of protein kinase A activation leading to adrenal Cushing
Background
syndrome
Pheochromocytomas (PHEO) are rare neuroendocrine tumors derived from
Stéphanie Espiard1,4, Matthias Knape2, Kerstin Bathon3, Guillaume Assié1,
chromaffin cells of the adrenal medulla. Catecholamins’ secretion is associated
Daniel Abid2, Simon Faillot1, Davide Calebiro3, Friedrich Herberg2,
with a high risk of cardiovascular complications. Malignancy is rare, but still
Constantine Stratakis4 & Jérôme Bertherat1
demands effective treatment. Metformin has been shown to have antiproliferative
1Team Endocrine Tumors and Signaling, Cochin Institute, Paris Descartes
properties in several cancer cell lines, possibly related to its ability to inhibit cell
University, Paris, France;2Department of Biochemistry, Kassel University,
proliferation pathways. Accordingly, we aimed to evaluate the effects of
Kassel, Germany;3Institute of Pharmacology and Toxicology and
metformin in the survival and proliferation of PHEO cells.
Bio-Imaging Center/Rudolf Virchow Center, University of Wurzburg,
Methods
Wurzburg, Germany;4Program on Developmental Endocrinology and
Cell viability was evaluated by MTT and TRIPAN assays using the PC12-Adh
Genetics, Eunice Kennedy Shriver National Institute of Child Health and
PHEO cell line treated with metformin in increasing concentrations (0-30 mM).
Human Development, National Institutes of Health, Bethesda, France.
A lipid peroxidation assay and determination of O2
consumption using a
respirometer were performed to evaluate cellular stress. The effects of metformin
Introduction
on cell proliferation markers were analyzed by western blot.
Alterations of the cAMP signaling pathway are described in adrenal tumors
Results and Discussion
causing Cushing syndrome, specifically mutations in the gene coding for the
Metformin at 20 mM induced an inhibition of 60% of cell viability after 48 h
protein kinase A (PKA) catalytic subunit alpha (PRAKCA) in cortisol producing
treatment, as compared to untreated controls, and increased cellular lipid
adenomas (CPA) with overt Cushing syndrome.
peroxidation, while decreased O2
consumption in PC12-Adh PHEO cells.
Materiel and Methods
Moreover, metformin treatment reduced the activation of proteins of the
Eight CPAs without PRKACA mutations were analyzed by whole exome
AMPK/PTEN/AKT/mTOR pathway, which suggests growth and cell prolifer-
sequencing. Direct sequencing of PRAKCB encoding for the catalytic subunit
ation impairment. We then performed a primary culture of a PHEO from a
beta (Cb) of the PKA was performed in 21 others. Interaction of WT or mutant Cb
10-year-old boy with VHL disease to test wheter metformin exerts its
with the PKA-regulatory subunits was studied by bioluminescence resonance
antiproliferative effects ex vivo. Our results suggest that metformin has a
energy transfer and surface plasmon resonance analysis. To study the PKA
moderate inhibitory effect on the viability of PC12-Adh PHEO cells. This effect is
activity, phosphorylation of the synthetic PKA-substrat Kemptide was analyzed
associated with enhanced lipid peroxidation and decreased O2 consumption by
in cellulae in HEK293 cells transfected with a combination of RIa and Cb and
those cells, which are both suggestive of increased cellular stress. Moreover,
in vitro with purified proteins.
metformin treatment induced a positive modulation of the AMPK/PTEN/AKT/m-
Results
TOR signaling pathway. Altogether our results corroborate the hypothesis of an
A PRKACB somatic mutation p.S54L was found in one CPA, from a 41-year-old
inhibitory effect of metformin on PHEO cellular proliferation in vitro.
patient presenting with a severe form of Cushing syndrome. Direct sequencing of
DOI: 10.1530/endoabs.49.GP26
PRKACB did not show any other mutations in additional samples. Functional
studies demonstrated loss of interaction between the mutant Cb and the regulatory
subunit type 1 (RIa, RIb). After stimulation by cAMP or forskolin, dissociation of
Cb and RIa was faster and stronger with the mutant than with the WT Cb. In
addition, basal PKA activity was higher for the mutant catalytic than the wild-
type while the maximal activity after stimulation was lower.
GP27
Conclusions
The role of in vivo metabolomics using H-MRS in SDH deficient disease
PRKACB is a new gene responsible for at least one CPA, mutated in the somatic
Ruth Casey1,3, Mary McLean1,2, Madhu Bassetti2, Ben Challis3,
state. This finding suggests that the Cb subunit of the PKA, too, may have specific
Helen Simpson3, Mark Gurnell1,3, Ramesh Bulusu3, Alison Marker3,
functions in the adrenal cortex. Particularly, the role of the residue Ser54 (as was
Olivier Giger1,3, Kieran Allinson3, Krishna Chatterjee1,3, Eamonn Maher1,3
previously suggested) may be very important for PKA function in the adrenal
& Ferdia Gallagher1,3
cortex.
1Cambridge University, Cambidge, UK;2Cancer Research UK, Cambridge,
UK;3Cambridge University Hospital NHS Foundation Trust, Cambridge,
DOI: 10.1530/endoabs.49.GP28
UK.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP29
GP31
Familial case of SDHB mutation presenting as a macroprolactinoma
Long-term treatment of acute ectopic ACTH syndrome with Etomidate
Edouard Mills, Pratibha Machenahalli, Ali Naqvi & Jeannie Todd
Zydrune Visockiene1,2, Vilija Guntaite3, Vigantas Dunauskas2,
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust,
Donatas Vajauskas1,2, Gintautas Kekstas1,2 & Giedre Vasyliene4
London, UK.
1Vilnius Univesity Faculty of Medicine, Vilnius, Lithuania;2Vilnius
University Hospital Santariskiu Clinics, Vilnius, Lithuania;3Republican
Siauliai Hospital, Siauliai, Lithuania;4Republican Panevezys Hospital,
Panevezys, Lithuania.
Germline mutations in the succinate dehydrogenase subunit-B gene (SDHB)
are well recognised for predisposing to head and neck paraganglioma,
sympathetic paraganglioma, phaeochromocytoma and renal cell carcinoma.
Case description
The co-existence with pituitary adenomas remains uncommon.
A 25-year-old male was admitted to the Intensive Care Unit due to progressive
We report a 31-year-old female who presented at age 29 years old with 9
muscle weakness, difficulty walking, weight loss, headache, chest discomfort,
months of secondary amenorrhoea. Prolactin was 3000 mIU/l and a 1.7-cm
type 1 diabetes for few months. He was confused and irritated, with “moon” face,
macroprolactinoma revealed on MR pituitary. Taking prolactin-lowering
facial plethora, acne, and hyperpigmentation of the skin, few obscure red-bluish
therapy, she achieved normal menses and subsequent MRI imaging
striae and significant wasting of proximal and distal muscles of lower limbs.
demonstrated reduction in the size of this macroprolactinoma. At age 30
Cortisol hypersecretion due to ectopic ACTH production was confirmed by
years, she was found to have a paraganglioma in the aortic-pelvic region. On
plasma ACTH (O1250 ng/l) and cortisol (1120-2145 nmol/l), 24-h urinary free
reflection, she had noticed anxiety, sweating, palpitations and extreme
cortisol (14 726 nmol/24 h), failure to supress cortisol on a high dose intravenous
exercise intolerance for the 2 years preceding diagnosis, which resolved
and 16 mg oral 2 days dexamethasone suppression tests. Severe hypercortisole-
following surgical resection. She was screened for familial paragangliomas,
mia resulted in critical fluid and electrolyte imbalance, deterioration in physical
which revealed she was a carrier of the SDHB mutation. Interval screening
and mental state. Daily Etomidate infusion 20-60 mg for 14 days stabilized
MRI neck to pelvis has since demonstrated no evidence of recurrent or new
condition and later was used for treatment on alternate days in the dose of 20-
disease. Plasma metanephrines have subsequently remained normal.
40 mg for 10 months in day care clinic. Alternative treatment with Ketoconazole
Her father, aged 64 years old, was referred for genetic counselling and
induced hepatic injury, Octreotide was ineffective, Metyrapone was not available.
testing. He too is an SDHB mutation carrier. His plasma metanephrines are
Following Etomidate infusions, plasma cortisol decreased to 280-560 nmol/l,
normal and MRI neck to pelvis has not revealed a paraganglioma or
potasium
- 3.7-4.3 mmol/l with oral supplementation of KCl
3 g/day and
phaeochromocytoma. Both the index case and father will remain under
Spironolactone 50 mg, glucose became normal without insulin. In 10 months
lifelong specialist care in a Neuroendocrine Tumours Clinic. Family
Metyrapone became available and 1 g/day was used to achieve control. Patient
members have been advised to seek genetic counselling.
refused from adrenalectomy.
Although uncommon, increasing incidence of pituitary adenomas in carriers
Pituitary MRI, chest and abdomen CT, somatostatin receptor scintigraphy,
of SDH mutations are being reported. These pituitary adenomas tend to be
bronchoscopy, esophagogastroduodenoscopy, colonoscopy revealed no potential
larger with macroprolactinomas commoner than other pituitary adenomas.
source of ectopic ACTH production. Further assessment by whole body 18F-FDG
Screening programmes vary widely for carriers of SDH mutations and tend
PET-CT and 68Ga-DOTATOTE PET-CT scans, selective sinus petrosus inferior
not to involve pituitary imaging. However, given the association with
sampling and enteroscopy failed to detect the source of ACTH. Thorax CT and
pituitary lesions, screening imaging might need to include the pituitary. At
colonoscopy was performed three times, abdominal CT and pituitary MRI - twice
present, however, it is thought that this is likely to be a low-yield strategy.
during 16 months. Primary tumour was not detected.
DOI: 10.1530/endoabs.49.GP29
Conclusion
Etomidate infusion could be used for long term treatment of ectopic ACTH
syndrome when other options are ineffective or unavailable.
DOI: 10.1530/endoabs.49.GP31
GP30
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with
cyclical ectopic adrenocorticotrophic hormone secretion
Pratibha Machenahalli, E Mills, N Ali & JF Todd
GP32
Imperial College Hospitals NHS Trust, London, UK.
Multiple pathologic fractures as the presenting manifestation of
Cushing’s syndrome in patients with vitamin D receptor FokI gene
polymorphism
Vasiliki Daraki1, Paraskevi Floroskoufi1, Theodoros Liarigkovinos1,
DIPNECH is pre-invasive precursor to carcinoid tumors and tmorlets, most
Maria Chrysoulaki1, Vasilios Tsamadias2, Emmanuel Economou2 &
of which present with pulmonary symptoms. We present a case of ectopic
Stathis Papavasiliou1
cyclical ACTH producing DIPNECH.
1Department of Endocrinology Diabetes and Metabolic Diseases, University
33-year lady presented with a short history of weight gain, abdominal striae,
Hospital of Crete, Heraklion, Greece;2Laboratory of therapeutic
proximal myopathy and secondary amenorrhoea. She reported a previous
individualization, University of Athens, Aretaieio University Hospital,
episode with similar symptoms one year earlier which resolved spon-
Athens, Greece.
taneously after a few weeks. Random cortisol 4000 nmol/l, ACTH 98 ng/l.
LDDST failure to suppress cortisol levels. IPSS showed no central:per-
ipheral ACTH gradient, representing ectopic ACTH source. CT chest
showed multiple pulmonary nodules, a dominant RLL nodule larger since
Rare cases of Cushing’s syndrome have been diagnosed only based upon
2006. 68-Gallium DOTATATE PET/CT scan was normal. Metyrapone was
bone manifestations. Fracture risk is related to individual susceptibility to
commenced. One week later, Metyrapone was stopped due to low cortisol
glucocorticoids that is genetically determined by several factors, including
levels. Off Metyrapone, cortisol levels remained low with concomitant
VDR gene polymorphism.
reduction of ACTH levels, indicating another spontaneous remission of
We report three patients with VDR FokI gene polymorphism and multiple
Cushing’s syndrome. Histology from an excision biopsy of the RLL nodule
non-traumatic pathologic fractures as the presenting manifestation of
revealed tumourlets with a typical carcinoid appearance and a background
Cushing’s syndrome.
of DIPNECH. Post-operatively, she was treated with hydrocortisone
Case reports
replacement for a couple of weeks. After a few months later symptoms of
The first case is a 55-year-old man who presented with pain in the right hip. CT
Cushing’s recurred and repeat imaging of the chest has not shown any
scan revealed fracture in the right femur. Additionally bone scintigraphy revealed
progression of the lung nodules. Repeat LDDST confirmed the biochemical
non-traumatic micro-fractures in ribs and pelvis.
excess of cortisol. She is currently awaiting bilateral adrenalectomy.
The second case is a 44-year-old woman who presented with pain in the left hip.
As per the literature review, DIPNECH is common in female. There is only
She reported weight gain (25 kg) in the last 6 years, depression, fatigue, and
one case presented with ACTH secretion. It is relatively a stable disease with
muscle weakness. MRI revealed fracture in the left hip, while bone scintigraphy
only
26% of the patients deteriorates clinically and radiologically.
showed multiple non-traumatic micro-fractures in ribs and right femur.
Octreotide has not shown to improve the prognosis.
The third case is a 64-year-old woman presented with recurrent rib and low
DOI: 10.1530/endoabs.49.GP30
extremities fractures the last 10 years. She also suffered from depression and
hypercholesterolemia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Dual-energy X-ray absorptiometry (DXA) revealed severe osteoporosis in all
GP34
patients. Additionally laboratory tests and imaging techniques confirmed the
Fat mass distribution and resistin are independent predictors of bone
diagnosis of Cushing’s syndrome due to an adrenal mass. Further investigation for
mass in postmenopausal, but not premenopausal women.
FokI and Bsm polymorphism of VDR gene by polymerase chain reaction and
Stefana Catalina Bilha1,2, Maria-Christina Ungureanu1,2, Petru Cianga3,4,
restriction fragment length polymorphism (PCR-RFLP) analysis showed that all
Catalin Buzduga1,2, Adrian Aancute1, Valentin Zaharia1,
patients had the ff genotype of the VDR FokI gene.
Daniela Constantinescu3,4, Ecaterina Anisie3, Adrian Covic5,6 &
Discussion
Dumitru Branisteanu1,2
VDR FokI gene polymorphism correlates significantly with an increased rate of
1Endocrinology Clinic, “Sf.Spiridon” Hospital, Iasi, Romania;
bone loss in ff postmenopausal women. However data of its functional
2Endocrinology Department, “Gr. T. Popa” University of Medicine and
significance on glucorticoid-induced osteoporotic fractures is lacking so far.
Pharmacy, Iasi, Romania;3Laboratory of Immunology and Genetics, ”Sf.
We report for the first time an association between the ff genotype and multiple
Spiridon” Hospital, Iasi, Romania;4Immunology Department, “Gr. T. Popa”
non-traumatic fractures as the predominant manifestation of Cushing’s syndrome.
University of Medicine and Pharmacy, Iasi, Romania;5Nephrology Clinic,
Our findings suggest that VDR FokI gene polymorphism may increase fracture
“Dr. C.I. Parhon” University Hospital, Iasi, Romania;6Nephrology
risk in ff subjects with endogenous hypercortisolism.
Department, “Gr. T. Popa” University of Medicine and Pharmacy, Iasi,
DOI: 10.1530/endoabs.49.GP32
Romania.
Introduction
Body weight and lean mass (LM) are classic bone mass determinants. However,
the association between total fat mass (FM), regional FM and bone remains
controversial, especially as fat is a source of adipocytokines, with both positive
Bone & Calcium Homeostasis 1
and negative bone consequences.
GP33
Materials and methods
“Hyperparanet”: a multicenter Italian study on Primary
Anthropometric, bone mass (assessed by Dual X-Ray Absorptiometry; DXA) and
Hyperparathyroidism
body composition parameters (assessed by DXA) and also serum adipocytokine
Federica Saponaro1, Filomena Cetani1, Valentina Camozzi2,
(leptin, adiponectin, resistin) levels were determined from 93 female volunteers
Antonella D’Angelo3, Salvatore Minisola3, Alfredo Scillitani4,
(38 premenopausal and 55 postmenopausal women). Correlation analysis was
Claudia Cipri5, Serena Palmieri6, Iacopo Chiodini6, Francesco Romanelli7,
performed in order to assess the association between body mass index (BMI),
Bruno Madeo8, Elena Castellano9, Laura Gianotti9, Antongiulio Faggiano10,
body composition parameters, adipocytokines and bone mass. Multivariable and
Luisella Cianferotti11, Maria Luisa Brandi11, Sabrina Corbetta12, Maria
hierarchical regression models were used to determine which of the above factors
Laura De Feo13, Andrea Palermo14 & Claudio Marcocci1
are independent predictors of bone mass.
1Endocrine Unit 2, University of Pisa, Pisa, Italy;2Endocrine Unit,
Results
University of Padova, Padova, Italy;3Department of Internal Medicine and
In correlation analysis, BMI, total LM, total FM and regional FM (trunk FM and
Medical Disciplines’Sapienza’ University, Rome, Italy;4Casa Sollievo della
lower limbs FM) were positively associated with bone mass in both groups.
Sofferenza,’’ IRCCS, San Giovanni Rotondo, Italy;5Endocrinology and
Correlations between adipocytokines and bone were found only in the
Metabolism Unit University-Hospital of Udine, Udine, Italy;6Unit of
postmenopausal group. In multivariable regression analysis, only LM remained
Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-
an independent predictor of bone mass in premenopausal women, explaining
Ospedale Maggiore Policlinico, Milan, Italy;7Department of Experimental
38.1% (P!0.001) of femoral neck, 24.5% (PZ0.002) of total hip and 20%
Medicine, Sapienza University of Rome, Rome, Italy;8Unit of Endo-
(PZ0.005) of whole-body bone mineral density (BMD) variance; in post-
crinology, Modena, Italy;9Division of Endocrinology, Diabetes and
menopausal women, LM, trunk-to-lower limbs FM ratio (together explaining
Metabolism, Santa Croce and Carle Hospital, Cuneo, Italy;10Endo-
30.9% of the variance of total hip BMD, P!0.001) and resistin (adipokine known
crinology, Federico II University of Naples, Naples, Italy;11Department of
to regulate bone cell proliferation and bone turnover) remained independent
Internal Medicine, University of Florence, Florence, Italy;12Area di
positive predictors of bone mass. Hierarchical regression showed no additional
Endocrinologia e Malattie Metaboliche, IRCCS Policlinico San Donato,
effect of BMI or of total FM to that of total LM in predicting bone mass in both
Milano, Italy;13Endocrinology Unit, Careggi Hospital and University of
groups.
Florence, Florence, Italy;14Department of Endocrinology and Diabetes,
Conclusions
University Campus Bio-Medico, Rome, Italy.
LM independently predicts bone mass in premenopause, while after menopause
FM distribution becomes an important factor in regulating bone mass together
with total LM and resistin. These parameters may find their place for fine tuning
The aim of the present study was to evaluate the phenotype of PHPT, the
the evaluation of fracture risk.
adherence to International Guidelines and the rate of surgical cure of PHPT in
DOI: 10.1530/endoabs.49.GP34
Italy. From January 2014-January 2016, we conducted a prospective, multicenter
(nZ29 endocrine tertiary referral centers) study on patients with PHPT, recording
clinical and biochemical data, parathyroid imaging and therapy choice at baseline
and at last follow-up. The study group included 604 patients with PHPT, with a
mean age of 61G14 yrs (F:MZ5:1). Most patients had sporadic PHPT (nZ566
(93.7%), mean age 63G13 yrs); the remaining 38 (6.3%, mean age 41G17 yrs)
were familial forms. Follow up data were available in 345 patients: 158 (45.8%)
with symptomatic and 187 (54.2%) with asymptomatic PHPT. Eighty-six patients
GP35
(54.4%) of the former group underwent PTx, mainly for symptomatic
nephrolithiasis (nZ71, 82.6%). One hundred twenty-one asymptomatic patients
Aldosterone and parathyroid hormone - is there a connection?
(64.7%) met at least one criterion for PTx according to the 2008 International
Mara Ventura, Miguel Melo, Diana Oliveira, Diana Martins, Adriana Lages,
guidelines for parathyroidectomy and 65 patients (53.7%) underwent surgery.
Nelson Cunha & Francisco Carrilho
Criteria for PTX were: serum calcium levels 1 mg above the upper normal limit
University and Hospital Center of Coimbra, Coimbra, Portugal.
(nZ37, 56.9%), osteoporosis (nZ35, 53.8%) and age !50 yrs (nZ14, 21.5%).
Surgery was not performed in the remaining patients (nZ56, 46.3%) despite the
Introduction
presence of serum calcium levels 1 mg above the upper normal limit (nZ12,
Recent studies seem to support a bidirectional positive interaction between
21.4%), osteoporosis (nZ44, 78.6%) and age !50 yrs (nZ11, 19.6%). Surgery
aldosterone and parathyroid hormone
(PTH). Understanding the normal
was also performed in 16 of the 66 (25.7%) patients who did not meet the criteria
physiological relationship between renin-angiotensin-aldosterone system
for surgery. A total of 168 patients underwent PTX. The histological diagnosis
(RAAS) and PTH is of clinical interest because their inappropriate activity may
was single adenoma in 89% of cases, hyperplasia in 9%, atypical adenoma in 1%,
negatively impact cardiovascular and skeletal health.
and carcinoma in 1%. The large majority (nZ158, 94%) of patients were cured.
Objective
Persistence of PHPT was observed in the remaining 10 patients, who were
To evaluate the presence of an interaction between aldosterone and PTH in a
apparently sporadic. Patients followed without surgery showed a stable clinical
cohort of patients assessed for suspicious hyperaldosteronism or hyperparathyr-
and biochemical disease, after one year of follow-up. This is the first multicenter
oidism.
Italian study with the specific aim of evaluating PHPT phenotype and therapeutic
Material and Methods
approach. International guidelines recommendations for surgery were observed in
We retrospectively evaluated consecutive patients followed in our Endocrinology
half of cases, either for symptomatic or asymptomatic patients.
Department between January 2014 and December 2016. We collected data about
DOI: 10.1530/endoabs.49.GP33
renin-angiotensin-aldosterone system and calcium metabolism from clinical and
laboratorial records and selected patients whenever both data were available.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
GP37
We identified
97
patients evaluated for suspicious hyperaldosteronism or
Effects of BCR-ABL targeted tyrosine kinase inhibitors on the whole
hyperparathyroidism. 51 patients were excluded due to insufficient data. From
transcriptome pattern of cultured murine osteoblasts
the 46 patients included, 8(17%) had confirmed primary hyperparathyroidism and
Bernadett Balla1, Gyongyi Kirschner1, Péter Horváth1, Gergely Lakatos2,
one had confirmed primary hyperaldosteronism; 74% (nZ34) were women, mean
János Kósa1 & Péter Lakatos1
age of 60.0G13.2 years and mean BMI of 27.8G4.1 Kg/m2. This group had a
1First Department of Internal Medicine, Semmelweis University, Budapest,
mean aldosterone level of 141.9G74.6 pg/ml (reference range: 40-310), PTH
Hungary;2Second Department of Internal Medicine, Semmelweis
level of 87.3G48.0 pg/ml (reference range: 9-72), 25(OH) vitamin D level of
University, Budapest, Hungary.
26.5G10.2 ng/ml and plasma calcium level of 9.6G1.1 mg/dl (reference range:
8.8-10.6). PTH and aldosterone levels presented a moderate correlation in our
cohort (rhoZ0.474, P ! 0.01). After exclusion of the patients with confirmed
Breakpoint cluster region abelson fusion oncoprotein
(BCR-ABL) targeted
disease, PTH and aldosterone levels presented a week correlation, though still
tyrosine kinase inhibitors (TKIs) are widely used in long-term medications of
statistically significant (rhoZ0.377, PZ0.021).
hematological malignancies. Numerous clinical observations confirmed that these
Conclusion
drugs significantly modify the physiology of bone tissue as a side effect.
Aldosterone levels were positively correlated to PTH levels in our sample. This
Currently, there are numerous contradictory results regarding the complex effects
interaction may be one of the mechanisms responsible for hypertension and
of TKIs on bone metabolism, as well as there is no clear evidence to explain them,
increased cardiovascular risk in patients with hyperparathyroidism. On the other
either in the level of basic or clinical research.
hand, hyperaldosteronism may indirectly impair calcium metabolism and bone
The aim of the present study was to analyze the whole transcriptome differences
health.
of cultured murine osteoblasts (MC3T3E1) after imatinib or nilotinib treatment
DOI: 10.1530/endoabs.49.GP35
using SOLiD next generation RNA sequencing technique. Based on the cell
viability test,
1 mM drug concentration and 6-day incubation period had the
greatest effects on the expression profile of osteoblastic cells.
The results showed only three common up-regulated genes in the TKI-treated
groups with almost the same expression activity compared to the control one.
Ingenuity Pathway Analysis was applied to reveal the cellular response for the
two drugs. Six and five top canonical pathways were identified from the whole
transcriptome sequencing data in case of imatinib and nilotinib, respectively.
GABA receptor cascade was found among the markedly upregulated signaling
GP36
pathways in both of the treated groups. During the bone remodeling process, this
Relationship between circulating microRNAs and bone mineral density
signal transduction network is deeply involved in bone cell proliferation,
in patients with active acromegaly
differentiation and development.
Elena Valassi1, Natalia García-Giralt2, Jorge Malouf3, Iris Crespo1 &
In conclusion, this was the first study to observe the complete mRNA pattern of
Susan M. Webb1
osteoblasts after selective TKI administration. These preliminary transcriptional
1Endocrinology/Medicine Department, Hospital Sant Pau, Centro de
results indicate various mechanisms of action of the examined TKIs on osteoblast
Investigación Biomédica en Red de Enfermedades Raras (CIBERER 747),
function that might be due to their different chemical profiles and non-kinase
target spectrum. Therefore, further investigation is required to verify the detected
II-B Sant Pau, ISCIII, Universitat Autònoma de Barcelona (UAB),
expression changes of the reported genes as well as to validate the biologically
Barcelona, Spain;2URFOA, IMIM (Institut Hospital del Mar d’Investiga-
significant targets.
cions Mèdiques), Universitat Autònoma de Barcelona, Barcelona, Spain;
3Mineral Metabolism Unit, Medicine Department, Hospital Sant Pau,
DOI: 10.1530/endoabs.49.GP37
Barcelona, Spain.
Objective
Acromegaly (ACRO) is associated with abnormal bone remodeling and reduced
volumetric bone mineral density (vBMD) at the lumbar spine and proximal
femur. Circulating microRNAs (miRNAs) modulate the activity of osteoblasts
and osteoclasts, and are currently being investigated as potential biomarkers of
osteoporosis. The aims of our study were: 1) To identify differentially expressed
miRNAs in the serum of five patients with active ACRO vs. healthy controls, and
GP38
2) To correlate selected miRNAs concentrations with altered bone parameters in
Decreased trabecular bone score but not bone mineral density
11 ACRO patients.
in patients with acromegaly and concurrent hypogonadism:
Patients and methods
cross-sectional study with healthy controls
Eleven patients with active ACRO (six females; mean age, 47.5G6.7 years; BMI,
Martin Kuzˇma1, Dušan Pavai2, Ivana Ságová3, Zdenko Killinger1,
27.2G3.8 kg/m2) and
11
age-, gender-, and BMI-matched controls were
Peter Jackuliak1, Anton Va
ˇ uga2, Peter Vanˇ uga2 & Juraj Payer1
recruited. Analysis of differential expression of miRs was performed in 5 of
1Comenius University Faculty of Medicine, Fifth Department of Internal
them (5 males; mean age, 44.3G4.3; BMI, 26.2G2.8). Areal BMD (aBMD) at
Medicine, University Hospital Bratislava, Bratislava, Slovakia;2National
lumbar spine and femur was assessed through dual energy X-ray- absorptiometry
Institute of Endocrinology and Diabetology, Lubochna, Slovakia;
(DXA); vBMD was measured by quantitative computed tomography (QCT).
3Comenius University Jessenius Faculty of Medicine, First Department of
Serum miRNA levels were assessed by qPCR. Osteocalcin (OC), type 1 amino-
Internal Medicine, University Hospital, Martin, Slovakia.
terminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTx) were
measured using electrochemiluminescent immunoassay.
Results
Introduction
Expression of miR-885-5p, miR-99a-5p, and miR-29a-3p was significantly
Acromegaly is associated with higher prevalence of vertebral fractures (VFx) and
higher, while that of miR-7-1-3p and miR-335-3p was significantly lower in the
bone microarchitecture potentially play a role in fracture development.
ACRO patients. Both miR-885-5p and miR-7-1-3p were inversely associated with
Trabecular bone score (TBS), a novel indicator of bone microstructure could
femoral aBMD (rZK0.64, PZ0.034 and rZK0.73, PZ0.009, respectively),
provide additional information.
and trocantheric vBMD (rZK0.66; rZ0.038 and rZ0.67; PZ0.023) in ACRO
Objectives
but not in the controls. They were also positively associated with P1NP (rZ0.82,
Assessment of BMD, TBS and bone turnover markers (BTM) in acromegaly
PZ0.002 and rZ0.79, PZ0.004, respectively) and CTx (rZ0.73, PZ0.010 and
patients in comparison to healthy controls with regard to gender, hypogonadism
rZ0.68, PZ0.019) in ACRO. MiR-99a-5p was inversely associated with femoral
and disease activity.
aBMD (rZK0.66, PZ0.26) and positively associated with P1NP (rZ0.83;
Patients and methods
PZ0.001) and CTx (rZ0.88, P!0.001) in ACRO only. The relationship
A cross-sectional study of acromegaly patients with age-, gender- and BMI-
between femoral aBMD and miR-99a-5p remained significant after adjusting for
matched healthy controls was conducted. Study group consisted from all
age and IGF-SDS (bZK0.52, PZ0.012).
acromegaly patients (regardless age, gender, disease duration or activity) which
Conclusions
came for follow-up visit during period 6/2016 - 12/2016 and the control group
Circulating miRNAs may be one of the mechanisms whereby BMD is impaired,
consisted of healthy subjects. In all subjects a single measurements of all pituitary
mainly at the femoral level. Further larger studies are needed to confirm these
axis hormones levels, BTM, BMD of total hip (TH) and lumbar spine (LS) and
preliminary data.
TBS was performed. N-terminal type 1 procollagen (P1NP) - marker of bone
DOI: 10.1530/endoabs.49.GP36
formation and C-terminal telopeptide (CTx) -marker of bone resorption were
analyzed.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
management of nine cases of synchronous PH and NMTC.
Thirty Seven acromegaly patients (12 males/25 females with mean age 56.7 years,
Cases
mean BMI 29.8 kg/m2) and 27 of control group subjects (seven males/20 females
Eight women and one man were included (mean age at diagnosis: 64G6.6 years).
with mean age 59.5 years, mean BMI 30.9 kg/m2) were included. TBS was
In all cases, PH was the initial diagnosis, whereas NMTC was detected
significantly lower in patients in comparison to controls (1.16 vs 1.22; P!0.05),
incidentally, after ultrasound assessment for PH. The histological diagnosis of
but no BMD and BTM difference was observed. Hypogonadal patients had lower
NMTC was classical papillary thyroid carcinoma (PTC) in all cases, with
TBS in comparison to patients without hypogonadism (TBS 1.13 vs 1.20;
follicular subtype in four cases. In one patient, medullary carcinoma was also
P!0.05) and no BMD difference. BTM were increased in hypogonadal patients
detected and a diagnosis of multiple-endocrine neoplasia type 2B syndrome was
(CTx 0.67 vs 0.38 ng/ml; P1NP 75.5 vs 47.5 ng/ml; both P!0.05). No difference
set. In three cases (33.3%), NMTC was multifocal. Extrathyroidal extension was
in TBS, LS BMD and BTM with regard to gender was observed.
detected in one case, but without metastatic disease. In seven cases (78%),
Conclusion
maximum NMTC diameter was !10 mm (mean diameter: 7.6G4.4 mm).
This study indicates that patients with acromegaly, especially those with
Thyroid autoimmunity was positive in two cases.
hypogonadism, despite unchanged BMD, may have impaired trabecular bone
The histological diagnosis of PHPT was single parathyroid adenoma (mean
microstructure, which can lead to increased prevalence of fractures.
diameter: 15.4G19.3 mm, in six cases on the right side) in all cases. In one case,
DOI: 10.1530/endoabs.49.GP38
the adenoma was intrathyroidal. Nephrolithiasis was diagnosed in one case,
hypercalciuria in two, whereas low bone mass in eight patients. Preoperative
mean parathyroid hormone (PTH) and total calcium concentrations were 133.5G
43.9 and 11.3G0.8 mg/dl (corrected calcium: 11G0.78 mg/dl), respectively.
Cardiovascular risk factors, such as arterial hypertension, dyslipidemia and/or
hyperglycemia were diagnosed in six cases (66.7%).
PH and NMTC were successfully managed with parathyroidectomy and total
thyroidectomy (mean post-operative PTH concentrations: 33.3G24.7 pg/ml). No
GP39
case developed post-operative hypocalcemia. Prophylactic central lymph node
resection was performed in one patient. No recurrence of either PH or NMTC has
Association of changes in serum urate level and bone mineral density
been reported (mean follow-up time: 3.8G5.1 years).
during treatment with teriparatide: a retrospective observational study
Conclusions
Tomaz Kocjan1, Gaj Vidmar2, Antonela Sabati Rajic1, Mojca Jensterle
NMTC may rarely be incidentally detected in patients with PH. It is usually
Sever1, Marija Pfeifer1, Janja Marc3, Nina Orehek3 & Barbara Ostanek3
unifocal microcarcinoma of classical PTC subtype, without extrathyroidal
1University Medical Centre Ljubljana, Ljubljana, Slovenia;2University
extension. The pathogenetic mechanisms linking these two endocrine entities
Rehabilitation Institute, Ljubljana, Slovenia;3Faculty of Pharmacy,
are currently unknown.
University of Ljubljana, Ljubljana, Slovenia.
DOI: 10.1530/endoabs.49.GP40
Serum urate level has recently been associated with increased bone mineral
density (BMD). Teriparatide, an osteoanabolic medication for osteoporosis, is
associated with increased incidence of hyperuricemia. Hence, we hypothesized
that changes in serum urate are associated with changes in BMD and procollagen
type 1 N-terminal propeptide (P1NP) during treatment with teriparatide.
We collected data from 151 women (mean age 72 years, mean BMI 26.6 kg/m2)
with severe postmenopausal osteoporosis who had been treated with teriparatide
for
2 years at our outpatient clinic. They were prescribed with vitamin D3
1000 IU daily and were instructed to ingest 1200 mg of calcium daily. BMD was
measured at the three standard sites by DXA at baseline, after 12 and 24 months
of treatment. Routine laboratory parameters (including serum urate), 25-hydro-
xyvitamin D and P1NP were measured at the same time-points. Estimated
glomerular filtration rate (eGFR) was calculated. The associations were assessed
GP41
using univariate correlations and multiple linear regression models (each fitted
Follow-up of patients with surgical hypoparathyroidism: unknown
using casewise deletion of records with missing data as well as missing data
cause of renal function decline?
imputation). Repeated-measures analysis of variance was used to verify the
Tess van de Meerhaeghe, Sergei Bukowski, Elien Coudenys, David Unuane,
increase in serum urate level and stability of eGFR.
Brigitte Velkeniers & Bert Bravenboer
During the 2-year treatment with teriparatide, we observed no notable univariate
UZ Brussels, Brussels, Belgium.
association between change of serum urate level and change of BMD. When
adjusting for basal eGFR, vitamin D sufficiency, previous bisphosphonate
Background
treatment, change of serum and of urinary calcium during the same period, we
Hypoparathyroidism is a rare endocrine disease with low calcium and insufficient
observed a weak positive association of serum urate level change with change of
parathyroid hormone levels. In most cases it is caused by thyroid surgery. The
BMD at lumbar spine. Conversely, change of serum urate level tended to be
objective of this retrospective cohort study was to evaluate if the typical therapy
weakly positively univariately associated with change of P1NP, but the
regimens of postsurgical hypoparathyroidism with calcitriol have a negative
association vanished when adjusting for the confounders listed above.
effect on renal function.
Our results may indicate that the effect of teriparatide on bone might be partly
Methods
mediated by changes in serum urate level.
We performed a chart analysis of patients that were seen in a tertiary care hospital
DOI: 10.1530/endoabs.49.GP39
in Brussels, Belgium. A total of 101 patients were identified as patients with
permanent post-surgical hypoparathyroidism, based on the hospital records of
patients who underwent a total thyroidectomy between 1996 and 2016, while still
being treated with calcitriol. Patients with pre-existing renal insufficiency and/or
active malignancy were excluded. The cohort was predominantly female of
Caucasian origin. Kidney function was evaluated before and after surgery (with a
maximum follow-up of 12 years), using the CKD-EPI equation.
Results
GP40
A multivariate linear regression model was used to correlate kidney function
Coexistence of primary hyperparathyroidism with papillary thyroid
decline with the duration of calcitriol therapy, while accounting for the mean
carcinoma: a case series
calcium-phosphate product and age. We found a statistically significant
Panagiotis Anagnostis1, Athanasios Panagiotou1, Fotini Adamidou1,
(PZ0.027) relation between the duration of calcitriol treatment and renal
Savvas Rafailidis2 & Marina Kita1
function decline at a rate of 1.06 ml/min/1.73 m2 per year of calcitriol therapy.
1Department of Endocrinology and Diabetes, Hippokration Hospital of
Conclusions
Thessaloniki, Thessaloniki, Greece;2Euromedica Kyanous Stavros,
Renal abnormalities are frequent finding in patients with hypoparathyroidism.
Thessaloniki, Greece.
Our study, although being retrospective, is the first one to demonstrate a
relationship between the duration of calcitriol therapy and progressive renal
insufficiency.
Introduction
Primary hyperparathyroidism (PHPT) may rarely coexist with non-medullary
DOI: 10.1530/endoabs.49.GP41
thyroid carcinoma
(NMTC). We report the clinical manifestation and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP42
Med Genet). These preliminary results prompt us to confirm the causative role of
found genetic variants, and to clarify their role in the pathogenesis of specific and
Expression of hypoxia-inducible factor-1a in Calbindin-D9k Knockout
unexpected clinical manifestations.
mice
Song Ai Kang, Seon Young Park, Jin Yong An & Eui-Bae Jeung
DOI: 10.1530/endoabs.49.GP43
Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Introduction
Hypoxia-inducible factors (HIF) are the key transcription factor induced by
hypoxic condition, which regulate expression of specific target genes including
GP44
angiogenic factors, erythropoietin, glucose transporters, and glycolytic enzymes.
Investigation of total and free 25OHD vitamin levels in patients with
Recently, many studies connected to intracellular calcium levels and regulation of
chronic renal failure on different dose of cholecalciferol
HIF-1a protein level. Calbindin-D9k is a cytosolic calcium-binding protein and
Erzsébet Toldy1,2, László Kovács3,4, Réka Németh2, Gyuláné Szakács4,
compensate with other calcium transporter protein for maintenance of cellular
Imre Kulcsár3,4 & Zoltán Locsei3
calcium level. It is expressed in primarily duodenum for absorption of calcium
1Institute of Diagnostics Faculty of Health Science, University of Pécs, Pécs,
and in kidney for resorption of calcium. The objective of this study is to
Hungary;2Central Laboratory, Markusovszky University Teaching Hospi-
investigate interaction between HIF-1a and calbindin-D9k.
tal, Szombathely, Hungary;3Department of General Internal Medicine of
Materials and methods
Markusovszky University Teaching Hospital, Szombathely, Hungary;
8-10 weeks old C57BL/6 mice and calbindin-D9K knockout mice were exposed to
4B. Braun Avitum 6th Dialysis Centre, Szombathely, Hungary.
hypoxia (12G2% O2) for 3 weeks in closed polycarbonate chamber with nitrogen
supply to remove the oxygen vs the normoxic groups. Calbindin-D9k-transfected
The total 25-hydroxy-vitamin-D (t-25OHD) level reflects the vitamin-D supply,
ACHN cells were cultured in normobaric hypoxia (1% O2), with match control in
but it is also influenced by the levels of vitamin-D-binding-proteins (DBP) and
normoxic conditions. Expression of HIF-1a and glucose transporter 1 (GLUT1, a
albumin. The type of dialysis influences the levels of serum proteins. The ‘free-
downstream gene of HIF-1a) were analyzed in mRNA or protein level.
hormone hypothesis’ states that only the free molecules (f25OHD) can diffuse
Results
intracellular. Our aim was to evaluate the total, calculated (c-f25OHD) and direct
Protein level of HIF-1a was increased in calbindin-D9K knockout mice compared
measured (dm-f25OHD) 25OHD levels in patients with chronic renal disease on
with that of control in normoxic condition. However, increased protein level of
cholecalciferol.
HIF-1a of calbindin-D9k knockout mice was reduced in hypoxic condition.
Methods
mRNA levels of GLUT1 showed similar pattern with HIF-1a expression. In
100 patients [45 men; 55 women; 69G14 years: 40 on haemodialysis (HD), 26
comparison to in vivo experiment, expression of HIF-1a and GLUT1 in mRNA
chronic renal failure (CRF) both on 1000 IUD3/day; 34 on peritoneal dialysis
and protein levels corresponded to that of Calbindin-D9k knockout mice.
(PD) on 3000 IUD3/day] were investigated. Their sera were analysed for DBP
Conclusions
(Dako), albumin, Ca, PTHi, t-25OHD (Roche), dm-f25OHD (DIAsource).
These results suggest that calbindin-D9k can regulate expression of HIF-1a in
Results
protein level.
Albumin levels were significantly lower (PD:38G5 HD:40G5; CRF:43G3 g/l;
DOI: 10.1530/endoabs.49.GP42
P!0,001) and DBP concentrations higher (390G55 CRF:352G42; HD:323G
61 mg/l; P!0,001) were in PD group. The t-25OHD and c-f25OHD were the
lowest in PD (t-25OHD: 65G30; CRF:78G38; HD:79G45 nmol/l, c-f25OHD:
14G7; CRF:18G9; HD:20G11 pmol/l, P!0.05). There were no significant
differences among dm-f25OHD levels
(PD:16G5; CRF:16G6; HD:15G
Bone & Calcium Homeostasis 2
6 pmol/l). The highest incidence of suboptimal vitamin D supply was found in
PD patients on the bases of t-25OHD (PD:65%; CRF:42%; HD:43%) and also in
GP43
c-f25OHD levels. These incidences decreased significantly into 15%-23%, when
Chromosome 2q37 microdeletions in two cases of sporadic PHP-1B with
dm-f25OHD was taken into consideration. Out of the three 25OHD fractions only
broad GNAS imprinting defects
dm-f25OHD levels gave the opportunity to prove significant relationship between
Arianna Pirelli1, Francesca Marta Elli1, Paolo Bordogna2, Luisa de Sanctis3,
PTHi/Ca and 25OHD level (ORZ3.8CI:1.024-14.4; PZ0.036).
Daniele Terraris3, Maura Arosio1,2 & Giovanna Mantovani1,2
Conclusions
1Department of Clinical Sciences and Community Health, Endocrinology
t-25OHD and c-f25OHD values underestimate the vitamin D supply particularly
and Metabolic Sciences, University of Milan, Milan, Italy;2Endocrinology
in PD patients. Patients on PD need much higher doses of cholecalciferol, without
and Metabolic Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale
any differences from other two groups in dm-f25OHD levels either. Patients, who
Maggiore Policlinico, Milan, Italy;3Department of Public Health and
have higher dm-f25OHD level have 3.8 times higher chance for normal Ca/PTHi
Pediatrics, University of Turin, Regina Margherita Children’s Hospital,
levels. In case of dm-f25OHD there was a significant relationship proven between
Turin, Italy.
25OHD level and related biomarkers. The dm-f25OHD seems to be a reliable
marker for estimation of vitaminD supply in patients with chronic renal disease.
DOI: 10.1530/endoabs.49.GP44
Pseudohypoparathyroidism type 1B (PHP-1B) is a rare, familial or sporadic,
imprinting disorder due to the epigenetic dysregulation of the GNAS locus, whose
main product is the a subunit of the stimulatory G protein (Gsa). Sporadic PHP-
1B cases (spor-PHP-1B) display broad methylation abnormalities at multiple
GNAS DMRs, but the underlying molecular mechanism is still unknown.
Classically, PHP-1B patients show PTH and TSH resistance, but, in the past
GP45
years, also physical features of Albright hereditary osteodystrophy (AHO) were
Methylation patterns at the novel DMR of GNAS (GNAS-AS2) in
described, suggesting the existence of an overlap among PHP subtypes.
pseudohypoparathyroidism 1B (PHP1B or iPPSD3) subtypes
Moreover, mutations in PRKAR1A and PDE4D genes, and deletions of 2q37
Patrick Hanna1, Anne Rochtus2, Harald Jueppner3, Deborah Mackay4,
were reported in small subsets of clinically diagnosed PHP patients with no
Bruno Francou5, Jérôme Bouligand5, Anne Mantel5, Elli Anagnostou6,
detectable GNAS defects, highlighting the clinical overlap with diseases in
Dominique Gaillard7 & Agnès Linglart1,8
differential diagnosis. Brachydactyly-mental retardation syndrome
(BDMR),
1INSERM U1169, Bicetre Paris Sud, France;2University of Leuven,
associated with 2q37 deletions, may present a spectrum of clinical features,
Leuven, Belgium;3Massachusetts General Hospital and Harvard Medical
including intellectual disabilities, developmental delays, behavioural abnormal-
School, Boston, USA;4University of Southampton, Southampton, UK;
ities and skeletal abnormalities, among which brachydactyly type E.
5APHP, Pharmacogenetics and Hormonology, Bicetre Paris Sud, France;
In the present study, we screened our series of spor-PHP-1B pts with (nZ21) or
6Obstetrics and Gynecology, Alexandra Hospital, Athens, Greece;
without AHO (nZ33) for BDMR-associated deletions to find modifier genes
7Génétique et Biologie de la Reproduction, Centre Hospitalier Universitaire,
possibly involved in the phenotypic heterogeneity observed in PHP-1B, and we
Reims, France;8APHP, CMR Calcium-Phosphore, Bicêtre Paris Sud,
detected 2 different deletions (ranging from w2.83-Mb up to w4.5-Mb) in 2
France.
unrelated pts with AHO. Additional analysis confirmed rearrangements and
allowed to roughly delineate the genetic defects extension.
Deletions overlapped with previously described rearrangements and included
PHP1B -iPPSD3 per the new proposed classification- is a rare disorder
several genes already proposed as causative for BDMR. Interestingly, our
characterized in most patients by proximal tubular resistance to PTH resulting
mutated patients displayed molecular (GNAS loss of imprinting) and endocrine
in hypocalcemia, hyperphosphatemia and elevated PTH. Loss-of-methylation
characteristics (overt PTH resistance) usually absent in BDMR, although so far
(LOM) at the Differentially Methylated Region (DMR) at GNAS exon A/B occurs
only one BDMR patient with raised PTH levels was described (Power et al. 1997 J
in all PHP1B patients, but methylation changes at other DMRs within GNAS
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
occur in some familial and most sporadic PHP1B cases. All patients with
GP47
autosomal dominant PHP1B (AD-PHP1B) due to a maternal deletion that
Recombinant human parathyroid hormone (rhPTH[1-84], parathyroid
comprises the STX16 region (delSTX16C) present with LOM restricted to the
hormone rDNA) improves hypercalciuria in patients with
GNAS-A/B DMR, while sporadic cases (sporPHP1B) present with broad GNAS
hypoparathyroidism: 3-year analysis from RACE study
methylation defects, including LOM at a novel, recently identified DMR within
Bart L Clarke1, Tamara J Vokes2, John P Bilezikian3, Henry G Bone4,
the GNAS locus referred to as antisense DMR2 (GNAS-AS2).
Douglas S Denham5, Hak-Myung Lee6, Michael A Levine7,
Objectives and patients
Michael Mannstadt8, Munro Peacock9, Jeffrey G Rothman10, Dolores
Characterize the methylation pattern at the GNAS-AS2 DMR in AD-PHP1B
M Shoback11, Mark L Warren12, Nelson B Watts13 & Alan Krasner6
delSTX16C (nZ9) and delSTX16- (nZ5) patients; furthermore, sporPHP1B
1Mayo Clinic, Rochester, Minnesota, USA;2University of Chicago
(nZ10) and healthy controls (nZ10) were investigated. STX16 and GNAS
Medicine, Chicago, Illinois, USA;3College of Physicians and Surgeons,
deletions were excluded in the delSTX16- patients by MLPA, genomic multiplex
Columbia University, New York, New York, USA;4Michigan Bone and
and quantitative PCR of the GNAS and STX16 regions.
Mineral Clinic, PC, Detroit, Michigan, USA;5Clinical Trials of Texas, Inc.,
Results
San Antonio, Texas, USA;6Shire Human Genetic Therapies, Inc.,
Lexington, Massachusetts, USA;7Children’s Hospital of Philadelphia,
1. The mean methylation index at the GNAS-AS2-DMR was significantly higher
Philadelphia, Pennsylvania, USA;8Massachusetts General Hospital and
in delSTX16- patients (32G14%) than in controls (24G6%), delSTX16C
Harvard Medical School, Boston, Massachusetts, USA;9Indiana University
(5G2%) and sporPHP1B patients (3C1%) (P!0.0001).
School of Medicine, Indianapolis, Indiana, USA;10Staten Island University
2. Bisulfite-treated DNA of PHP1B patients with delSTX16- was PCR amplified
Hospital, Staten Island, New York, USA;11Endocrine Research Unit,
across the GNAS-AS2-DMR and products were cloned into pcDNA3.1. First,
Department of Veterans Affairs Medical Center, Department of Medicine,
we identified 2 CG-rich subdomains (SD1 and SD2) within the GNAS-AS2
University of California, San Francisco, California, USA;12Physicians East,
DMR that are separated by 184 bp. Second, in delSTX16- patients we observed
PA, Greenville, North Carolina, USA;13Mercy Health, Cincinnati, Ohio,
a unique pattern of methylation including an gain of methylation at SD1 and a
USA.
methylation pattern at SD2
similar to that of controls, whereas both
delSTX16C and sporPHP1B patients displayed full LOM at SD1 and SD2.
Conclusion
We have further refined the GNAS-AS2-DMR and identified a subgroup of
Hypoparathyroidism (HPT) is characterised by hypocalcaemia and impaired
PHP1B patients with a specific pattern of methylation at the GNAS-AS2-DMR.
renal phosphate excretion and calcium conservation. Oral calcium
Our findings reinforce the hypothesis that delSTX16- patients carry a defect in an
supplements and calcitriol can improve serum calcium levels but lack the
element that controls the methylation both at the GNAS-A/B DMR and at the
physiologic effects of PTH on renal reabsorption of calcium. RACE is an
GNAS-AS2 DMR.
ongoing open-label study evaluating the long-term safety of recombinant
human parathyroid hormone
1-84
(rhPTH[1-84], parathyroid hormone
DOI: 10.1530/endoabs.49.GP45
rDNA) in adults with HPT (NCT01297309). In this interim analysis, we
report the 3-year treatment effect with 25-100 mg/day rhPTH(1-84) on 24-h
urinary calcium levels, with or without thiazide diuretics. All data are
presented as mean (SD). The study cohort comprised 49 patients enrolled at
12 USA centres; 38 (78%) completed 36 months of rhPTH(1-84) treatment.
Baseline demographics were as follows: 82% women, age 48 (9.8) years,
HPT duration of
16
(12.5) years,
100% taking prescribed calcium
GP46
supplements and calcitriol. In response to rhPTH(1-84), albumin-corrected
Vitamin D correction elevates apolipoprotein levels in a sex-specific
serum calcium remained within the target range over the 3 years; 2.1 (0.17)
manner
mmol/l at baseline (i.e., start of rhPTH[1-84], nZ49) and Month 36 (nZ36).
Nasser Al-Daghri1, Spiros Garbis2, George Chrousos3, Shaun Sabico1,
Treatment with rhPTH(1-84) also led to a reduction in urinary calcium, from
Naji Aljohani4 & Yousef Al-Saleh5
baseline 8.9 (5.0) mmol/24 h to 6.5 (2.8) mmol/24 h (nZ35; P!0.05).
1King Saud University, Riyadh, Saudi Arabia;2University of Southampton,
Urinary calcium excretion at Month 36 was similar for men compared with
Southampton, UK;3University of Athens, Athens, Greece;4King Fahad
women, and in patients taking or not taking thiazide diuretics. Overall, 71%
Medical City, Riyadh, Saudi Arabia;5King Saud bin Abdulaziz University
of rhPTH(1-84)Ktreated patients with baseline hypercalciuria had normal
for Health Sciences, Riyadh, Saudi Arabia.
24-h urinary calcium excretion at Month 36 (nZ12/17). Treatment with
rhPTH(1-84) improved calcium-phosphate product from baseline 3.4 (0.5)
mmol2/l2 (nZ49) to 2.9 (0.5) mmol2/l2 (nZ36) (P!0.0001). eGFR was
Numerous studies have identified several extra-skeletal health outcomes to
baseline 108.2 (36.4) ml/min (nZ41) and 115.7 (47.3) ml/min (nZ36) at
be associated with vitamin D deficiency, yet a definitive causal link is yet to
Month 36 (P!0.0772). Over 3 years, rhPTH(1-84) maintained target levels
be discovered. Our recent 3D LC-nESI-FTMS proteomic analysis among
of serum calcium and reduced urinary calcium to normal levels in HPT
normal and overweight but apparently healthy adult Saudis identified
patients. More information is needed to understand the timing of the
apolipoproteins, a known independent cardiovascular risk factor, as one of
beneficial effect on urinary calcium excretion.
the serological molecular signatures that modulate vitamin D levels. The
DOI: 10.1530/endoabs.49.GP47
present interventional study aims to compare and validate the identified
apolipoproteins among vitamin D deficient subjects that have achieved full
vitamin D status correction. 199 Saudi adults [89 males, mean age 42.0G
10.4; BMI 28.6G4.4 kg/m2; 110 females, mean age 39.1G12.0; BMI
30.7G5.3]
(with vitamin D deficiency
[25(OH)D
!50 nmol/l] were
GP48
recruited and given 50 000 IU cholecalciferol (VitaD50000w) weekly for
2 months, then twice a month for 2 months, followed by daily 1000 IU
Vitamin D levels after 4 weeks of very low calorie diet (VLCD)
(VitaD1000w) until month 6. Blood samples were taken at baseline and
MaÁngeles Bennasar Remolar, Ignacio Pérez Catalán & María Guinot Soler
after 6 months. Serum 25(OH)D was measured using electrochemilumines-
Hospital General Universitario, Castellón, Spain.
cence and apolipoproteins
(AI, AII, B, CI, CII, CIII and E) using
commercially available kits. In all subjects, serum
25(OH)D increased
significantly from baseline and after
6 months (32.6G11.1 vs 63.4G
Introduction
16.4 nmol/l; P!0.001). In parallel, a significant increase in apolipoproteins
Vitamin D is a liposoluble molecule which takes part in calcium-phosphorous
B, CI, CII, CIII and E (P-values!0.05) after 6 months compared to baseline
homeostasis of the human body. Its optimum levels according to SEIOMM range
was observed. After stratification according to sex, only apolipoproteins CII
between 30 and 75 ng/ml. Being liposoluble substances they require the presence
and CIII were significantly increased in males (P-values!0.001), and only
of biliar salts for their absorption; 80% is absorbed in the yeyune and in a lesser
apolipoprotein CI was significantly increased in females
(P!0.001),
extent in the duodene. The correct concentration of vitamin D is of key
showing sexual dimorphism in the effects of vitamin D with regards to
significance in obesity, particularly its visceral type. An excessive body weight is
apolipoprotein levels. The rest of the apolipoproteins were not significantly
thought to represent a significant determinant of a reduced vitamin D
different pre- and post-vitamin D correction. The present study partially
concentration in serum. Due to its high metabolic activity, visceral adipose
explains the effects of vitamin D correction in the reduction of
tissue promotes sequestration and alterations in turnover of the vitamin-
cardiovascular risk through significant modification of apolipoproteins,
resembling hormone. Care for elimination of the factors which promote
particularly the apolipoprotein C class. These effects differ according to sex.
deficiencies is particularly essential in obese persons in whom degree of adiposity
DOI: 10.1530/endoabs.49.GP46
correlates with reduced concentrations of this vitamin in blood. Given the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
importance of this vitamin in the body we have analysed its levels in obese
PHPT should be questioned for UGI symptoms and evaluated with UGI
patients which were going to follow a VLCD (600 kcal) before undergoing
endoscopy when needed.
bariatric surgery. The patients followed a VLCD during 4 weeks before the
DOI: 10.1530/endoabs.49.GP49
surgery. The values of vitamin D were analysed at two different moments: before
beginning the diet and after the diet, 4 weeks later.
Method
We have designed a prospective observational study; 18 patients were analysed
with IMC O35 kg/m2 with associated comorbility or IMC O40 kg/m2, between
18 and 60 years old, candidate for bariatric surgery with laparoscopic gastric
GP50
by-pass. Vitamin D concentrations were monitored at two different moments: 1
Localisation of parathyroid adenomas using11C-methionine-PET/CT
month before surgery and at the moment of surgery, 4 weeks after the VLCD.
when conventional imaging methods are negative
Objective
Lassi Nelimarkka1,7, Aapo Ounaslehto7, Eija Eloranta4, Leena Moilanen5,
To establish whether there are statistically significant variations in the values of
Saija Hurme3, Marko Seppänen2,6 & Pirjo Nuutila1,2
vitamin D before and after following a VLCD.
1Turku University Hospital, Department of Medicine, Division of
Results
Endocrinology, Turku, Finland;2Turku PET Centre, Turku University
We obtain an average level of vitamin 25 (OH) D of 16,31 ng/ml in the analytical
Hospital, Turku, Finland;3Department of Biostatistics, University of Turku,
evaluation 1 month before surgery and 21,32 ng/ml at the time of the surgery,
Turku, Finland;4Department of Medicine, Division of Medicine and
which takes place at the end of the VLCD. Statistically significant differences are
Pulmonary Diseases, Oulu University Hospital, Oulu, Finland;5Division of
observed between the levels of vitamin 25 (OH) D 1 month before surgery and at
Endocrinology, Department of Medicine, Kuopio University Hospital,
the time of the chirurgical act.
Kuopio, Finland;6Department of Nuclear Medicine, Turku University
Conclusions
Hospital, Turku, Finland;7Department of Medicine, University of Turku,
According to the results, patients that follow a 4-week VLCD significantly improve
Turku, Finland.
the levels of vitamin 25 (OH)D in blood. Those levels do not reach a normal level
after the diet, however it is evident the benefit of the recommended process, and it
would be interesting to evaluate in the long term if such a tendency remains.
In primary hyperparathyroidism
(pHPT) an exact localization of the
DOI: 10.1530/endoabs.49.GP48
pathological parathyroid gland(s) is essential before minimally invasive
parathyroidectomy. We have previously shown in a small group of pHPT
patients, that11C-methionine-PET/CT provides additional information if
123
I/99m Tc-sestamibi (MIBI) scan remains negative. The aim of the present
study was to evaluate the clinical value of11C-Met-PET/CT in a larger
GP49
pHPT patient cohort.
Upper gastrointestinal symptoms, endoscopic and pathological features,
Methods
and serum gastrin and chromogranin A levels in patients with primary
Totally 89 patients with pHPT (66 females, 23 males, age 18-81 years) and
hyperparathyroidism
negative or inconclusive localisation findings with123I/99mTc- MIBI-SPECT/CT
Osman Ersoy1, Berna Evranos Ogmen2, Sefika Burcak Polat3,
(78,7%) or99mTc-MIBI-SPECT/CT (21.3%) were studied with11C-Met-PET/CT.
Levent Ozturk5, Berrak Gumuskaya Ocal4, Bekir Cakir3 & Reyhan Ersoy3
Most of the patients (87.6%) were surgical treatment naive and the rest of them
1Yildirim Beyazit University, Faculty of Medicine, Ataturk Education and
(12.4%) were previously operated 1-2 times.
Research Hospital, Department of Gastroenterology, Ankara, Turkey;
Results
2Ataturk Education and Research Hospital, Department of Endocrinology
11C-Met-PET/CT revealed the pathologic parathyroid gland in 48 (60.8%) of the
and Metabolism, Ankara, Turkey;3Yildirim Beyazit University, Faculty of
79 surgically treated patients. Totally 26 patients (32.9%) had a negative11C-
Medicine, Ataturk Education and Research Hospital, Department of
Met-PET/CT finding and 16 of them had further explorative surgery, whereas 10
Endocrinology and Metabolism, Ankara, Turkey;4Yildirim Beyazit
of these Met-PET negative patients were not operated, but treated conservatively
University, Faculty of Medicine, Ataturk Education and Research Hospital,
instead. In five cases (6.3%) Met-PET detected a false-positive finding, i.e. the
Department of Pathology, Ankara, Turkey;5Yildirim Beyazit University,
pathological parathyroid gland was found in another location. On a per-lesion
Faculty of Medicine, Ataturk Education and Research Hospital, Department
level PET results were 48 true positive (60.8%) and 21 false negative (26.6%).
of Anesthesiology, Ankara, Turkey.
The lesion-based sensitivity was 75.4% (positive predictive value 94.6%) and
specificity 40.0% (negative predictive value 10.5%). The diagnostic accuracy of
11
C-Met-PET/CT in this study was 73%. Based on the histological examinations
Introduction
67 adenomas (84.8%) and six hyperplastic (7.6%) parathyroid glands were found.
In five cases the finding was normal parathyroid tissue or unspecified. Ten
Upper gastrointestinal (UGI) symptoms are frequently encountered in patients
patients (12.7%) had more than one pathological parathyroid glands. There were
with primary hyperparathyroidism
(PHPT). Some of these symptoms may
no parathyroid carcinomas detected in this study. Totally
79 patients had
improve after PHPT treatment, while hypercalcemic state may also cause
parathyroid surgery and 55 (69.6%) of them were biochemically cured, but in 16
permanent effects. We aimed to evaluate UGI symptoms, UGI endoscopic and
patients (20.3%) pHPT persisted and in eight patients (10.1%) the postoperative
pathologic features and determine the relationship between these features with
status remained unknown.
serum chromogranin A (CgA) and gastrin in PHPT patients.
Conclusion
Methods
11C-methionine-PET/CT offers an additional noninvasive imaging method to
Seventy-one patients diagnosed with PHPT were included in the study after
localize hyperfunctiong parathyroid glands in a situation when conventional
exclusion of patients who refused UGI endoscopy, had an UGI surgery or used
imaging methods99mTc or123I/99mTc-sestamibi SPECT/CT fail or are equivocal.
drugs that affect serum chromogranin A or gastrin. Patients were questioned
regarding UGI symptoms. Serum CgA and gastrin were measured. Endoscopy
DOI: 10.1530/endoabs.49.GP50
was performed and gastric biopsy specimens were taken to evaluate atrophic
gastritis.
Results
There were 60 females and 11 males, and median age was 52 years. Mean serum
CgA and gastrin levels were
134.10G19.43 ng/ml
(28-620) and
219.39G
GP51
48.6 pg/ml (14-2255), respectively. Dyspepsia, epigastric pain and weight loss
Calcium to phosphorous ratio (Ca/P) as helpful index to recognize
were the most common symptoms and presented in 61, 51.7 and 46.6% of
primary hyperparathyroidism, but not primary hypoparathyroidism: a
patients, respectively. Endoscopy was normal in 25(35.2%) patients. Erosive
big-data approach
antral gastritis, atrophic gastritis, gastric ulcers, duedonal ulcers, reflux gastritis
Sara De Vincentis1,2, Daniele Santi1,2, Vincenzo Rochira1,2, Monica Setti3,
and nodular gastritis were present in 14 (19.7%), 12 (16.9%), 6 (8.5%), 5 (7%), 4
Simonetta Tagliavini4, Manuela Varani4, Tommaso Trenti4,
(5.6%) and 4 (5.6%) patients, respectively. Intestinal metaplasia, gastric atrophy,
Manuela Simoni1,2 & Bruno Madeo1,2
gastric neuroendocrine tumor and Helicobacter pylori infection were detected in
1Unit of Endocrinology, Department of Biomedical, Metabolic and Neural
29.2,
20,
1.4
and 66.2% of patients, respectively. Serum CgA was similar
Sciences, University of Modena and Reggio Emilia, Modena, Italy;2Unit of
in patients with and without atrophic gastritis, while serum gastrin was higher in
Endocrinology, Department of Medicine, Endocrinology, Metabolism and
patients with atrophic gastritis (PZ0.024). Presence of intestinal metaplasia and
Geriatrics, Azienda OU of Modena, Modena, Italy;3Service of Clinical
Helicobacter pylori infection did not affect serum CgA and gastrin levels.
Engineering, Azienda USL of Modena, Modena, Italy;4Department of
Conclusion
Laboratory Medicine and Pathological Anatomy, Azienda USL of Modena,
Dyspeptic symptoms are common in patients with PHPT. The frequencies of
Modena, Italy.
atrophic gastritis and peptic ulcers are increased. We think that patients with
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
in the lung, especially ACE2. The precocious LIR treatment in the inflammatory
Primary hyperparathyroidism
(HyperPT) and primary hypoparathyroidism
phase prevented all these pathogenic alterations.
(HypoPT) are often underdiagnosed. Several strategies have been investigated in
DOI: 10.1530/endoabs.49.GP52
the past in order to identify diagnostic parameters, although the diagnosis of both
HyperPT and HypoPT remains challenging so far, especially in asymptomatic
patients. Calcium (Ca) and phosphorus (P) are inversely related together, thus the
Ca/P ratio could be an useful tool to define these conditions. Recently, we proposed
for the first time a cut-off of 3.5 for Ca/P ratio for the diagnosis of HyperPT.
Aim
To evaluate the diagnostic value of the Ca/P ratio for HyperPT and HypoPT
GP53
through a big-data approach.
Clinical, laboratory and cardiac parameters in overt primary
Methodology
hypothyroidism versus overt central hypothyroidism
A retrospective, observational, case-control study on big-data was carried out. All
Melania Balas1, Florina Parv2, Mihaela Vlad1, Ioana Golu1, Daniela Amzar1
examinations of parathyroid hormone (PTH), Ca and P performed at the laboratory
& Ioana Zosin1
of Modena Hospital from
2010 to
2016 were consecutively included. We
1Department of Endocrinology, Victor Babes University of Medicine and
considered only patients between 18 and 90 years of age. Laboratory ranges of
Pharmacy, Timisoara, Romania;2Department of Cardiology, Victor Babes
normality for both PTH and Ca were used to divide records in HyperPT, HypoPT
University of Medicine and Pharmacy, Timisoara, Romania.
and controls.
Statistical analysis
Background
The diagnostic accuracy of Ca/P ratio was investigated using receiver operator
Hypothyroidism affects cardiac function, leading to cardiomyopathy, pericarditis,
characteristics (ROC) curves in order to define cut-off points, which show higher
lower left ventricular performance, etc. The present study investigates different
sensitivity and specificity for the identification of affected patients.
parameters (clinical, hormonal, biochemical, echocardiographic) in overt primary
Results
hypothyroidism (OPHypo) and overt central hypothyroidism (OCHypo).
46 597 records were considered. 576 HyperPT (1.2%), 323 HypoPT (0.7%) and
Material and methods
45 698 controls (98.1%) were found. Ca/P ratio was significantly different among
The study included 33 untreated patients with OCHypo (5 with empty sella, 3
groups (P!0.001). In particular, Ca/P ratio was significantly higher in HyperPT
with idiopathic hypopituitarism, 7 with Sheehan’s syndrome, 18 with different
than controls (P!0.001). For the diagnosis of HyperPT, the threshold of 3.17 for
types of pituitary macroadenomas, before or after surgery) and 67 cases with
Ca/P ratio was obtained by means of the ROC curve analysis, with 85% of both
OPHypo, respectively with chronic autoimmune thyroiditis. Among the patients
sensitivity and specificity. HypoPT showed lower Ca/P ratio compared to controls
with OCHypo,
4
presented partial pituitary insufficiency
(2
cases on
(P!0.001), although no useful threshold for the diagnosis was found at ROC curve
gonadotropins and TSH secretion and 2 cases on growth hormone and TSH
because of the low sensitivity.
secretion), the rest of the cases showing global pituitary insufficiency. Patients
Conclusions
with acromegaly and Cushing’s disease were excluded.
We confirm the high sensitivity and specificity of Ca/P ratio for the diagnosis of
Results
HyperPT using the largest cohort of patients available so far in the literature. On the
The clinical picture was more severe in OPHypo as in OCHypo (dominated by
contrary, Ca/P ratio does not contribute to identify patients with HypoPT and
fatigue, edema, dry skin, neurological alterations). The values of serum thyroxin
further researches are needed to better describe this condition. In conclusion, Ca/P
were significantly lower in OPHypo (P!0.0001). 40% of OPHypo patients
ratio is a simple and inexpensive diagnostic tool to recognize HyperPT.
presented pericarditis, as compared to OCHypo
(2
cases, PZ0.0003). No
DOI: 10.1530/endoabs.49.GP51
statistical differences were noted between the two groups, regarding heart rate,
systolic and diastolic blood pressure values, isovolumic contraction time.
Nonetheless, the isovolumic relaxation time was significantly higher in OPHypo
group (91.8G8.5 ms), as in OCHypo (80.2G9.9 ms, P!0.0001). Coronary
artery disease was more common in OPHypo group (21 cases, 31.3%), as
compared to OCHypo (5 cases, 15.1%, PZ0.095). Hyponatremia was recorded in
4 patients with OPHypo and in 3 cases with OCHypo (PZ0.68). The values of
serum total cholesterol, LDL-cholesterol, glycemia, creatin-kinase, transamin-
Cardiovascular & Lipid Endocrinology
ases, creatinine were significantly higher in OPHypo group, correlated to lower
GP52
values of serum thyroxin. The incidence of anemia was similar in both groups (18
Liraglutide prevents right ventricle hypertrophy by avoiding ACE1 &
cases in OPHypo group, 6 cases in OCHypo group, PZ0.456).
ACE2 reduction in an experimental model of idiopathic pulmonary
Conclusion
fibrosis
The metabolic and cardiac parameters were more profound altered in primary
Juan Fandin˜ o, Laura Toba, Hugo Ogando, Yolanda Diz, Lucas González &
hypothyroidism, as compared to central hypothyroidism.
Federico Mallo
DOI: 10.1530/endoabs.49.GP53
Biomedical Research Centre (CINBIO, Vigo, Galicia, Spain.
The Glucagon-like peptide-1 (GLP-1) receptor is expressed in the lung having a
very important role in the modulation of the Angiotensin Converting Enzymes
(ACEs). ACE1 cleaves angiotensin-I into angiotensin-II, which is converted by
ACE2 to Ang(1-7). Ang(1-7) has vasodilating effects. The Idiopathic Pulmonary
Fibrosis
(IPF) is characterized by excessive extracellular matrix deposition
GP54
disrupting the alveolar architecture and physiology. IPF develops by a sequence
of inflammation multifocal process that leads to a fibrotic response. IPF presents
Correlation between triglyceride glucose index (TyG) and coronary
pulmonary hypertension and right ventricle hypertrophy.
artery calcification in Korean adults
The aim of this study is to elucidate the effect of precocious treatment with LIR
Jihong You, Kahui Park, Jung Hye Kim, Sang Bae Lee, Yusik Kim,
during the inflammatory phase of IPF in ACE1 & ACE2 in the late fibrotic phase
Ji sun Nam, Jong Suk Park & Chul Woo Ahn
in an experimental model of IPF.
Gangnam Severance Hospital, Seoul, Republic of Korea.
IPF was induced in rats by a single intra-tracheal instillation of Bleomycin (BLM,
2.5 mg/kg) on day 0 (D0). From day K1 to day 6, animals were treated with
Objective
Liraglutide (LIR, 100 mg/kg/12h subcutaneous). On D21 rats were sacrificed.
Triglyceride glucose (TyG) index is considered a surrogate marker of insulin
Heart ventricles and lungs were isolated, weighted and frozen. Histology of lungs
resistance, and insulin resistance is known risk factor of cardiovascular disease.
confirmed interstitial lung fibrosis in all BLM-treated rats.
Until now, few studies have investigated the relationship between TyG index and
The real time-PCR levels of ACE-1 & ACE-2 were lower in lungs of BLM-IPF
coronary artery calcification (CAC), thus we investigated the correlation between
than in controls (40% and 48% reduction, respectively). Right ventricle weight
TyG index and CAC in healthy Korean Adults.
was markedly increased in BLM-IPF rats (C66%). The treatment with LIR at the
Methods
beginning of the inflammatory phase completely restored the levels ACEs at the
A total of 4,463 participants underwent cardiac computed tomography in health
fibrotic phase (21D), and prevented the right ventricle hypertrophy.
promotion center were enrolled. TyG index was calculates as ln[fasting
In conclusion BLM instillation causes local injury with inflammation and
triglycerides(mg/dl) X fasting glucose(mg/dl)/2]. Multi-detector CT was used
alteration of lung vasculature with pulmonary hypertension reflected by right
to measure coronary artery calcium score (CACS) and CACSO0 was defined as
ventricle hypertrophy and related to a reduction in the expression levels of ACEs
the presence of CAC.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
to determine whether circulating PCSK9 concentration is linked to coronary
There were significant differences in cardiovascular parameters among the groups
damage severity in patients with acute coronary syndrome (ACS). We studied 137
and the prevalence of CAC significantly increased with TyG index levels. In the
patients with ACS who underwent coronary angiography. The study population
logistic regression analysis after adjusted for multiple risk factors, the odds ratios
was divided into two groups depending on the presence of coronary artery lesion
(95% CI) for the prevalence of CAC were 1.0, 1.03 (0.72-1.45), 1.23 (0.85-1.74),
(lesion (C): nZ112, lesion (K): nZ25). Baseline characteristics and PCSK9
1.68
(1.15-2.44) for increasing TyG index level (P!0.05).
levels were measured and coronary lesions were evaluated using the SYNTAX
Conclusion
scoring system. After adjustment for established CVD risk factors including age,
There was a significant association between TyG index and prevalence of CAC.
body mass index (BMI), total cholesterol and low-density lipoprotein-cholesterol
TyG index, a simple measure reflecting insulin resistance, might be useful to the
(LDL), ACS patients with coronary artery lesion have significantly higher PCSK9
indicator of atherosclerosis. TyG index is even simple to calculate and seems a
levels than patients without lesion (178.26G63.9 ng/ml vs. 223.0G76.1 ng/ml,
useful marker of atherosclerosis, and reflect cardiovascular risk.
PZ0.026). Spearman’s correlations revealed that PCSK9
was positively
DOI: 10.1530/endoabs.49.GP54
associated with the number of involved coronary artery (Pearson coefficient,
0.034; PZ0.01) and the global registry of acute coronary events (GRACE) risk
score which is a risk prediction tool applicable for ACS patients
(Pearson
coefficient, 0.209; PZ0.015). Furthermore, we found that plasma PCSK9 level
was positively correlated with SYNTAX score
(Spearman’s RZ0.115,
PZ0.048). In the present study, we show that Serum PCSK9 concentration is
GP55
associated with angiographic severity of ACS and GRACE score after
adjustments for established CVD risk factors. Further studies are needed to
Both oral and vaginal combined hormonal contraceptives induce
confirm this observation.
unbeneficial metabolic effects in women with PCOS: a randomized
study
DOI: 10.1530/endoabs.49.GP56
Maria-Elina Mosorin1,2, Terhi Piltonen1,2, Juha Tapanainen3,4 &
Laure Morin-Papunen1,2
1Department of Obstetrics and GynecologyOulu University Hospital, Oulu,
Finland;2Department of Obstetrics and Gynecology, PEDEGO, MRC,
University of Oulu, Oulu, Finland;3Department of Obstetrics and
Gynecology, University of Helsinki, Helsinki, Finland;4Department of
Obstetrics and Gynecology, Helsnki University, Helsinki, Finland.
GP57
Oral combined hormonal contraceptives (CHCs) have been suggested to induce
Clinical significance and hormonal relationships of visceral adiposity
more unbeneficial metabolic effects than vaginal CHCs. CHCs are used routinely
index (VAI) in independently living old subjects
to treat the clinical symptoms of polycystic ovary syndrome (PCOS), but there are
Mireia Mora1,2, Elisabet Palomera3, Mateu Serra-Prat3 &
no studies investigating whether the vaginal route is safer in women with known
Manel Puig-Domingo4
metabolic risks.
1Department of Endocrinology and Nutrition1, Hospital Clínic i Universitari
Twenty-five women with PCOS defined according to the Rotterdam criteria were
of Barcelona, Barcelona/, Spain;2Group of Endocrine Disorders, IDIBAPS,
randomized to use either oral contraceptive pills (desogestrel-ethinylestradiol)
Barcelona, Spain;3Research Unit and Ciberhep, Hospital de Mataró,
(nZ14) or contraceptive vaginal rings (etonogestrel-ethinylestradiol) (nZ11)
Mataró, Spain;4Department of Endocrinology and Nutrition,
continuously for 9 weeks. Blood samples were drawn and OGTT performed at
Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
baseline and at 9 weeks.
Serum levels of SHBG increased and consequently the free androgen index (FAI)
decreased in both study groups from baseline to 9 weeks of treatment [oral: 3.2
Introduction
(95% confidence interval, CI: 2.2; 4.3) to 0.7 (0.5; 1.0); vaginal: 3.8 (1.8; 5.8) to
The Visceral Adiposity Index (VAI) has been proven to be an indicator of adipose
0.6
(0.5; 0.8), P%0.003 in both groups]. Insulin sensitivity was reduced at 9
distribution and function that indirectly expresses cardiometabolic risk, in
weeks according to the Matsuda index [oral: 2.5 (0.1; 4.8) to 0.2 (0.2; 0.3),
particular in specific populations such as women with polycystic ovary syndrome,
PZ0.035]; vaginal: 3.0 (0.4; 4.4) to 0.2 (0.1; 0.2), PZ0.366]. Serum levels of
acromegaly or type 2 diabetes. Little information is known about its usefulness in
triglycerides [oral 0.9 (0.7; 1.2) to 1.3 (0.8; 1.8) mmol/l, PZ0.132; vaginal 0.8
the definition of cardiometabolic risk in ageing population.
(0.6;
1.0) to
1.3
(0.9;
1.7) mmol/l, PZ0.003] hs-CRP (PZ0.034) and the
Objective
AUCglucose during the OGTT (PZ0.017) rose significantly only in the vaginal
To study VAI in relation to metabolic and hormonal data, frailty and mortality in
group. The AUCinsulin
(oral: PZ0.36, vaginal: PZ0.16) increased non-
non-institutionalized people more than 70 years old of the Mataró Ageing Study.
significantly from baseline to 9 weeks in both treatment groups. There were no
Methods/Design
differences in serum levels of glucose, insulin, hs-CRP, lipids or testosterone
289
participants
(142
men/147
women) were included. Individuals were
between the treatment groups at baseline or after 9 weeks.
characterized by anthropometric variables, metabolic syndrome (MS) parameters
Against our hypothesis, vaginal CHCs were not metabolically safer than oral
by IDF and ATP-III as well as hormonal factors (TSH, free-T4, growth hormone,
CHCs. These results emphasize the importance of monitoring glucose
IGF-I, ghrelin, cortisol, dehidroepiandrosterone -DHEA-, DHEAs, testosterone,
metabolism during CHC use regardless of the route of administration, especially
SHBG, estradiol, estrone, cortisol/DHEA and cortisol/DHEAs), grip strength,
in PCOS women displaying typically risks of type 2 diabetes or cardiovascular
Barthel and assessment of cognitive impairment (MiniCognoscitive Examination
diseases.
-MCE- Spanish version) and frailty by Fried criteria. VAI was calculated
DOI: 10.1530/endoabs.49.GP55
according to Amato et al.
Results
The whole cohort showed a statistically significant association of the individual
components the MS with VAI. In women but not in men, a lineal trend association
was observed between the prevalence of diabetes and VAI categorized in
quartiles. However, VAI showed no association in our sample population with the
presence of cardio or cerebrovascular disease. The multiple regression analysis
showed that ghrelin (BZK0.240, PZ0.005) and SHBG (BZK0.199, PZ0.034)
GP56
were the only hormonal variables independently associated to VAI in women,
PCSK9 in relation to coronary damage severity in patients with
while no associations were found in men. After a prospective follow-up of two
cardiovascular disease
years, those individuals with higher VAI at basal time point were associated to
Nan Hee Cho, Kwi Hyun Bae, Gwon Soo Jung, Mi Jin Kim,
frailty condition at two years (media (SD): 2.47 (2.19) in frail vs 1.71 (0.97) in
Yeon Kyung Choi, Jung Beom Seo & Keun Gyu Park
non-frail, PZ0.064). No significant association was found between VAI and
Kyungpook National University Hospital, Dae Gu City, Republic of Korea.
mortality 2 and 8 years follow-up.
Conclusions
Proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that
VAI does not provide additional information to MS criteria in ageing individuals
promotes degradation of the low density lipoprotein (LDL) receptor, has been
in relation to cardiovascular risk or mortality in our population. However, VAI
emerged as a novel therapeutic target for the dyslipidemia. It is well known that
was associated to frailty in the whole cohort, and in women, with diabetes and
the pathogenesis of cardiovascular disease (CVD) involves lipid metabolism
ghrelin.
alteration, but the predictive value of circulating PCSK9
level concerning
DOI: 10.1530/endoabs.49.GP57
coronary disease severity is largely unknown. The main objective of this study is
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP58
Results
Descriptive data of the subjects were BMI 24.4 kg/m2 (22.4-26.6), waist 88 cm
Circulating levels of miR24-1 cluster microRNAs are increased in
(82-94), percentage lean body mass 79.1% (75.6-82.5), percentage fat mass
primary aldosteronism
17.2% (18.8-21.1), total testosterone 20.7 nmol/l (17.0-25.4), SHBG 27 nmol/l
Josie van Kralingen1, Cali Anderson1, E. Marie Freel1, John M. Connell2,
(21-34) and VO2max 160.3 ml/min/kg 0.73 (143.3-177.6) (median (interquartile
Scott M. MacKenzie1 & Eleanor Davies1
range). In bivariate analysis, lean body mass (%) (rZ0.62), SHBG (rZ0.26),
1University of Glasgow, Glasgow, UK;2University of Dundee, Dundee,
total testosterone
(rZ0.24), and free testosterone
(rZ0.13) were positively
UK.
associated with VO2max, whereas fat mass
(%)
(rZK0.63) and waist
(rZK0.47) were negatively associated with VO2max (all P!0.001). Fat mass
Introduction
(%) and lean body mass (%) were closely associated (rZK0.998, P!0.001). In
Measurement of microRNA (miRNA) in aldosterone-producing adenoma (APA)
multivariate regression analysis, models with VO2max as the dependent variable
tissue from primary aldosteronism (PA) patients show levels of the miR24-1
and lean body mass (%) or fat mass (%) as independent variables were the best
cluster miRNAs (i.e. miRNAs 24-1, 27b and 23b) are significantly reduced
predictors of VO2max (both models R2Z0.47), whereas the models including
relative to normal adrenal tissue. Our previous studies also show that miRNA-24
testosterone (total, free or bioavailable testosterone) or SHBG as independent
directly targets CYP11B2 (aldosterone synthase) gene expression. Circulating
variables had lower R2 values (R2Z0.09-0.13). All models were adjusted for age
miRNAs released into the bloodstream may be diagnostic biomarkers or
and smoking.
signalling molecules. Here, we assessed whether circulating levels of miR24-1
Conclusion
cluster miRNAs differ significantly between PA patients and essential
Body composition measures were the best predictors of VO2max in young men.
hypertensives, and whether they correlate with relevant phenotypic traits.
VO2max was more closely associated with waist than testosterone or SHBG.
Methods
DOI: 10.1530/endoabs.49.GP59
Patients with essential hypertension patients (nZ18) were drawn from the British
Genetics of Hypertension (BRIGHT) study and matched with 18 confirmed PA
patients for age, gender and systolic blood pressure. Circulating miRNA was
isolated from 200 mL EDTA plasma and analysed using quantitative realtime
assays for miRNAs 24, 27b and 23b.
Results
PA patients had significantly increased circulating levels of miRNAs
24
(P!0.05) and 23b (P!0.0001) relative to primary hypertensive patients; there
were also trends towards higher miRNA-27b but this was not significant.
MiRNA-23b negatively correlated with diastolic pressure
(P!0.05), left
ventricular mass (P!0.01) and age (P!0.05). MiRNAs 27b and 23b positively
correlated with BMI (P!0.05).
Conclusions
We have identified and validated increased circulating miR24-1 cluster miRNA
GP60
levels in PA patients. These contrast with the significantly reduced levels of these
miRNAs observed in APA tissue. Interestingly, miR-24 has been proposed to act
Probiotics and nutraceuticals as a new frontier in obesity prevention
as a feedback signal, repressing CYP11B2 expression when aldosterone levels are
and management
high. Therefore, increased secretion of these miRNAs into the circulation may be
Nazarii Kobyliak1, Tetyana Falalyeyeva2, Petro Bodnar1 &
the result of high aldosterone levels and be intended to suppress its release. Future
Tetyana Beregova2
studies will examine the role of these miRNAs in the aetiology and pathology
1Bogomolets National Medical University, Kyiv, Ukraine;2Taras
of PA.
Shevchenko National University of Kyiv, Kyiv, Ukraine.
DOI: 10.1530/endoabs.49.GP58
Introduction
The beneficial interaction between the microbiota and humans is the way how
bacteria contained within the gut ‘talk’ to the immune system. Into this landscape
probiotics and nutraceuticals play a major role. The study aims to determine
whether probiotics plus nutraceuticals such as smectite or omega-3 are superior to
probiotic alone on the monosodium glutamate (MSG) induced obesity model in
rats.
Methods
Totally 75 rats divided into five groups were included (nZ15, in each). Rats of
group I were intact. Newborns rats of groups II-V were injected with MSG. The
III (Symbiter) group received 2.5 ml/kg of multiprobiotic “Symbiter” containing
concentrated biomass of 14 probiotic bacteria genera. The IV (Symbiter-Omega)
and V (SymbiterCSmectite) groups received combination of probiotic biomass
GP59
supplemented with flax and wheat germ oil (250 mg of each, concentration of
omega-3 fatty acids 1-5%) or smectite gel (250 mg) respectively. Anthropo-
Body composition and testosterone determined VO2max in 780 young
metric, biochemical parameters of lipid and carbohydrate metabolism, and level
men - results from the Odense Androgen Study
of proinflammatory cytokines (IL)-1b, IL-12Bp40, INF-g) and anti-inflammatory
Louise Lehmann Christensen, Torben Leo Nielsen, Pernille Hermann,
cytokines (IL-4, IL-10, TGF-b) were measured.
Dorte Glintborg & Marianne Andersen
Results
Odense University Hospital, Odense C, Denmark.
In all interventional groups significant reduction of total body and VAT weight as
compared to MSG-obesity were observed. However, the lowest prevalence of
Background
obesity was noted for Symbiter-Omega (20% vs 33.3% as compared to other
Cardiorespiratory fitness is a measure for physical activity and a prognostic health
interventional groups). Moreover, supplementation of probiotics with omega-3
indicator. However, measurement of maximal oxygen consumption (VO2max) is
lead to more pronounced decreasing of HOMA-IR (2.31G0.13 vs 4.02G0.33,
not possible in clinical practice.
P!0.001) and elevation of adiponectin level
(5.67G0.39
vs
2.61G0.27,
Aim
P!0.001) as compared to obesity group. Both nutraceuticals combination with
We hypothesized that body composition and testosterone levels could be used as
probiotic and probiotic alone equally attenuated inflammation that was confirmed
possible determinants of VO2max in young men.
by the decrease of the pro-inflammatory and the activation of anti-inflammatory
Participants and design
system.
The Odense Androgen Study, a population-based, observational study including
Conclusion
780 men aged 20-30 years. VO2max (ml/min/kg 0.73) was indirectly measured
Probiotics and nutraceuticals led to a significantly lower prevalence of obesity,
by a mechanically braked cycle ergometer. Fat mass (%) and lean body mass (%)
reduction of insulin resistance, total and VAT weight. Our study demonstrated
were assessed by whole-body DXA scans. Total testosterone levels (nmol/l) were
that supplementation of probiotics with omega-3 may have most beneficial
measured (RIA using extraction and chromatography). SHBG levels (nmol/l)
antiobesity properties.
were determined by immunoluminometric assay. Bioavailable and free
DOI: 10.1530/endoabs.49.GP60
testosterone were calculated.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP61
Overexposure to dexamethasone during fetal development intensifies the process
of degeneration of germ cells in the ovary, contributing thus the reduction of
Constructing a long-acting leptin analogue
reproductive potential for the individual.
Suleyman Nahit Sendur1, Ian R Wilkinson2 & Richard J Ross2
1Hacettepe University Department of Endocrinology and Metabolism,
DOI: 10.1530/endoabs.49.GP62
Ankara, Turkey;2University of Sheffield Department of Oncology and
Metabolism, Sheffield, UK.
Introduction
Leptin is a 16-kDa peptide hormone secreted by adipose tissue and acts as a
GP63
sensor for energy stores. It feedsback at the hypothalamic arcuate nucleus to
Does the loss of RAD52 in PC contribute to resistance to antiandrogen
suppress appetite. Leptin treatment has been highly effective in suppressing
therapy?
appetite in the rare cases of leptin-deficient obesity and improving the metabolic
Mahmoud A. Alfaqih1,2, Ching yi Chang2, John Norris2 &
profile in congenital generalised lipodystrophy. These patients require 2.5-10 mg
Donald P. McDonnell2
once daily recombinant leptin treatment. We hypothesised that prolonged
1Jordan University of Science and Technology, Irbid, Jordan;2Duke
constant exposure to leptin with a long acting leptin may have a more potent
University Medical Center, Durham, NC, USA.
metabolic action and appetite supression and therefore we designed a long acting
leptin molecule.
Recent statistics indicate that prostate cancer (PC) is the most frequent cancer in
Aim
men worldwide and is the leading cause of cancer death in men above 50 years of
To construct, express, purify and test for bioactivity a long acting leptin.
age. The Androgen receptor (AR), a member of the superfamily of nuclear
Methods
hormone receptors, plays a well-established role in the development and
We have previously demonstrated that a fusion of growth hormone to growth
progression of the disease. PC localized to the prostate is commonly treated
hormone binding protein (GHBP) generated a long acting GH. In this project we
with surgical removal of the gland and is often associated with a favorable
utilise GHBP as a fusion partner with leptin the concept being that linking a fusion
outcome. However, metastatic PC requires more aggressive treatment modalities
protein to the C-terminus will decrease clearance through reduced proteolysis and
often consisting of gonadotropin releasing hormone (GnRH) agonists and/or an
renal clearance. We further modified this molecule by introducing a W104A
AR antagonist (ex: bicalutamide). Although initially successful in alleviating
(Tryptophan-Alanine amino acid substitution) in the GHBP to prevent GHBP
symptoms, the disease progresses to a castrate resistant state, where drugs
binding to GH in the circulation.
targeting the AR axis have limited clinical utility. Several mechanisms were
Results
suggested to explain resistance to antiandrogen treatment including AR
GHBP(W104A)-leptin fusion was cloned in to a modified invitrogen pSecTag
mutations, AR amplification and/or local production of androgens. Additionally,
plasmid with the secretion sequence for leptin. This plasmid was transfected into
some studies also suggest that deregulation of AR cofactor expression may permit
CHO Flp-In cells by reagent-mediated transfection. Protein was expressed in
weak androgens or even antiandrogens to function as full AR agonists and fuel
CHO cells grown in roller bottles in the presence of valproic acid at a set
tumor growth, a mechanism that contributes to the castrate resistance phenotype.
temperature of 31 8C and purified by antibody affinity chromatography. In vitro
This puts into context our observation that RAD52, a protein involved in DNA
bioactivity was assessed by luciferase expression induced by leptin. Approxi-
repair machinery also functions as an AR cofactor whose deregulation affects
mately two times fold induction was achieved.
PC response to antiandrogens. Herein, using PC cell models, we found that
Conclusion
knockdown of RAD52
increases AR protein levels and enhances AR
We have demonstrated it is possible to generate a fusion of leptin to GHBP and
transcriptional activity in the presence of low levels of androgens. More
that this fusion retains bioactivity. Future studies will assess pharmacodynamic
importantly, we found that RAD52 knockdown converts the AR antagonist
and pharmacokinetic properties of this molecule.
bicalutamide into a full agonist in cell reporter assays and on AR target genes; an
DOI: 10.1530/endoabs.49.GP61
activity associated with enhanced recruitment of AR to target gene promoters.
Taken together, our results suggest that deregulation of RAD52 expression may
mediate PC resistance to antiandrogen therapy.
DOI: 10.1530/endoabs.49.GP63
Developmental & Protein Endocrinology
GP62
GP64
Effects of prenatal dexamethasone on fetal rat ovary
Thyroid hormone protects hepatocytes from HBx-induced
Natasa Ristic1, Lazo Pendovski2, Milica Manojlovic-Stojanoski1,
carcinogenesis by enhancing mitochondrial turnover
Dragana Miljic3, Marko Miler1, Vladimir Ajdzanovic1,
Hsiang-Cheng Chi & Kwang-Huei Lin
Svetlana Trifunovic1, Natasa Nestorovic1 & Verica Milosevic1
Chang-Gung University, Taoyuan, Taiwan.
1Institute for Biological Research “Sinisa Stankovic”, University of
Belgrade, Belgrade, Serbia;2Faculty of Veterinary Medicine, Ss. Cyril and
Infection by hepatitis B virus (HBV) accounts for 50w80% of hepatocellular
Methodius University in Skopje, Skopje, Macedonia;3Department of
carcinoma (HCC) development worldwide, in which the HBV encoded X protein
Neuroendocrinology, Clinic for Endocrinology, Diabetes and Metabolic
(HBx) plays critical role in the induction of carcinogenesis. Several studies have
Diseases, Clinical Center of Serbia, Belgrade, Serbia.
shown that thyroid hormone (TH) suppresses HCC development and protects
hepatocytes from HBx induced damage, thus it is of interest to examine whether
Glucocorticoids affect the growth and maturation of fetal organ systems, but
TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx-
overexposure to exogenous glucocorticoids retard fetal growth and may alter
transgenic mice with or without TH, we confirmed the protective effects of TH on
developmental process in sensitive tissues. On the other hand, fetal ovary is not
HBx-induced hepatocarcinogenesis, which was achieved via reduction of ROS
characterized by definitive follicular structure, but the clusters of germinative cells are
inflicted DNA damage. We further found that TH induced biogenesis of
predominant. Germ cells may be in meiotic prophase or with sign of degeneration.
mitochondria
(MITO) and autophagy of HBx-targeted mitochondria simul-
The aim of this study was to determine whether prenatal exposure to
taneously, consequently leading to suppression of HBx-promoted ROS and
dexamethasone (Dx) altered normal structure and development of ovary in
carcinogenesis. Using microarray data analysis, this protective effect of TH was
19 day old rat fetuses. Pregnant females in the experimental group received
found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in
subcutaneous injections of 1.0, 0.5 and 0.5 mg Dx /kg body weight on days 16-18
hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to
of pregnancy. Control mothers were injected with the same amount of saline. On
ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The
day 19 of pregnancy, the dams and their fetuses were sacrificed under ether
pathological significance of the TH/PINK1 pathway in liver protection was
anesthesia and the fetuses were referred to as 19-day-old fetuses. Fetal ovaries
confirmed by the concomitant decrease in expression of both TR and PINK1 in
were prepared for further stereological examination.
matched HCC tumor tissues and negatively correlated with aggressive
The volume of the fetal ovary estimated using Cavalieri’s principle was
progression of cancer and poor prognosis. Our data indicates that TH/PINK1/-
significantly reduced after exposure to Dx by 22% (P!0.05) in comparison
Parkin pathway plays a critical role in protecting hepatocytes from HBx-induced
with control ovary. Using a fractionator-physical disector method, a reduction in
carcinogenesis. Notably, several liver-targeting therapeutic derivatives of thyroid
total number of germ cells in meiotic prophase by 43% (P!0.05) was observed,
hormone facilitating prevention or therapy of steatosis have been identified.
while total number of germ cells with sign of degeneration increased by 54%
Furthermore, our proof-of-concept experiments suggest that application of T3
(P!0.05), when compared with control values.
constitutes an effective novel therapeutic or preventive option for HCC. Thus, the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
utilization of the agonists of TRs could be the meaningful strategy in liver relative
severity. To achieve a valid basis of comparison of efficacy outcomes across trials
diseases, ranging from simple hepatic steatosis to HCC.
(VELOCITY, VERTICAL, VISTA (long-term safety)), distribution of clinical
DOI: 10.1530/endoabs.49.GP64
characteristics known to affect HV should be similar between treatment arms
(somavaratan vs daily rhGH) and between trials. The same primary efficacy
endpoint (HV) and similar eligibility criteria were used across trials. Stratification
for Phase 3 randomization (somavaratan vs daily rhGH) was based on region,
expected age, and expected baseline IGF-I SDS. In VELOCITY
(nZ104
somavaratan; nZ32 daily rhGH), meanGS.D. baseline ages were 7.07G2.0 vs
GP65
7.03G2.4 years, respectively, mean GHmax 5.77G2.6 vs 5.87G2.5 ng/ml, mean
3-year safety and efficacy Update of the VERTICAL & VISTA trials of
height-SDS K2.76G0.7
vs K2.64G0.7, mean IGF-I SDS
-1.72G0.7
vs
somavaratan (VRS-317), a long-acting rhGH, in children with Growth
K1.87G0.9, and mean bone ages 5.28G1.9 vs 5.29G2.2 years. In VERTICAL
Hormone Deficiency (GHD)
(NZ64), mean age was 7.8G2.4 years, mean height-SDS K2.6G0.6, mean IGF-
Bradley S. Miller1, Wayne V. Moore2,3, Patricia Y. Fechner4,5, Quentin
I SDS K1.7G0.8, and mean bone age 6.4G2.4 years. No clinically meaningful
L. Van Meter6, John S. Fuqua7, David Ng8, Eric Humphriss9,
differences in baseline characteristics were noted between trials, or between
R. William Charlton9 & George M. Bright9
VELOCITY treatment arms. Collectively, similar populations were achieved
1University of Minnesota Masonic Children’s Hospital, Minneapolis, MN,
between trials by use of consistent eligibility and stratification procedures. This
USA;2Children’s Mercy Hospital, Kansas City, MO, USA;3University of
allowed balanced treatment arms for clinical characteristics that may influence
Missouri-Kansas City, Kansas City, MO, USA;4Seattle Children’s Hospital,
the primary efficacy outcome, thereby achieving a valid basis of comparison
Seattle, WA, USA;5University of Washington, Seattle, Seattle, WA, USA;
between trial populations.
6Van Meter Pediatric Endocrinology, P.C., Atlanta, GA, USA;7Indiana
DOI: 10.1530/endoabs.49.GP66
University School of Medicine, Indianapolis, IN, USA;8ResearchPoint
Global, Inc., Austin, TX, USA;9Versartis, Inc., Menlo Park, CA, USA.
Requirement for daily rhGH injections is a treatment burden that can compromise
adherence and efficacy in patients with GHD. Somavaratan is a novel long-acting
GP67
rhGH fusion protein in clinical development for pediatric and adult GHD. In a
Karyotype and mid-childhood gonadotropin concentrations in
multicenter, randomized Phase 1b/2a study, somavaratan significantly improved
prediction of spontaneous puberty in Turner syndrome patients
height velocity (HV) and IGF-I in pre-pubertal children with GHD. Preliminary
Aneta Gawlik1, Magdalena Hankus2, Kamil Soltysik3, Kamila Szeliga2 &
efficacy and safety in subjects who have completed 3 years of somavaratan
Ewa Malecka-Tendera1
treatment are presented. Of 64 subjects randomized in the Phase 2a VERTICAL
1Department of Pediatrics and Pediatric Endocrinology, School of Medicine
study to receive 5.0 mg/kg/month (weekly/twice-monthly/monthly dosing) for
in Katowice, Medical University of Silesia, Katowice, Poland;2Department
6 months, 60 elected to continue treatment in the long-term safety study, VISTA.
of Pediatrics and Pediatric Endocrinology, Upper-Silesian Pediatric Health
Initial IGF-I response supported a dose increase, and all subjects transitioned to
Center, Katowice, Poland;3Department of Anatomy and Molecular Cell
somavaratan 3.5 mg/kg twice-monthly by the 2nd treatment year. Data cutoff was
Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
December 8, 2016. Of 48 subjects (24 males, 24 females), the meanGSD age was
7.6G2.4 years, and mean IGF-I SDS was K1.6G0.8 at baseline. In Year 3, IGF-I
SDS increased to 1.2G1.7 at peak (3-5 days post-injection) and K0.3G1.0 at
Gonadotropin levels in all Turner syndrome (TS) patients present a diphasic
trough (end of dosing cycle). Mean HV remained consistent during Years 1, 2,
pattern: highest in early childhood, declining at 6-10 years of age, and then
and 3, at
8.4G2.0, 8.3G1.6, and 7.8G1.6 cm/year, and height
(HT)-SDS
increasing again. Here, we have investigated whether karyotype or FSH&LH can
continued to increase from K2.6G0.6 at baseline to K2.1G0.6, K1.6G0.7, and
be used as indicators of spontaneous puberty in TS. From a consecutive group of
K1.2G0.8; delay in bone age (years) was K1.48G0.81 at baseline, K1.34G
139 TS girls treated at one clinical center (1996-2015) the clinical & biochemical
0.89
(Year 1, nZ48), K1.09G1.02 (Year 2, nZ47), and K0.66G0.82 (Year 3,
data were finally analyzed in 110 TS patients (1268 visits). The study population
nZ25). Treatment-related AEs were generally transient and mild. Overall, IGF-I,
was divided into two subsets based on karyotype (type A- 45X, 54%; type B-
HV, HT-SDS, and bone age showed continued improvement through 3 years of
others excluding 45X/46XY). The mean diagnosis age and duration of follow-up
somavaratan treatment in pre-pubertal children with GHD. Dose increase to
were 10.7G4.0 and 5.9 years, resp. The average number of visits was 10.4.
somavaratan 3.5 mg/kg twice-monthly resulted in consistent growth rates through
Spontaneous puberty was confirmed in 48.2% and menarche in 20%, both less
3 years of treatment, and overall Year 3 growth was consistent with daily rhGH
common in group A than B (31.1% and 9.8.% vs 69.4% and 32.6%, resp.,
from US registries. A Phase 3 study of somavaratan 3.5 mg/kg twice-monthly in
P!0.05). The mean age of Tanner B2 and menarche in all girls were 13.7G2.4
treatment-naïve GHD children is ongoing.
and 14.2 years, no difference between the groups (13.5G2.5 and 13.2G1.0 years
DOI: 10.1530/endoabs.49.GP65
(A) vs 13.8G2.3 and 14.6G1.7 years (B), PO0.05). The median FSH and LH
values in all patients at the age of 6-10 were 8.16 and 0.35 IU/l resp., significantly
lower comparing to younger (44.6 and 0.76 IU/l) and older (93.0 and 16.1 IU/l)
age (P!0.0001). LH were similar in both groups, whereas in group B FSH values
were significantly higher only in the older age. At the age of 6-10 FSH and LH
levels Rthan 6.7 and 0.2 resp. decrease the chance of spontaneous menarche
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(33.3% vs 13.9% and 28.6% vs 11.8%). Conclusion: Nearly half of our TS
Achievement of a suitable basis of comparison in phase 2 and 3 clinical
patients showed spontaneous puberty symptoms and every fifth had spontaneous
trials (VERTICAL/VISTA, and VELOCITY) comparing somavaratan
menarche with higher frequency in non-45,X girls. The diphasic pattern of
vs daily rhGH for pediatric GH deficiency
FSH&LH was confirmed, however using their cut-off values one can predict the
Philippe Backeljauw1, Bradley S Miller2, Nancy Wright3,
chance for spontaneous menarche.
Aristides Maniatis4, Michael Stalvey5, Eric Humphriss6,
DOI: 10.1530/endoabs.49.GP67
R William Charlton6 & George M Bright6
1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;
2University of Minnesota Masonic Children’s Hospital, Minneapolis, MN,
USA;3Nancy Wright MD p.a., Tallahassee, FL, USA;4Rocky Mountain
Pediatric Endocrinology, Centennial, CO, USA;5University of Alabama at
Birmingham, Birmingham, AL, USA;6Versartis, Inc., Menlo Park, CA,
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USA.
Assessment of reports of behaviour by patients and their parents in
paediatric Cushing disease
Margaret Keil, Elena Belyavskaya, Charalampos Lyssikatos, Maya Lodish
Efficacy of rhGH for treatment of pediatric GH deficiency (PGHD) may depend
& Constantine Stratakis
on several variables at treatment initiation (age, body weight, height velocity
NIH, NICHD, Bethesda, MD, USA.
(HV), IGF-I SDS, skeletal maturation, GHmax), but may be compromised by
poor adherence to required daily injections. Somavaratan is a novel, long-acting
rhGH fusion protein that demonstrated clinically meaningful improvements in
Context
HV and IGF-I concentration in PGHD patients. Over 200 pre-pubertal GHD
Prior studies of children with endogenous Cushing syndrome (CS) have identified
subjects have enrolled in somavaratan trials to date, including 137 in the Phase 3
cognitive decline despite reversal of brain atrophy after remission as well as
noninferiority VELOCITY trial comparing somavaratan vs daily rhGH. In the
residual impairment of quality of life measures. Although parental observations
randomized Phase 1b/2a VERTICAL study in pre-pubertal children with GHD,
support personality changes with CS, significant psychopathology has not been
primary determinants of Year 1 HV included age at treatment initiation and GHD
described. We investigated the feasibility of using paediatric Patient-reported
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
outcomes (PROMIS) using a computer interface to assess patient perception of
GP70
burden of illness and correlation with parent proxy report using Child Health
The adverse effects of prescribed glucocorticoids are worsened by
Questionnaire (CHQ).
co-administration of 5a-reductase inhibitors
Setting
Tom Marjot, Nantia Othonos, Conor Woods, Jonathan Hazlehurst,
Subjects were enrolled in a clinical protocol at the National Institutes of Health
Ahmad Moola, Leanne Hodson & Jeremy Tomlinson
Clinical Center in Bethesda, MD, USA.
Oxford Centre for Diabetes, Endocrinology and Metabolism, NIHR
Method
Biomedical Research Centre, Churchill hospital, University of Oxford,
We report 9 children (6F, 12G3.5 years) diagnosed with Cushing disease (CD).
Oxford, UK.
Prior to surgical treatment, subjects completed paediatric PROMIS measures and
parents completed CHQ using an online secure website.
Results
Introduction
PROMIS measures scores (meanGS.D.): anxiety (54G9), depression (55G11)
Glucocorticoids (GC) are prescribed to 2-3% of the population of the UK and
anger (50G9), and emotional support (52G10) (higher scores indicate more of
USA. Their use is associated with a significant side effect profile that includes
the concept being measured); CHQ total Psychosocial score (meanGS.D.) (43G
the development of central obesity, insulin resistance and type
2 diabetes.
10)
(lower values are associated with a greater deficit in functioning). A
5a-reductase (5aR) inhibitors (Finasteride and Dutasteride) are also commonly
significant correlation was found between Psychosocial summary score of CHQ
prescribed in the context of prostate disease, where they inhibit the conversion of
and paediatric PROMIS measures of anxiety
(rZK70.5; P!0.03) and
testosterone to dihydrotestosterone. Additionally, they have a role to inactivate
depression (rZK0.9; P!0.002). No correlation was found between urinary
and clear GC. We have therefore hypothesised that 5aR inhibitors have the
free cortisol level or midnight serum cortisol and PROMIS measures.
potential to exacerbate the adverse metabolic effects of GC.
Conclusion
Methods
Prior to treatment for CS, a significant correlation was found between children’s
We conducted a prospective, randomised, study in 19 healthy male volunteers
endorsement of anxiety and depression symptoms and parental proxy report of
(age; 45G8.5 years, BMI; 27.1G3.1 kg/m2). Participants underwent detailed
psychosocial function. Our findings support that paediatric PROMIS measures
metabolic assessments including a 2-step hyperinsulinaemic euglycaemic clamp
represent feasible and potentially valuable instruments for future studies to assess
incorporating stable isotopes, adipose tissue microdialysis and biopsy. They were
behavioural symptoms in children diagnosed with CS prior to and after treatment.
then randomised to receive either prednisolone (10 mg OD) or prednisolone
DOI: 10.1530/endoabs.49.GP68
(10 mg OD) and a 5aR inhibitor (finasteride 5 mg OD or dutasteride 0.5 mg OD)
for 7 days, metabolic assessments were then repeated.
Results
We have previously shown that high dose parenteral GC administration decreases
glucose utilization (M value; 3.1G0.4 vs 1.6G0.1 mg/kg per min, PZ0.001) and
5aR inhibitors alone are without effect (M value; 3.5G0.4 vs 3.3G0.4 mg/kg per
min, PZ0.42). In this study, prednisolone only did not alter glucose utilization
(M-value; 3.2G1.3 vs 2.8G1.6 mg/kg per min, PZ0.37), however, co-adminis-
GP69
tration of prednisolone and 5aR inhibitors significantly decreased it (M-value;
5b-reductase (AKR1D1) is a potent regulator of carbohydrate and lipid
4.0G2.0 vs 2.6G1.3 mg/kg per min, PZ0.02). Similarly, high dose GC, but not
5aR inhibitors alone, impair insulin-mediated suppression of circulating non-
metabolism and inflammation in human liver
esterified fatty acids
(NEFA). Prednisolone 10mg OD did not alter insulin-
Nikolaos Nikolaou1, Laura Gathercole3, Charlotte Green1,
mediated suppression of NEFA (0.15G0.27 vs 0.13G0.13, PZ0.88), however,
Catriona McNeil1, Wiebke Arlt2, Leanne Hodson1 & Jeremy Tomlinson1
co-administration with 5aR inhibitors impaired the ability of insulin to suppress
1University of Oxford, Oxford, UK;2University of Birmingham,
NEFA (0.15G0.1 vs 0.29G0.18, PZ0.01).
Birmingham, UK;3Oxford Brookes University, Oxford, UK.
Conclusion
5aR inhibitors exacerbate the adverse metabolic effects of prescribed GCs. This
Non-alcoholic fatty liver disease
(NAFLD) is the hepatic manifestation of
has significant translational implications, not only with regards to the need to
metabolic disease. 5b-reductase (AKR1D1) is highly expressed in human liver
consider steroid dose reductions, but also the necessity for increased vigilance for
where it inactivates steroid hormones and catalyzes a fundamental step in bile
the development of adverse effects.
acid synthesis. Steroid hormones, including glucocorticoids, as well as bile acids
DOI: 10.1530/endoabs.49.GP70
are established regulators of metabolic phenotype. We hypothesized that
AKR1D1 plays a crucial regulatory role in hepatic metabolic homeostasis.
Genetic manipulation of AKR1D1 (over-expression, siRNA knockdown) was
performed in human liver HepG2 and Huh7 cells. Gene expression changes were
confirmed by qPCR. Functional activity, assessed using gas chromatography mass
spectrometry to measure cortisone clearance and tetrahydrocortisone generation
was paralleled by the anticipated changes in glucocorticoid receptor activation
measured by luciferase reporter assays. AKR1D1 knockdown in HepG2 cells
increased glucose transporter mRNA expression and extracellular glucose
Diabetes & Complications 1
concentrations in the cell media decreased (15.3G1.5 vs 12.1G0.9 mmol/mg,
GP71
P!0.05) while intracellular glycogen levels were increased (18.9G0.3 vs 22.7G
Carbohydrates metabolism and H. pylori: case-control study
0.3 mg/ml, P!0.05). AKR1D1 knockdown increased Fatty Acid Synthase and
Isabel Ma Cornejo-Pareja1, M Mar Roca-Rodríguez2, Leticia
Acetyl CoA Carboxylase
1
expression, the rate-limiting step in de novo
Coín-Araguez3, Araceli Mun˜ oz-Garach1, María Molina-Vega1,
lipogenesis, DNL)
(0.52G0.06
vs
0.89G0.04, P!0.01), and increased
Cristina Díaz-Perdigones1, Carmen Hernández-García1, Juan
intracellular triglyceride (54.3G12.7 vs 73.3G11.0 nmol/mg, P!0.01). Further-
Alcaide-Torres3, Carlos Clu-Fernández1, Laura Vin˜ uela-González4,
more, 3-hydroxybutyrate levels in the cell media were reduced, indicative of
Laura Mora-Navas4, Isabel Mancha-Doblas1 &
impaired fatty acid oxidation (18.7G2.3 vs 11.4G2.7 nmol/mg, P!0.01). Mass
Francisco J Tinahones-Madue
˜o1
spectrometry analysis of lipid composition demonstrated increased palmitic and
1Endocrinology and Nutrition Department. Virgen de la Victoria Hospital,
palmitoleic acid production consistent with increased DNL and fatty acid
Málaga, Spain;2Endocrinology and Nutrition Department Puerta del Mar
saturation. In addition, bile acid composition was altered with a significant
Hospital, Cádiz, Spain;3Research Laboratory IBIMA, Málaga, Spain;
increase in chenodeoxycholic acid levels. Conversely, pharmacological manipu-
4Microbiology Department, Virgen de la Victoria Hospital, Málaga, Spain.
lation of the bile acid receptors FXR and LXR using the FXR agonist GW4064
and LXR antagonist
22-S-Hydroxycholesterol rescued HepG2
cells from
metabolic dysfunction by reducing the expression of lipogenic genes.
Introduction
Furthermore, AKR1D1 knockdown increased proinflammatory cytokine IL-1,
H. pylori infection has been related with extragastric diseases such as type 2
IL-6 and IL-8 mRNA expression; changes were confirmed by elevated cell media
diabetes.
IL-8
levels
(4.68G0.70
vs
13.39G2.28 ng/ml, P!0.05), increased IkBa
Aim
degradation and induced IRE-1a protein expression, indicative of inflammation
to evaluate changes in carbohydrate metabolism induced by 75g oral glucose
and cellular ER stress. In conclusion, AKR1D1 activity regulates steroid hormone
tolerance test (OGTT), before and after antibiotic eradication treatment in patients
and bile availability, potently modulating hepatic carbohydrate and lipid
colonized by H. pylori compared to healthy controls.
metabolism in addition to an inflammatory phenotype suggesting a crucial role
Materials and methods
in the pathophysiology of NAFLD.
A prospective case-control study. Biochemical parameters, carbohydrate profile,
DOI: 10.1530/endoabs.49.GP69
ghrelin and GLP1 levels before and after antibiotic eradication treatment were
analyzed.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
GP73
We studied 40 cases and 21 controls (60% and 57.1% women, respectively).
Permanent neonatal diabetes in a 24 year old Spanish patient
Mean age: 46,95G2,02 vs 44,52G2,73 years, family history of digestive
Milagros Sierra, Elena Garcia, David Males, Juan Carlos Romero,
disorders: 70% vs 57.1% and clinical history of gastrointestinal disease: 57,5% vs
Carlos Silva, Gonzalo Allo & Guillermo Martinez
42.9%, respectively. After antibiotic treatment, significant improvements in
12 De Octubre University Hospital Endocrinology and Nutrition
HbA1c (PZ0,014), glucose levels post OGTT at 600 and 1200 (PZ0,018 and
Department, Madrid, Spain.
PZ0,019, respectively) and HDL Cholesterol
(PZ0,021) were observed.
Significant changes in basal ghrelin levels (PZ0,05) were found, but C peptide
levels did not change. We observed differences between infected population by
Introduction
H. pylori and healthy people: lower post OGTT insulin levels at 300 and 600
Neonatal diabetes mellitus is a rare form of diabetes, diagnosed within the first six
(PZ0.042 and PZ0.03, respectively) in infected patients. Those differences
months of life. We report a case of a 24-year-old patient with permanent neonatal
disappeared after treating the infection. In cases and controls, we found significant
diabetes.
positive correlations in carbohydrate metabolism, and significant negative
Case Report
correlations in controls between ghrelin with basal insulin and C peptide. No
The patient had no relevant family history. Her mother had no gestational
significant correlations respect to GLP1 were found. 90% of patients completed
diabetes. Personal history included: Normal birth weight, polycystic ovarian
correctly the treatment, 31,6% needed ranitidine and 97,5% eradicated H. pylori
syndrome and ovarian teratomas. She was diagnosed of diabetes at 3 months of
after conventional antibiotic treatment.
age, starting immediately with insulin treatment. Glucose control had always been
Conclusion
optimal (HbA1c l !6.7%). Acute diabetic complications included: symptomatic
1) H. pylori eradication improved carbohydrate metabolism.
2) Significant
hypoglycemias every 3 days, usually after dinner and, less frequently nighttime
positive correlations in carbohydrate metabolism in cases and controls were
hypoglycemias. No hyperglycemias that required in hospital management. No
found. 3) Negative correlations between ghrelin and pancreatic reserve were
chronic metabolic complications. The patient came to our clinic to continue
observed in cases. 4) Carbohydrate metabolism differences between healthy and
follow up. We completed her work up doing islet antibodies detection (anti
infected people disappeared after eradication treatment. 5) More than 95% of
GAD65, anti tyrosine phosphatase IA2, anti insulin and anti zinc transporter), and
patients achieved H. pylori eradication with conventional antibiotic treatment.
as expected the results were negative. Considering the age of the diagnosis,
DOI: 10.1530/endoabs.49.GP71
genetic testing for monogenic forms of diabetes was performed, discovering a
heterozygous mutation c.323Ag (pY108C) in INS gene. Family genetic mutation
are still pending.
Discussion
Neonatal diabetes mellitus have an incidence of 1 in 500000 live births. Most
common genes are KLF 11, ABCC8 and less frequently INS gene (30%, 19% and
14% respectively). Depending on the severity of the mutations insulin bioactivity
will be affected, ranging from a decreased biosynthesis to altered transcription.
Clinical implications include transient requirement of insulin, later switching to
sulfonylureas or even completely stopping hypoglycemic treatment; and
permanent insulin treatment. In the latter, the risk of ketoacidosis also depends
GP72
and the recessive or dominant inheritance.
Specific plasma amino acids alternations associated with metabolic
Conclusions
syndrome
Monogenic forms of diabetes are uncommon, however it is important to consider
Marta Siomkajło1, Jacek Rybka3, Andrzej Gamian2,3, Joanna
them in the differential diagnosis of particular cases. Genetic mutation study is
Stankiewicz-Olczyk1, Marek Bolanowski1 & Jacek Daroszewski1
important to assess future treatment options and the risk of ketoacidosis.
1Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw
DOI: 10.1530/endoabs.49.GP73
Medical University, Wroclaw, Poland;2Department of Medical Biochem-
istry, Wroclaw Medical University, Wroclaw, Poland;3Ludwik Hirszfeld
Institute of Immunology and Experimental Therapy, Polish Academy of
Sciences, Wroclaw, Poland.
GP74
Objectives
Rescue study of trapped AVPR2 mutants with chemicals
Amino acids (AA) plasma profile is associated with cardiometabolic diseases
(CMD), predicts diabetes mellitus type 2 (DM2) and cardiovascular diseases
Beril Erdem, Emel Saglar, Tugce Karaduman, Merve Ozcan, Dilara Sahin
(CVD) many years in advance. Metabolic syndrome (MS) defines the area of
& Hatice Mergen
metabolic disturbances that precede DM2 and CVD development. The primary
Department of Biology, Faculty of Science, Hacettepe University, Ankara,
Turkey.
objective of the study was to examine the association between BCAA (branched
chain amino acids), AAA (aromatic amino acids) profile and MS’s phenotype and
to evaluate its clinical utility for MS diagnosis.
Diabetes insipidus (DI) is a disorder that characterized by producing large volume
Methods
of urine for daily due to the problems at the arginine vasopressin (AVP-NPII),
263 healthy, professionally active men, with and without MS (MSC, nZ165;
aquaporin 2 (AQP2) and arginine vasopressin receptor 2 (AVPR2) genes. These
MSK, nZ98) were included into the study. Anthropometrical, biochemical and
problems can be inherited or acquired. Among these genes, AVPR2 is a G protein
AA measurements were performed. AA were tested for the ability to discriminate
coupled receptor and most of the inherited type of DI are caused by mutations in
subjects with MS and insulin resistance irrespectively. Based on logistic
AVPR2 gene. Mutations can cause improper folding of the receptor protein and
discrimination multivariate early MS diagnostic model was built and its
this situation causes to retention of the protein in cellular compartments such as
discrimination properties were evaluated.
endoplasmic reticulum
(ER) or Golgi apparatus. For treatment strategies,
Results
researchers try to use chemicals to rescue of mutant proteins from the control
2 functionally independent AA clusters were identified. BCAA and phenylalanine
mechanisms to make them at least functional. In this study, we aimed to do pre-
differed strongly between MSC and MS- participants (pZ0.003), appeared as
research for the rescuing mutant receptors
(R68W, V162A, T273M,
significant indicator of MSC individuals (AUC 0.66; 95%CI: 0.5757-0.7469)
R67_G69del/G107W, V88M, R106C, G12E). We performed functional
and correlated with cardiometabolic factors. No statistical significant differences
characterization of these mutant receptors in our previous study and they were
in AAs concentrations between IRC and IRK groups were noted and none of the
observed as trapped in the ER or Golgi apparatus. In the present study, COS-7
AA group appeared as meaningful IRC indicator. Proposed MS multivariate
cells were transfected with mutant and wild type AVPR2s. 48 hours after the
diagnostic model consisted of phenylalanine, insulin, leptin, adiponectin and had
transfection, different concentrations of DMSO and glycerol were performed to
good discrimination properties - AUC 0,79; (95% CI: 0.7239-0.8646).
the cells. 16-18 hours after the treatment of DMSO and glycerol, cell surface
Conclusions
ELISA were performed to understand cell surface expression of the mutant
MS is associated with selective hiperaminoacydemia that could be a part of CMD
proteins when they were treated with different concentrations of DMSO and
pathogenesis. Present study suggests that AA disturbances do not derive directly
glycerol. According to the ELISA results, mutant receptors showed different
from insulin sensitivity impairment nor obesity or muscle mass. AA utility for MS
rescue profile compared to the wild type receptor. As a result, we can say that
diagnosis needs further evaluation. The original outcome of the study became MS
rescuing trapped mutant receptors from ER or Golgi apparatus control
diagnostic model creation - MS screen test, with good discrimination properties
mechanisms using with chemicals could be a forward step for the treatment of
and that could be validated in the next coming studies.
DI. Receptors that have mutations which cause retention in ER or Golgi apparatus
DOI: 10.1530/endoabs.49.GP72
may be functional if they are rescued by chemicals. For further studies, instead of
chemicals, pharmacochaperons could be use. We can conclude that, rescue
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
studies of mutated proteins by using chemicals or pharmacochaperons shed light
were calculated from the glucose and insulin response during OGTT.
to the treatment strategies of DI. This work was supported by The Scientific and
Results
Technological Research Council of Turkey (Project Numbers: 216S304 and
After controlling for confounding factors, the group treated with statins during the
112S513).
entire follow-up had a, nominally significant, 79% (95% CI 1.16, 2.76 PZ0.008)
DOI: 10.1530/endoabs.49.GP74
increased risk of developing incident diabetes, compared to the group without statins,
and statin use was significantly associated with higher levels of fasting plasma
glucose (FPG) and 2 hour plasma glucose (2hPG). Statin therapy was associated with
a reduced CIR30, but not IGI30. Beta blocker therapy was associated with a
nominally significant 63% increased risk of developing incident diabetes.
Conclusion
Statin treatment is associated with an increased risk of incident diabetes, higher
GP75
levels of FPG and 2hPG, and reduced insulin secretion. Beta blocker therapy is
GLP-1 acutely regulates carbohydrate and lipid metabolic routes in
associated with an increased risk of incident diabetes.
the liver
DOI: 10.1530/endoabs.49.GP76
Laura Toba, Yolanda Diz-Chaves, Juan Fandin˜ o, Hugo Ogando,
Lucas González-Matías & Federico Mallo
University of Vigo, Vigo, Spain.
The Glucagon-like peptide-1 receptor is widely expressed in diverse tissues
GP77
including the liver. GLP-1
contributes itself to the regulation of glucose
Susceptibility to type 2 diabetes may be modulated by haplotypes in
homeostasis and has important effects in lipid metabolism even preventing liver
G6PC2, a target of positive selection
steatosis induced by high fat diets.
Mario Clerici1, Nasser Al-Daghri2, C Pontremolli1, R Cagliani1,
The aim of this study was to analyse the short-term effects of liraglutide on key
Diego Forni1, Majed Alokail2, Omar Al-Attas2, Shaun Sabico2,
enzymes of the hepatic energy metabolism.
S Riva1 & M Sironi1
Thirty-six Sprague-Dawley young adult male rats were studied (weight range
1University of Milano, Milan, Italy;2King Saud University, Riyadh,
350-400 g). Control rats were fed ad libitum, while the fast group (F) were
Saudi Arabia.
deprived of food for 48 hours, and treated with liraglutide (100 mg/Kg/12 h;
CT/LIR; F/LIR) or vehicle (CT/VEH; F/VEH) for 48 hours. Rat body weight was
measured at 0, 24 and 48 hours. At 48 h, rats were sacrificed and liver samples
Introduction
were collected and stored at K80 8C until analysis. mRNA expression of G6P,
The endoplasmic reticulum enzyme glucose-6-phosphatase catalyzes the
PCK-1, DGAT-1, GPAT4, CPT1A and ACACA in the liver were assessed by real
common terminal reaction in the gluconeogenic and glycogenolytic pathways
time PCR.
and plays a central role in glucose homeostasis. In most mammals, different G6PC
CT/LIR rats gained less body weight (K6.4 g/100 g, P!0.0001) than CT/VEH at
subunits are encoded by three paralogous genes (G6PC, G6PC2, and G6PC3).
24 h and still less at 48 h (K2.9 g/100 g, P!0.0001). The expression levels of
Mutations in G6PC and G6PC3 are responsible for human Mendelian diseases,
G6P and PCK-1, key enzymes in gluconeogenesis, decreases in rats treated with
whereas variants in G6PC2 are associated with fasting glucose (FG) levels.
liraglutide by a 58% (P!0.05) and 75% (P!0.01) respectively. On the other
Methods
hand, DGAT-1 and GPAT4 levels, involved in synthesis of triacylglycerol, were
We analyzed the evolutionary history of G6Pase genes in mammals. Results
not modified by LIR. In addition, CPT1a and ACACA, enzymes implicated in the
indicated that negative selection was the major force shaping diversity at these
synthesis & metabolism of fatty acids, yielded no significant differences. Fasting
genes. Nonetheless, site-wise estimation of evolutionary rates at corresponding
just increased CPT1 levels
(271% F/VEH vs CT/VEH, P!0.01), and LIR
sites revealed weak correlations, suggesting that G6Pases have evolved different
treatment reduced them (92% F/LIR, P!0.01 vs F/VEH).
structural features over time. We also detected pervasive positive selection at
In conclusion, Liraglutide modifies the metabolism of energy substrates in the
mammalian G6PC2 genes. Most selected residues are located in the C-terminal
liver reducing glucose production in normal feeding and CPT1a specially in
protein region, where several human variants associated with FG levels also map.
fasting, limiting lipid access to mitochondria. These metabolic changes may
This region was thus re-sequenced in a cohort of w560 subjects from Saudi
underlie the prevention of liver steatosis attributed to GLP-1 analogues.
Arabia, 185 of whom suffering from type 2 diabetes (T2D).
DOI: 10.1530/endoabs.49.GP75
Results
The frequency of rare missense and nonsense variants was not significantly
different in T2D and controls. Association analysis with two common missense
variants (V219L and S342C) revealed a weak but significant association for both
SNPs when analyses where conditioned on rs560887, previously identified in a
GWAS for FG. Two haplotypes were significantly associated with T2D with an
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opposite effect direction.
Increased risk of diabetes and hyperglycaemia associated with
Conclusion
treatment with statins, beta-blockers and diuretics: the PPP-Botnia
These results, although preliminary, suggest that distinct haplotypes at the G6PC2
study
locus modulate susceptibility to T2D.
Liisa Hakaste1,2, Teo Helkkula2, Bo Isomaa2, Marja-Riitta Taskinen3,4,
DOI: 10.1530/endoabs.49.GP77
Leif Groop5,6 & Tiinamaija Tuomi1,2
1Endocrinology, Helsinki University Hospital, Helsinki, Finland;
2Folkhalsan Research Center; Diabetes and Obesity Research Program,
University of Helsinki, Helsinki, Finland;3Research programs Unit,
Diabetes and Obesity, University of Helsinki, Helsinki, Finland;4Heart and
Lung Center, Helsinki University Hospital, Helsinki, Finland;5Lund
University Diabetes Center, Malmo, Sweden;6Finnish Institute for
Molecular Medicine, University of Helsinki, Helsinki, Finland.
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Background
Contribution of genetic predisposition and lifestyle to gestational
Statin medication is commonly used in prevention of cardiovascular diseases.
diabetes risk
Pooled evidence shows that statin therapy is associated with increased risk of
Polina Popova1,2, Alexandra Tkachuk1, Yana Bolotko1,
incident diabetes, but studies vary in results and there is no consensus of the
Andrey Gerasimov1, Alexandra Klyushina1, Anna Kostareva1 &
diabetogenic mechanism of statins. Beta blockers and diuretics are commonly
Elena Grineva1,2
used antihypertensive agents that also have been shown to increase the risk of
1Almazov Federal North-West Medical Research Centre, Saint-Petersburg,
incident diabetes. Our objective was to examine the effects of statins, beta
Russia;2St Petersburg Pavlov State Medical University, Saint-Petersburg,
blockers and diuretics on glucose metabolism and the risk of incident diabetes.
Russia.
Methods
5208 subjects from western Finland identified through the Population registry
participated in the baseline PPP-Botnia Study, and 3,614 subjects participated in
Aim
the follow-up study after a mean time of 6.7 years. Participants underwent oral
The aim of our study was to assess the contribution of genetic variation in some
glucose tolerance tests
(OGTT) and gave information about their use of
previously reported gestational diabetes mellitus (GDM) susceptibility loci and
medication. Insulinogenic index
(IGI) and corrected insulin response
(CIR)
lifestyle parameters to GDM risk.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
T1DM high-risk HLA- DR/DQ haplotypes. In conclusion, our data confirms the
We performed a case-control study of 278 GDM cases and 179 controls who had
association between the ERBB3 rs2292239 and risk for T1DM in a population
filled up special questionnaires concerning their lifestyle habits during the oral
from Southern-Brazil.
glucose tolerance test (OGTT) on the 24-32 week of gestation. The questionnaire
DOI: 10.1530/endoabs.49.GP79
consisted of the following sections, stratified in a semi-quantitative manner: the
consumption of major food groups and drinks, the amount of physical activity and
smoking before and during pregnancy. GDM was diagnosed according to the
IADPSG criteria. Maternal blood was sampled for further genotyping of single
nuclear polymorphisms (SNPs) in MTNR1B (rs10830963 and rs1387153), GCK
(rs1799884), KCNJ11 (rs5219), IGF2BP2 (rs4402960), TCF7L2 (rs7903146),
CDKAL1 (rs7754840) and IRS1 (rs1801278). Binary logistic regression (forward
conditional) was accomplished to identify the contribution of «classical» risk
factors for GDM (advanced maternal age, higher body mass index (BMI), history
of GDM, impaired glucose tolerance, arterial hypertension, family history of
diabetes), lifestyle parameters and the above mentioned SNPs to the assessment
GP80
of GDM risk.
Trace elements as an oxidative stress marker in women with gestational
Results
diabetes and their neonates
After automatic lineal modeling the following factors proved to be associated
Georgios Boutzios1, Eleni Koukoulioti1, Ioannis Papoutsis2,
with the increased GDM risk: age (ORZ1.11, 95% CIZ1.06-1.16, P!0.001),
Sotirios Athanaselis2, Gerasimos Tsourouflis1 & Evangelia Zapanti3
BMI (ORZ1.09, 95% CIZ1.05-1.14, P!0.001), the presence of G allele of
1Endocrine Unit, Department of Pathophysiology, Laiko University
rs10830963
(ORZ2.1, 95%CIZ1.4-3.1, PZ0.001), T allele of rs1799884
Hospital, Medical School, University of Athens, Athens, Greece;
(ORZ2.1, 95%CIZ1.3-3.4, PZ0.003) and consumption of sausage O 3 times a
2Department of Toxicology, Medical School, University of Athens, Athens,
week (ORZ2.55, 95%CIZ1.36-4.78, PZ0.004) compared to less consumption.
Greece;3Endocrine Unit, Alexandra Maternity Hospital, Athens, Greece.
Legumes consumption 1-2 times a week was associated with the decreased risk of
GDM, when compared to less consumption (ORZ0.59, 95%CIZ0.36-0.97,
PZ0.036).
Background and aims
Conclusion
Gestational diabetes (GD) is closely related to unbalanced zinc (Zn) and cooper
MTNR1B and GCK variants, some eating habits along with an increment in
(Cu) serum levels. The aim of this study was to investigate serum zinc and cooper
maternal age and BMI were associated with the increased risk of GDM.
levels in relation to the metabolic profile, and the impact on fetal development in a
DOI: 10.1530/endoabs.49.GP78
cohort of gestational diabetes GD(N) neonates and their mothers GD(M)
compared to normal pregnancies.
Material and Methods
Prospective controlled study in a tertiary Academic medical center. The study
population included 101 mother/neonate pairs; 50 control group (C) and 51 GD
group. Intervention: Diet and/or insulin administration in GD(M). Anthropo-
metric, metabolic parameters, and trace elements serum levels were assessed.
Results
Age and body weight change during pregnancy (DBW) were similar in both
groups. HbA1c was comparable between C and GD group (5.37G0.34 and
5.39G0.48%, for C and GD respectively, PZ0.844). Mean serum Cu levels were
(150.1G45.85, 32.16G43.37)mg/dl in C and (203.53G65.63, 23.62G13.42)
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mg/dl in GD, mean Zn levels (87.8G17.48, 120.47G37.16)mg/dl in C and (88.1G
27.1,
113.76G36.77)mg/dl in GD, for mothers and neonates, respectively.
The rs2292239 polymorphism in the ERBB3 gene is associated with risk
Neonates had statistically significantly lower serum Cu levels but higher Zn levels
for type 1 diabetes mellitus
compared to their mothers (P!0.0001, P!0.0001). Serum cooper levels in
Daisy Crispim1,2, Cristine Dieter1,2, Natalia Lemos1,2, Tais Assmann1,2,
mothers (Cu(M) levels were statistically significantly higher in GD(M) compared
Guilherme Duarte1,2, Luiza Dorfman3 & Andrea Bauer1,2
to C(M) (P!0.0001). There was a negative correlation between Zn(M) and
1Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,
Rio Grande do Sul, Brazil;2Post-graduation Program in Medical Sciences:
insulin levels(M) in C (rZK0.284, PZ0.045), between Zn(M) and insulin(N) in
GD (rZK0.372, PZ0.012), and between Zn(N) and head circumference in C
Endocrinology, Faculdade de Medicina, Universidade Federal do Rio
group (rZK0.423, PZ0.013). There was a positive correlation between Cu(N)
Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;3Universidade do
and insulin(N) in GD (rZ0.365, PZ0.019), and between Cu (M) and birth weight
Vale do Rio dos Sinos - UNISINOS, Sao Leopoldo, Rio Grande do Sul,
in C (rZ0.304, PZ0.042).
Brazil.
Conclusions
Serum cooper levels are higher in women with gestational diabetes and
Background and Aim
independently of diabetes control. Both serum trace element levels in neonates
Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from the
seem to correlate with neonatal head circumference and birth weight only in
complex interaction among multiple genes, environmental factors and the
control group.
immune system. Genome-wide association studies identified ERBB3 (Erb-b2
DOI: 10.1530/endoabs.49.GP80
receptor tyrosine kinase 3) gene as a main susceptibility locus for T1DM. This
gene encodes a member of the family of intracellular receptors of protein tyrosine
kinases, which activates multiple signaling pathways including PI3K-Akt and
MAPK; thus, regulating cell survival and proliferation. Moreover, ERBB3 seems
to contribute to T1DM pathogenesis by modulating antigen-presenting cell
function and autoimmunity as well as beta-cell apoptosis and insulin production.
Therefore, the aim of this study was to investigate the association of the
rs2292239 (C/A) polymorphism in the ERBB3 gene with susceptibility to T1DM
in a Brazilian population from Southern-Brazil.
Methods
Frequencies of the rs2292239
polymorphism were analyzed in 461 T1DM
patients
(cases) and
570
non-diabetic subjects
(controls). Genotyping was
performed using Real-Time PCR and TaqMan MGB probes (Thermo Scientific).
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Results
Genotype distributions of the ERBB3
rs2292239
polymorphism were in
agreement with those predicted by the Hardy-Weinberg Equilibrium in the
Abstract withdrawn.
control group (P R0.05), with the A/A genotype being more frequent in T1DM
patients compared with non-diabetic subjects (PZ0.007). The A allele frequency
was 39.7% in the T1DM group and 32.8% in the control group (PZ0.008).
Moreover, the A allele was significantly associated with T1DM risk when taking
into account additive (ORZ1.67, 95% CI 1.07 - 2.61; PZ0.023) and recessive
(ORZ1.58, 95% CI 1.04 - 2.40; PZ0.031) inheritance models, adjusting for
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP82
PZ9!10K6) and 1,25(OH)2D3 (median 59.05 vs
41.15 pg/ml PZ0.006)
compared to HC with the same genotype.
Reduced level of soluble TLR2 in type 2 diabetes despite increased
Conclusion
TLR2 monocyte expression
We describe an association of the IL1b with T2D in German patients.
Emanuela Zaharieva1, Tsvetelina Velikova2, Elena Vikentieva3,
Significantly lower 25(OH)D3 and 1,25(OH)2D3 levels were observed in T2D
Dora Popova3, Adelina Tsakova4 & Zdravko Kamenov1
patients with the GG genotype. Whereas the major allele A appears to be
1Medical University Sofia, Alexandrovska University Hospital, Clinic of
protective, the minor allele G is may predispose to T2D in combination with a
Endocrinology, Sofia, Bulgaria;2Medical University Sofia, St Ivan Rilski
vitamin D deficiency. Our results suggest that VD deficiency enhances the genetic
University Hospital, Laboratory of Clinical Immunology, Sofia, Bulgaria;
risk for T2D conferred by the genotype GG of IL1b SNP rs16944. Whether and
3Military Medical Academy, Department of Clinical Laboratory and
how vitamin D interacts with IL1b through this polymorphism is subject to further
Immunology, Sofia, Bulgaria;4Medical University Sofia, Alexandrovska
studies.
University Hospital, Central Clinical Laboratory, Sofia, Bulgaria.
DOI: 10.1530/endoabs.49.GP83
Background
Chronic low-grade inflammation is a major factor in the pathogenesis of type 2
diabetes. One way for promoting inflammatory cytokines secretion is through
activation of toll-like receptors (TLR). Their overexpression on monocytes has
been demonstrated in insulin resistance and type 2 diabetes. Soluble forms of toll-
like receptors (sTLR) are considered a regulatory mechanisms of their activation.
Their role has been described in modulation of bacteria-induced infective diseases
but has not been analysed in diabetes. The aim of the study was to evaluate the
place of sTLR2 in type 2 diabetes and compare it with monocyte expression.
Subjects and methods
We performed a cross-sectional study that included 63 patients with type 2
GP84
diabetes and 25 controls. All were assayed for soluble forms of TLR2 through
Antidiabetic medication use and the risk of fracture in type 2 diabetic
Enzyme-Linked Immunosorbent Assay. We evaluated monocyte expression of
patients: a nested case-control study
TLR2 in
28
diabetic patients and
14
control subjects through direct
Eladio Losada1, Berta Soldevila2,3, M. Sanni Ali4, Daniel Martinez-
immunofluorescence with conjugated monoclonal antibodies. All participants
Laguna5, Xavier Nogués6,7, Adolfo Diez-Perez6,7, Manel Puig-Domingo2,3,
were assayed for Interleukin
6
(IL-6) through Electro-Chemiluminescence
Dídac Mauricio2,3 & Daniel Prieto-Alhambra4,5
Immunoassay and high sensitivity C-reactive protein (hs-CRP) through Particle
1Section of Endocrinology, Hospital Can Misses, Ibiza, Spain;2Department
Enhanced Immunoturbidimetric Assay.
of Endocrinology and Nutrition. University Hospital & Health Sciences
Results
Research Institute “Germans Trias i Pujol”, Badalona, Spain;3CIBER of
TLR2 expression in patients with type 2 diabetes was higher compared to controls
Diabetes and Associated Metabolic Diseases (CIBERDEM). Carlos III
(89.85G9.66% vs. 50.20G36.91% for CD14CCCD16C monocytes, PZ0.003
Institute of Health, Madrid, Spain;4Oxford NIHR Musculoskeletal
and
34.54G12.38% vs.
17.12G15.39%, PZ0.011
for CD14CCD16CC
Biomedical Research Unit. Nuffield Department of Orthopaedics. Rheu-
monocytes) but sTLR2 was significantly lower in diabetic subjects (1.15G
matology and Musculoskeletal Sciences. University of Oxford., Oxford,
0.65 ng/ml vs 1.44G0.60 ng/ml, PZ0.019). Inflammatory status between groups
UK;5GREMPAL Research Group. IDIAP Jordi Gol Primary Care Research
was confirmed significantly different concerning hs-CRP (2.79G2.89 mg/l vs.
Institute. Autonomous University of Barcelona, Barcelona, Spain;6Internal
0.70G0.89 mg/l, PZ0.000) and IL6 (2.65G2.46 ng/ml vs 1.44G0.22 ng/ml,
Medicine Department. IMIM (Hospital del Mar Research Institute).
PZ0.005) with higher values in diabetic group, although correlations with TLR2
Autonomous University of Barcelona, Barcelona, Spain;7Cooperative
expression were not established (PO0.05).
Research Network on Aging and Fragility (Spanish acronym: RETICEF).
Conclusion
Carlos III Institute of Health, Madrid, Spain.
Type 2 diabetes-associated chronic inflammatory state is characterised by
elevated monocyte expression of TLR2 but decreased serum sTLR2 level. This
poses the question about presence of an impaired immunomodulation of TLRs’
Background
activation in diabetes.
Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility
DOI: 10.1530/endoabs.49.GP82
fractures. Anti-diabetic oral agents and insulin may also impact on fracture risk.
There is however scarce data available on the effect of such therapies combined as
usually prescribed in real-life practice conditions.
Objectives
The objective of this study was to compare the risk of fracture among T2DM
patients who are users of different antidiabetic treatments.
Methods
A nested case-control study was conducted using incident T2DM patients
registered in computerised primary care records in the Sistema d’Informació per
Diabetes & complications 2
al Desenvolupament de la Investigació en Atenció Primària (SIDIAP) between
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2006-2012, with follow-up available until end/2013. Each case
(incident
fractures of the hip, spine, wrist, or proximal humerus in 2006-2013) was risk-
Vitamin D metabolites and IL1b RS16944 polymorphism in type 2
set matched with five controls of the same gender, calendar year of T2DM
diabetes patients: evidence for functional interaction
diagnosis and age at index date (G10 years). Study exposure included metformin
Nojan Nejatian, Marissa Penna-Martinez & Klaus Badenhoop
mono-therapy (reference category) and other antidiabetic medications (alone or in
Division of Endocrinology, Diabetes and Metabolism, University Hospital
combination as prescribed in actual practice) in the 180 days before the index
Frankfurt, Frankfurt am Main, Hessen, Germany.
date. Conditional logistic regression analysis was used to estimate odds ratios and
95% confidence interval adjusting for the following confounders: age, gender,
We investigated the SNP rs16944 in German type 2 diabetes (T2D) patients and
HbA1c level, body mass index, history of fracture, co-morbidities, and
healthy controls (HC) and correlated the findings with concentrations of VD
concomitant medication use.
metabolites.
Results
Methods
Data on 12,277 T2DM patients (2,049 cases and 10,2280 controls) was analysed.
504 T2D patients and 447 HC were genotyped by a Taqman assay. Additionally
Insulin use was associated with increased fracture risk (adj OR 1.63 [95%CI 1.30-
25(OH)D3 and 1,25(OH)2D3 plasma levels of 76 T2D patients and 267 HC were
2.04]), as was the combination of metformin C sulphonylureas (adj OR 1.29
measured by radioimmunoassay.
[1.07-1.56]). No significant association was found with other antidiabetic
Results
medications and/or combinations.
The AA genotype was significantly less frequent in T2D compared to HC whereas
Discussion
GG and AG genotypes were more frequent in T2D (AA: 48.5 vs 37.95%; AG
Insulin and sulphonylureas use appear to be associated with an increased fracture
40vs 49.7%; GG: 11.4 vs 12.4%; PZ0.003). Furthermore the allele A was less
risk when compared to metformin amongst recently diagnosed T2DM patients.
(68.6 vs 62.7% ORZ0.77; 95% CI: 0.64-0.93) and allele G was more frequent
Residual confounding cannot be ruled out, and more studies are needed to confirm
(31.4
vs
37.3% ORZ1.3 95% CI: 1.07-1.57, PZ0.008) in T2D patients
these findings. Given their impact, risk of fracture should be taken into account in
compared to HC. Both T2D patients and HC with IL1b genotypes AA and AG did
the management of T2DM patients.
not differ for the VD metabolites. However T2D patients with the GG genotype
DOI: 10.1530/endoabs.49.GP84
showed significantly lower levels of 25(OH)D3 (median 34.95 vs 13.7 ng/ml
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP85
glucose, AUC-insulin, and etc.) were monitored; in addition, ex vivo glucose-
stimulated insulin secretion (GSIS) and glucagon secretion (GSGS) with isolated
islets were performed.
Results
Abstract withdrawn.
Insulin secretion in response to high glucose stimulation
(16.7 mM) was
significantly higher in islets isolated from the groups administered 50, 100,
150 mg/kg baicalin compared to HF control; glucagon secretion was significantly
suppressed by high glucose stimulation in islets from the same groups.
Conclusion
This study showed that baicalin had positive effects on glycemic control by
regulating secretion of insulin and glucagon, possibly through GABAAR
mediation.
DOI: 10.1530/endoabs.49.GP87
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Increased incidence of diabetes mellitus 30 years after the radiation
impact in persons exposed to ionizing radiation during the Chernobyl
NPP accident
Oleksii Kaminskyi, Dmitrii Afanasyev, Olga Kopilova, Irina Chikalova,
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Irina Muravyova, Olena Tepla, Oleksii Pronin, Irina Kiselova,
Effect of insulin on neurotrophins’ levels in the muscular wall of mice
Natalia Dombrovska & Dimitrii Bazyka
intestine and colon
National Research Center for Radiation Medicine of NAMS of Ukraine,
Mohammad Alqudah, Ayman Mustafa, Mohammad Allouh,
Kiev, Ukraine.
Othman Alshboul & Ahmad AlDwairi
Jordan University of Science and Technology, Irbid, Jordan.
Several million people in Ukraine and other countries had been exposed to
ionizing radiation during the Chernobyl nuclear power plant accident (ChNPPA)
Background
on April 26, 1986. The ChNPPA clean-up personnel involved in emergency and
Neurotrophins are implicated in the physiology and pathophysiology of the
recovery works in the 30-kilometer exclusion zone of power plant in the nearest
mature gastrointestinal tract (GIT) such as motility and inflammatory bowel
days or months and/or for a long time had received the highest radiation doses due
disease. Moreover, GIT disturbances has been attributed to hyperinsuliemia.
to external gamma-exposure and from incorporated radioactive isotopes with high
Insulin-neurotrophins interactions in the (GIT) have not been investigated yet.
affinity to endocrine organs, including the thyroid, pancreas, and cerebral
Aim
endocrine structures. Consequently a dramatic elevation in non-cancer endocrine
To test the effect of Insulin on the expression of neurotrophins in the muscular
morbidity emerged due to thyroid disease, pre-diabetes, diabetes mellitus, and
wall of mice intestine and colon.
obesity. Despite pancreas was previously considered resistant to ionizing
Methods
radiation the recent research however suggests high sensitivity of endocrine
Total protein extracts from intestinal and colonic muscular wall treated for
cells, particularly pancreatic beta cells to radiation exposure. It just explains a
24 hours with insulin were subjected to ELISA assays specific for different
high prevalence of diabetes mellitus (up to 23%) in the ChNPPA survivors, whilst
neurotrophins and data were analyzed using suitable statistical test with graph
the respective value for population of Ukraine is much lower, i.e. from 3 to 7%
pad.
depending on data source. According to retrospective review of endocrine system
Results
data from the ChNPPA clean-up workers (nZ13,158) the prevalence of pre-
Insulin treatment resulted in significant reduction of neurotrophin-3
(NT-3)
diabetes and diabetes mellitus had increased dramatically 10 years upon the
protein levels in the muscular wall of both mice intestine and colon. Moreover,
accident and continues to increase 30 years later. Now it is in average w16% and
neurotrophin-4 (NT-4) levels were significantly reduced in response to insulin
w12% respectively. At that not only a radiation dose but also the duration of
treatment in muscular tissue from both intestine and clone as well. Interestingly
moderately intensive gamma-exposure, namely 0.082G0.01 Gy, is critical for the
the effect of insulin was more profound in the colon on NT-3 and NT-4.
onset of type 2 diabetes mellitus. Persons involved in recovery operations for
Conclusion
more than 4-6 months are of concern here. Survey results in the ChNPPA
These results indicate that changes in GIT structure and function seen in
emergency workers demonstrate an increased incidence of latent autoimmune
hyperinsulinemia might be due to the effect of insulin on neurotrophins
diabetes in adults (LADA).
expression levels. However, functional studies are needed to elucidate the exact
interactions between insulin and neurotrophins in the GIT.
DOI: 10.1530/endoabs.49.GP86
DOI: 10.1530/endoabs.49.GP88
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Baicalin lowers glucose intolerance by controlling pancreatic hormone
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in high fat-induced obese diabetic rats
Clinical assessment of trabecular bone microstructure in type 2 diabetes
Kahui Park, Jung Hye Kim, Sang Bae Lee, Ji Hong You, Yusik Kim,
mellitus with Trabecular Bone Score (TBS)
Ji sun Nam, Jong Suk Park & Chul Woo Ahn
María Dolores Avilés Pérez, Antonia García Martín, Cristina
Gangnam Severance Hospital, Seoul, Republic of Korea.
Novo Rodríguez, Rafael Nieto Serrano, Elena Torres Vela &
Manuel Mun˜ oz Torres
Hospital Campus de la Salud, Granada, Spain.
Objective
Bacalin was known as an allosteric modulator of the benzodiazepine sites of the
g-aminobutyric acid A receptor (GABAAR), which produce anxiolytic effects in
Introduction
mice without myorelaxant or sedative effects. Baicalin occur flavonoid found in
Type 2 diabetes mellitus (T2DM) is a risk factor for osteoporotic fractures
naturally in the genus Scutellaria. It has been recently shown to exert metabolic
although bone mineral density is increased. As such, there is a need for improved
effects by attenuating hyperglycemia-induced mitochondrial damage in b-cells in
approaches to estimate fracture risk in such individuals. The Trabecular Bone
diabetic rats, high-fat diet- (HFD-) induced body weight gain, and lipid deposits
Score
(TBS) is a new technique to determine the trabecular bone micro-
in the liver and systemic inflammation in mice. This study investigated the effects
architecture.
of baicalin on islet functions and diabetic status in HFD-induced obese diabetic
Objective
mice.
Our aim was to evaluate evaluate the usefulness of TBS in T2DM patients.
Methods
Methods
C57BL/6 mice were grouped into normal control, HF control, HF sham, and 4
We compared TBS values in T2DM group (n: 31) and control group (n: 25) and
different baicalin dose-administered groups (25, 50, 100, and 150 mg/kg). HFD
we analized its relationship with bone mineral density (BMD), history of prior
containing 60% fat and water were fed ad libitum for 24 weeks. Designated doses
fractures and glycemic control. BMD was evaluated by conventional bone
of baicalin or
0.9% saline were administered intraperitoneally 5d/wk. Body
densitometry (DXA) and 3D (3D-DXA).TBS values were determined using TBS
weight (BW) and conventional glucose homeostasis parameters (FPG, FPI, AUC-
InSightw software.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
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T2DM patients had lower TBS than controls
(1.14G0,17
vs
1.25G0,16,
Dipeptidyl peptidase-4 inhibitor therapy and risk of diabetic
PZ0.013). However, there were no differences in the densitometric or volumetric
retinopathy: a population based study
parameters measured by conventional DXA and 3D-DXA. In T2DM group, TBS
Nam Hoon Kim1, Hye Suk Kim2, Hye Jin Yoo1, Ji A Seo1, Nan Hee Kim1,
at the lumbar spine showed degraded microarchitecture (TBS % 1.2) in 16
Kyung Mook Choi1, Sei Hyun Baik1, Juneyoung Lee1, Jung Hyun Noh3 &
patients (51.6%); 13 patients (41.9%) had partially degraded structure (TBS O
Sin Gon Kim1
1.20 & ! 1.35); and only 2 patients (6.5%) had normal TBS values (TBS R1.35).
1Korea University College of Meidicine, Seoul, Republic of Korea;
TBS results differed between groups close to statistical significance (Default 1).
2Anyang SAM Hospital, Anyang, Republic of Korea;3Inje University
We did not find diferences in TBS values according densitometric diagnosis of
College of Medicien, Ilsan, Republic of Korea.
osteoporosis (Tscore % 2.5 S.D.) or history of prior fracture in either group. We
found a significant correlation of TBS with age, body mass index and lumbar
spine BMN both in diabetic patients and controls (P ! 0.05). Finally, we did not
Background
observe relationship with glycemic control or duration of diabetes in T2DM
Given the possible association between dipeptidyl peptidase-4 (DPP-4) inhibitor
group.
and risk of diabetic retinopathy (DR), we examined whether DPP-4 inhibitors are
Conclusion
beneficial or harmful for DR compared with other glucose-lowering agents.
TBS is shown as a promising method in the clinical assessment of trabecular bone
Methods
microstructure in T2DM.
From a Korean population-based cohort, we identified 67,743 adults with type 2
DOI: 10.1530/endoabs.49.GP89
diabetes treated with oral glucose-lowering agents between 2008 and 2013.
Matching (1:1) was done for comparative groups: ever-used (case) and never-
used (control) DPP-4 inhibitors (nZ14,522 each group). Cox regression analyses
assessed the risk of DR events: vitreous hemorrhage, vitrectomy or photo-
coagulation, intravitreal agent use, and blindness.
Results
During a median follow-up of 28$4
(14.0-45.2) months, there were 305 (control
group) and 342 (case group) composite DR events, respectively. Use of DPP-4
inhibitors was not associated with overall risk of composite DR events (adjusted
hazard ratio [HR] 1.08, 95% CI 0.93-1.26). Each DR events including vitreous
hemorrhage, vitrectomy or photocoagulation, use of intravitreal agents, and
blindness were also not increased with DPP-4 inhibitor therapy. The results were
consistent according to baseline retinopathy. However, in the analyses by
duration of treatment, a DPP-4 inhibitor treatment duration of !12 months was
associated with increased risk of composite DR events (adjusted HR 1.95, 95% CI
1.61-2.36).
Conclusion
DPP-4 inhibitor treatment did not increase the overall risk of DR compared with
GP90
other oral glucose-lowering agents. Given that short-term DPP-4 inhibitor use
The G allele of the BDKRB1 rs12050217 polymorphism is associated
was associated with increased risk of DR, the need to assess the aggravation of
with protection for diabetic retinopathy
retinopathy in the early phase of DPP-4 inhibitor use is warranted.
Leticia A. Brondani1,2, Julia Pisco1, Jorge A. Guimarães1,2, Daisy Crispim1,2
DOI: 10.1530/endoabs.49.GP91
& Markus Berger1
1Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil;2Universidade
Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Background
Diabetic retinopathy (DR) is a chronic diabetic complication occurring in most
diabetic patients after
20 years of disease. Progression of DR to its sight
GP92
threatening stages is usually associated with worsening of underlying retinal
vascular dysfunction and disease. The plasma kallikrein kinin system is activated
Non-genetic rat model of nephropathy in type 2 diabetes with
during vascular injury, mediating important functions in inflammation, blood
attenuated streptozotocin-induced tubular alteration
flow, and coagulation. Bradykinin B1 receptor (B1R) is expressed in human
Valentina Bayrasheva1,2, Alina Babenko1,2, Ivan Pchelin3, Anna Arefjeva2,
retina, and retinal B1R levels are increased in murine models of diabetes.
Svetlana Chefu1,2, Ivan Shatalov4, Yurii Dmitriev1, Alexandra Ivanova3,5,
Furthermore, experimental studies reveal that B1R antagonists ameliorate retinal
Pavel Andoskin1, Parvis Aliev2 & Elena Grineva1,2
functional abnormalities caused by diabetes in rodents. Thus, B1R gene
1Federal Almazov North-West Medical Research Centre, Saint Petersburg,
(BDKRB1) is a candidate gene for DR.
Russia;2Pavlov First Saint Petersburg State Medical University, Saint
Objective
Petersburg, Russia;3Saint Petersburg State University, Saint Petersburg,
To investigate the association between rs12050217A/G polymorphism in the
Russia;4Saint Petersburg National Research University of Information,
BDKRB1 gene and DR in patients with type 2 diabetes mellitus (T2DM).
Technologies, Mechanics and Optics, Saint Petersburg, Russia;5Komarov
Methods
Botanical Institute of the Russian Academy of Sciences, Saint Petersburg,
We analyzed 1129 T2DM patients and 416 non-diabetic subjects. T2DM patients
Russia.
were categorized by the presence of non-proliferative DR (NPDR, nZ476),
proliferative DR (PDR, nZ275) and absence of DR (nZ200). The local ethic
Non-genetic animal models of diabetic nephropathy (DN) are most commonly
committee approved the study, and all subjects signed a consent form. The
reproduced by using streptozotocin (STZ) which preferentially gets into b-cells
BDKRB1 rs12050217A/G polymorphism was genotyped by Real-Time PCR
via GLUT2 transporters. However, STZ administration results in nephrotoxic
using TaqMan MGB probes.
effects as well, due to expression of GLUT2 by renal tubular epithelial cells. We
Results
hypothesized that nicotinamide
(NA), which is considered to attenuate the
The genotype frequencies of the BDKRB1 rs12050217A/G polymorphism are in
severity of STZ-induced b-cell damage, could also prevent tubular alteration.
Hardy-Weinberg equilibrium, and did not differ between T2DM patients and
Starting at 3 weeks after unilateral nephrectomy, thirty adult male Wistar rats
normoglycemic subjects (PO0.05). The presence of the minor G allele of the
were fed the high-fat diet for 5 weeks and then successively received either NA
rs12050217 polymorphism was less frequent mainly in patients with PDR when
(230 mg/kg) and STZ
(65 mg/kg, NA-STZ-group) or STZ in a low dose
compared to patients with NPDR and without DR (31.5, 41.8 and 41.2%,
(40 mg/kg, LD-STZ-group) intraperitoneally in
15-min interval. Control
PZ0.034; respectively). Interestingly, we observed that the presence of the G
nondiabetic uninephrectomized rats received vehicle and were fed normal
allele was associated with protection for PDR, which was confirmed after
chow (C-group). At weeks 10, 20, and 30 (the end of the study), metabolic
correction for the presence of hypertension, ethnicity, diabetes duration and age
parameters, creatinine clearance, albuminuria, and urinary tubular injury markers
((95% CI) Z0.580 (0.398-0.843); PZ0.004).
(NGAL, KIM-1) were evaluated as well as renal ultrastructural and light
Conclusions
microscopic changes at weeks
20
and
30. NA-STZ-group showed higher
The BDKRB1 rs12050217 G allele is associated with protection for the advanced
reproducibility and stability of metabolic parameters. By week 10, NA-STZ-
stage of DR in T2DM patients.
injected rats showed overweight (328.9G22.7 g (NA-STZ) vs 285.4G20.5 g
DOI: 10.1530/endoabs.49.GP90
(C)), mild hyperglycemia (HbA1c 5.39G0.24% vs 3.6G0.29%), significant
increase in insulin resistance
(HOMA-IR 3.2G0.39 vs 1.93G0.29),and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
dyslipidemia (total cholesterol 2.89G0.25 mmol/l vs 1.55G0.35; triglycerides
GP94
1.05G0.18 mmol/l vs 0.57G0.1), P!0.05 each, that were observed until the end
The A allele of the -866G/A polymorphism in UCP2 gene decreases high
of the study. At 20 weeks, development of early stage of DN was confirmed by
glucose-induced UCP2 expression in HUVECs
glomerular basement membrane thickness, gradual decline in creatinine
Tais Assmann1,2, Daisy Crispim1,2, Michelle Rodrigues2, Liana Silva2,
clearance, and mild albuminuric status
(478.4G63.3 m/24 h vs
35.8G
Ana Paula Bouças1,2, Rodrigo Carlessi2, Leticia Brondani1,2, Luis
3.6 m/24 h), with progression by week 30, when light microscopic features of
Henrique Canani1,2 & Bianca Souza1,2
DN were observed. Morphofunctional renal changes in NA-STZ appeared to be
1Postgraduate Program in Medical Sciences: Endocrinology, Universidade
more pronounced than those in LD-STZ despite lower levels of KIM-1 and
Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;
NGAL (2535.8G303.9 ng/24 h (LD-STZ) at week 30) vs 1704.4G444.7 ng/24 h
2Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,
in NA-STZ, PZ0.037. We have described a model of type 2 diabetes and DN
Rio Grande do Sul, Brazil.
with attenuated STZ-induced tubular alteration in rats that is characterized by
stable metabolic disorders and renal morphofunctional changes similar to
relatively early stages of human DN.
Uncoupling protein
2
(UCP2) is a mitochondrial protein located in the
DOI: 10.1530/endoabs.49.GP92
mitochondrial inner membrane, and it uncouples substrate oxidation from ATP
synthesis, thereby dissipating the membrane potential energy and consequently
decreasing reactive oxygen species (ROS) formation by mitochondrial respiratory
chain. ROS overproduction is related to diabetic retinopathy (DR), a chronic
complication of diabetes mellitus (DM). Recently, our group reported that the
-866A/55Val/Ins haplotype (-866G/A, Ala55Val and Ins/Del polymorphisms) of
the UCP2 was associated with risk for proliferative DR in both type 1 and type 2
diabetic patients. Additionally, this haplotype influenced UCP2 expression in
human retina samples. Indeed, some studies suggest that the
-866G/A
polymorphism directly affect UCP2 expression; however, its effect on endothelial
cells under different glucose concentrations is not well defined.
Objective
To investigate the effect of -866G/A polymorphism on UCP2 expression in an
endothelial cell line under different glucose concentrations.
Methods
HUVECs cells were transfected with pGL3 plasmids containing the promoter
Diabetes therapy & complications 1
region of UCP2 gene and the coding sequence of firefly luciferase, using LTX
GP93
Lipofectamine (Life Technologies). The test conditions were: 1) transfection with
microRNA expression profile in plasma from patients with diabetic
the wild-type allele-containing plasmid (pGL3-UCP2-G); and 2) transfection with
kidney disease
the mutated allele (pGL3-UCP2-A), under conditions of normoglycemia (4 mM)
or hyperglycemia (25 mM) after 24 h and 48 h. Plasmid pCMV encoding renin
Tais Silveira Assmann1,2, Marcia Punales3, Balduino Tschiedel3, Luis
luciferase and pEGFP were co-transfected as internal control and transfection
Henrique Canani1,2, Andrea Carla Bauer1,2 & Daisy Crispim1,2
control, respectively. Luciferase levels were measured with Luminescent Dual-
1Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul,
luciferase Assay (Promega).
Brazil;2Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;
Results
3Instituto da Criança com Diabetes, Porto Alegre, Brazil.
HUVECs cells transfected for 24 h and 48 h with the plasmid containing the
-866A allele under normal glucose conditions had 47% and 37% decrease in
Introduction
UCP2 expression than cells transfected with the plasmid containing the G allele
Diabetic kidney disease (DKD) is the major cause of end-stage renal disease;
(PZ0.011 and PZ0.0001; nZ3). Interestingly, under high glucose conditions,
however, the pathogenesis of this disease is not fully understood. Currently
cells containing the A allele had a more drastic decrease in UCP2 expression
available therapies are not totally efficacious in the treatment and prognosis of
(70% and 54%) compared to cells with the G allele (PZ0.0001 and PZ0.028;
DKD, suggesting that further understanding of the molecular mechanisms
nZ3) after 24 and 48 h.
underlying the pathogenesis of this disease is necessary to improve its
Conclusion
management. Recently, research on microRNAs (miRNAs) has become a hotspot
Our preliminary results demonstrate that the UCP2 -866A allele decreases UCP2
because of their critical role in regulating posttranscriptional levels of protein-
expression in HUVEC cells, which is exacerbated under high glucose conditions.
coding genes. Several miRNAs were found to participate in DKD pathogenesis;
The -866G/A polymorphism of the UCP2 gene is associated with increased UCP2
nevertheless, results are still inconclusive. Therefore, the identification of
protein concentrations in human retina, which may explain the previous reported
miRNAs involved in DKD may help in the diagnosis and treatment of this
association between the -866A/55Val/Ins haplotype and risk for DR.
disease.
DOI: 10.1530/endoabs.49.GP94
Objective
To identify a miRNA expression profile associated with DKD in plasma from
patients with type 1 diabetes mellitus (T1DM) with different degrees of this
diabetic complication.
Design
Expressions of 48 miRNAs were investigated in the plasma from 46 T1DM
patients: 24 patients in group 1 [patients with T1DM for more than 10 years, with
GP95
urinary excretion of albumin (UEA) !30mg/g and estimated glomerular filtration
The relation between PON-1 activity and 25-OH hydroxyvitamin D3
rate (eGFR) R60 ml/min/1.73 m2)], 11 in group 2 (patients with T1DM with
levels and other biochemical parameters in diabetic patients with
UEA 30-300mg/g or eGFR 45-59 ml/min/1.73 m2) and 11 in group 3 (patients
respect to obesity and diabetic complications
with T1DM with UEAO 300 mg/g or eGFR 15-29 ml/min/1.73 m2), using Stem-
Pinar Karakaya1, Meral Mert1, Hamide Karagoz1 & Bahar Ozdemir2
loop RT-PreAmp Real-time PCR and TaqMan Low Density Array cards (Thermo
1Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul,
Scientific Inc).
Turkey;2Department of Internal Medicine, Bakirkoy Dr. Sadi Konuk
Results
Training and Research Hospital, Istanbul, Turkey.
Eighteen miRNAs were differently expressed between T1DM patients without
DKD (controls) and T1DM patients with different levels of DKD (cases).
Seventeen miRNAs were downregulated (miR-126, miR-146a, miR-155, miR-
Objective
192, miR-200a, miR-200b, miR-204, miR-216a, let-7b, miR-29c, miR-200a,
To evaluate the relation of mean platelet volume (MPV) levels with serum
miR-20b, miR-216a, miR-25, miR-320, miR-92a and miR-638) and one miRNA
paraoxonase-1 activity in diabetic patients with respect to obesity and diabetic
was upregulated (miR-124) in cases compared to controls. In addition, miRNAs
complications.
let-7b, miR-155, miR-200a, miR-20b, miR-216a, miR-25, miR-29c, miR-320 and
Methods
miR-92a were downregulated in T1DM patients with severe DKD (group 3)
A total of 201 diabetic patients grouped with respect to obesity obese (nZ89) and
compared to controls.
non-obese (nZ112) and diabetic complications with (nZ50) or without (nZ150)
Conclusion
microvascular complications and with
(nZ91) or without (nZ108) macro-
Our preliminary results show that some circulating miRNAs are differentially
vascular complications groups were included. Data on demographic and lifestyle
expressed between T1DM patients with and without DKD.
characteristics of patients, anthropometric measurements, diabetes related
DOI: 10.1530/endoabs.49.GP93
microvascular and macrovascular complications, Correlation of MPV values to
paraoxonase and arylesterase activities.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
GP97
Mean(SD) paraoxonase and arylesterase values were
119.8G37.5 U/l and
Comparison of current perception threshold measured by Neurometer
149.0G39.9 U/l, respectively in the overall population, with no significant
in patients with type 2 diabetes mellitus to a group of normal individuals
difference with respect to obesity and macrovascular diabetic complications,
Chin-Hsiao Tseng1,2
whereas significantly lower values for paraoxonase 107.5G30.7 vs. 123.9G
1National Taiwan University College of Medicine, Taipei, Taiwan;
38.8 U/l, (PZ0.007) and arylesterase 132.1G30.2 vs. 154.G41.2 U/l (PZ0.001)
2National Taiwan University Hospital, Taipei, Taiwan.
were noted in patients with than without diabetic microvascular complications.
Mean(SD) MPV values were 9.10G0.87 fL in the overall population, with no
significant difference with respect to obesity and diabetic complications. No
Purpose
significant correlation of MPV values to paraoxonase and arylesterase activities.
To determine the proportion of abnormal current perception threshold (CPT) in
A significant positive correlation was determined with plasma
25-(OH)
patients with type 2 diabetes mellitus.
hydroxyvitamin D3
levels
(rZ0.398, PZ0.001 and rZ0.484, respectively
Methods
PZ0.001). HOMA-IR exhibited a significant negative correlation with PON and
A total of
1360
patients with type
2
diabetes mellitus involved in an
arylesterase in the groups.
epidemiological study received an examination of CPT measured by Neurome-
Conclusion
terw CPT/C (Neurotron, Inc., Baltimore, Maryland, USA) on a supine position.
In conclusion, our findings revealed a significant decrease I PON-1 activity in
The measurement was taken for three frequencies, i.e., 5, 250 and 2000 Hz at
diabetic patients with microvascular rather than macrovascular complications,
three sites: the preauricular area (trigeminal nerve), the index finger (median
whereas regardless of obesity and diabetic complications, no increase in
nerve) and the great toe (superficial peroneal nerve) on both sides. The three
thrombogenic activity and no relation of thrombogenic activity with PON-1
frequencies measure small unmyelinated C fiber (5 Hz), small myelinated Ad
activity. PON-1 activity exhibited a significant negative correlation, independent
fiber
(250 Hz), and large myelinated Ab fiber (2000 Hz), respectively. The
of obesity, sex and age, with plasma glucose, HbA1c and HOMA-IR values in all
normative data from 75 normal individuals were used as control and an “abnormal
patients and a significant positive correlation with 25-OH vitamin D3 values. Low
CPT” was defined as a value greater than the normal mean plus 3 standard
PON-1 activity and 25 OH vitamin D3 levels may be a marker of inadequate
deviations derived from the normal individuals. Age, sex, body height and body
glycemic control independent of obesity in diabetic patients They may play an
weight were treated as potential confounders. Student’s t test, Chi-square test,
important role for early atherosclerosis who had only in obese diabetic especially
correlation coefficient and stepwise regression were used for statistical analyses
microvascular diabetic complications well glysemic control of the most factor
and a P value !0.05 was considered as statistically significant.
that it prevents diabetic complications and also well glysemic control and
Results
apropiate vitamin D levels have good affect on diabetic complications.
Accept for a significantly older age in the diabetes group, the distribution of sex, body
DOI: 10.1530/endoabs.49.GP95
height and body weight were not different significantly. CPT measurements on the
right and left sides correlated significantly with correlation coefficients mostly O0.7
(P!0.0001) in the diabetes patients. The trigeminal nerve had the most commonly
reported “abnormal CPT” that involved approximately 60% of the diabetes patients,
followed by the superficial peroneal nerve (50%) and the median nerve. The median
nerve showed frequency-dependent abnormality with higher proportion of “abnormal
CPT” involving lower frequency. For the frequency of 2000, 250 and 5 Hz,
“abnormal CPT” was observed in 15-20, 30-33 and 56-59%, respectively. In
stepwise regression analyses, diabetes and age were consistently predictive for CPT.
Conclusions
GP96
Patient with type 2 diabetes mellitus have higher CPT values than normal individuals
in all anatomical sites. The application of Neurometerw for screening of diabetes
High prevalence of lower extremity peripheral artery disease in type 2
neuropathy awaits further confirmation.
diabetes patients with diabetic nephropathy and the role of netrin-1
levels
DOI: 10.1530/endoabs.49.GP97
Ahmet Kor, Suleyman Baldane, Suleyman Hilmi Ipekci,
Kamile Marakoglu, Ali Altinok, Ali Unlu, Fatih Colkesen, Bahadir Ozturk,
Cem Onur Kirac & Levent Kebapcilar
Selcuk University, konya, Turkey.
Background
Netrin-1 is an early biomarker of acute kidney injury. Besides, recent studies have
GP98
showed that netrin-1 promotes angiogenesis; but its usefulness for peripheral
Gestacional diabetes mellitus: the new screening criteria and its
artery disease (PAD) in type 2 diabetes patients is unknown.This study aimed at
outcomes
investigating whether netrin-1 levelsare increased in peripheral artery disease
Pedro Gouveia, Maritza Sá, Eduarda Resende, Margarida Ferreira &
among patients with type 2 diabetes and also investigating possible associa-
Silvestre Abreu
tionsbetween diabetic nephropathy (DN) and PAD.
Centro Hospitalar do Funchal, Funchal, Portugal.
Material and Methods
This was a cross-sectional observational clinical study. This study involved a total
of 84 adults with type 2 DM, who underwent ABI (low ankle-brachial index)
Background
measurement in an outpatient clinic. PAD was defined as ABI !0.9 in either leg.
Gestational Diabetes Mellitus (GDM) is one of the most common illness of
ABI of 42 patients with PAD were compared with 42non-PADpatients. Diabetic
pregnancy. Despite its frequency, there’s no worldwide accepted screening
nephropathy was evaluated by estimated glomerular filtration rate and urinary
criteria for GDM. In 2011, Carpenter and Coustan (CC) screening (50-g glucose
albumin-creatinine ratio (ACR).
challenge test (GCT) followed by 100-g glucose tolerance test (OGTT) if GCT
Results
screen was positive) was abandoned and began the implementation of the
Compared with control group, the levels of Netrin-1
levels and diabetic
screening of the International Association of Diabetes and Pregnancy Study
nephropathy subjects were significantly increased in the PAD group. As regards
Group (IADPSG) 2010 (75-g OGTT).
similar GFR values, patients with higher urinary albumin-creatinine ratio (ACR)
Aims
values had significantly lower ABI parameters than the patients without
Asses and compare perinatal outcomes of these two screening criteria.
albuminuria.(Right:
0.96G0.1 vs 1.05G0.01, Left:
0.94G0.1 1.04G0.01vs
Materials and methods
P!0.01).Binary logisticregression analysis revealed that diabetic nephropathy
We undertook a retrospective study, of gestacional diabetes followed on
(vs non-DN) was associated with PAD (OR Z2.94, 95%CI: 1.2-7.1; PZ0.017)
Endocrinology department. Two groups were constituted: CC
(followed in
.In multivariate models, adjusted additionally for the mean duration of diabetes,
2009 and 2010) and IADPSG (followed in 2014 and 2015). All patients were
gender, BMI, HbA1c, hyperlipidemia and hypertension, theassociations with
treated with nutrition and exercise. When target glucose levels were not met,
netrin-1and PAD persisted (beta: 0.238, PZ0.042).
insulin was initiated, no oral antidiabetic agents were used. Analysed data
Conclusion
included birthweight, premature delivery, macrosomia, mode of delivery,
Our study in patients with type 2 DM demonstrated that PAD was associated with
maternal parity, body mass index (BMI) and insulin treatment.
diabetic nephropathy and netrin-1 levels. In conclusion, changes in netrin-1 levels
Results
are likely to be used as a biomarker for monitoring the risk of PAD in patients
In 2009 and 2010, of 4705 childbirths in the hospital, 259 (5.5%) women met the
with Type 2 diabetes.
CC criteria, of which 134 were included in this study. In 2014 and 2015, of 3496
DOI: 10.1530/endoabs.49.GP96
childbirths in the hospital, 348 (9.9%) women met the IADPSG criteria, of which
221 were included in this study. Those with GDM per IADPSG criteria had more
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
insulin treatment (46.6 vs 23.1%; P!0.0001), fewer large for gestacional age
Results
fetus
(3.6
vs
9.0%, PZ0.038) and less premature delivery
(1.4
vs
5.2%,
Fifteen articles fulfilled the inclusion criteria and passed the quality control
PZ0.033).
evaluation. In most studies, hearing loss (HL) was defined as pure tone greater
Conclusions
than 25 dB in the worse ear of at least one frequency. The incidence of HL ranged
Although the application of the IADPSG criteria increased the number of women
between 0 and 48% for diabetics, which was higher than in controls (ORZ12.43
diagnosed with GDM, there was an increase in insulin treatment, and an overall
95% CI 3.09-49.95). The tendency of mean PTA (pure tone audiometry)
better newborn outcomes. This could mean that the IADPSG criteria identified a
thresholds were greater in diabetics than in controls for higher frequencies,
group of women with a increased risk of perinatal outcomes that were not
however the results were not significant. Auditory brainstem response (ABR)
recognized by the CC screening.
latencies were longer in diabetic patients compared to controls. Statistical
DOI: 10.1530/endoabs.49.GP98
significance was obtained in wave III and V (ZZ3.18, PZ0.001 I2Z82%;
Z89% respectively).
ZZ2.55, PZ0.01, I2
Conclusions
Patients with type
1 diabetes have a significantly greater incidence of HL
compared to the control group. However, hearing thresholds seems to be not
significantly different from control subjects. Mean PTA thresholds were greater at
6000 and 8000 Hz. Despite a trend of higher threshold difference at higher
GP99
frequencies tested, the mean differences between groups at any frequency were
Higher levels of adiponectin might contribute to lower bone mass
not statistically significant. A significant prolonged ABR of waves III and V
observed in patients with type 1 diabetes, through alterations in
latencies in the diabetic group suggest a retro-cochlear involvement in hearing
osteocalcin energy circuit signaling of bone cells.
damage in type 1 diabetes.
Charalampos Tsentidis1, Dimitrios Gourgiotis2, Lydia Kossiva1,
DOI: 10.1530/endoabs.49.GP100
Artemis Doulgeraki3, Antonios Marmarinos2 & Kyriaki Karavanaki1
1Diabetes Clinic, Second Pediatric Department, University of Athens, “P&A
Kyriakou” Children’s Hospital, Athens, Greece;2Biochemistry Laboratory,
Second Pediatric Department, University of Athens, “P&A Kyriakou”
Children’s Hospital, Athens, Greece;3Department of Bone and Mineral
Metabolism, Institute of Child Health, “Aghia Sophia” Children’s Hospital,
Athens, Greece.
GP101
Introduction
Abstract withdrawn.
Recent advances in energy homeostasis revealed a significant interconnection
between bone and adipose tissue through osteocalcin. Reduced bone mass
documented in type 1 diabetes mellitus (T1D) could be related to disregulation of
adipokine signaling on bone.
Materials and Methods
We evaluated 40 children and adolescents with T1D (meanGS.D. age 13.04G
3.53 years, meanGS.D. T1D duration 5.15G3.33years) and 40 healthy age- and
gender-matched controls (meanGS.D. age 12.99G3.3years). Adiponectin, leptin
and bone metabolism markers were measured, while lumbar spine (LS) and total
body (TB) Bone Mineral Density (BMD) were evaluated with dual energy X-ray
absorptiometry (DXA).
GP102
Results
Comparison of the effects of combinations of different antihypertensive
Lower BMD values have already been documented in patients, as well as lower
therapies on microalbuminuria and renal functions in type 2 diabetic
osteocalcin (log(osteocalcin) 3.44G0.5 vs 3.6G0.51). Patients had higher levels
patients
of adiponectin (18078G8645 vs 13536G6703 ng/ml, PZ0.007) while leptin
Muge Erek1, Alparslan Ersoy1 & Canan Ersoy2
levels were comparable between groups
(8.85G8.73 vs 10.03G8.75 pg/ml,
1Uludag University Medical Faculty, Department of Nephrology, Bursa,
PZ0.13). Both adipokines were associated with Body Mass Index (BMI) in both
Turkey;2Uludag University Medical Faculty, Department of Endocrinology
groups. Adiponectin was positively associated with osteocalcin only in controls
and Metabolism, Bursa, Turkey.
(RhoZ0.31, PZ0.05) possibly indicating altered energy signaling in bone of
T1DM patients, whereas in patients it was negatively associated with IGF1
(RhoZK0.30, PZ0.05) and positively associated with HbA1c (RhoZ0.38,
Renin angiotensin system blockers are currently used in the treatment of diabetic
PZ0.01) and i-phosphorus (RhoZ0.39, PZ0.01). No associations of leptin with
nephropathy. Carvedilol, 3. generation beta-blockers, may provide additional
bone markers were observed.
benefits in diabetic patients. Its antiproteinuric activity is not investigated in
Conclusion
patients with diabetic nephropathy. We aimed to compare short-term additive
Increased adiponectin might contribute to lower bone mass observed in young
effects of losartan with cilazapril or carvedilol combination on blood pressure,
T1D patients with altered interconnection of energy signaling in bone cells,
proteinuria and renal functions in microalbuminuric patients with type 2 diabetes
through osteocalcin circuit.
mellitus and hypertension.
Methods
DOI: 10.1530/endoabs.49.GP99
Thirty patients with type 2 diabetes, stage 1 hypertension and albuminuria of 30-
300 mg/day, were enrolled in the study. After the 2 week follow-up period, all
patients were started on losartan
50 mg/day for 6 weeks. Then, they were
randomized to three groups for 6 weeks: 1st group (n:10) on losartan 100 mg/day,
2nd group (n:10) on carvedilol 25 mg/day C losartan 50 mg/day and 3rd group
(n:10) on cilazapril 5 mg/day C losartan 50 mg/day treatment.
GP100
Results
Type 1 diabetes and hearing loss: a meta-analysis
Characteristics of groups were similar. In all groups, systolic and diastolic
Mario Mujica-Mota & Neel Patel
blood pressures (BP) were significantly decreased. Greatest decrease in systolic
Montreal, Québec, Canada.
(16.5G7.4 mmHg) and diastolic (10.5G2.8 mmHg) BPs were seen in group 3
and smallest decreases were seen in group 1 (systolic BP: 9G6.1 mmHg, diastolic
BP: 3G4.8 mmHg). Microalbuminuria levels in all groups decreased signi-
Objective
ficantly when compared to the period of 50 mg losartan alone (P!0.05). Renal
Evidence shows type 1 diabetes leads to vascular damage and neuropathy. The
functions of the groups did not change significantly. But creatinine clearances
purpose of this study was to perform a systematic review and a meta-analysis to
significantly increased in all groups after the randomization, although there was
asses the evidence of the effects of type 1 diabetes on hearing function.
no significant difference between groups.
Methods
Conclusion
Three different electronic databases were used to identify eligible studies
We observed that the combination of carvedilol in hypertensive type 2 diabetics
including a manual searching of references. The articles obtained were
patients with microalbuminuria safely controlled blood pressure more effectively
independently reviewed by two authors using predefined inclusion criteria to
without additional benefit in reducing microalbuminuria
identify eligible studies. Meta-analysis was performed on pooled data of hearing
DOI: 10.1530/endoabs.49.GP102
loss incidence, PTA thresholds and ABR wave latencies.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Diabetes therapy & complications 2
Excess consumption of saturated fatty acids may lead to an increased production
of ceramides that contribute to development of insulin resistance and type 2
GP103
diabetes. Substantial research demonstrated that inhibition of ceramide
biosynthesis ameliorates atherosclerosis, hepatic steatosis, insulin resistance
and obesity. However, as ceramides and their sphingolipid products are involved
Abstract withdrawn.
in multiple fundamental cellular processes, concerns exist about possible risks or
adverse effects resulting from overall inhibition of sphingolipid synthesis for
treatment of chronic diseases. Therefore, the inhibition of specific ceramide
species represents a new strategy for pharmaceutical intervention. Recent
research demonstrated that specifically CerS6 mediated C16 ceramide synthesis
plays a key role in the development of obesity mediated insulin resistance.
In the current study, we investigated the effects of specifically knocking-down
CerS6 in ob/ob mice using CerS6 anti-sense oligonucleotides (ASO). In this
animal model, CerS6 expression is significantly higher vs. lean control mice (w2
fold in the liver and BAT) which correlates with a 4-fold increase of C16
GP104
ceramide in the plasma and a 2-fold increase in the liver. CerS6 ASO treatment
led to selective and significant w80% knockdown of the CerS6 expression in the
Non-stimulated c-peptide is independently associated with requirement
liver and correlated with a significant 50% reduction of C16 ceramide in the liver
at 1 year for insulin therapy in patients with diabetes: a retrospective
and plasma compared to control ASO-treated ob/ob mice. CerS6 knockdown
cohort study of 872 patients
protected against body weight gain and was associated with a significant
Emma Leighton1, Karen Smith2, Christopher Sainsbury1 & Gregory Jones
reduction in fat mass and blood glucose levels. Moreover, insulin resistance was
1Gartnavel General Hospital, Glasgow, UK;2Glasgow Royal Infirmary,
significantly improved by ASO treatment as evidenced by oral glucose tolerance
Glasgow, UK.
and insulin tolerance tests (w50% reduction in AUC during oGTT).
In conclusion, CerS6 dependent C16 ceramide synthesis represents a distinct
Introduction
sphingolipid species, which contributes to the development of obesity and insulin
C-peptide is frequently used in clinical practice to estimate insulin secretion, and
resistance and therefore may represent a unique and attractive novel target to treat
guide need for future insulin treatment. Present practice is based on studies with
obesity and type 2 diabetes.
small patient numbers.
DOI: 10.1530/endoabs.49.GP105
Aim
To explore the association between non-stimulated c-peptide and progression to
insulin therapy in patients with diabetes.
Patients and Methods
1971 patients with c-peptide measurements were identified (February 2007-
December 2016) within a single health board. 940 individuals also appeared on
national diabetes database. 872 individuals within this dataset have a defined
diabetes diagnosis and were analysed. The date of first encashed insulin
prescription for each individual was extracted from the national diabetes dataset.
Insulin-free survival (time to first insulin prescription or end of follow-up) in
individuals who were insulin-naive at the time of c-peptide measurement was
GP106
investigated using survival analysis. Individuals with c-peptide values below
Outcomes of integrating personal continuous glucose monitors with
median were compared with those above median value. Time to insulin
insulin pumps in a University Diabetes Unit
prescription was analysed using cox proportional hazard model with age and
Ali Rizvi & Kyoka Smith
BMI as covariables. The positive predictive value
(PPV) of c-peptide for
University of South Carolina School of Medicine, Columbia, SC, USA.
predicting insulin use at 1 year was calculated in 0.2 nmol/l increments.
Results
Objective
458 individuals had BMI data available, and were insulin-naive at the time of
Personal continuous glucose monitoring (pCGM) with interstitial fluid glucose
c-peptide measurement. In this cohort a c-peptide in the lower half of the range of
sensing is rapidly becoming the standard of care for real-time, intensive insulin
observed values (!0.76 nmol/l) is associated with a significantly decreased
therapy of diabetes. We report our experience of glycemic control in patients in an
insulin-free survival time (P!0.001, HR 3.0). PPV for initial c-peptide(nmol/l)
academic setting using minimally invasive pCGM with continuous s.c. insulin
increments were: c-peptide 0.01-0.2 PPVZ0.95, 0.2-0.4 PPVZ0.67, 0.4-0.6
infusion (CSII, or insulin pump) vs CSII alone.
PPVZ0.6, 0.6-0.8 PPVZ0.43, 0.8-1.0 PPVZ0.3.
Methods
Conclusion
Over a two-year period, we reviewed all patients treated with insulin pumps at the
Unstimulated c-peptide is independently associated with increased probability of
Diabetes Unit of the Palmetto Health-University of South Carolina Medical
requiring insulin at 1 year. This is a simple test which offers potentially useful
Group. Group A (CSII alone) used only meters to self-monitor blood glucose, and
information allowing patients to plan for future treatment.
while Group B additionally used pCGM integrated with CSII to adjust pump
DOI: 10.1530/endoabs.49.GP104
settings, including basal rate and/or short-acting bolus insulin doses, and change
insulin-to-carbohydrate ratio and supplemental factor. The data was analyzed
with respect to age, gender, glucose control as assessed by glycosylated
hemoglobin (HbA1c), and severe hypoglycemia.
Results
There were 54 patients in group A and 59 in group B. They were comparable in
mean age and gender breakdown (47.3 vs 45.2 years, and 66.8% vs 62.7%
females, respectively). The average glycosylated hemoglobin (HbA1c) changed
from 8.8% to 8.2% and from 8.2% to 7.3% from baseline to the end of one year in
the two groups respectively. The number of severe hypoglycemic episodes per
patient during the one year was 0.2 and 0.07 respectively.
Discussion
CSII patients who used pCGM were similar in demographics to those who used
GP105
insulin pumps alone, but had a lower baseline A1c, exhibited a larger decrease in
Ceramide synthase 6 inhibition as a novel therapeutic approach for
A1c at one year (0.9% vs 0.6%), and had fewer severe hypoglycemic events.
obesity and type 2 diabetes
Conclusions
Maximilian Bielohuby1, Surya Prakash1, Bodo Brunner1, Anja Pfenninger1,
The better outcomes with pCGM-integrated pump therapy may be explained by a
Ulrich Werner1, Sarah Turpin-Nolan2, Jens Bruning2 & Norbert Tennagels1
higher motivation ability for self-monitoring and care, and by the pCGM being a
1Sanofi-Aventis Deutschland GmbH, R&D Diabetes Division, Industriepark
valuable informational tool in assessing glucose trends when used in properly
Hochst, Frankfurt am Main, Germany;2Max Planck Institute for Metabolic
chosen insulin pump patients who are managed by qualified experts.
Research, Cologne, Germany.
DOI: 10.1530/endoabs.49.GP106
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP107
and treated with liraglutide as add-on to metformin, 0.6 mg/day for two weeks,
followed by a dose of 1.2 mg/day. At baseline and every 6 months fasting samples
Specific Oct1 gene variants are associated with changes in the risk of
were taken for laboratory analyses and carotid-intima media thickness (cIMT)
cardiovascular death in metformin users
was assessed by B-mode ultrasound. Statistical analysis was performed by
Natascha Schweighofer1,7, Bernd Genser2,3, Winfried März4,5, Marcus
ANOVA and the Spearman correlation method.
E Kleber6, Thomas R Pieber1,7 & Barbara Obermayer-Pietsch1,7
Results
1Division of Endocrinology and Diabetology, Department of Internal
After18 months of liraglutide therapy HbA1creduced significantly in both groups
Medicine, Medical University Graz, Graz, Austria;2BG Statistical
(from
9.02G1.06
to
6.93G1.25
and from
8.50G0.71
to
6.74G0.90%,
Consulting, Vienna, Austria;3Institute of Public Health, Social and
respectively) as well as fasting glycemia
(from
9.57G3.33
to
7.16G
Preventive Medicine, Medical Faculty of Mannheim, University of
2.83 mmol/l; and from 9.14G3.71 to 7.28G2.29 mmol/l, P!0.0001 for all.
Heidelberg, Mannheim, Germany;4Clinical Institute of Medical and
Anthropometric parameters changed although not significantly. Lipids, with the
Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria;
exception of HDL-cholesterol, reduced significantly only in pre-elderly subjects
5Synlab Center of Laboratory Diagnostics, Heidelberg, Germany;6Vth
(triglycerides from 1.94G1.48 to 1.57G0.80 mmol/l, PZ0.0458; total choles-
Department of Medicine (Nephrology, Hypertensiology, Endocrinology,
terol from 4.90G1.57 to 4.27G1.04 mmol/l, PZ0.0025; LDL-cholesterol from
Diabetology, Rheumatology), Medical Faculty Mannheim, Heidelberg
2.92G1.44 to 2.34G0.91 mmol/l, PZ0.0054. cIMT significantly decreased in
University and Competence Cluster of Nutrition and Cardiovascul,
both groups (from 0.96G0.18 to 0.78G0.20 mm; and from 0.98G0.17 to 0.79G
Heidelberg/Halle-Jena-Leipzig, Germany;7CBmed GmbH, Center for
0.20 mm, respectively; P!0.0001 for both). Changes in cIMT were positively
Biomarker Research in Medicine, Graz, Austria.
associated only with changes in triglycerides in both pre-elderly
(rZ0.245,
PZ0.0398) and elderly (rZ0.566, P!0.0001) groups.
Aim
Conclusion
Increased cardiovascular incidents and a high risk for microvascular compli-
Liraglutide significantly reduced cIMT in both pre-elderly and elderly subjects
cations are associated with type 2 diabetes. Worldwide, metformin is the most
with T2DM, beyond glycemic control.
commonly prescribed antidiabetic drug. Polymorphisms in the Oct1 gene can
DOI: 10.1530/endoabs.49.GP108
alter the function or activity of organic cation transporter 1 (Oct1), thus changing
metformin efficacy (Oct1 acting as its main transporter) as well as influencing the
actions of Oct1 physiological substrates. In the past, polymorphisms in Oct1 were
associated with cardiovascular risk factors, thus they might contribute to
cardiovascular risk development.
We investigated, whether the Oct1 polymorphism rs3777392 is associated with
increased risk for cardiovascular death in a cohort of patients with and without
type 2 diabetes (T2DM) on various therapies.
Methods
Data from the LURIC study (nZ3316), a prospective cohort study of Caucasians
scheduled for coronary angiography were analysed. We identified 1820 non-
GP109
diabetics,
1220 T2DM patients, including
73 metformin users
(Met),
154
Treatment of diabetic ketoacidosis at type 1 diabetes mellitus
sulfonylurea users
(SF) and
967
T2DM individuals without medication.
presentation: 13 year experience from a tertiary centre (2004-2016)
Cardiovascular mortality was assessed in all groups according to Oct1
Joana Serra-Caetano1, Lia Gata1, Alexandra Dinis1, Rita Cardoso1,
rs3777392 genotypes using Cox proportional hazard models and associations
Isabel Dinis1, Miguel Patrício2 & Alice Mirante1
with cardiovascular biomarkers were investigated.
1Pediatric Hospital, Coimbra Universitary Hospital Centre (CHUC),
Results
Coimbra, Portugal;2Laboratory of Biostatistics and Medical Informatics
Cardiovascular mortality risk for each minor allele copy was HR 2.08 (95% CI:
and IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
1.01, 4.28) only in metformin users. Variants of rs3777392 were associated with
BMI, baseline insulin values and triglyceride levels in all T2DM patients
(PZ0.016, PZ0.048 and PZ0.007, respectively), patients without medication
Introduction
(PZ0.006, PZ0.041, PZ0.008, respectively) and non-diabetics (PZ0.021,
Diabetic ketoacidosis (DKA) is an endocrine emergency and the leading cause of
PZ0.074, PZ0.125, respectively) but not in the Met and SF groups.
morbi-mortality in children with type 1 diabetes mellitus (1DM). DKA treatment
Conclusion
is still controverse, mainly regarding hydroelectrolytic replacement and insulin
In our study, the minor allele of rs3777392 in the Oct1 gene was associated with
dose.
an increased cardiovascular mortality risk in T2DM patients on metformin
Aims
therapy, which might be due to loss of association with cardiovascular
To evaluate efectiveness and safety of our tertiary centre protocol in DKA
parameters. Besides very positive effects in the majority of metformin users,
treatment, which included initial volume expansion with isotonic saline in the first
some individuals may profit from a pre-treatment genotyping and careful
two hours followed by 0.45% sodium chloride with 5% glucose and insulin
monitoring.
infusion (0.1 U/kg per h). Potassium replacement with potassium phosphate in the
first 12 h.
DOI: 10.1530/endoabs.49.GP107
Methods
Retrospective study of all children with moderate and severe DKA
1DM
presented from 2004 to 2016. Data collected: insulin infusion dose, glycemia, pH.
Osmolarity, corrected sodium, potassium and phosphate along the first 12 h of
treatment. Statistic analysis with SPSS21 (P!0,05).
Results
179 new cases of 1DM were admitted and 45 (25%) had DKA at presentation (15
GP108
severe, 12 moderate and 18 mild DKA). Within moderate and severe DKA
Liraglutide improves carotid intima-media thickness in pre-elderly and
(NZ27), 18(67%) were female and mean age at diagnosis was 8.5G3.8 years.
elderly patients with type-2 diabetes: an 18-month prospective, real life
Means at admission were:
528G138 mg/dl glycemia,
310G12 mosm/kg
study
osmolarity, 146G5 mmol/l corrected sodium, 4.5G0.73 mmol/l potassium and
Ali Rizvi1, Angelo Maria Patti2, Giuseppa Castellino2, Carlo Mannina2,
1.5G0.5 mmol/l phosphate. Mean insulin infusion dose at treatment start was
Dragana Nikolic2, Rosaria Vincenza Giglio2, Roberta Chianetta2,
0.08G0.03 U/kg per h. Along the first 12 h mean replacement doses were 4.3G
Giuseppe Montalto2 & Manfredi Rizzo1,2
1.3 gr/U per h of glucose, 0.13G0.04 mmol/kg per h of potassium, 0.33G
1University of South Carolina School of Medicine, Columbia, SC, USA;
0.1 mmol/kg per h of sodium and 0.06G0.02 mmol/kg per h of phosphate. There
2University of Palermo, Palermo, Sicily, Italy.
were 12(45%) cases of hypokalemia and 10(37%) of hypophosphatemia. There
was no hypocalcemia nor cerebral edema. There was statistical significance in
Introduction
variation regarding glucose, pH, corrected sodium and osmolarity along the 12 h
Liraglutide exerts cardio-protective effects beyond of those on glucose
(P!0.0001). Sodium decreased in the first 8 h. Potassium decreased along the
metabolism, affecting several cardio-metabolic parameters, such as subclinical
first 4 h and rose from 8 h forwards.
atherosclerosis. However, it is not known if those effects differ in the long-term
Conclusions
between pre-elderly and elderly subjects with type-2 diabetes (T2DM).
Our protocol allowed a safe treatment of DKA at 1DM presentation, with gradual
Methods
correction of dehydration and acidosis. However, sodium and potassium
We included 135 subjects with T2DM divided in 2 groups: i) 71 pre-elderly
replacement should be adjusted, leading to our actual protocol.
subjects (46 men and 25 women, 55G7 years), and ii) 64 elderly subjects (33 men
DOI: 10.1530/endoabs.49.GP109
and 31 women, 70G5 years). All subjects were naïve to incretin-based therapies
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP110
Conclusion
In our study, six- month therapy with Liraglutide improves, not only risk factors
The method of reporting hypoglycemia in Randomized Control Trials
for cardiovascular disease, but also hepatic steatosis as shown by a decrease in
(RCTs): a systematic review on RCTs conducted for SGLT-2 inhibitors
HSI index and ALT.
Noor Kassir1, Sarah Medeiros2 & Pendar Farahani3
1National University of Ireland, Galway, Ireland;2University of Western
DOI: 10.1530/endoabs.49.GP111
Ontario, London, Ontario, Canada;3McMaster University, Hamilton,
Ontario, Canada.
Background
Hypoglycemia is an important side effect in pharmacotherapy of patients with
GP112
diabetes mellitus. Medical organizations have tried to define hypoglycemia in
Exenatide treatment causes suppression of serum fasting ghrelin levels
clinical practice and RCTs with scientific statements and guidelines.
in patients with type 2 diabetes Mellitus
Objective
Metin Guclu1, Sinem Kiyici1, Zulfiye Gul2 & Sinan Cavun2
To explore the method of reporting hypoglycemia conducted on SGLT-2 inhibitor
1Department of Endocrinology and Metabolism, Health Sciences
RCTs.
University, Bursa Yuksek Ihtisas Education and Training Hospital, Bursa,
Methods
Turkey;2Uludag University Medical Faculty, Department of Pharmacology,
A systematic review using PubMed to find data on RCTs conducted for SGLT-2
Bursa, Turkey.
inhibitors, limited to English language.
Results
Aim
Of 155 RCTs, 95(61.3)
(n(%)) were found to have defined and reported
Ghrelin plays an important role in the stimulation of food intake and long-term
hypoglycemia. The results showed that 8(5.2) RCTs were reported as event/arm,
regulation of body weight. In present study we investigate the long term effect of
15(9.7) as event/combined all arms, 69(44.5) as event/patient/arm and 3(1.9)
exenatide treatment on serum fasting ghrelin levels in patients with type 2
RCTs reported as both event/arm and event/combined all arms. Additionally,
diabetes mellitus.
3(1.9) RCTs defined hypoglycemia but did not report it. Hypoglycemia was
Methods
neither defined nor reported in 57(36.8) of the RCTs. In addition, 41(26.5) RCTs
Type 2 diabetic patients who were using metformin with and without the other
had hypoglycemic episodes that were confirmed, by glucose threshold, whereas
oral antihiperglycemic drugs on a stable dose for at least 3 months were enrolled
only 24(15.5) RCTs had episodes that were reported as symptoms from patients.
in the study. Body mass index (BMI) O 35 kg/m2 and hemoglobin A1c (HbA1c)
Hypoglycemic episodes were reported and confirmed in 5(3.2) of the RCTs and
O 7.0% were the additional inclusion criteria. Oral antihyperglycemic drugs
27(17.4) showed that the episodes were reported or confirmed.
other than metformin were stopped and metformin treatment was continued at
Conclusion
2000 mg per day. Exenatide treatment was initiated at 5 mcg per dose sc twice
This study illustrates that around 40% of RCTs on SGLT-2 inhibitors did not
daily and after one month the dose of exenatide was increased to 10 mcg twice
define and report hypoglycemia. The method of reporting hypoglycemia was
daily. Changes in anthropometric variables, glycemic control, lipid parameters,
variable among the RCTs. Almost half the RCTs reported as event/patient/ arm.
and total ghrelin levels were evaluated at baseline and following 12 weeks of
Additionally, a quarter of RCTs only reported hypoglycemic episodes with
treatment.
confirmation of glucose threshold. Future RCTs should unify the reporting of
Results
hypoglycemia for safety assessment of diabetic medication.
Thirty-eight patients (male/femaleZ7/31) with type 2 diabetes mellitus entered to
DOI: 10.1530/endoabs.49.GP110
the study. Mean age of patients was 50.5G8.8 years with mean diabetes duration
of 8.5G4.9 years. Mean BMI was 41.6G6.3 kg/m2 and mean HbA1c of patients
was 8.9G1.4%. Percentage change in weight of patients was K5.2G3.7%
following 12 weeks of treatment. BMI and HbA1c levels of patients were
decreased significantly (P!0.001 and P!0.001; respectively) while there was no
GP111
change in lipid parameters. Serum fasting ghrelin levels were suppressed
Hepatic effects of GLP-1 receptor agonist Liraglutide in patients with
significantly after 12 weeks of exenatide treatment compared with baseline values
type 2 diabetes
(328.4G166.8 vs 245.3G164.8 pg/ml) (PZ0.024).
Maria Hayon1, Marta Fernandez1, Silvia Maraver2, Teresa Muros1,
Conclusion
Daniel Cepero3, Martin Lopez1, Miguel Quesada1, Joaquin Pechuan4 &
These results suggest that the effect of exenatide on weight loss may be related
Gonzalo Piedrola1
with the suppression of serum fasting ghrelin levels, which is an orexigenic
1Complejo Hospitalario Universitario de Granada, Granada, Spain;2Clínico
peptide.
Virgen de la Victoria Hospital, Malaga, Spain;3Torrecardenas Hospital,
DOI: 10.1530/endoabs.49.GP112
Almeria, Spain;4Endocrinology Private Office, Granada, Spain.
Introduction
The aim of this study was to analyze the effects of Liraglutide in hepatic steatosis
as well as clinical and biochemical data before and after 6 months.
Endocrine Nursing
Methods
We have retrospectively analysed epidemiological, anthropometric and labora-
GP113
tory data of 83 type 2 diabetic patients treated with Liraglutide and followed at
Impact of the socio-economic level on the management in type 2
different endocrinology units across east Andalusia. We have evaluated
diabetes
nonalcoholic fatty liver disease using liver enzymes and hepatic steatosis index
Boulbaba Kolsi1, Mouna Elleuch1, Rihab Ben Abdallah2,
(HSI). HSIO36 reflects fatty liver, !30 absence, and intermediate values are
Feten Haj Kacem1, Fatma Mnif1 & Mohamed Abid1
considered indeterminated.
1Hedi Chaker Hospital, Sfax, Tunisia;2Faculty of Sciences of sfax, Sfax,
Results
Tunisia.
Of the 83 cases evaluated, 54.2% were male, mean age 56.76G9.87 years, time
from diagnosis 9.46G5.46 years. Prior to treatment, patients had BMI 37.68G
6.82 kg/m2, blood pressure
138.80/82.87 mmHg, fasting glucose
187.33G
Diabetes is a chronic disease whose associated comorbidities are largely
55.11 mg/dl, glycated hemoglobin
(HbA1C) 8.62G1.3%, total cholesterol
influenced not only by pathology but also by socio-economic conditions. The
178.1G35.74 mg/dl (c-LDL 97.66G32.16 mg/dl, c-HDL 44.54G13.78 mg/dl),
aim of this study is to investigate the influence of social conditions on the
triglycerides 197.64G24.19 mg/dl, AST 29G20.311 U/l, ALT 39.88G31.69 U/l
evolution of diabetes. A retrospective, comparative study of 111 patients with
and HSI 46.44G6.48.
type
2 diabetes Follow-up in the Endocrinology-Diabetology department in
Clinical and biochemical figures at 6 months were: BMI 36.08G6.32 kg/m2,
hospital Hedi Chaker of Sfax. Patients were divided into two groups with
blood pressure 132.76/77.41 mmHg, fasting glucose 165.16G56 mg/dl, HbA1C
unfavorable (G1) and good (G2) socio-economic conditions, both groups had 58
7.73G1.33%, total cholesterol 170.6G39.19 mg/dl (c-HDL 46.25G15.03 mg/dl,
and 53 patients, respectively. The average age of our patients was 54 in G1 and 49
c-LDL 87.74G30.5 mg/dl), triglycerides 198.29G22.29 mg/dl, AST 24.97G
in G2 (PZ0.7). A female predominance was noted in the G 1/64% while the male
12.49 U/l, ALT 32.76G18.24 U/l, and HSI 43.98G6.38.
sex was predominant in the G 2: 80%. The age of diabetes was comparable
Statistically significant differences were found regarding several variables, such
between the two groups (12.5 years vs 11 years, PZ0.09). Fasting glucose was
as BMI, HbA1C, fasting glucose, blood pressure and c- LDL, as well as in ALT
significantly higher in G 1 (15 mmol / l) versus 9 mmol / l in G2 (P!0.0001). The
and HSI, showing an amelioration in hepatic steatosis. No differences were found
number of hospitalizations was higher in G1: 2.8 versus 1.3 in G2 (PZ0.005).
in total cholesterol, c-HDL, triglycerides and AST.
The food investigation showed a higher caloric intake in G2
estimated at
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
2615 Kcal/d versus
2184 Kcal/d for the G1. Infectious complications and
Endocrine teams and in particular the specialist nurses role involves teaching
amputation were significantly more frequent in G 1 compared to G2. Similarly,
patients with new diagnosis as well as building on information they have gained
microangiopathic complications were more frequent in G1
patients. This
from their consultations etc. We wanted to see how many patients with
imbalance was related to management difficulties, so no patient of G1 group
pituitary/adrenal failure have gaps in the understanding of their condition,
was placed under insulin analogs versus 23% of G2 patients. Socioeconomic
particularly in relation to their sick day rules.
status seems to play a crucial role in the glycemic balance and the occurrence of
We surveyed 18 patients on hydrocortisone replacement who completed a
chronic complications of diabetes. This is mainly due to the restriction of access
questionnaire assessing their knowledge and understanding of their condition.
to health care structures and therapeutic, sometimes expensive, and the level of
When asked what action they would take if they had flu and a high temperature,
instruction of these disadvantaged classes.
nine would double their steroid dose, three would triple it. This leaves six patients
DOI: 10.1530/endoabs.49.GP113
at potential risk of admission. When asked about vomiting and/or diarrhoea, six
said they would double their dose, one would triple it and one would take their
emergency hydrocortisone injection, potentially leaving ten patients at risk of an
Addisonian crisis. Within this group of patients seven had been given intra
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muscular hydrocortisone, but only four had been shown how to use it.
The national annual admission rate for patients with Addison’s disease/syndrome
Outcomes of a nurse-led thyroid clinic at a tertiary-care endocrine
is 8%. Within this sample group the admission rate was 27.7%.
centre
We need more resources to build on our initial and ongoing education/teaching
Violet Fazal-Sanderson1, Niki Karavitaki2, Ashley Grossman3 &
programme to work on patient awareness of their condition as a whole, including
Atul Kalhan4
sick day rules.
1Royal Berkshire Hospital, Reading, UK;2Queen Elizabeth Hospital,
Birmingham, UK;3Oxford University Hospitals NHS Foundation Trust,
DOI: 10.1530/endoabs.49.GP115
Oxford, UK;4Royal Glamorgan Hospital, Wales, UK.
Introduction
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A Nurse-led Thyroid Clinic (NLTC) in a tertiary-care Endocrinology centre (EC)
Recovery of the hypothalamus-pituitary-adrenal axis after
in Oxford was set up in 2005. The patients were managed by an Endocrine
transsphenoidal surgery for pituitary adenomas
Advanced Nurse Practitioner.
J P van Eck, S J C M M Neggers, J A M J L Janssen, Y B de Rijke,
Aims
A H G Dallenga, A P Nagtegaal, A J van der Lely & R A Feelders
To evaluate standard of clinical care (SOCC) quality of service provision (QOSP)
Erasmus Medical Center, Rotterdam, The Netherlands.
and cost effectiveness (CE) of the NLTC.
Methods
Three aspects of service were assessed:
Purpose
Hypopituitarism is frequently associated with lifelong replacement therapy.
a) SOCC: Data were collected for patients managed over 12 months between
However, it has been suggested that recovery from hypopituitarism after
1/2014 and 1/2015. Diagnosis, investigations and management plans for
transsphenoidal surgery (TSS) for pituitary adenomas may occur during follow
individual patients were compared against accepted regional and national
up. The aim of this study was to assess the frequency of hypothalamus-pituitary-
guidelines.
adrenal (HPA) axis recovery after TSS in patients with non-functioning pituitary
b) QOSP was evaluated from standardised patient feedback questionnaires (PFQ)
adenomas and acromegaly.
that were anonymised for confidentially
Methods
c) CE was analysed through collection of retrospective data of filed patients clinic
Over the 3-year observational study-period, 146 patients underwent transsphe-
lists between 1/2014 and 1/2015. A new patient (NP) tariffed at £120, follow-
noidal pituitary surgery. The metyrapone test was used to assess the HPA-
up, at £90 per visit according to finance department protocol. Annual data
integrity after 1 week and after 3-12 months after TSS. The pituitary-thyroid,
recorded of non-face-to-face-telecommunication (NFTFT) costed at £30 per
-gonadal and growth hormone axis were measured one week after TSS.
call.
Results
Results
Patients with Cushing’s disease and panhypopituitarism were excluded from the
study. 44 subjects had a sufficient HPA-axis one week after surgery. 14 subjects
a) SOCC: 214 patient appointments for 134 patients were reviewed; 112 patients
with an insufficient HPA-axis were excluded, as the
11-deoxycortisol after
had Graves’ disease, 10 subacute thyroiditis,10 toxic nodular diseases and
metyrapone was !100 nmol/l. Eighteen patients were eligible to re-assess the
two subclinical thyrotoxicosis. Patients were managed with a departmental
HPA-integrity. In 10 out of 18 patients, insufficiency of the HPA-axis appeared to
protocol based on British Thyroid Association guidelines 2006.
be reversible. Eight patients had persistent secondary adrenal insufficiency. The
b) QOSP: 50 out of 60 PFQ were returned (34 women/16 men, median age 52.3
number of other pituitary hormone insufficiencies one week after TSS was
years, range 21-85). Majority of the patients expressed high satisfaction with
associated with recovery of the HPA-axis after TSS.
the quality of services provided, with 86% “Extremely Likely” to recommend
Conclusion
the TNLC to friends and family.
After TSS, recovery of the HPA-axis over time does occur in a proportion of
c) CE: New and follow-up patients generated an annual income of £20,490.
subjects. Therefore it is recommended to re-assess the HPA-integrity during
NFTFT calls (908 patients) generated an income of £27,240. 41 empty NP
follow up to prevent unnecessary glucocorticoid replacement therapy. Pituitary
clinic slots, 22 follow up cancellations and 19 patients who failed to attend the
adenoma, reversible hypopituitarism, recovery HPA-axis, pituitary surgery,
clinic, amounted to a loss of £8610.
adrenal insufficiency.
Conclusions
Key words
The audit supports the value of NLTCs in EC’s with a significant thyroid-
Pituitary adenoma, reversible hypopituitarism, recovery HPA-axis, pituitary
dysfunction workload. These clinics can provide high quality of clinical care and
surgery, adrenal insufficiency.
potentially be cost-effective.
DOI: 10.1530/endoabs.49.GP116
DOI: 10.1530/endoabs.49.GP114
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The Swedish Pituitary Register Nursing Group (SPRNG) Projects and
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Experiences
Education, patient empowerment and admission avoidance
Maria Forsgren1, Caroline Alkebro2, Margareta Lindgren3, Helena Wik4,
Anna Hawkins, Edel Casey & Khash Nikookam
Maria Warn5 & Christina Dahlgren6
Barking, Havering & Redbridge University NHS Trust, ESSEX, UK.
1Uppsala University Hospital, Uppsala, Sweden;2Orebro University
Hospital, Orebro, Sweden;3Norrland University Hospital, Umeå, Sweden;
4
Sahlgrenska University Hospital, Gothenburg, Sweden;5Karolinska
It is paramount to educate our patients, thereby empowering them to manage their
University Hospital, Stockholm, Sweden;6Linkoping University Hospital,
chronic conditions. This is an evidence based fact. As healthcare professionals our
Linkoping, Sweden.
challenge is to provide and ensure patients have been well informed in order to
understand and manage their condition successfully on a daily basis.
In today’s healthcare service patient education has become a casualty of the
Background
reduced resources; there are ever increasing restrictions on both the length and
The Swedish Pituitary Register (SPR) is a national quality register founded in
frequency of consultations.
1991 by the Swedish Pituitary Group and it provides important data in the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
continuous quality assessment and improvement work within the Swedish health
GATA4 downstream targets in the adrenocortical tumors in both, inha/Tag and
care system.
human could be of importance to find potential therapeutic targets for human
The Swedish Pituitary Register Nursing Group (SPRNG) was formed by nurses at
adrenocortical tumors.
the University Hospitals, working with the register, in 2011.
DOI: 10.1530/endoabs.49.GP118
Purpose
To increase the coverage rate and improve the data quality in the register.
To strengthen the endocrine nurse role and encourage and promote the nurses to
own register projects.
Methods
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The SPRNG, consisting of endocrine nurses, one responsible for the register at
each University Hospital. Meetings are performed 1-2 times /year. The SPRNG is
Targeted molecular analysis in adrenocortical carcinomas: a way
working for the same routines considering the register and is actively working
towards personalized medicine
with projects in the SPR.
Cristina L Ronchi1, Juliane Lippert2, Silke Appenzeller3, Silviu Sbiera1,
Results
Sonja Steinhauer1, Raimunde Liang1, Andrea Gehrig2, Matthias Kroiss1,
Since the SPRNG was started the coverage rate and the reporting speed in the SPR
Simone Rost2, Andreas Rosenwald4, Clemens Muller-Reible2 &
Martin Fassnacht1
have increased. Several nurse projects during
2016. Implement PREM and
1Division of Endocrinology and Diabetes, University Hospital of
disease-specific PROM variables. User Survey in the register. Register data
Wuerzburg, Wuerzburg, Germany;2Institute of Human Genetic, University
template for the hospitals operations managers and for the public to increase the
of Wuerzburg, Wuerzburg, Germany;3Core Unit Bioinformatics, Compre-
knowledge of this patient group.
hensive Cancer Center Mainfranken, University Hospital of Wuerzburg,
A study ‘Time from first symptoms to diagnosis’, where approximately 600
Wuerzburg, Germany;4Department of Pathology, University of Wuerzburg,
patients with pituitary tumours
(Acromegaly, Mb Cushing, NFPA and
Wuerzburg, Germany.
Prolactinomas) are included, will be compiled 2017. The purpose of this study
is to find these patients earlier and to identify how we can do that.
The SPRNG have been active at international conferences with several abstracts.
Adrenocortical carcinoma (ACC) is a rare tumor with heterogeneous outcome and
Meeting and sharing experiences of the register with finish endocrine nurses.
no available targeted therapy. The aim of the study is to identify prognostic
Conclusion
molecular markers and novel potential drug targets.
The SPRNG has contributed to increase the data quality and coverage rates in the
A total of 43 FFPE tumor samples were retrospectively investigated for somatic
SPR.
mutations and copy number variations (CNV) by next-generation sequencing
The SPRNG is a good example of how nurses can be supported by each other and
(160
cancer-related genes, Qiagen). Gene expression was evaluated by
share experiences, skills and knowledge but also operate their own project.
quantitative RT-PCR in a subgroup of 25 ACC samples (84 cancer drug targets,
DOI: 10.1530/endoabs.49.GP117
Qiagen). The major clinical endpoint was progression free survival (PFS).
We observed 123 protein-altering mutations in 47 genes (median 2 per sample),
with the most frequent known to be ACC-related: TP53 (28% of samples),
CTNNB1 (26%), ZNRF3 (19%), NF1 (16%) and GNAS (14%). Notably, we also
detected recurrent mutations in genes previously not clearly associated with ACC
Endocrine Tumours
(i.e. ABL1, KDM6A, TSC1, FBXW7, DNMT3A, BRCA1, BRCA2). Some focal
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CNV were found in O30% samples (i.e. gains of CDK4, MDM2, IL7R, and losses
Luteinizing hormone receptor mediated GATA4 induction promotes
of TNFRSF14). A noisy pattern was associated to a shorter median PFS than
adrenocortical tumorigenesis in gonadectomized mice
chromosomal or quiet pattern (4.5 vs 7 vs 14 months, respectively, PZ0.07).
Milena Doroszko1, Marcin Chrusciel1, Joanna Stelmaszewska2,
Most affected genes were involved in p53/Rb or Wnt/b-catenin pathway or
Tomasz Slezak3, Adolfo Rivero-Muller4,5, Artur Padzik4,
chromatin remodeling, but also in immune response or DNA repair mechanisms.
Slawomir Anisimowicz6, Slawomir Wolczynski2, Ilpo Huhtaniemi1,7,
Patients with alterations in DNA repair genes had longer PFS than others
Jorma Toppari1,8 & Nafis Rahman1,2
(PZ0.067, HRZ1.78). At mRNA level, most frequently overexpressed genes (O
1Department of Physiology, Institute of Biomedicine, Turku, Finland;
2.5 fold change) were IGF2 (92%), TOP2A (92%), CDK1 (72%) and PLK1
2Department of Reproduction and Gynecological Endocrinology, Medical
(60%). Tumors with increased BUB1B-PINK1 (O5.9) were associated with a
University of Bialystok, Bialystok, Poland;3Department of Biochemistry
trend to worst PFS (PZ0.16, HRZ1.98).
and Molecular Biology, University of Chicago, Chicago, Illinois, USA;
This pilot study demonstrates the feasibility of molecular analysis in FFPE
4Turku Center for Biotechnology,
˚boAkademi and University of Turku,
samples. We identified some genetic variants previously not associated with ACC
Turku, Finland;5Department of Biochemistry and Molecular Biology,
and new potential drug target genes. These results will be validated in a larger
Medical University of Lublin, Lublin, Poland;6Center of Gynecology and
series in order to path the way to a personalized medicine in ACC.
Reproductive Endocrinology Artemida, Bialystok, Poland;7Institute of
DOI: 10.1530/endoabs.49.GP119
Reproductive and Developmental Biology, Imperial College London,
London, UK;8Department of Pediatrics, Turku University Hospital, Turku,
Finland.
The role of luteinizing hormone (LH) and its receptor (LHCGR) signaling in the
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adrenal gland remains unknown. Gonadectomy-induced chronically elevated LH
Evaluation of the occurrence of the manifestations of Carney complex
levels trigger neoplastic transformation in genetically susceptible mouse strains
in a french cohort of 70 patients during a three years standardized
(DBA/2J) or transgenic mice expressing the Simian Virus
40
T antigen
follow-up
(SV40Tag) oncogene under inhibin-a promoter (inha/Tag). In order to study
Stéphanie Espiard1,2, Catherine Cardot-Bauters2, Gerald Raverot3,
the functional role of LHR and GATA4
in the onset and progression of
Marie-Laure Nunes4, Françoise Brucker-Davis5, Muriel Houang6,
adrenocortical tumors in ovariectomized (OVX) inha/Tag females in vivo and
Françoise Archambeaud-Mouveroux7, Anne Lienhardt8, Hervé Lefebvre9,
in vitro, we crossbred the inha/Tag with LHR knockout
(LuRKO) mice.
Olivier Chabre10, Antoine Tabarin4, Marie-Christine Vantyghem2 &
Additionally we knocked out Lhr (Lgr-ko) and Gata4 (Gata4-ko) in the Ca1 cell
Jérôme Bertherat1
line derived from an adrenal tumor of inha/Tag mice. In inha/Tag mice, we
1Department of Endocrinology, Paris Public University Hospitals, Cochin
identified two distinct types of SV40Tag expressing neoplastic cells. The first
Hospital, Paris, France;2Department of Endocrinology, Diabetology and
type, subcapsular non-steroidogenic spindle-shaped A-like cells, which never
Metabolism, Lille University Hospital, Huriez Hospital, Lille, France;
developed to tumors, were found in both intact and OVX inha/Tag females. The
3Department of Endocrinology, Lyon Public University Hospitals, Lyon,
second type, parenchymal tumor cells in the topmost layer of zona fasciculata,
France;4Department of Endocrinology, Diabetology and Metabolism,
later forming tumor foci, were found only in OVX inha/Tag mice. Lack of LHR
Bordeaux University Hospital, Haut-Lévêque Hospital, Pessac, France;
in OVX inha/Tag/LuRKO mice adrenals prevented tumor formation. Histological
5Department of Endocrinology, Diabetology and Reproductive Medicine,
and immunohistochemical analyses revealed the presence of hyperplastic cells
Nice University Hospital, Nice, France;6Department of Pediatric
expressing SV40Tag in parenchyma. These cells were devoid of GATA4 and
Endocrinology, Paris Public University Hospital, Armand-Trousseau
showed signs of apoptosis. In vitro, a complete inactivation of Gata4 significantly
Hospital, Paris, France;7Department of Endocrinology, Limoges University
decreased cell proliferation, expression of tumor markers (Inha, SV40Tag, Lhcgr
Hospital, Le Cluzeau Hospital, Limoges, France;8Department of Pediatry,
and Esr1) and gonadal-like steroidogenic phenotype of Ca1 cells. Our results
Limoges University Hospital, Limoges, France;9Department of Endo-
suggest that at first, the tumor formation was LH-dependent, but later on became
crinology, Diabetology and Metabolism, Rouen University Hospital, Rouen,
LH-independent. GATA4
is responsible for the Inha/SV40Tag expression,
France;10Department of Endocrinology, Grenoble University Hospital,
gonadal steroidogenic phenotype and possibly pro-survival pathways. Identifying
Albert Michallon Hospital, Grenoble, France.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
In conclusion, ACC patients are characterized by increased circulating immune
The Carney Complex is a multiple endocrine and non endocrine neoplasia mostly
inhibitory Tregs and tumour infiltrating CD4CT-helper cells have a positive
due to PRKAR1A mutations. Spectrum of manifestations and genotype-
influence on patient survival.
phenotype correlations have been previously described by retrospective studies.
DOI: 10.1530/endoabs.49.GP121
A prospective study evaluating the occurrence of the different manifestations was
needed to precise the optimum follow-up.
Methods
Multi-center national prospective study (Clinical Trials NCT00668291) including
70 patients mutated or wild-type for PRKAR1A followed prospectively during
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3years with screening of the different manifestations by annual clinical, biological
The natural history of adrenal incidentaloma - results from the
and radiological evaluation.
international prospective multi-centre EURINE-ACT study
Results
Irina Bancos1,2, Vasileios Chortis2, Katharina Lang2, Alessandro Prete2,
The cohort was compound of 50 females and 20 males with a mean age at
Massimo Terzolo3, Martin Fassnacht5, Marcus Quinkler8, Darko Kastelan9,
35.4years C/K16.7. Prevalence of cardiac myxomas at the end of the follow-up
Dimitra Vassiliadi7, Felix Beuschlein5, Urszula Ambroziak4, Alice Sitch10,
was 22.9% with newly diagnosis during the study period for 3 patients. Forty-
Jonathan Deeks10 & Wiebke Arlt2
four% of patients with myxomas had related stroke attack and
56% had
1Mayo Clinic, Rochester, MN, USA;2Institute of Metabolism and Systems
recurrences. Median delay between recurrences was
3.8years
(minimum-
Research, University of Birmingham, Birmingham, UK;3University of
maximum: 0.8-24). Primary pigmented adrenal nodular disease was diagnosed
Turin, Turin, Italy;4Warszawski Uniwersytet Medyczny, Warszawa,
in 57.1%. Skin manifestations, abnormal somatotroph hormonal tests and thyroid
Poland;5Universitatsklinikum Wurzburg, Wurzburg, Germany;6Klinikum
tumors were observed respectively in 58.6, 21.4 and 12.9%. Four% had melanotic
der Ludwig-Maximilian-Universitat Munchen, Munchen, Germany;7Attiko
shwannomas confirmed by histology. Spinal magnetic resonance imagery
University Hospital, Athens, Greece;8Charité Universitatsmedizin Berlin,
revealed lesions for 8.6%. Characteristic multiples calcified tumors on testicular
Berlin, Germany;9University Hospital Zagreb, Zagreb, Croatia;10Institute
ultrasonography were present in 35% of male patients. Ten% of female patients
of Applied Health Research, University of Birmingham, Birmingham, UK.
had surgery for breast myxoma or adenofibroma. Forty% had lesions classified
ACR2-3 at mammography. Interestingly, four patients
(8%) had breast
Background
adenocarcinomas
(11.1% of female older than
30years). Eighty-three% of
Adrenal masses are discovered in 5% of abdominal imaging scans. Work-up aims at
patients had PRKAR1A mutations. Patients carrying the mutation c.709-7del6
exclusion of malignancy and hormone excess. However, estimates of these risks derive
(34% of the cohort) had no manifestation or phenotype restricted to adrenal,
from retrospective studies only, mostly small and with significant selection bias.
lentigines and abnormal somatotroph test.
Methods
Conclusion
Prospective multi-centre study (2011-2016) in 14 centres (11 countries) of the
The penetrance of the disease is high after screening except for patient carrying
European Network for the Study of Adrenal Tumours (ENSAT) with prospective
the c.709-7del6 mutation. This study highlights the importance of an annual
consecutive enrolment of patients with newly diagnosed adrenal mass. Extra-adrenal
follow-up, with especially annual cardiac imaging for patients with history of
malignancy and phaeochromocytoma were exclusion criteria. Diagnosis was
cardiac myxomas and earlier and regular senologic evaluation.
confirmed by histology or imaging follow-up.
DOI: 10.1530/endoabs.49.GP120
Results
We enrolled 1994 patients, 1746 (87.6%) with a benign adrenocortical adenoma
(ACA), 83 (4%) with other benign masses (e.g. adrenomyelolipoma, cyst), 106 (5.3%)
with adrenocortical carcinoma (ACC) and 59 (3%) with other malignant masses (e.g.
metastases, sarcoma). Risk of ACC was highest in young patients (!40yrs:13%; 40-
60yrs:6%;O60yrs:3%, P!0.0001) and in large masses (O4 cm:21%, !4 cm:0.4%,
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P!0.0001). Of 1746 patients with ACA, imaging for exclusion of malignancy
Immunity in adrenocortical carcinoma patients - interplay between
included unenhanced CT in 1301 patients, with tumour density !10HU indicative of a
anti-cancer immunity and steroid hormones
benign tumour in 69%, with 16% borderline (10-20HU) and 15% suspicious
Silviu Sbiera1,2, Thomas Dexneit1,3, Iuliu Sbiera1, Jochen Schreiner1,
(O20HU) results. MRI with chemical shift results in 271 ACA patients were indicative
Cristina L. Ronchi1, Matthias Kroiss1,2 & Martin Fassnacht1,4
of a benign lesion in 79%. In 829/1746 (47%) ACA patients, two or more imaging
1Division of Endocrinology and Diabetes, University Hospital, University of
studies were performed; 19% underwent three or more. Upon re-imaging after R6
Wurzburg, Wuerzburg, Germany;2Comprehenssive Cancer Center Main-
months, the adrenal mass appeared stable in size 601 of 629 ACA patients (96%). Mild
franken, University of Wurzburg, Wuerzburg, Germany;3Department of
autonomous cortisol excess (MACE) was detected in 547/1316 (42%) patients with
Neurosurgery, University Hospital, University of Wurzburg, Wuerzburg,
ACA. Adrenalectomy was performed in 21% (370/1746) of ACA patients. Of those,
Germany;4Clinical Chemistry and Laboratory Medicine, University
222
(60%) had overt hormone excess and 64 (17%) had MACE (70; 18%); the
Hospital, University of Wurzburg, Wuerzburg, Germany.
remaining 84 patients (23%) had non-functioning ACA.
Conclusions
Adrenocortical carcinoma
(ACC) is one of the most aggressive endocrine
Overall risk of ACC is 5.3% and is highest in young patients with adrenal mass size
malignancies. By applying a ‘multiple omics’ approach, we recently identified
O4 cm. ACAs are frequently misclassified as malignant by routine imaging,
two distinct subgroups of ACC patients, a good prognosis “immune” and bad
resulting in a high rate of interval imaging and unnecessary adrenalectomies.
prognosis “steroid” phenotype.
DOI: 10.1530/endoabs.49.GP122
We hypothesized that the steroid phenotype is associated with glucocorticoid-
induced suppression that can be ‘rescued’ by reactivating the immune system
using immune checkpoint inhibitors and inhibitors of steroidogenesis.
To assess changes induced by ACC on circulating immune cells we isolated
PBMCs from blood of 19 healthy controlsZHC and 163 ACC patients (41:
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tumour freeZTF, 82: tumour present without cortisol excessZTP and 40: tumour
Outcome of patients with adrenocortical cancer after discontinuation of
present and cortisol excessZCE) and performed FACS analyses to quantify
adjuvant mitotane therapy
T-cells (CD3CCD4C and CD3CCD8C), B-cells (CD19), monocytes (CD14)
Massimo Terzolo1, Vittoria Basile1, Felix Megerle2, Wiebke Hermann2,
and regulatory T-cells
(T-reg) as a sign of immune suppression
(CD4C
Federica Cicciarella1, Rossella Libè3, Eric Baudin4, Harm Haak5,
CD25highFOXP3C). Using immunofluorescence, we analysed the presence of
Massimo Mannelli6, Marco Boscaro7, Marcus Quinkler8,
tumour infiltrating T-cells, Tregs, B-cells, dendritic cells (CD209C) in full FFPE
Isabelle Bourdeau9, Paola Perotti1, Stefanie Hahner2, Felix Beuschlein10 &
from 58 primary ACC tumours. Furthermore, expression of immune checkpoint-
Martin Fassnacht2
markers programmed death 1 (PD1) and its ligand PDL1 was analysed by IHC.
1Department of Clinical and Biological Sciences, University of Turin, Turin,
From the peripheral cells the percentage of Treg in the circulating T-cell
Italy;2Department of Internal Medicine 1, University of Wurzburg,
population correlated significantly with tumoural and steroid secretion status
Wurzburg, Germany;3Cochin Hospital, Endocrinology Unit, Paris, France;
(4.4G1.2 in HC, 7.9G6.1 in TF, 9.0G7.9 in TP and 11.0G7.8 in CE, P!0.01).
4Department of Nuclear Medicine and Endocrine Tumors, Institut Gustave
Using median as cut-off, patients with increased percentage of peripheral Treg
Roussy, Villejuif, France;5Maxima Medisch Centrum, Internal Medicine,
had a lower survival rate (HRZ1.8, 95%CI 1.0-3.1, PZ0.02). Most tumours
Eindhoven, The Netherlands;6Department of Experimental and Clinical
presented a tumour infiltrate (T-cells: 80%, 37G65 cells/HPF, cytotoxic T-cells:
Biomedical Sciences, University of Florence, Florence, Italy;7Department
72%, 24.9G53.0, T-helper: 57%, 19.3G16.9 cells/HPF, Treg: 48%, 3.8G3.8,
of Medicine, University of Padua, Padua, Italy;8Endokrinologie in
dendritic cells: 73%, 5.8G3.7, B-cells: 0%, PD1: 36%, 14.7G30.1, PDL-1: 83%,
Charlottenburg, Berlin, Germany;9Department of Medicine and Research
34.6G81.6). The only tumour infiltrating cells associated overall survival were
Centre, University of Montreal, Montreal, Canada;10University of Munich,
the CD4CT-helper cells (HR for death: 0.34, 95%CI 0.12-0.95, PZ0.005).
Medizinische Klinik und Poliklinik IV, Munich, Germany.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
requiring intervention both in univariate (PZ0.03) and multivariate analysis
Adjuvant mitotane therapy is frequently used in Europe following surgery for
(Hazard ratio 2.9, 95% confidence interval 1.2-7.2, PZ0.02).
adrenocortical carcinoma (ACC). Management of adjuvant mitotane is mainly
Conclusion
empirical and a major open question is the optimal duration of therapy, because
Lesion diameter should be the pivot factor in directing PNETs management in
no study has ever addressed this issue.
vHLd. Among patients with a largest PNET diameter O1.2 and !3 cm, VHL
Objective
genotyping may be useful for risk stratification.
We aimed to assess the outcome of ACC patients who were treated with adjuvant
DOI: 10.1530/endoabs.49.GP124
mitotane for at least one year following surgery and then discontinued therapy for
other reasons than ACC recurrence.
Design
We did a retrospective analysis of 132 patients (91 F, 41 M; median age 44 years)
with histologically confirmed ACC who were treated at 9 European centres and 1
centre in Canada since 1999.
Results
Tumour stage was ENSAT I, 11%; ENSAT II, 79%; ENSAT III, 20%; hormone
secretion was present in 44% and resection status was R0, 83% and Rx, 17%.
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Median Ki-67 was 10% and Weiss 6. Duration of adjuvant mitotane therapy was
GPER-stimulation increases proliferation in colorectal cancer via the
34 months (12-141). Median duration of follow-up was 79 months (31-280),
Hippo signalling pathway
including 34 months after discontinuation (1-263). Seventeen patients (13%)
Anastasia Arvaniti, Karthik Basker, Ali Gondal, Habibur Rahman,
recurred after treatment discontinuation with a recurrence-free survival from
Lorna Gilligan & Paul Foster
surgery of
74
months
(31-277) and tumour-free survival after mitotane
University of Birmingham, Birmingham, West Midlands, UK.
discontinuation of
32
months
(1-263). The only difference in prognostic
characteristics between patients with recurrent ACC and the remainders was a
higher number of secreting tumours. Interestingly, no recurrence was observed
Colorectal cancer (CRC) is the 2nd most commonly diagnosed cancer in Europe.
among the 41 patients (31%) treated for O48 months; such patients had similar
Previously, we have shown steroid sulphatase (STS), the enzyme that converts
prognostic characteristics and follow-up duration after mitotane discontinuation
conjugated oestrogens to their active forms, is significantly upregulated in human
than the remainders.
CRC tissue. Furthermore, increased STS activity substantiates greater CRC
Conclusions
tumour burden in mouse models. Here we demonstrate that this oestrogen-
These first results suggest that a prolonged duration of adjuvant mitotane therapy
induced increase of CRC proliferation is mediated by G-protein coupled
may be associated with better recurrence-free survival.
oestrogen receptor
(GPER) via Hippo pathway signalling through the yes-
DOI: 10.1530/endoabs.49.GP123
associated protein 1 (YAP1), transcriptional coactivator with PDZ-binding motif
(TAZ), and connective tissue growth factor (CTGF).
To examine how GPER effects CRC proliferation we employed in vitro BrdU
proliferation assays and in vivo mouse models of CRC treated with G1, a GPER
agonist, oestrogens and G15, a GPER antagonist. To investigate whether YAP1,
its target gene CTGF, and its transcriptional co-activator TAZ, were altered by
oestrogen-induced GPER signalling, we used immunoblotting and immunohis-
tochemistry. YAP1 knockdown cells were also examined by treating them with
G1, oestrogens and verteporfin, a YAP1 inhibitor, to assess the role of YAP1 on
proliferation.
GPER-stimulation by G1 and oestrogen increased CRC proliferation in a dose-
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dependent manner, with this effect inhibited by G15 in vitro and in vivo CRC
VHL Genotype and risk stratification of pancreatic neuroendocrine
xenografts. YAP1 mediated this pro-proliferative response in CRC cells in
tumors in patients with von hippel-lindau disease
contrast to colon adenoma cells. These findings were underpinned by increased
Amit Tirosh1,2, Jasmine Shell3, Patience Green3, Xavier M. Keutgen4,
phosphorylation of YAP1 and increased protein expression of TAZ and CTGF
Samira M. Sadowski5, Mustapha el Lakis3, Pavel Nockel3, Dhaval Patel3,
after oestrogen and G1 treatment. Intriguingly, CTGF up-regulation correlated
Naris Nilubol3 & Electron Kebebew3
with elevated GPER in human CRC tissue. In line with the above results,
1National Institutes of Health, Bethesda, MD, USA;2Sackler Faculty of
pharmacological inhibition of YAP1 and YAP1 knockdown blocked G1-induced
Medicine, Tel Aviv University, Tel Aviv, Israel;3Endocrine Oncology
cellular proliferation supporting the functional pro-proliferative role of YAP1
Branch, National Cancer Institute, Bethesda, MD, USA;4Department of
in CRC.
Surgery, Rush University Medical Center, Chicago, IL, USA;5Endocrine
Taken together, our results propose a new oestrogen-driven pro-proliferative
and Thoracic Surgery, University Hospitals of Geneva, Geneva,
GPER-stimulated pathway through Hippo signalling in CRC. Further studies are
Switzerland.
required to establish whether this early metabolic response translates into
increased cellular viability and cancer development.
Background
DOI: 10.1530/endoabs.49.GP125
About 8-20% of patients with von Hippel-Lindau disease (vHLd) develop
pancreatic neuroendocrine tumors (PNETs). However, prognostic markers for
these tumors are lacking. The VHL gene mutation type is associated with the
clinical phenotype of vHLd. Hence, we aimed to determine whether VHL
mutation characteristics may be associated with PNETs phenotype in patients
with vHLd.
Methods
A prospective study of patients with vHLd and PNETs with follow-up imaging.
GP126
VHL mutation type and position were defined using Sanger sequencing of
germline DNA.
Inhibition of hRAS and CDK4/6 leads to an antiproliferative activity,
blocks cell cycle and induces cell death in anaplastic thyroid cancer
Results
cell lines
182 patients (476 PNETs) were followed for a median of 52 months (range 3-84).
Marta Pojo1, Sara Lopes-Ventura1, Ana Matias1, Valeriano Leite1,2 &
The VHL gene was sequenced in 154 patients: 75 patients (48.7%) had a missense
Branca Cavaco1
mutation [MisM], 51 (33.1%) - deletion, 12 (7.8%) - nonsense, one (0.6%) -
1Unidade de Investiga
¸a˜o em Patobiologia Molecular (UIPM), Instituto
rearrangement, and 15 (9.7%) had frameshift mutations. Patients with a largest
Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal;
lesion diameter
!1.2 cm had a lower risk for metastases (Log-Rank test,
2Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa
PZ0.006) compared with larger diameters, whereas those with diameter O3 cm
Francisco Gentil E.P.E., Lisbon, Portugal;3Faculdade de Ciências Médicas,
had higher risk for metastases compared with other patients (Log Rank test,
Universidade Nova de Lisboa, Lisbon, Portugal.
PZ0.007). Patients with MisM had a higher risk of requiring an intervention
(Log-Rank test PZ0.01) and for developing metastases during follow-up
(PZ0.007) compared to those with other mutation types. Among patients with
The unresponsiveness of anaplastic thyroid carcinomas (ATCs) to multimodal
a largest lesion diameter between 1.2 and 3 cm, those with MisM had higher risk
therapy represents the major challenge in thyroid cancer treatment. Our group
for metastases (Log-Rank test, PZ0.048) compared to other mutation types, and
previously showed that genes involved in cell cycle are differentially expressed in
patients with mutation positioned in exon 3 of the VHL gene had higher risk for
ATCs compared to normal thyroid, and that the most common mutations found in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
these tumours are related with proliferation and cell cycle genes, namely TP53,
GP128
RAS, CDKN2A and CDKN2B. Therefore, these genes are promising new targets in
Peptides derived from the sst5TMD4 extracellular domain increase
ATCs.
malignancy of endocrine-related cancer cells
Here, we investigated if the inhibition of HRAS by Tipifarnib (TIP) and CDK4/6
Manuel D Gahete, Mercedes del Rio-Moreno, Emilia Alors-Perez,
by Palbociclib (PD) could be an option in ATC treatment. Different ATCs cell
Patricia Borges de Souza, Maria E Prados-Gonzalez, Justo P Casta
˜o&
lines with distinct mutational patterns for RAS, CDKN2A and CDKN2B were used
Raul M Luque
to evaluate the cytotoxic effects of these drugs. The IC50 for TIP and PD were
Maimonides Institute of Biomedical Research of Cordoba; Reina Sofía
determined, and the effects of these compounds in cell cycle, cell death and cell
University Hospital; Department of Cell Biology, Physiology and
proliferation were analysed.
Immunology, University of Cordoba; CIBER Physiopathology of Obesity,
Cell culture studies demonstrated that low doses of TIP, at 48 h, induced cell
Cordoba, Spain.
cycle arrest in G2/M phase (50%, P!0.01), cell death (20%), and inhibition of
cell viability
(P!0.001), only in the HRAS mutated cell line. PD at low
concentration increased significantly cell cycle arrest on G0/G1 phase (80%,
A growing number of studies suggest that extracellular fragments derived from
P!0.05), only in cell lines with deletion/mutation in CDKN2A or CDKN2B
plasma membrane receptors can play relevant functional roles in the development
genes, however only higher doses induced more than 50% of cell death. The
and progression of certain tumoral pathologies which might, therefore, serve as
inhibition of cell viability was more pronounced in cell lines with deletion/muta-
novel tools in the diagnostic and prognostic of such pathologies. In this scenario,
tion in CDKN2A or CDKN2B genes than in wild type thyroid cancer cell lines or
the truncated somatostatin receptor sst5TMD4, which is overexpressed in various
in normal thyroid cells (P!0.05).
endocrine-related cancers
(i.e. breast, prostate, neuroendocrine, liver and
In conclusion, this study suggests that TIP and PD, which are currently in clinical
pituitary), is an aberrant splicing variant with only 4 transmembrane domains,
trials for other types of cancer, could play a relevant role in inhibiting the
wherein its C-terminal tail is exposed towards the extracellular matrix and could,
progression of ATC, depending on the specific molecular profile of the tumour.
therefore, be the substrate for proteolytic enzymes. Thus, to explore the plausible
DOI: 10.1530/endoabs.49.GP126
generation of soluble peptides derived from the sst5TMD4 extracellular domain
and their potential patho-physiological implications, in silico and in vitro
approaches were implemented using several cancer-derived cell lines (i.e. breast,
prostate, neuroendocrine and liver). Firstly, in silico analysis predicted the
existence of two cleavage sites for metalloproteases (MMP) 2, 9, 14 and/or 16,
which could generate the release of three possibly soluble peptides. We, then,
chemically synthetized these sst5TMD4-derived peptides and demonstrated that
they were able to enhance malignancy features (proliferation, migration and
dedifferentiation processes) in all the tumoral cell lines tested, probably acting
through PI3K/Akt and/or MEK/ERK signalling pathways. Moreover, treatment
with sst5TMD4-derived peptides altered the expression pattern of several genes
involved in cancer development and progression (e.g. certain MMPs, Ki67,
ARP2/3 or CD24/44). Therefore, based on these results, it is possible that
sst5TMD4-derived peptides could be linked to the pathological role of sst5TMD4
previously observed in these tumoral pathologies. Altogether, these studies
provide new information about the patho-physiological role of this truncated
GP127
variant of sst5 and suggest that sst5TMD4-derived peptides could be potential
Benign prostatic hyperplasia is associatied with liver inflammation: it’s
candidates for future studies aimed to identify novel diagnostic, prognostic and/or
time for prevention?
therapeutic targets in certain endocrine-related cancers.
Giorgio Ivan Russo2, Aldo E. Calogero1, Giuseppe Morgia2,
DOI: 10.1530/endoabs.49.GP128
Rosita Angela Condorelli1 & Sandro La Vignera2
1Andrology Center of Catania University, Catania, Italy;2Urology Center of
Catania University, Catania, Italy.
Metabolic Syndrome (MetS) has been frequently associated with an overall
GP129
inflammation status, called “metaflammation”, including atherosclerosis and non-
Androgen receptor activation inhibits endothelial cell proliferation
alcholic steatohepatitis
(NASH), In this study we aimed to evaluate the
through an extra-nuclear signaling pathway
relationship between intra-prostatic inflammation and NASH in a cohort of
Yen-Nien Huo1, Shauh-Der Yeh2, Chih-Ming Chou3 & Wen-Sen Lee4
patients affected by BPH. Between January
2012 and January
2016,
132
1Graduate Institute of Medical Sciences, Medical College, Taipei Medical
consecutive patients with BPH-related lower urinary tract symptoms (LUTS) who
University, Taipei 110, Taiwan;2Departments of Urology, Taipei 110,
underwent transurethral resection of the prostate were prospectively enrolled. The
Taiwan;3Departments of Biochemistry and Molecular Cell Biology,
presence of NASH was evaluated using the NASH score: 1.18*MetS (yesZ1)C
Taipei 110, Taiwan;4Departments of Physiology, School of Medicine,
0.45*Diabetes
(yesZ2)C0.15*fasting serum insulin C0.04*serum AST
-
Medical College, Taipei Medical University, Taipei 110, Taiwan.
0.94*(AST/ALT) - 2.89. A cut-off of 1.05 was set to predict NASH (AUC:
0.82). Prostate samples were anlaysized for the evaluation of inflammation and
this was classified accordindg to Irani score (score from 0 to 6). Patients with viral
The effect of androgen on angiogenesis has been documented. However, its
hepatitis or alcohol steatohepatitis were excluded. A final cohort of 132 patients
molecular mechanisms underlying has not been well illustrated. Here, we show
were included. The median age was 70.8 (interquartile range (IQR) 64.65-73.97),
that treatment with an androgen receptor (AR) agonist, metribolone (R1881) at
the median IPSS was 24.0 (IQR; 20.0-25.75) and the median prostate volume was
a range of concentrations (0.05-5 nM) or dihydrotestosterone (DHT) at a range
50.5
(IQR: 40.0-72.25). The prevalence of patients affected by MetS alone was
of concentrations
(0.4-40 nM) caused concentration-dependent inhibition of
56.8% (76/132), by NASH in 56.8% (76/132) and by severe intraprostatic
proliferation in human umbilical venous endothelial cells (HUVEC). The R1881-
inflammation (Irani R4) in while by the both disease in 27.3% (36/132). When
induced proliferation inhibition was also observed in human dermal micro-
considering patients with Irani score R4, we observed significant increase of
vascular endothelial cells
(HDMVE). Blockade of the AR activity by pre-
NASH score (K0.45 vs K1.01; P!0.01). The age-adjusted linear regression
treatment with HF (5 nM), an AR antagonist, or knockdown of AR expression
analysis demonstrated that waist circumference
(rZ0.35; P!0.01), fasting
using the shRNA technique abolished the R1881-induced proliferation inhibition
glucose (rZ0.32; P!0.01), LDL (rZ0.15; P!0.05), tryglycerides (rZ0.42;
in HUVEC, suggesting that AR receptor activation can inhibit endothelial cell
P!0.01) and Irani score (rZ0.12; P!0.05) were associated with increase in
proliferation. To further delineate the signaling pathway involved in the AR
NASH score. The age adjuested logistic regression analysis revealed that Irani
activation-induced proliferation inhibition, our data indicate that R1881 inhibited
score R4 (OR: 3.06; P!0.05) was an independent risk factor of NASH. Further,
proliferation in vascular endothelial cells through activating the AR/cSrc/AKT/-
the combination between MetS and NASH was significantly associated with
p38/ERK/NFkB signaling pathway, which in turn up-regulated the expression of
severe intra-prostatic inflammation (OR: 10.8; P!0.01) while vs MetS as single
p53, p21 and p27 protein, and finally reduced endothelial cell proliferation. Using
alteration. Patients with BPH are more frequently associated with a parallel liver
the zebrafish model, we also demonstrate that R1881 inhibited angiogenesis
inflammation. These findings can be explained by the metaflammation condition,
through the AR-mediated pathway in vivo. The findings of the present study
associated with metabolic aberration. Further studies should be conducted with
highlight the molecular mechanisms underlying AR activation-induced prolifer-
the scope to revert or prevent prostate related inflammation.
ation inhibition in vascular endothelial cells.
DOI: 10.1530/endoabs.49.GP127
DOI: 10.1530/endoabs.49.GP129
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP130
an important mediator of hot flushes in rodents and elevated hypothalamic
expression occurs in menopausal women. Neurokinin B acts via the neurokinin 3
Long non-coding RNA expression profiles in human parathyroid
receptor. We therefore hypothesised that neurokinin 3 receptor antagonism could
tumors
be a novel treatment for menopausal hot flushes.
Annamaria Morotti1, Irene Forno1, Valentina Andrè2, Andrea Terrasi1,
Methods
Chiara Verdelli2, Vito Guarnieri3, Alfredo Scillitani4, Leonardo Vicentini5,
This phase
2, randomised, double-blind, placebo-controlled, crossover trial
Edoardo Beretta6, Valentina Vaira1,7 & Sabrina Corbetta8
assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901)
1Division of Pathology, Department of Pathophysiology and Trans-
on menopausal hot flushes in an ambulatory setting
(Clinicaltrials.gov
plantation, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale
NCT02668185). Sixty-eight women were screened between February and
Maggiore Policlinico, Milan, Italy;2Laboratory of Experimental Endo-
October 2016 in a single-centre, of which 37 were randomised and included in
crinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy;3Genetic
an ITT analysis. Twenty-eight participants (aged 49-62yrs, experiencing O7 hot
Medicine, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo
flushes/24 h some of which were reported as bothersome or severe), completed
(FG), Italy;4Endocrinology Unit, IRCCS Casa Sollievo della Sofferenza,
the trial, and were included in a Per-Protocol analysis. They received 4 weeks of
San Giovanni Rotondo (FG), Italy;5Endocrine Surgery, IRCCS Fondazione
MLE4901 and placebo in random order separated by a washout period.
Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;6Endocrine
Randomisation was completed by a central computer, and participants were
Surgery, IRCCS Ospedale San Raffaele, Milan, Italy;7Istituto Nazionale
allocated to treatment number in numerical order. Primary outcome was total
Genetica Molecolare “Romeo ed Enrica Invernizzi” (INGM), Milan, Italy;
number of hot flushes during the final week of both treatment periods.
8Endocrinology Unit, Department of Biomedical Sciences for Health,
Findings
University of Milan, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
MLE4901 significantly reduced the total weekly number of hot flushes by 45%
compared to placebo
(adjusted means: placebo
49.01
(CI:
40.81-58.56),
Aberrant epigenetic signatures have been preliminary detected in parathyroid
MLE4901 19$35
(CI:
15.99-23.42), P!0.0001)
(ITT). MLE4901
also
tumors, in terms of microRNAs (miRNAs) and methylome deregulation. In this
significantly reduced weekly hot flush severity, bother, and interference compared
study, we profiled the expression of 90 long non-coding (Lnc) RNAs in 4
to placebo by
41% (P!0.0001), 45% (P!0.0001), and 58% (P!0.0001)
parathyroid carcinomas
(PCas),
12
parathyroid adenomas
(PAds) and
2
respectively. Treatment was well tolerated.
parathyroid glands from normocalcemic patients
(PaNs). Matched miRNA
Interpretation
profiles were available for a subset of cases. Unsupervised clustering distributes
Treatment with a neurokinin 3 receptor antagonist (MLE4901) could be practice
samples in two groups clearly distinguishing PCas from PaNs. Further analyses
changing as it safely and effectively relieves hot flush symptoms without the need
identified
9 LncRNAs significantly deregulated between PCas and PaNs, 12
for oestrogen exposure. Larger scale studies of longer duration are now indicated.
LncRNAs between PAds and PaNs, and 23 LncRNAs between PAds and PCas.
Funding
Five LncRNAs with a fold change O
2.0, namely MEG3, SGNH6
and
MRC (UK) (MR/M024954/1)
KCNQ1OT1 downregulated in PCas, NEAT1 and HAR1B upregulated in PAds,
DOI: 10.1530/endoabs.49.GP131
were validated by qPCR in an independent series of 3 PCas, 4 atypical PAds, 22
PAds and 2 PaNs. PCas and atypical PAds showed similar expression levels of the
5 LncRNAs, whereas PAds were distinguished in two clusters with 10 PAds
similar to PaNs. Clinically, PAds with the LncRNA profile similar to normal
glands had lower mean serum calcium and ionized calcium than PAds with the
LncRNA profile similar to PCas and PAds with intermediate profile (10.2G0.5 vs
12.1G0.2 vs 11.5G0.8 mg/dl; PZ0.006 and 1.36G0.06 vs 1.81G0.11 vs 1.51G
0.08 mmol/l; PZ0.0001). Correlating LncRNA and miRNA profiles, we detected
an association between the 5 deregulated LncRNAs and a set of miRNAs,
GP132
including miR-296-5p, previously identified signifcantly downregulated in PCas.
Testosterone administration decreases insulin sensitivity (IS) in adult
Finally, 10 PAds were characterized for the MEN1 gene expression level: PAds
female sheep born to testosterone treated mothers
with lower nuclear menin expression had decreased expression of two LncRNAs
Albert Carrasco1, Monica P Recabarren1, Daniel Sandoval1,
mapping on chromosome 11: KCNQ1OT1 on 11p15.5 and NEAT1 on 11q13.1. In
Teresa Sir-Petermann2 & Sergio E Recabarren1
conclusion, LncRNAs are deregulated in parathyroid tumors and identify 3
1Laboratory of Animal Physiology and Endocrinology, Faculty of
clusters of parathyroid tumors with different clinical activity. Moreover,
Veterinary Sciences, Universidad de Concepcion, Faculty of Veterinary
LncRNAs deregulation in PAds may be modulated by the genetic background,
Medicine, Chillan, Region del BioBio, Chile;2Laboratory of Endocrinology
while they may be involved in miRNAs deregulation.
and Metabolism, Western School of Medicine, Universidad de Chile
DOI: 10.1530/endoabs.49.GP130
Western School of Medicine, Santiago, Chile.
Different animal models have been used to study the postnatal effect of a prenatal
exposure to an androgen excess on the female offspring. We have established a
sheep model to test the hypothesis that the intrauterine environment of the PCOS
mother may play a role in the etiology of the PCOS. In this regard, our sheep
Female Reproduction
model for the study of PCOS has the advantage that provides mainly an
androgenized milieu to the fetus in comparison to pregnant PCOS women who
GP131
offers a hyperandrogenic and hyperinsulinemic intrauterine environment to the
Neurokinin 3 receptor antagonism as a novel treatment for menopausal
fetus. Previous results from our laboratory have demonstrated that female sheep
hot flushes: a phase 2, randomised, double-blind, placebo-controlled
born to mothers receiving testosterone (T) during part of their pregnancy exhibit
trial
features from early postnatal life until adulthood resembling those of PCOS
Julia Prague1, Rachel Roberts1, Alexander Comninos1, Sophie Clarke1,
women. In the present work the programming effect of prenatal T on the IS was
Channa Jayasena1, Zachary Nash1, Chedie Doyle1, Deborah Papadopoulou1,
explored in adult females born to T treated mothers (T-females), and born to
Stephen Bloom1, Pharis Mohideen2, Nicholas Panay3,4, Myra Hunter5,
untreated mothers (C-females). Our aim was to establish if exogenous T may
Johannes Veldhuis6, Lorraine Webber7, Les Huson8 & Waljit Dhillo1
exacerbate the insulin resistance due to programming effect of prenatal exposure
1Department of Investigative Medicine, Imperial College, London, UK;
to T. Both groups were injected with T, twice weekly (40 mg per dose), for 8
2Millendo Therapeutics, Inc., Michigan, USA;3Department of
weeks, beginning at 30 weeks of age. Females were estrous synchronized with
Gynaecology, Queen Charlotte’s & Chelsea Hospital and Chelsea &
prostaglandin and 48 hours after the last T dose, an IVGTT was carried out. On
Westminster Hospital, London, UK;4Institute of Reproductive and
the day of the IVGTT, there was no difference in plasma concentration of
Developmental Biology, Imperial College London, London, UK;5Institute
estradiol, progesterone and T between groups. IS indexes were calculated with the
of Psychiatry, Psychology and Neuroscience, King’s College, London, UK;
plasma insulin and glucose concentrations during the IVGTT. Plasma levels of
6Mayo Clinic, Minnesota, USA;7Scientific Partnering & Alliances,
glucose were not different during the IVGTT but T-females secreted more insulin
Innovative Medicines & Early Developmental Biotech Unit, Astrazeneca,
(P!0.05) than C-females. The ratio insulin/glucose before the IVGTT tended to
Melbourn, UK;8Division of Experimental Medicine, Imperial College,
be higher in T-females (PZ0.054) and the IS Index-C tended to be lower in
London, UK.
T-females compared to C-females (PZ0.054). Results show that T administration
to T-females amplifies the effect of a glucose challenge on the insulin secretion
Background
compared to C-females, suggesting an exacerbation of the insulin resistance
Hot flushes affect 70% of menopausal women, can be long-lasting, and often
induced by fetal programming.
severely impact on physical, psychosocial, sexual, and overall wellbeing.
DOI: 10.1530/endoabs.49.GP132
Hormone replacement therapy is effective but not without risk. Neurokinin B is
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP133
Results
Among the randomized patients in the preceding study (NZ487), 397 were
Influence of BMI on AMH levels in non-PCOS women
enrolled in this extension study; 77 to placebo, 78 to 89 to relugolix groups, and
Joana Simo˜ es-Pereira1, Joaquim Nunes2, Ana Aguiar2, Sandra Sousa2,
69 to leuprorelin. Baseline characteristics were similar between randomized
Cátia Rodrigues2, J Sampaio Matias3 & Carlos Calhaz-Jorge2
patients and all patients who entered the extension study. The incidences of
1Endocrinology Department, Instituto Português de Oncologia de Lisboa,
adverse events including metrorrhagia, menorrhagia, and hot flush in the relugolix
Francisco Gentil, Lisbon, Portugal;2Reproductive Medicine Unit, CHLN-
40 mg group were similar to those in the leuprorelin group. Dose-dependent bone
Hospital de Santa Maria, Lisbon, Portugal;3Clinic Pathology, CHLN-
density loss was observed with relugolix treatment, with the relugolix 40 mg
Hospital de Santa Maria, Lisbon, Portugal.
result consistent with the leuprorelin result. The change from baseline in mean
visual analogue scale score for pelvic pain (in mm) during the last 4 weeks of
Introduction
treatment period was K3.222 in the placebo group, K6.849, K9.032, and
Anti-Mullerian Hormone (AMH) is a useful marker of ovarian reserve (OR),
K11.924 in relugolix
10 mg, 20 mg and 40 mg groups, respectively, and
since it remains stable inter/intra-cycles and presents a good correlation with
K12.552 in the leuprorelin group. Estradiol levels decreased with increasing dose
ultrasonographic antral follicular count. Obesity/overweight are increasing and
of relugolix and were maintained below the postmenopausal levels throughout the
may affect the reproductive health. However, previous studies regarding the effect
24-week relugolix 40 mg treatment period.
of body mass index (BMI) on AMH levels are discordant. Our main goal was to
Conclusion
evaluate the influence of BMI in AMH levels in women with infertility.
Treatment with relugolix for
24
weeks was generally well tolerated and
Methods
demonstrated similar pelvic pain reduction as leuprorelin in women with EM.
Revision of medical records of 995 women who performed AMH determinations
Relugolix, a once-daily oral nonpeptide GnRH receptor antagonist, demonstrated
as part of their fertility workup, between 2011-2016. Women diagnosed with
similar benefit to injectable leuprorelin in this Phase 2 study.
polycystic ovarian syndrome (Rotterdam criteria) were excluded. We analysed
DOI: 10.1530/endoabs.49.GP134
the influence of BMI, age, ethnicity, smoking and previous ovarian surgery on
AMH levels.
Results
Median AMH concentration was 1.75(0-26)ng/dL and median age at AMH
determination was 35(19-40)years. These women evidenced a median BMI of
23(15-39) kg/m2 and had been struggling with infertility for 60(7-432) months.
The majority [700(70.4%)] presented primary infertility. Caucasian women were
more represented [889(89.3%)]. Smoking habits (present/past) were present in
359(36.1%), and
147(14.8%) harboured a history of ovarian surgery. On
univariable analysis AMH was not correlated with BMI (rZ0.52/PZ0.10); the
only factors influencing AMH were age (P!0.001), ethnicity (PZ0.005) and
GP135
previous surgery (P!0.001). On multivariable analysis, age was the only variable
Brown adipose tissue thermogenesis in women with polycystic ovary
significantly associated with AMH, evidencing a reduction of 6.2% for each
syndrome
additional year (P!0.0001). Furthermore, we verified a trend suggesting an
Soulmaz Shorakae1,2, Eveline Jona1, Barbora de Courten1,2,
AMH reduction of 22% (PZ0.08) in melanodermic patients comparing with the
Gavin Lambert3,4, Elisabeth Lambert3, Sarah Phillips3, Iain Clarke5,
caucasian ones, when controlling for the other variables.
Helena Teede1,2 & Belinda Henry6
Conclusion
1Monash Centre for Health Research and Implementation, Monash
We report one of the largest series evaluating the influence of BMI on AMH
University, Melbourne, Australia;2Diabetes and Vascular Medicine Unit,
levels and, consequently, on OR. BMI does not seem to affect AMH levels. The
Monash Health, Melbourne, Australia;3Human Neurotransmitters
reported concerns on infertility in overweight/obese women may be related to
Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;
follicular development/endometrial disorders, rather than decreased OR.
4Department of Physiology, Monash University, Melbourne, Australia;
DOI: 10.1530/endoabs.49.GP133
5Neuroscience Program, Monash Biomedicine Discovery Institute,
Department of Physiology, Melbourne, Australia;6Metabolic Disease and
Obesity Program, Monash Biomedicine Discovery Institute, Department of
Physiology, Melbourne, Australia.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of
reproductive age women and is characterized by reproductive, metabolic and
psychological features exacerbated by weight gain. Weight management in PCOS
is challenged by propensity to weight gain and lack of sustainable dietary
interventions. Body weight is regulated by calorie intake and the rate of energy
expenditure. Metabolically active brown adipose tissue (BAT), contributing to
energy dissipation, has been described in humans. The thermogenic activity of
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BAT is controlled by the sympathetic nervous system (SNS). Sex hormones also
Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor
play role in modulating BAT. Human studies confirm association of
antagonist, in women with endometriosis (EM)-associated pain: Phase 2
supraclavicular skin temperature, where most human BAT is located, with
safety and efficacy 24-week results
BAT activity. This observational study aimed to explore BAT thermogenesis and
Yutaka Osuga1, Yoshifumi Seki2, Masataka Tanimoto2, Takeru Kusumoto2,
its associations, for the first time, in PCOS. Cutaneous wireless temperature
Kentarou Kudou2 & Naoki Terakawa3
probes (2 cm diameter, 0.5 depths) were taped to supraclavicular (BAT) and
1The University of Tokyo, Tokyo, Japan;2Takeda Pharmaceutical Company
upper arm (muscle) regions of 49 premenopausal women with PCOS, over
Limited, Osaka, Japan;3Tottori University Faculty of Medicine, Yonago,
96 hours, (mean age: 29.85G5.93, mean BMI: 29.02G5.43), recruited from
Japan.
community. Multiunit muscle SNS activity (by microneurography) and plasma
noradrenaline levels were measured as markers of SNS activity. Fasting lipids,
Objective
serum androgens, markers of insulin resistance and inflammation were measured.
The objective of this Phase 2 study was to evaluate the safety of relugolix when
Recorded temperature data from both regions were available in 41 participants.
administered for 24 weeks in women with EM-associated pain. Efficacy was
Supraclavicular temperature was significantly higher than arm temperature
exploratory assessed using leuprorelin as a reference.
(33.87G0.65
vs
32.23G0.85, P
! 0.0001). Supraclavicular temperature
Design
correlated with testosterone
(rZK0.410, PZ0.011), noradrenaline
(rZK
This was an open-label extension study evaluating safety of 3 doses (10 mg,
0.488, PZ0.005) and triglycerides (rZK0.393, PZ0.015) which remained
20 mg, and 40 mg) of relugolix administered orally once daily for a total of 24
significant after adjustment for BMI. Arm temperature did not correlate with
weeks in women with EM-associated pain, who had participated in a preceding
testosterone, noradrenaline and triglycerides. This is the first study of BAT
12-week study.
thermogenesis in PCOS using cutaneous temperature probes. The negative
Materials and methods
correlation of BAT temperature with noradrenaline levels could implicate a
Premenopausal women with EM-associated pain who completed a preceding
maladaptive thermogenic response to chronic SNS activation in PCOS. Chronic
12-week study and were eligible to continue for an additional 12-week treatment
sympathoexcitation and hyperandrogenism play potential roles in modulation of
were enrolled. The primary endpoint was the safety including assessment of
BAT thermogenesis in PCOS.
change in bone mineral density using dual energy x-ray absorptiometry. Analysis
DOI: 10.1530/endoabs.49.GP135
sets were defined as all patients who were administered the study drug.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP136
Results
Despite no difference in total-testosterone levels, in PCOS with AH (nZ58,
Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin improved beta cell
18.9%) the SHBG (27.6G3.6 vs 44.5G3.3 nmol/L, P! 0.0002) was lower and
function and prevented a conversion rate to MTG and DM2 in
FAI (14.0G2.2 vs 8.7G0.7, P! 0.002), 2-h insulin in OGTT (111.2G26.0 vs
metformin intolerant PCOS with high metabolic risk
77.3G6.9 mUI/L, P!0.044) and systolic BP
(123.7G4.26
vs
114.4G
Andrej Janez, Simona Ferjan & Mojca Jensterle
1.8 mmHg, P!0.045) were higher than in PCOS without AH. SNPs
University Medical Center Ljubljana, Ljubljana, Slovenia.
corresponding to at least 15 genes were positive in CT test with DHEAS levels.
Among them, INSR and CDH13 were the most significant with numerous SNPs
Objective
having a P value ! 1.0!10-5 after Bonferroni correction. In genetic association
Metformin is the first-line therapy for PCOS with high metabolic risk, yet a large
by logistic regression between two groups, other genes were also confirmed, the
proportion of patients cannot tolerate it due to associated gastrointestinal adverse
most influential being IL2RA, PTER, SORCS1, LGR4 and KSR2. For instance,
events. The alternative pharmacological strategy when metformin cannot be
LGR4 (Chr 11) was associated with P! 0.005, OR 5.6, 95%CI [1.6-19].
tolerated is not well established in this population. Our aim was to evaluate
Conclusion
whether sitagliptin
(SITA) preserves metabolic profile in metformin (MET)
These data indicated that, in PCOS patients, AH may be in part explained by
intolerant PCOS with high metabolic risk.
genetic susceptibility. Despite a full array of genes involved, the insulin-
Design and methods
resistance appears as potential actor of AH in PCOS.
A 12-week prospective randomized open-label study was conducted with 30
DOI: 10.1530/endoabs.49.GP137
obese MET intolerant women with PCOS (aged 35.0G7,2 years, BMI 36,9G
5.5 kg/m2). They were randomized to lifestyle intervention and SITA 100mg QD
or lifestyle intervention alone as controls (CON). All participants underwent
standard anthropometric, endocrine measurements and OGTT. Model derived
indexes of insulin resistance (IR) and b-cell function were calculated.
Results
SITA improved beta cell function as assessed by HOMA beta for 45,9G35,8
(PZ0,001), modified beta cell function index (MBCIZI0XG0/(G120CG60-7))
for 7,9G7 (PZ0,002) and QUICKI for K0,03G0,03 (PZ0,002) and increased
IR as assessed by HOMA-IR and insulin action index (IAIZ1/G0XI0) for 1,8G
1,7 (PZ0,002) and K0,01G0,01(PZ0,003). By contrast, beta cell function
decreased in CON arm. The between group differences were significant for
HOMA-beta (PZ0,000), MBCI (PZ0,010) and QUICKI (PZ0,025). The
conversion rate from normal glucose tolerance to impaired glucose tolerance
(IGT) or T2DM was prevented in SITA (3/15 of subjects with MTG before and
after the study). In CON 4 women had IGT at the beginning. After 12 weeks IGT
GP138
was observed in 2 and T2DM in 3 subjects.
Turner’s syndrome and abnormal liver chemistry: relationship with
Conclusion
karyotype in a large dedicated clinic
SITA improved beta cell function and prevented a conversion rate to IGT and
Matilde Calanchini1,3, Ahmad Moolla1, Jeremy W Tomlinson1,
T2DM in metformin intolerant PCOS with high metabolic risk when compared to
Jeremy Cobbold2, Andrea Fabbri3, Ashley Grossman1 & Helen Turner1
lifestyle alone.
1Oxford Centre for Diabetes, Endocrinology and Metabolism - Churchill
DOI: 10.1530/endoabs.49.GP136
Hospital, University of Oxford, Oxford, UK;2Department of Hepatology,
John Radcliffe Hospital, Oxford, UK;3Department of Endocrinology, CTO
Alesini & S. Eugenio, University of Rome Tor Vergata, Rome, Italy.
Introduction
Abnormal liver function tests
([LFTs) are frequently observed in Turner’s
syndrome (TS), although the aetiology is unclear. Obesity is reported as one of the
causes; recently an increased prevalence of elevated GGT was found in TS
patients with a ring X karyotype.
Aim
To analyse the association between abnormal LFTs and TS-related conditions,
and in particular their relationship with the different TS-karyotypes.
Methods
Data on adult TS-patients were collected.
[LFTs was defined as elevated
GP137
aminotransferases G GGT and ALP, for more than 6 months. TS-karyotypes
Genetic susceptibility for adrenal hyperandrogenism in polycystic
were classified in eight groups.
ovary syndrome
Results
Nicoleta Baculescu1,2, Sarah Haydar3, Monica Livia Gheorghiu1,2,
109 TS women were studied: mean age 36(G13.1)y, BMI 28.3(G6.9)Kg/m2.
Serban Radian1,2, Corinne Lautier3, Catalina Poiana1,2, Michel Pugeat4 &
45,X was found in 47 patients (46.1%), mosaicism 45,X/46,XX or 45,X/47,XXX
Florin Grigorescu3
in 15 (15.7%), 4 (3.9%) del(X)(p), 1 (1%) del(X)(q), 10 (9.8%) isochromo-
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
some(X)(q), 10 (9.8%) ring X, presence of Y in 4 (3.9%) and 10 (9.8%) other
2C.I. Parhon Institute of Endocrinology, Bucharest, Romania;3IURC,
TS-karyotypes.
UMR-204 NUTRIPASS, University of Montpellier, Montpellier, France;
38/109 (35%) presented with [LFTs, most frequently a [GGT. Differences
4Fédération d’Endocrinologie, Hopital Neuro-Cardio, University of Lyon,
between the normal-LFTs-group versus the [LFTs-group were found for age
Lyon, France.
(33.8 vs 41y, PZ0.008), Tot-Chol (4.9 vs 5.5 mmol/L, PZ0.005), LDL-Chol (2.7
vs 3.2 mmol/L, PZ0.006), and triglycerides (1.1 vs 1.5 mmol/L, PZ0.02). No
Background
differences were noted analysing anthropometric values, HbA1c, history of
Hyperandrogenism is a main feature of the polycystic ovary syndrome (PCOS).
diabetes, hypertension or autoimmunity.
Although its ovarian origin is well recognized, laboratory investigation suggested
The prevalence of [LFTs was significantly higher in the isochromosome(X)(q)-
the contribution of adrenal gland, albeit of unknown mechanism.
group (PZ0.0003); the mosaicism-group had a decreased prevalence of [LFTs
Aim
(PZ0.0092). Using the stringent ALT cut-off of 19UI/L, this was commoner only
To understand the contribution of genetic factors in adrenal hyperandrogenism
in the i(X)(q)-group (PZ0.0134). The i(X)(q)-group showed a similar clinical
(AH) we investigated genome wide SNPs in subgroups of PCOS patients stratified
phenotype compared to 45,X and no increased prevalence of autoimmune disease.
as function of DHEAS levels in two ethnic populations (Romanians and French).
Conclusions
Subjects and methods
This study shows 1) [LFTs are common in TS; 2) the prevalence of [LFTs
Patients recruited during European MEDIGENE program (FP7-279171) with
increases with age and is associated with increased cholesterol and triglycerides;
PCOS (nZ307) of 18-42 years old were stratified in two groups as function of
3) for the first time, a relationship between [LFTs and karyotype was found,
DHEAS level greater than 95th percentiles in age-matched controls. Genotyping
suggesting that liver biochemical abnormalities could be triggered by over-
was performed with customized MEDISCOPE microarray chip with 759 000
expression of Xq genes escaping inactivation.
SNP. Influential SNPs were determined by correlation trend (CT) test and then by
DOI: 10.1530/endoabs.49.GP138
genetic association in two subgroups of patients.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP139
(ANOV,PCOM). NAFLD was assessed using NAFLD liver fat score (NAFLD-
LFS) cutoff O K0.640. Differences between groups were age adjusted.
Sensitivity of hypothalamo-pituitary-adrenal axis in women with PCOS
Results
Djuro Macut1, Ivana Bozic-Antic1, Jelica Bjekic-Macut2, Dusan Ilic1,
NAFLD was more prevalent in PCOS in comparison to controls (59.7 vs 44.4%,
Danijela Vojnovic-Milutinovic3, Olivera Stanojlovic4, Tamara Bogavac1,
PZ0.009). Our PCOS group consisted of 268 women with phenotype A, 129 with
Bojana Popovic1, Tatjana Isailovic1, Valentina Elezovic1 &
phenotype B, 47 with phenotype C and 35 with phenotype D. Prevalence of
Sanja Ognjanovic1
NAFLD in phenotypes were: A: 59%, B:61%, C:53% and D:66%. There were
1Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of
significant differences in the prevalence of NAFLD between controls and
Medicine, University of Belgrade, Belgrade, Serbia;2CHC Bezanijska kosa,
phenotype A (PZ0.015), phenotype B (PZ0.015) and phenotype D (PZ0.028).
Faculty of Medicine, University of Belgrade, Belgrade, Serbia;3IBISS,
There were no significant differences between phenotypes.
University of Belgrade, Belgrade, Serbia;4Institute of Physiology, Faculty
Conclusions
of Medicine, University of Belgrade, Belgrade, Serbia.
NAFLD is more prevalent in obese PCOS women than in obese BMI-matched
controls. All four phenotypes have the same risk for NAFLD which confirms
Introduction
susceptibility of PCOS as a whole to develop metabolic derangements.
Increased adrenal androgen production is present in 20-60% of women with
DOI: 10.1530/endoabs.49.GP140
polycistic ovary syndrome (PCOS). Possible mechanism is not clarified yet and
could be related to altered hypothalamic-pituitary-adrenal-axis (HPA) activity or a
consequence of adrencortical steroidogenic abnormalities. The aim of the study was
to assess HPA sensitivity in PCOS women using different doses of dexamethasone.
Methods
We analyzed 359 women with PCOS diagnosed using ESHRE/ASRM criteria (age:
GP141
25.6G5.3 years, BMI: 25.1G6.4 kg/m2), and 58 BMI-matched healthy controls
Effects of central sympathoinhibition with moxonidine on the elevated
(age 28.79G6.1 years, BMI 23.7G6.1 kg/m2). In all subjects serum ACTH,
sympathetic nervous activity and downstream metabolic abnormalities
morning serum cortisol (SC), and DHEAS were measured, and SC and DHEAS
observed in polycystic ovary syndrome
determined after overnight dexamethasone test with 0.5 mg (Dex0.5mg) and 1 mg
Soulmaz Shorakae1,2, Elisabeth Lambert3,4, Eveline Jona1, Carolina
(Dex1mg), and marked as SCdex0.5, SCdex1, DHEASdex0.5
and DHEASdex1,
Ika Sari3, Barbora de Courten1,2, Gavin Lambert3,4 & Helena Teede1,2
respectively. Differences between groups were age adjusted and data are presented
1Monash Centre for Health Research and Implementation, Monash
as ANCOVA-mean (95%CI).
University, Melbourne, Australia;2Diabetes and Vascular Medicine Unit,
Results
Monash Health, Melbourne, Australia;3Human Neurotransmitters
SC was borderline higher [437.9(421.6-454.3) vs. 395.7(356.7-437.8)nmol/l, PZ0.052]
Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;
and DHEAS significantly higher [7.7(7.3-8.2) vs. 5.6(4.6-6.7)nmol/l, P!0.001] in PCOS
4Department of Physiology, Monash University, Melbourne, Australia.
than in controls. There was no difference in ACTH among groups. After dexamethasone
tests, both groups significantly lowered SC and DHEAS in comparison to basal analyses. In
The role of the sympathetic nervous system (SNS) in the pathophysiology of
comparison to controls, PCOS had borderline higher SCdex0.5 [49.9 (22.9-76.9) vs.
PCOS and associated cardiometabolic risks is emerging. Previous studies support
78.5(67.8-89.1)nmol/l, PZ0.055] but similar percentage of SC suppression [86.5 (80.6-
increased SNS activity in PCOS, potentially contributing to metabolic features via
92.3) vs. 82.8(80.4-85.3)%, PZ0.26]. PCOS had lower SCdex1 [26.8 (23.5-30.2) vs.
multiple mechanisms including insulin resistance. Moxonidine is a second-
22.9(21.6-24.2)nmol/l, PZ0.055] and suppressed SC more than controls [92.5(91.6-93.5)
generation imidazoline I1 agonist, acting centrally, inhibiting sympathetic outflow
vs.
94.5(94.1-94.9)%, P!0.001]. There were no differences in DHEASdex0.5 and
at the level of rostral ventrolateral medulla with known beneficial effects on
DHEASdex1 between groups. Suppression of DHEAS was similar after Dex0.5mg
hypertension, insulin sensitivity, dyslipidemia and inflammation. This study
(PZ0.92), but PCOS suppressed DHEAS after Dex1mg less than controls [32.1 (25.9-
aimed to explore pharmacological modification of SNS activity, for the first time,
38.3) vs. 47.7(34.0-61.4)%, PZ0.04].
in women with PCOS, using moxonidine. 51 premenopausal women (mean age:
Conclusions
29.8G5.9 years, mean BMI: 29.0G5.4 kg/m2) with PCOS were recruited, from a
Our women with PCOS, in comparison to BMI-matched controls have increased age-
community setting, in a double blind placebo controlled clinical trial. 48 women
adjusted HPA axis sensitivity to 1 mg but not to 0.5 mg of dexamethasone. DHEAS
were weaned off any interacting medication for 3 months then randomized to
production in PCOS seems to be more independent of ACTH than in controls.
moxonidine (0.2mg daily initially, up titrated to 0.4mg daily in 2 weeks) (nZ23)
DOI: 10.1530/endoabs.49.GP139
or placebo (nZ25) for 3 months. Multiunit muscle SNS activity (MSNA by
microneurography), heart rate variability
(HRV) and endothelial function
(ischaemic reactive hyperaemia index (RHI)) were examined. Fasting lipids,
serum androgens, markers of insulin resistance and inflammatory markers were
measured prior to and following intervention. 45 women completed the trial (19
moxonidine and 23 placebo). Change in MSNA (K3.23G6.71 vs K2.81G8.2
bursts per minute, PZNS), HRV
(5.26G13.56
vs
2.95G15.37 nu in low
frequency component, PZNS) and endothelial function (0.10G0.70 vs 0.06G
GP140
0.67 in RHI, PZNS) did not differ significantly with moxonidine compared to the
Nonalcoholic fatty liver disease liver fat score (NAFLD-LFS) could be
placebo. Mean changes in BP, fasting lipids, HOMA-IR, hs-CRP and androgens
used for the assessment of NAFLD in women with PCOS
were similar in both groups. In women on moxonidine, change in BMI correlated
Jelica Bjekic-Macut1, Ivana Bozic-Antic2, Konstantinos Tziomalos3,
positively with change in MSNA (r2Z0.593, PZ0.03). Central sympathoinhibi-
Dusan Ilic2, Danijela Vojnovic-Milutinovic4, Olivera Stanojlovic5 &
tion with moxonidine does not modify higher SNS activity and downstream
Djuro Macut2
metabolic abnormalities in PCOS. Sympathoexcitation in PCOS may be driven
1CHC Bezanijska kosa, Faculty of Medicine, University of Belgrade,
peripherally or from other brain regions with further research needed.
Belgrade, Serbia;2Clinic of Endocrinology, Diabetes and Metabolic
DOI: 10.1530/endoabs.49.GP141
Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia;
3Department of Medicine, University of Thessaloniki, Thessaloniki, Greece;
4IBISS, University of Belgrade, Belgrade, Serbia;5Institute of Physiology,
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
GP142
Introduction
Steroid receptors involvement in enamel hypomineralization resulting
A relation between polycystic ovary syndrome (PCOS) and nonalcoholic fatty
from exposure to low-dose DEHP and bisphenol A
liver disease (NAFLD) was demonstrated recently. Both NAFLD and PCOS are
Bui Ai Thu1,2, Sophia Houari1,2, Sophia Loiodice1,2, Katia Jedeon1,2,
associated with increased risk for type 2 diabetes and cardiovascular disease.
Ariane Berdal1,2 & Sylvie Babajko1,2
NAFLD liver fat score (NAFLD-LFS) has been implicated as a non-invasive
1University Paris Diderot, Paris, France;2INSERM, Paris, France.
surrogate marker for NAFLD. The aim of this study was to identify the prevalence
of NAFLD in different PCOS phenotypes using NAFLD-LFS.
Methods
The environment has become increasingly contaminated by various pollutants
We evaluated 489 obese PCOS women (PCOS: 33.2G5.7 kg/m2; 25.6G6.2
including endocrine disrupting chemicals (EDCs). This has led to an increase in
years) diagnosed using ESHRE/ASRM criteria and 97 BMI-matched obese
the incidence and gravity of known pathologies and the emergence of new ones,
healthy women (controls: 32.5G5.5 kg/m2; 31.7G5.1 years). PCOS group was
including dental pathologies as the Molar Incisor Hypomineralization (MIH).
divided into 4 phenotypes: A [anovulation (ANOV), hyperandrogenism (HA),
Among the thousands of EDCs, bisphenol A (BPA) and phthalates (DEHP) are
polycystic ovary morphology (PCOM)], B (ANOV,HA), C (HA,PCOM) and D
widely used by the plastic industry and responsible to frequent contaminations.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
We previously showed a link between experimental exposures to low-dose BPA
GP144
and enamel defects similar to MIH (1). The characterization of enamel defects
Altered protein expression of cell cycle- and EMT-associated genes by
may be helpful to propose them as early markers of exposure to EDCs thanks to
bisphenol compounds in MCF-7 CV human breast cancer cells via
enamel unique properties.
estrogen receptor dependent pathway
The aims of the present work are 1) to compare mouse enamel defects resulting
Ana Patricia Ayala-Cuellar, Kyung-A Hwang & Kyung-Chul Choi
from exposure to low-dose BPA and/or DEHP and,
2) to approach the
Laboratory of Biochemistry and Immunology, College of Veterinary
mechanism, of action of both EDCs during amelogenesis.
Medicine, Chungbuk National University, Cheongju, Chungbuk,
The study was carried out on mice exposed to 5 and 50 mg/kg per day DEHP with
Republic of Korea.
or without 5 mg/kg per day BPA. Exposed animals present enamel defects on their
incisors with similar characteristics than those of MIH affected teeth. In addition,
11% of DEHP mice presented enamel breakdown suggesting a weak enamel
Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical
structure. As both EDCs act through steroid receptors, their presence and
(EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and
expression levels were investigated in ameloblasts by immunofluorescent assays
bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-
and RT-qPCR respectively. We found that dental epithelium express a specific
dependent cancer has been reported rarely compared with the numerous cases of
combinatory of steroid receptors (AR, ERs, ERRs, RARa/RXRa, VDR, GR, MR
BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the
and PGR) depending on their stage of differentiation. These data suggest that
proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7
depending on their nature and the time of exposure, phthalates and BPA could
clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors
affect enamel quality (through AR) and/or quantity (through ERRg and ERa).
(ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased
Studies are currently driven to decipher the functional role of AR in the
proliferation of MCF-7 CV cells compared to control (DMSO) as did 17b-
mechanism of action of both EDCs in ameloblasts.
estradiol (E2). In Western blot assay, BPA, BPS, and BPF enhanced the protein
References
expression of cell cycle progression genes such as cyclin D1 and E1. In addition,
(1) Jedeon et al., Am J Pathol, 2013, 183(1):108-18.
MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology
DOI: 10.1530/endoabs.49.GP142
by the treatment of BPA, BPS, or BPF for 24 h. In cell migration assay, BPA,
BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2.
In relation with the EMT process, BPA, BPS, and BPF increased the protein
expression of N-cadherin, while they decreased the protein expression of
E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER
antagonist, proliferation effects were reversed, the expression of cyclin D1 and
cyclin E1 was down-regulated, and the altered cell migration and expression of
N-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control
level. Thus, these results imply that BPS and BPF also have the risk of breast
cancer progression as much as BPA in the induction of proliferation and
migration of MCF-7 CV cells by regulating the protein expression of cell cycle-
related genes and EMT markers via ER-dependent pathway. (This work was
supported by a grant from the Next-Generation BioGreen 21 Program (no.
PJ011355-2015), Rural Development Administration, Republic of Korea.)
Keywords: Human breast cancer cells, endocrine disrupting chemicals, bisphenol-A,
bisphenol-S, bisphenol-F, epithelial-mesenchymal transition, migration
DOI: 10.1530/endoabs.49.GP144
Male Reproduction and Endocrine Disruptors
GP143
In vitro effects of Bisphenol A on two metabolic receptors signaling:
MC4R and FFAR1
Mathilde Munier1,4, Mathilde Louvigné5, Hélène Rudelle4,
Louis Gourdin1,3, Claire Briet4,3, Daniel Henrion1,2, Marie Chabbert1,2,
Régis Coutant3,5 & Patrice Rodien3,4
1UMR CNRS6015-INSERM1083, Angers, France;2MITOVASC Institute,
GP145
Angers, France;3Reference Center for Rare Diseases of Hormonal
Reproductive toxicity of low dose nonylphenol in mice: a
Receptivity, Angers, France;4Department of Endocrinology, Angers,
two-generation study
France;5Department of Pediatric Endocrinology, Angers, France.
Sung-Ho Lee, Yong Bin Kim & Hee Su Kim
Sangmyung University, Seoul, Republic of Korea.
Metabolic diseases (type 2 diabetes (T2D) and obesity) prevalence is increasing in
the world. This is partly related to a change in lifestyle with an increase of caloric
Nonylphenol (NP), a member of alkylphenol family, has been widely used in both
intake and a decrease of physical activity. Environmental causes are also involved
industry and household. NP is classified as an endocrine-disrupting chemical and
among them exposure to bisphenol A (BPA). The mode of action of the latter is
is known to act as an agonist of the GPER (GPR30). The aim of this study was to
unknown. Beyond a suggesting effect relayed by nuclear receptors, we propose
address the two-generational effects of para-nonylphenol
(NP) on the body
that BPA can act by modulating the functionality of G protein-coupled receptors
weights, reproductive organ weights and histopathologies of ICR mice. We also
involved in the pathophysiology of metabolic disorders. In order to test this
test the potential reproductive toxicity of octylglucuronide (OG), a substitute
hypothesis, we analyzed the effect of BPA on the activity of MC4R and fatty acid
candidate for NP. The testing drugs were administered as drinking water (50 and
receptor FFAR1 (GPR40). MC4R is involved in obesity by regulating dietary
500 ug/l) throughout the pre-mating period of P0 animals and lactation of F2
intake and energy balance. There are two ligands of MC4R: aMSH (agonist) and
animals. Significant decreases were found in the weights of testis, prostate and
AgRP (inverse agonist). FFAR1
increases the glucose-dependent insulin
seminal vesicle in the F1 NP500 group, in the weights of testis and epididymis in
secretion. It is a new therapeutic target in T2D.
F2 NP50 and NP500 groups. There was no weight change in the OG-treated
Each receptor is transiently expressed in HEK293, and its activity is assessed by
groups. In female, significant decreases in the weights of ovary and uterus in F1
measuring cyclic AMP (cAMP) for MC4R, using a biosensor kit, or calcium for
NP50 group, uterus of F1 NP500 group, and F2 NP500 group were found. The
FFAR1, using a fluorimetric calcium sensor.
weights of ovary in F1 OG50 and OG500 were also significantly decreased.
At a concentration of 10 nM, BPA increased by up to 30% the cAMP production
Histopathological studies revealed that the numbers of Leydig cells were reduced
induced by aMSH and reduced by half the inhibition induced by AgRP, without
in the testes of F1 and F2 NP50 groups. There were no changes in the Leydig cell
modifying the basal activity. These effects are specific for MC4R as BPA did not
numbers of OG groups. In F1 NP500 mice, the increased numbers of primary and
change the activity of the downstream effectors of cAMP pathway (adenylate
secondary follicles and decreased number of corpora lutea were observed. There
cyclase, G protein or phosphodiesterases) or one of endogenous adenosine
was no change in OG-treated group gonad. Finally, vaginal opening was delayed
receptor (negative control).
in F1 NP50 and NP500, and F2 NP50 animals. Present study demonstrated that
In addition,
10 pM BPA decreased by one-third the calcium mobilization
the potential reproductive toxicity in animals long-term exposed to low dose NP
stimulated by GW9508 (a synthetic agonist of FFAR1).
(approximately 15-150 ng of daily intake). Our study also show that OG seems to
We show here new effects of BPA with a disruption of G protein-coupled
be a promising alternative to NP, and further studies are warranted. This work was
receptors activity, which may be worth to take into account when addressing the
supported by the National Research Foundation of Korea Grant funded by the
question of the link between endocrine disruptor and metabolic diseases.
Korean Government (NRF-2016904200).
DOI: 10.1530/endoabs.49.GP143
DOI: 10.1530/endoabs.49.GP145
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP146
MetS rabbits, was significantly ameliorated by MET and completely normalized
by PhyEx. HFD determined a net reduction of electrical field (EF)-vasorelaxation
Psychological rather than organic and/or relational components are
in CC. The relaxant response to sildenafil, abolished in HFD rabbit CC, was
involved in sexual dysfunction in Young/Middle aged human
restored by PhyEx. PhyEx normalized sodium nitroprusside
(SNP)-induced
immunodeficiency virus (HIV)-Infected Men
relaxation, that was enhanced in MetS rabbits. Genes related to NO signaling
Maria Chiara Decaroli1, Sara De Vincentis1, Chiara Diazzi1, Stefano Zona2,
were up-regulated by PhyEx, but not by MET. Similar results were obtained for
Giovanni Guaraldi2, Daniele Santi1 & Vincenzo Rochira1
smooth muscle-related genes. PDE5 expression was decreased in MetS rabbits
1Unit of Endocrinology, University of Modena and Reggio Emilia, Modena,
and completely restored by PhyEx. Accordingly, sildenafil-induced increase in
Italy;2Unit of Infectious Diseases, University of Modena and Reggio
SNP relaxation was completely normalized by PhyEx.
Emilia, Modena, Italy.
In conclusion, PhyEx more than metformin, completely restored T levels and
responsiveness to Ach and sildenafil in experimental MetS, even though it was
Background
less effective than metformin in reducing metabolic abnormalities. The effect of
HIV-infection is associated to an increased prevalence of erectile dysfunction
exercise training is most probably related to an improved NO signaling, including
(ED). In HIV-infected men ED seems to be less related to serum Testosterone (T),
PDE5. Hence, PhyEx can be considered a new strategy to treat hypogonadism and
depending from other factors.
ED related to MetS.
Aim
DOI: 10.1530/endoabs.49.GP147
To investigate the role of different components (organic, relational, psycho-
logical) of erectile function by using validate questionnaires in HIV-infected men
with normal serum T.
Methodology
Prospective, cross-sectional, observational study on eugonadal HIV-infected male
patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the
Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15,
IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to
assess sexual function. Sexual desire was further evaluated through a direct question
during the visit. LC-MS/MS was used to assess gonadal status.
Results
225 HIV-infected patients were enrolled (mean age 45.19G5.36 years). SIEDY
scores at appendix and scale 3 were significantly higher in patients with ED at IIEF-
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15
(nZ136, 60.4%) compared with those without ED (P!0.001 and PZ0.015,
Impacts of a single ablative dose of radio iodine therapy for
respectively). Conversely, scale 1 (PZ0.448) and 2 (PZ0.503) of SIEDY did not
differentiated thyroid carcinoma on testicular function: results from
differ between patients with or without ED, suggesting a predominance of the
the SAPIRA study
psychological basis of ED in our cohort. The erectile function domain at IIEF-15
Nathalie Bourcigaux1, Carole Rubino2, Isabelle Berthaut3,
was directly correlated with IIEF-5 score (0.778, P!0.001). Similarly, the score at
Bruno Donadille2, Marie Elisabeth Toubert4, Laurence Leenhardt5,
SIEDY appendix was significantly different among ED degrees at IIEF-15
(P!0.001). In particular, lower score was found in HIV-infected men without ED
Catherine Corone6, Isabelle Petrot-Keller1, Sylvie Brailly-Tabard7,
compared to those with mild, moderate and severe ED (P!0.001, PZ0.001, and
Julie Beaufaron10, Tabassome Simon1, Jean-Pierre Siffroi8, Florent De
P!0.001, respectively), confirming the reliability of these tools. Sexual desire was
Vathaire2, Martin Sclumberger2, Philippe Bouchard9 & Sophie
impaired in 73 patients (31.33%) at interview with a good correlation with the
Christin-Maitre1
specific item of IIEF-15 (P!0.001).
1Hôpital St Antoine, Greater Paris University Hospitals, Paris, France;
Conclusions
2Institut Gustave Roussy, Villejuif, France;3Hôpital Tenon, Greater
The psychological component impacts in a significant manner on ED in HIV-
University Paris Hospitals, Paris, France;4Hôpital St Louis, Greater Paris
infection context. Despite the high prevalence of comorbidities in these patients, the
University Hospitals, Paris, France;5Hôpital Pitié Salpétrière, Greater Paris
organic component does not affect erectile function. All the three validated
University Hospitals, Paris, France;6Centre René Huguenin, St Cloud,
questionnaires seem to be trustworthy in the diagnosis of ED in this setting.
France;7Hôpital Le Kremlin-Bicêtre, Greater Paris University Hospitals, Le
Kremlin-Bicêtre, France;8Hôpital Armand Trousseau, Greater Paris
DOI: 10.1530/endoabs.49.GP146
University Hospitals, Paris, France;9Hôpital Foch, Suresnes, France;
10Cabinet Médical, Nouméa, New Caledonia.
Background
Radioactive iodine therapy (RAI) is a classical therapeutic approach in patients
with differentiated thyroid carcinoma (DCT). Few data are currently available on
RAI’s potential impacts on testicular function.
Design
A longitudinal prospective multi-center study (PHRC N8P040419) included male
patients before a single radioiodine dose of 3.7 GBq of I131 (V0), at 3 months
GP147
(V3) and 13 months (V13) post treatment.
Effects of physical exercise or metformin on testosterone deficiency and
Method and Patients
erectile dysfunction associated to metabolic syndrome
Hormonal assessments (FSH, LH, Testosterone, inhibin B) as well as sperm
Linda Vignozzi2,3, Sandra Filippi1, Paolo Comeglio2, Ilaria Cellai2,
parameters (number, mobility and morphology), DNA fragmentation and sperm
Francesca Corcetto2, Chiara Corno2 & Mario Maggi2,3
FISH analysis in order to detect chromosomal abnormalities were performed at
1Interdepartmental Laboratory of Functional and Cellular Pharmacology of
V0, V3 and V13.
Reproduction, Department of Neuroscience, Phychology, Drug Research
Results
and Child Care, University of Florence, Florence, Italy;2Sexual Medicine
Thirty six patients were included in the study. At V0, all patients had normal gonadal
and Andrology Unit, Department of Experimental and Clinical Biomedical
function. At V3, FSH median levels were significantly increased as compared to V0,
Sciences, University of Florence, Florence, Italy;3INBB, Rome, Italy.
respectively 9 UI/lG4.8 (N: 3-7 UI/l) versus 4 UI/lG3 (P!0.0001). Between V3 and
V13, FSH levels decreased but remained higher than baseline levels. Inhibin B median
Metabolic Syndrome (MetS) is a cluster of clinical conditions, associated to an
levels decreased significantly at V3 (P!0.0001) and returned to V0 levels at V13. LH
increased cardiovascular and metabolic risk, to hypogonadism and erectile
and T levels were not modified at V3 or V13.
dysfunction (ED). Lifestyle modification (including physical exercise, PhyEx)
Median sperm concentration significantly decreased at V3 as compared to V0 (20 vs 48
and metformin
(MET) are well-known treatments for the condition. We
million/ml; P!0.0001) and returned to V0 levels at V13. In parallel, a statistically
established an animal model of MetS that recapitulates the human phenotype,
significant decrease in sperm morphology was observed at V3. Sperm mobility and DNA
including andrologic derangements.
fragmentation were not modified after RAI. However sperm chromosomal abnormalities
The aim of this study was to investigate in experimental MetS the effect of PhyEx
were increased at V3 (P!0.0005) and V13 (P!0.01), as compared to V0.
or MET on penile erection and on hormonal and metabolic parameters.
Conclusion
Control (RD) and MetS rabbits were treated with MET (the last 18 days) or
In this prospective study, RAI transiently altered FSH, inhibin B and sperm number.
exercise-trained to run on a treadmill for 12 weeks. Penile tissue was collected for
Furthermore, chromosomal abnormalities observed at V3 were found to persist 13
in vitro contractility study or gene expression.
months after RAI. Therefore, our study illustrates that counseling about fertility could
MET, but not PhyEx, induced a reduction in visceral adiposity, blood pressure,
be interesting in male patients with DCT treated by a single dose of radioiodine.
triglycerides, glucose level and tolerance. MET increased testosterone
(T),
DOI: 10.1530/endoabs.49.GP148
whereas PhyEx completely restored it. Ach-induced relaxation, hampered in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP149
Levels of follicle stimulating hormone were unchanged 2.3 (1.4-4.4) vs 2.2 (1.5-
3.3) U/l (PZ0.47). There were no differences on semen volume 3.0 (1.5-5.0) vs
Presentation, clinical features and long-term follow-up of Leydig cell
3.2
(2.3-4.3) ml (PZ0.33), sperm concentration 35 (6-62) vs 43 (22-73) mill/ml
tumours of the testis: 77 cases from a single center experience
(PZ0.1), or total sperm counts 102 (8-236) vs 136 (65-235) mill (PZ0.09).
Andrea M. Isidori, Vincenzo Giannetta, Daniele Gianfrilli, Rosa Lauretta,
Forty-seven percent of patients and 77% of controls had normal semen quality,
Maria Grazia Tarsitano, Giorgio Fattorini, Riccardo Pofi, Carlotta Pozza &
WHO criteria (volume O1.5 ml, concentrationO15 mill/ml and AB-motile
Andrea Lenzi
spermO42%) (PZ0.001). Three had azoospermia. Testicular size was
unchanged 18 (13-25) vs 20 (19-25) ml (PZ0.46).
Conclusion
Introduction
Patients with acquired pituitary insufficiency had reduced semen quality,
With the improved imaging techniques, Leydig cell tumours
(LCTs) are
supporting the need for early cryopreservation of semen in this group of patients.
frequently found, accounting up to
22% of testicular tumours. The natural
However, despite severe Leydig cell insufficiency almost half of patients had
history of LCTs is relatively unknown, because of the small size and
normal semen quality based on determination of three variables. This finding is in
heterogeneity of available studies. Since LCTs are often removed, long-term
contrast to men with hypergonadotrpic hypogonadism where spermatogenesis is
follow-up is missing. The aim of this study was to report the experience with a
often severely compromised before Leydig cell insufficiency occurs.
large cohort of prospectively collected LCTs.
DOI: 10.1530/endoabs.49.GP150
Materials and methods
Patients with LCTs were enrolled from 2005 to 2016. Clinical and biochemical
features of LCTs were compared with two matched cohorts: patients with
seminomas and patients without testicular lesions (noL) randomly selected among
patients referred in the same period.
Results
Neuroendocrinology & Growth Hormones
77 patients had LCTs, 90 had seminomas, and 1420 had no lesion (noL). Groups
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were matched for age and BMI. Infertility was the reason for referral in more than
Growth hormone-releasing hormone (GHRH) antagonists, MIA-602
half of LCTs. Testicular volumes (PZ0.002), sperm concentration (PZ0.001)
and MIA-690, inhibit survival and proliferation of human pleural
and morphology (P!0.001) were significantly lower in LCTs compared to noL;
mesothelioma cells
gonadotropins were higher (P!0.001) and testosterone was lower (PZ0.008) in
Tania Villanova1, Iacopo Gesmundo1, Marina Taliano1, Ezio Ghigo1,
LCTs vs noL. No differences were found in gonadal steroid after hCG test,
Andrew V Schally2,3 & Riccarda Granata1
between groups. When compared to seminomas, LCTs did not show differences
1Division of Endocrinology, Diabetology and Metabolism, Department of
in hormonal status except for higher SHBG levels (PZ0.028), LH/Te ratio
Medical Sciences, University of Torino, Torino, Italy;2Endocrine,
(P!0.001), and lower sperm concentration (PZ0.04). LCTs lesions were smaller
Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Miami,
compared to Sem (P!0.001). Cryptorchidism
(c2Z45.658 P!0.001) and
Florida, USA;3Department of Pathology and Department of Medicine,
gynecomastia (c2Z54.923, P!0.001) were associated with a higher risk of
Divisions of Hematology, Oncology and Endocrinology, University of
LCTs. After a median follow-up of 32.5 months, no metastases have been
Miami Miller School of Medicine, Miami, Florida, USA.
detected. Non-operated LCTs developed subclinical hypogonadism (PZ0.018)
compared to surgically removed LCTs.
Conclusions
Human malignant pleural mesothelioma
(MPM) is a rare but aggressive
LCTs have a good prognosis when correctly recognized. Based on the largest
neoplasm, arising from pleural mesothelial cells, generally due to asbestos
existing series, we showed that infertility, gynecomastia,low testicular volume,
exposure. Different growth factors are involved in the pathogenesis of MPM and
and cryptorchidism are frequently associated with LCTs, supporting the
in resistance to therapy; moreover, chemotherapy with cisplatin and antifolates,
hypothesis that testicular dysgenesis syndrome could play a role. Active
like pemetrexed (PEM), is the first-line treatment for inoperable MPM. Growth
surveillance, as an alternative to surgical removal, appears to be a safe option,
hormone-releasing hormone (GHRH), apart from stimulating GH secretion in the
but monitoring of Leydig cell failure remains necessary.
pituitary, exerts many extrapituitary functions, including stimulation of cell
DOI: 10.1530/endoabs.49.GP149
proliferation and survival. GHRH and GHRH receptor (GHRH-R) are expressed
in different cancer cell types, where they modulate their proliferative effects.
Moreover, GHRH-R antagonists were found to inhibit the proliferation of
different cancer cells in vitro and in vivo; however, the role of GHRH antagonists
in MPM remains unknown. Thus, in the present study, we investigated the effects
of the GHRH antagonists MIA-602 and MIA-690 on survival, proliferation and
apoptosis of human MPM cells. Our results show that MIA-602 and MIA-690
GP150
reduce survival and proliferation of MSTO-211H
(biphasic) and REN
(epithelioid) MPM cells, but have no effect in MeT-5A (human non-malignant
Semen quality in patients with adult-onset hypogonadotropic
mesothelial cells). Moreover, MIA-602 and MIA-690 promoted apoptosis and
hypogonadism
reduced the expression of the antiapoptotic protein Bcl-2 in MSTO-211H and
Mikkel Andreassen1, Anders Juul2, Ulla Feldt-Rasmussen1 &
REN cells. Cell cycle analysis of REN cells treated with GHRH antagonists
Niels Jørgensen2
showed an increase in the Sub-G1 apoptotic phase and a decrease in the G2 pre-
1Department of Endocrinology, Rigshospitalet, Faculty of Health Science,
mitotic phase. Furthermore, MIA-602 and MIA-690 inhibited cell migration in
University of Copenhagen, Copenhagen, Denmark;2Department of Growth
REN cells and increased the cytotoxic action of PEM in both MPM cell lines.
and Reproduction Rigshospitalet, Faculty of Health Science, University of
These results suggest a novel therapeutic role for GHRH antagonists in the
Copenhagen, Copenhagen, Denmark.
treatment of MPM, alone or in combination with standard therapies, by reducing
the chemotherapy doses and their associated side effects.
Introduction
DOI: 10.1530/endoabs.49.GP151
Gonadotropins from the pituitary gland are essential for testosterone production
and spermatogenesis. However, little is known about semen quality in patients
with adult onset gonadotropin insufficiency.
Aim
To investigate semen quality in men with adult onset hypogonadotropic
hypogonadism requiring testosterone replacement therapy.
GP152
Patients and method
Somapacitan expected to provide IGF-I levels suitable for once-weekly
A single center study comprising all hypogonadal men with pituitary disease (year
dosing in children
2003-2016, nZ28, (median(IQR) 30 (27-37) years), who accepted cryopreserva-
Rasmus Juul, Michael Rasmussen, Henrik Agersø & Rune Overgaard
tion of semen before initiation of testosterone therapy. On the day semen samples
Novo Nordisk A/S, Bagsvaerd, Copenhagen, Denmark.
were cryopreserved, reproductive hormone levels were measured. Semen
parameters, hormone levels and size of testicles were compared to those of
young men (nZ340, 19 (18-20) years) from the general population.
Somapacitan is a long-acting growth hormone (GH) intended for once-weekly
Results
subcutaneous administration. As for GH, the mechanism of action of somapacitan
Patients vs controls had lower serum testosterone 5.6 (3.5-7.8) vs 19.7 (15.5-
is either directly or indirectly via insulin-like growth factor I (IGF-I). A PK/PD
24.5) nmol/l (P!0.001), free testosterone index 33.3 (18.1-55.1) vs 73.7 (57.8-
model of somapacitan was developed from the pharmacokinetics (PK) and IGF-I
91.7)
(P!0.001), luteinizing hormone
1.5
(1.1-2.1) vs
3.1
(2.3-4.0) U/l
levels from three phase 1 trials data: a single dose/multiple dose trial (0.02-
(P!0.001), and inhibin-B 142 (126-187) vs 229 (176-285) ng/l (P!0.001).
0.24 mg/kg per week) in healthy adults, a multiple dose trial in adults with growth
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
hormone deficiency [GHD] (0.02-0.12 mg/kg perweek) and a single dose trial in
GP154
children with GHD (0.02-0.16 mg/kg). Somapacitan exposure-response was
The effect of chronic hypothalamic-pituitary-adrenal axis activation on
described with a non-linear relationship between dose and exposure and a delay in
hypothalamic glucagon-like peptide-1 action in an animal model of
response observed between Cmax PK and Cmax IGF-I. Somapacitan PK levels and
depression and in vitro studies
IGF-I response was found to correlate to body weight bridging exposure and
Jan Detka, Anna Kurek, Mateusz Kucharczyk, Joanna Slusarczyk,
response between children and adults. The PK/PD model was based on goodness
Katarzyna Glombik, Wladyslaw Lason & Boguslawa Budziszewska
of fit judged adequate to describe somapacitan exposure and IGF-I levels and
Department of Experimental Neuroendocrinology, Institute of
simulate the expected IGF-I profiles after multiple doses in children. Descriptive
Pharmacology, Polish Academy of Sciences, 12 Smętna Street,
IGF-I exposure-response analysis of single dose data in GHD paediatric patients
31-343, Cracow, Poland.
indicated that the dose range
0.04-0.16 mg/kg provided change in IGF-I
comparable to daily hGH. Based on the PK/PD model of somapacitan, once-
weekly dosing of 0.04 mg/kg per week are expected to provide Cmax IGF-I levels
Hypersensitivity of hypothalamic-pituitary-adrenal (HPA) axis is considered to
that match the average daily human GH (hGH) treatment; 0.08 mg/kg per week
be an important factor in the pathogenesis of depression. Interestingly, glucagon-
are expected to provide Cavg IGF-I levels that match the average daily hGH
like peptide-1 (GLP-1) - an incretin hormone involved in the maintenance of
treatment; and 0.16 mg/kg per week are expected to provide higher IGF-I levels
glucose homeostasis in the periphery is known to activate HPA axis. The aim of
than with daily hGH, with average concentrations not exceeding C2 SDS. In
the present study was to investigate whether prenatal stress (an animal model of
conclusion, the PK/PD of somapacitan is well characterised in adults and children
depression) may influence levels of GLP-1 and GLP-1 receptor (GLP-1R) in the
in GHD in support of once-weekly dosing.
hypothalamus. Since prenatal stress may not change the level of the investigated
DOI: 10.1530/endoabs.49.GP152
factors in basal conditions, but may change the response to adverse factors in the
adulthood, our studies were also conducted on animals subjected to acute stress
and oral glucose administration (1 g/kg). In parallel in order to study the direct
influence of GLP-1 receptor agonists on the activity of corticotropin-releasing
hormone (CRH) promoter gene, a hypothalamic cell line mHypoA-2/12 was
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stably transfected with plasmid DNA containing the sequence (from K663 to
Evaluating CHARGE syndrome in CHD7-positive CHH patients:
C124 bp) of human CRH promoter gene conjugated with luciferase reporter
clinical implications
gene. The cells were treated with GLP-1 and exendin-4 (20 and 200 nM) for 6, 24
Cheng Xu1, Daniele Cassatella1, Almer van der Sloot2, Michael Hauschild1,
and 48 h. The amount of GLP-1 in the hypothalamus was not altered by prenatal
Richard Quinton3, Christian De Geyter4, Christa Fluck5, Katrin Feller5,
stress in basal conditions, however it was significantly lower in a group subjected
Deborah Bartholdi5, Attila Nemeth6, Irene Halperin7, Sandra
to acute stress. Prenatal stress and glucose loading significantly decreased the
Pekic Djurdjevic8, Georgios Papadakis1, Andrew Dwyer9, Laura Marino1,
concentration of GLP-1R in the hypothalamus. Obtained results suggest that
Duarte Pignatelli10, Carol Huang11, Nicolas Niederlander1, James Acierno1
attenuated central incretin hormone signaling may contribute to metabolic
& Nelly Pitteloud1
disturbances, evident in depression. In contrast, transfected mHypoA-2/12 cells
1Lausanne University Hospital, Lausanne, Switzerland;2Institute for
treated with selected GLP-1R agonists displayed no significant differences in
Research in Immunology and Cancer, Quebec, Montreal, Canada;3Institute
reporter gene activity, which may suggest that GLP-1R activation does not
for Genetic Medicine, University of Newcastle-on-Tyne, Newcastle-on
stimulate CRH expression in this experimental model.
Acknowledgments
Tyne, UK;4University Hospital, University of Basel, Basel, Switzerland;
This work was supported by the Operating Program of Innovative Economy 2007-
5Inselspital, Bern, Switzerland;6St John’s Hospital, Budapest, Hungary;
2013, grant No. POIG.01.01.02-12-004/09 and grant 2012/07/N/NZ7/04394;
7Hospital Clínic, Universitat de Barcelona, Barcelona, Spain;8Institute of
National Science Centre, Poland
Endocrinology, University Clinical Center, Belgrade, Serbia;9University of
Lausanne, Lausanne, Switzerland;10Faculty of Medicine of the University
DOI: 10.1530/endoabs.49.GP154
of Porto, Porto, Portugal;11Alberta Children’s Hospital, Calgary, Canada.
Context
Congenital hypogonadotropic hypogonadism (CHH) and CHARGE syndrome are
clinically and genetically overlapping syndromes, with mutations in the CHD7
GP155
gene presenting in both disorders. However systematic evaluation of CHARGE
A novel purified polyclonal antibody towards T-Pit is a reliable marker
features in CHD7-positive CHH patients is seldom performed.
of corticotroph cell differentiation
Objective
Evelina Sjostedt1, Jens Bollerslev3,4, Fredrik Pontén1,2 &
This study aims to systematically evaluate CHARGE features in CHD7-positive
Olivera Casar-Borota1,2
patients and explore the phenotype-genotype correlation.
1Department of Immunology, Genetics and Pathology, Uppsala University,
Design
Uppsala, Sweden;2Department of Clinical Pathology, Uppsala University
Whole exome sequencing was performed on 130 CHH probands to identify
Hospital, Uppsala, Sweden;3Department of Specialized Endocrinology,
mutations in 24 CHH genes, including CHD7. Putative mutations were defined as
Rikshospitalet, Oslo University Hospital, Oslo, Norway;4Faculty of
rare sequence variants (RSVs, minor allele frequency !1%) that were either
Medicine, University of Oslo, Oslo, Norway.
protein-truncating variants
(PTVs) or missense variants predicted to be
deleterious by SIFT and/or PolyPhen2. Missense mutations were also evaluated
using Bergman criteria, integrating computational algorithms, population and
Classification of pituitary neuroendocrine tumours (NETs) or pituitary adenomas
segregation data
(Bergman, Human Mutation,
2012). CHD7-positive CHH
is based on the expression of the anterior lobe pituitary hormones (FSH, LH, GH,
patients were evaluated for CHARGE features.
Prolactin, TSH, ACTH and alpha-subunit of the glycoprotein hormones).
Results
Assessment of the transcription factors SF-1, Pit-1
and T-Pit has been a
We identified 16 CHH patients harboring heterozygous mutations (two PTVs and 14
complement to the classification. Tumours negative for both pituitary hormones
missense), of whom 14 were available for re-evaluation. After detailed phenotyping,
and transcription factors have been designated as null-cell adenomas. However,
three probands (one PTV and two missense) were re-classified as CHARGE
lack of sensitive and specific antibodies towards T-Pit has presented difficulties
syndrome. Four probands with missense mutations present additional CHARGE
for the inclusion of these transcription factors into the classification system of
features, while the remaining seven probands exhibit no additional CHARGE feature
pituitary endocrine tumours. Here, we present a novel purified polyclonal
(one PTV and six missense). Both the missense mutations underlying CHARGE
antibody (HPA072686) towards T-Pit and demonstrate its high sensitivity and
syndrome were categorized as pathogenic using Bergman criteria, while the other
specificity for immunohistochemistry-based identification of the cells with
missense mutations were classified as either benign or of unknown significance. Of
corticotroph differentiation. In an immunohistochemical study of a large cohort of
note, 3/4 CHH patients with additional CHARGE features also had mutations in other
pituitary adenomas of different types from
246 patients, a distinct nuclear
CHH genes, contributing to the variable expressivity.
expression of T-Pit was demonstrated in all ACTH-immunolabelled tumours,
Conclusions
silent and clinically functioning, as well as in a proportion of tumours previously
50% of CHD7-positive CHH patients exhibit additional CHARGE features, with
diagnosed as null-cell adenomas. None of the tumours that were immunoreactive
21% meeting the clinical diagnosis of CHARGE syndrome. While the Bergman
for Pit-1, SF-1 or pituitary hormones, other than ACTH, expressed T-Pit. We
criteria accurately predict the most severe mutations resulting in CHARGE
expect that the availability of a reliable T-Pit antibody as a marker of corticotroph
syndrome, it is unable to distinguish isolated CHH from CHH with additional
cell differentiation will contribute to: i) more precise classification of pituitary
CHARGE features. The results of this study have diagnostic and genetic counseling
neuroendocrine tumours, particularly, those with sparse or no hormone
implications for CHD7-positive CHH patients.
expression, ii) better identification of silent corticotroph tumours that may have
DOI: 10.1530/endoabs.49.GP153
more aggressive clinical behaviour than silent gonadotroph tumours, and which
are at the moment difficult to identify in cases with sparse or no ACTH
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
expression, iii) more cost effective immunohistochemical screening of pituitary
DI onset risk (RR 0.264 (0.132; 0.53), PZ0.02). Patients with corticotropinomas
tumours based primarily on the use of the three transcription factors and iv)
and somatotropinomas had higher risk of transient and three-phased DI (RR 0.212
identification of potential corticotroph cell differentiation in non-pituitary NETs.
(0.061; 0.734), PZ0.02, RR 0.459 (0.311; 0.677), PZ0.04, for corticotropino-
DOI: 10.1530/endoabs.49.GP155
mas, respectively; RR 4.559 (1.049; 19.813), PZ0.03, RR 1.977 (1.033; 3.783),
PZ0.07 for somatotropinomas, respectively). Macroadenoma also increased risk
of transient and three-phased DI (RR 5.739 (1.32; 24.962), PZ0.01, RR 2.593
(1.357; 4.955), PZ0.02, respectively).
Conclusions
ACTH- and GH-secreting adenomas, macroadeomas and postoperative adrenal
GP156
insufficiency can be considered as predictors of transient and three-phased
Liraglutide treatment prevented the increased expression of
diabetes insipidus. Panhypopituitarism can be considered as predictor of
proinflammatory cytokines in the hippocampus of male pups in a
permanent diabetes insipidus.
perinatal stress model of food restriction
DOI: 10.1530/endoabs.49.GP157
Yolanda Diz-Chaves1, Laura Toba1, Juan Fandin˜o1, Lucas
González-Matías1, Luis Miguel Garcia-Segura2 & Federico Mallo1
1University of Vigo, CINBIO, Vigo, Spain;2CSIC, Instituto Cajal, Madrid,
Spain.
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Adverse events during gestation in rodents, results in an enhancement of immune
The effect of chronic tianeptine administration on NLRP3
function, including elevated levels of inflammatory cytokines in the brain.
inflammasome pathway - study in an animal model of depression
Liraglutide is a GLP-1 receptor agonists known to exert neuroprotective effects in
Ewa Trojan, Anna Kurek, Katarzyna Chamera, Joanna Slusarczyk,
brain. The aim of this study was to elucidate if liraglutide given to food restricted
Katarzyna Glombik & Agnieszka Basta-Kaim
(FR) pregnant rats may prevent the deleterious effects of FR in the hippocampal
Department of Experimental Neuroendocrinology, Institute of
inflammatory status of male and female pups at 21 days of age (D21). 20 Sprague-
Pharmacology PAS, Cracow, Poland.
Dawley pregnant rats were included. Controls (CT) were fed ad libitum, whereas
dams in restricted group were fed with 50% (50FR) daily intake of control dams.
Pregnant rats were treated with liraglutide
(100 mg/kg per 12 h; 50FR/LIR,
Introduction
CT/LIR) or vehicle (50FR/VEH, CT/VEH) from gestational day 14 to 21. During
Recently, the immune hypothesis of depression has gained a new dimension
lactation FR was increased to 30%. At D21 and before weaning, pups were
because of inflammasomes. NLRP3 inflammasome is a protein complex and its
sacrificed. The hippocampi were obtained and stored at K80 8C until analysis.
activation leads to stimulation of the enzyme caspase 1 responsible for generation
mRNA expression levels of IL1b, IL6,NFKb,IL 10 and Arginase1 in the
of active form of pro-inflammatory cytokines: IL-1
b and IL-18. Recently
hippocampus were assessed by RT-PCR. Immunohistochemistry analysis for Iba1
postulated ‘inflammasome theory of depression’ assumes that depression is based
(marker of microglia) was performed in dentate gyrus (DG). The FR-mothers
on a disturbance of the mechanisms regulating NLRP3
complexes and
model promoted a proinflammatory state in the hippocampus just in male but not
uncontrolled synthesis of IL-1b.
in female pups. 50FR male rats displayed increased mRNA expression of IL1b,
Aim
IL6
and NFKb compared to control males. LIR treatment decreased the
The aim of present study was to examine whether prenatal stress influence the
expression of these cytokines and increased IL6 in control males. Furthermore,
inflammasome NLRP3 system (subunits: NLR, ASC, protease caspase-1) in the
LIRA treatment increased the anti-inflammatory cytokine IL10 in 50FR male and
frontal cortex and hippocampus of adult rats offspring. Furthermore the impact of
CT female rats and the mRNA expression of the arginase1 (marker of microglia
chronic antidepressant drug - tianeptine administration on the above-mentioned
M2-like phenotype) in 50FR male rats. The number of IBA1 immunopositive
parameters were evaluated.
cells were increased in the DG of 50FR males compared to controls, and were
Methods
reduced by the treatment with LIRA. In conclusion, LIRA prevents the
Pregnant rats were subjected to restraint stress. At 3 months of age, control and
proinflammatory status induced by FR of the mother in male pups and enhanced
prenatally stressed rats were tested for behavioural changes in forced swimming
anti-inflammatory markers.
test. After that male offspring were administered i.p. for 14 days with tianeptine or
DOI: 10.1530/endoabs.49.GP156
vehicle. The animals’ behaviour were tested again and rats were sacrificed. The
protein level of all NLRP3 inflammasome subunits was determined by Western
blot analyses.
Result
Prenatal stress procedure cause long-lasting behavioral alterations expressed as an
increase in immobility and a decrease in swimming and climbing time measured
GP157
in the forced swim test. Chronic treatment of tianeptine normalized all above-
Predictors of permanent, transient and three-phase postoperative
mentioned changes in prenatally stressed offspring. Prenatal stress procedure
diabetes insipidus
increased concentration of all NLRP3 subunits in frontal cortex. In hippocampus
Daria Mikhaylova, Larisa Dzeranova, Ekaterina Pigarova,
prenatal stress affected caspase-1 levels but had no effect on the other NLRP3
Ludmila Rozhinskaya, Andrey Grigoriev, Vilen Azizyan &
inflammasome subunits. Chronic tianeptine treatment attenuated all evoked by
Oksana Ivashenko
stress changes.
Endocrinology Research Centre, Moscow, Russia.
Conclusion
Prenatal stress procedure leads not only to persistent behavioral disturbances but
also malfunction in brain NLRP3 inflammasone pathway. NLRP3 pathway can be
Objectives
indicate as an potential attractive target for antidepressant drug action.
To evaluate predictors of permanent, transient and three-phase diabetes insipidus
Acknowledgement
(DI) in patients undergoing endoscopic endonasal transsphenoidal surgery.
Supported by the grant no. 2015/17/N/NZ7/00924.
Patients and methods
DOI: 10.1530/endoabs.49.GP158
The study included 154 patients undergoing endoscopic endonasal transsphenoi-
dal surgery (122 women and 32 men) age from 18 to 65 years (median 40 (31;52)).
73 patients with Cushing disease, 66 patients with acromegaly, four patients with
prolactinomas, nine patients with non-functioning pituitary adenomas, one patient
with thyrotropinoma, one patient with Nelson’s syndrome and three patients with
multihormonal secreting adenomas we examined. Patients were monitored for
GP159
hormones, balance of fluids, serum electrolytes, plasma and urine osmolality.
Pituitary androgen receptor signalling is a novel negative regulator of
Results
prolactin production
Postoperative permanent DI occurred in 27 patients, among them four as three-
Laura O’Hara, Paul Le Tissier & Lee Smith
phased disturbances. Transient DI occurred in 42 patients, among them nine as
University of Edinburgh, Edinburgh, UK.
three-phased disturbances. Onset arised on the 1th day-2nd month after surgery
(median 1 day (1;5)) for the permanent DI’s and on the 1th day-4th month for
transient DI’s (median 1 day (1;5)). Duration for transient DI was 1 day-1 year
The classical paradigm of lactotroph prolactin production and release is based
and 3 month (median 2 (1;30)), in 38% patients transient DI occurred as single
around tonic inhibition by hypothalamic dopamine and stimulation by factors
polyuria-polydipsia episode. Adrenal insufficiency incrised risk of transient and
such as estrogen. We have recently shown that conditional ablation of pituitary
three-phased DI development (RR 0.516 (0.287; 0.927), PZ0.02, RR 0.056
androgen receptor
(Foxg1-Cre ARKO) surprisingly does not change the
(0.008; 0.42), PZ0.0003, respectively), panhypopituitarism increased permanent
concentration of circulating gonadotrophins but increases circulating prolactin
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
in male mice; highlighting androgen signalling as a novel negative regulator of
vs 639, PZ0.043; nZ22). Postoperative normalization of plasma ACTH was
prolactin production. We aimed to refine our knowledge of the site and
reached more frequently in patients with WT tumors (4/12, 33% vs 1/10, 10%) but
mechanism of action of this control by performing further genetic, pharma-
without statistical significance
(PZ0.323). No differences were observed in
cological and surgical experiments to ablate the production and/or action of
tumor control after surgery.
prolactin and/or androgens. Male mice with a genetic ablation of AR in neurons
Conclusion
(Nestin-Cre ARKO) do not have an increase in circulating prolactin, confirming
Somatic mutations in the USP8 gene are common in Nelson’s syndrome and may
that the increase in prolactin seen in the Foxg1-Cre ARKO mouse is not due to
be related to a more severe hormonal phenotype.
loss of hypothalamic AR, but specifically pituitary AR. However, Foxg1-Cre
DOI: 10.1530/endoabs.49.GP160
ARKO mice treated with the dopamine agonist bromocriptine show a decrease in
circulating prolactin levels suggesting that the mechanism of prolactin increase
originates with the hypothalamic dopamine system that normally controls
prolactin. Male mice with postnatal AR ablation in w50% lactotrophs (Prolactin-
Cre ARKO) do not show an increase in circulating prolactin, suggesting that
Obesity
either the mechanism is not lactotroph-specific or that ablation of AR needs to
GP161
occur earlier or in a greater number of lactotrophs to result in an increase in
circulating prolactin. Mice castrated in adulthood do not show an increase in
The association between olfaction and taste functions with serum
circulating prolactin which suggests that the control mechanism is not an acute
ghrelin and leptin levels in obese women
response to changes in androgens but is programmed during the pre-adult
Burçin Uygun1, Sinem Kiyici1, Suay Ozmen2, Zulfiye Gul3, Deniz Sigirli4 &
development of the pituitary. Further experiments are currently being undertaken
Sinan Cavun3
to ablate AR in other pituitary cell populations and at earlier time points with the
1University of Health Sciences, Bursa Yuksek Ihtisas Education and
aim of pinpointing the spatio-temporal mechanism of control of prolactin
Training Hospital, Department of Endocrinology and Metabolism, Bursa,
production by androgen receptor signalling.
Turkey;2University of Health Sciences, Bursa Yuksek Ihtisas Education
and Training Hospital, Department of Otorhinolaryngology, Bursa, Turkey;
DOI: 10.1530/endoabs.49.GP159
3Uludag University Medical Faculty, Department of Pharmacology, Bursa,
Turkey;4Uludag University Medical Faculty, Department of Bio-statistics,
Bursa, Turkey.
GP160
Aim
Somatic mutations in USP8 are frequent events in pituitary tumors
Olfaction and gustation have great importance on feeding behavior and food
causing Nelson’s syndrome
preferences. Recent published data suggests that olfaction and taste functions are
Luis G Perez-Rivas1, Marily Theodoropoulou1,2, Troy H Puar3, Julia Fazel1,
modulated in response to changing levels of various molecules such as ghrelin and
Mareike R Stieg2, Francesco Ferraù4, Guillaume Assié5, Monica
leptin which are play important roles on feeding and energy balance. We aimed to
R Gadelha6, Timo Deutschbein7, Maria C Fragoso8, Benno Kusters9,
investigate the olfaction and taste functions in obese female patients and the
Márta Korbonits4, Jérôme Bertherat5, Gunter K Stalla2, Ad R Hermus3,
association between serum ghrelin and leptin levels compared with healthy controls.
Felix Beuschlein1 & Martin Reincke1
Methods
1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat
Fifty two obese women who have body mass index O30 kg/m2 and 15 healthy
Munchen, Munich, Germany;2Department of Clinical Neuroendocrinology,
women were included in to the study. After 8 h of fasting, blood samples were taken
Max Planck Institute of Psychiatry, Munich, Germany;3Department of
for serum biochemical parameters, ghrelin and leptin levels measurement. For the
Internal Medicine, Division of Endocrinology, Radboud University Medical
quantitative assessment of olfactory function, all participants underwent on
Centre, Nijmegen, The Netherlands;4Centre for Endocrinology, William
N-butanol threshold test and odor identification test by using 12 Sniffin’ Sticks
Harvey Research Institute, Barts and The London School of Medicine and
ready-made fragrance sticks. The gustatory function was tested by administering a
Dentistry, Queen Mary University of London, London, UK;5Inserm Unité
whole-mouth above-threshold test using sucrose solutions.
1016, Centre National de la Recherche Scientifique Unité Mixte de
Results
Recherche, Institut Cochin, Université Paris Descartes, Paris, France;
The sucrose taste threshold score in obese women was significantly higher than the
6Division of Endocrinology, Hospital Universitário Clementino Fraga Filho,
controls (PZ0.004). N-butanol smell threshold was not significantly different between
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;7Division of
the two groups (PZ0.149) while the Sniffin’ Sticks smell test scores were significantly
Endocrinology and Diabetology, Department of Internal Medicine,
lower in obese women compared with the controls (PZ0.007). Serum leptin levels were
Universitatsklinikum Wurzburg, University of Wurzburg, Wurzburg,
also significantly higher in obese women (P!0.001) although there was no significant
Germany;8Unidade de Neuroendocrinologia, Laboratório de Hormônios e
difference in serum ghrelin levels between the two groups (PZ0.768).
Genética Molecular/LIM42, Disciplina de Endocrinologia e Metabologia,
Conclusion
Hospital das Clínicas da Faculdade de Medicina da Universidade de São P,
No significant association was observed between olfaction and taste functions and
Sa˜o Paulo, Brazil;9Department of Pathology, Radboud University Medical
serum ghrelin levels of obese individuals. It was found that serum leptin levels were
Centre, Nijmegen, The Netherlands.
increased while taste and smell functions were decreased in obese women. These
results might suggest that leptin, which is an anorexigenic peptide, may have a
negative effect on taste and smell functions.
Recent studies have reported a high prevalence of USP8 mutations in corticotroph
adenomas causing Cushing’s disease. Nelson’s syndrome is a potentially life-
DOI: 10.1530/endoabs.49.GP161
threatening complication of bilateral adrenalectomy in patients with refractory
Cushing’s disease that is caused by the development of an ACTH-secreting tumor
in the pituitary gland. Whether USP8 alterations are also present in Nelson’s
tumors has not been studied in detail so far.
GP162
Methods
Sarcopenic obesity and associated factors in older adults with diabetes: the
We have screened for mutations in the exon 14 of USP8 in tumors from 32
2009-2010 Korean National Health and Nutrition Examination Survey
patients who were diagnosed with Nelson’s syndrome (28 females, four males).
Jin Hwa Kim1, Hee Jung Ahn1, Tae Young Yang2 & Sang Yong Kim1
Genomic DNA was extracted from fresh-frozen or FFPE adenomas. The presence
1Chosun University Hospital, Gwangju, Republic of Korea;2Teayoung21
of mutations was analyzed by Sanger sequencing. Mutational status was
Hospital, Gwangju, Republic of Korea.
correlated to clinical data.
Results
In our cohort, 15/32 tumors presented a mutation in the exon 14 of USP8, a
Objective
prevalence similar to that reported in Cushing’s disease, with c.2159COA
Sarcopenic obesity is a double burden for older people because it carries the cumulative
(p.Pro720Gln) being the most frequent (8/32), followed by c.2155_2157delTCC
risk of functional abnormality, metabolic, cardiovascular risk, and mortality compared
(p.Ser718del, 4/32) and c.2152TOC (p.Ser718Pro, 3/32). Two USP8 WT cases
to either sarcopenia or obesity alone. Diabetes is related to an increase in visceral
were categorized as atypical pituitary tumors and excluded from subsequent
adiposity and is associated with the risk of sarcopenia. The objective was to explore the
analyses. Mutations were found exclusively in females (15/27, 55%; vs 0/3 males).
association between sarcopenic obesity and diabetes and determine the associated
Other variables, such as age at diagnosis of Nelson’s syndrome, BMI,
factors with sarcopenic obesity in older people with diabetes.
hyperpigmentation, visual field defects, adenoma size or mortality did not
Research design and methods
significantly differ between patients with WT and mutant tumors. Regarding the
This study was based on data from the Korean National Health and Nutrition
hormonal status, patients with mutant tumors tended to exhibit higher levels of
Examination Survey (KNHANES), conducted by the Korean Ministry of Health and
plasma ACTH at time of Nelson’s diagnosis (median WT 1335 pg/ml vs mutant
Welfare, from 2009 to 2010. Out of 19,491 participants, the analysis included data for
1668 pg/ml; PZ0.098; nZ25) and significant changes after surgery (median 131
3,206 older people. Multivariate logistic regression analyses were used to identify
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
independent associated factors with sarcopenic obesity. The complex sample analysis
Obesity is one of the major causes of morbidity and mortality worldwide and is
was used for the KNHANES data for weighting all values following the guidance of
considered a risk factor for metabolic syndrome, type
2
diabetes and
statistics form the Korea Centers for Disease Control and Prevention.
cardiovascular disease
(CVD). miRNAs are epigenetic regulators of several
Results
aspects of metabolism and energy homeostasis and are involved in obesity and
The Prevalence of nonsarcopenic nonobesity, nonsarcopenic obesity, sarcopenic
regulation of insulin sensitivity. miR 26b is among the obesity-related micoRNAs
nonobesity, and sarcopenic obesity were 43.2, 7.7, 23.5 and 25.6%, respectively, in
and is differentially expressed in preadipocytes and mature adipocytes in humans
all subjects. The prevalence of sarcopenic obesity in older people with diabetes was
and is upregulated during adipocyte maturation. Visfatin which is implicated in
significantly higher than those without diabetes (33.9% vs. 23.4%, P-value !0.001).
insulin resistance and metabolic syndrome is a target of miR-26b. The aim of this
Diabetes was an independent associated factor with sarcopenic obesity after fully
study was to investigate the levels of miR-26b levels in obesity and its association
adjusting for confounding factors, including chronic disease, sociodemographic
with insulin resistance and metabolic parameters.
influences, and lifestyle. Among the older people with diabetes, undiagnosed
Methods
diabetes, diabetes duration with more than 10 years, elevated diastolic blood
Seventy children and adolescents (35 controls; 35 obese), between the ages of 8
pressure, known hypertension, increased intake of protein, and number of
and 18 years, were selected and clinically evaluated. The expression of miR-26b
comorbidity were independent associated factors with higher risk of sarcopenic
was measured after microRNA extraction from plasma samples. The extracted
obesity. History of stroke and increased vitamin D level were independently
microRNAs were elongated using poly A polymerase reaction followed by cDNA
associated with a lower risk of sarcopenic obesity.
synthesis. Real-time PCR was performed using SYBR green and delta Ct was
Conclusion
calculated by the formula: Ct (reference gene)-Ct (target gene). miR-16 was used
Diabetes influenced the risk of sarcopenic obesity in older people. Undiagnosed
as the reference gene. Insulin and visfatin levels were measured using ELISA, and
diabetes, diabetes duration with more than 10 years, elevated diastolic blood
insulin resistance was calculated by the homeostasis model of assessment of
pressure, known hypertension, increased intake of protein, number of comorbidity,
insulin resistance
(HOMA-IR). Fasting plasma glucose, triglyceride, total
history of stroke, and vitamin D level were independently associated with
cholesterol, LDL-C and HDL-C were also measured colorimetrically.
sarcopenic obesity in older people with diabetes.
Results
DOI: 10.1530/endoabs.49.GP162
miR-26b expression were significantly lower in obese subjects compared with
control group and were also lower in subjects with insulin resistance compared to
those without insulin resistance. miR-26b was significantly correlated with insulin
levels and HOMA-IR. It also showed a significant negative correlation with
visfatin which was higher in obese subjects compared with control subjects.
GP163
Conclusion
Resistance training reduces skeletal muscle inflammation even after
Decreased miR-26b expression in obese children and adolescents may be
4-week detraining in obese rats
involved in insulin resistance and increased visfatin levels.
Patricia Seraphim1, Marcelo Freitas1, Marcos Teixeira1, Giovana Teixeira1,
DOI: 10.1530/endoabs.49.GP164
Maria Tereza Nunes2 & José Carlos Camargo Filho1
1School of Sciences and Technology - Sao Paulo State University/UNESP,
Presidente Prudente/SP, Brazil;2Institute of Biomedical Sciences -
University of Sao Paulo, Sao Paulo/SP, Brazil.
The ingestion of high-fat diet has been considered a crucial factor in the genesis of
GP165
subclinical systemic inflammation and insulin resistance. The resistance training
The effect of FTO polymorphism rs 9939609 on obesity and metabolic
(RTr) can be an effective tool for the prevention and treatment of immune-
disturbances in Polish people from Lower Silesia
metabolic disorders through physiological and morphological adaptations. The
Aleksandra Zdrojowy-Welna1, Katarzyna Kolackov1, Katarzyna Zatonska2,
purpose of the present study was to analyze the effects of RTr and cessation of
Malgorzata Tupikowska-Marzec3, Marek Bolanowski1 &
training on muscle inflammation and expression of genes related to glucose
Grazyna Bednarek-Tupikowska1
metabolism in obese rats. Thirty male Wistar rats aged 2 months were subdivided
1Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw
into three groups: High-Fat Diet
(DH), Trained High-fat Diet
(DHT) and
Medical University, Wroclaw, Poland;2Department of Social Medicine,
Detrained High-fat Diet (DHD). RTr was performed for 12 weeks (wk), 3!/wk,
Wroclaw Medical University, Wroclaw, Poland;3Department of
three sets of 12 repetitions per session. In the 8th wk, DHD group interrupted
Dermatology, Venerology and Allergology, Wroclaw Medical University,
training for 4 wk. RT-PCR was performed to analyze genes code TNFa, AMPK,
Wroclaw, Poland.
GLUT4 and MEF2A, and Western blotting was assayed to analyze the expression
of TNFa in the soleus muscle. Additionally we analyzed the insulin sensitivity by
ITT, and muscle fiber area by HE staining. The results showed that RTr (DH vs.
Background
DHT) caused increase of muscle fiber area (P!0.05), and insulin sensitivity by
The association between fat mass and obesity-associated gene
(FTO)
34% (P!0.05), increased AMPK gene levels by 23% (P!0.05), GLUT4 by 24%
polymorphism rs 9939609 and obesity was found in some European countries.
(P!0.05) and MEF2A by 20% (P!0.05), and reduced protein and gene levels by
However, the data concerning Polish population is insufficient. The relationship
51 and 28% of TNFa (P!0.05), respectively. Detraining (DHD vs DHT)
between FTO and metabolic disorders remains unclear.
increased body weight (P!0.05), and provoked reduction of muscle fiber area
Methods
(P!0.05). However, TNFa expression remained reduced even after cessation of
The study group consisted of 686 women and 418 men from Lower Silesia in
training. We conclude that RTr exerts positive effects on reduction of the local
Poland, aged
30-80 years
(mean age 54.2G9.26 years). The examination
inflammation, and improves the expression of genes related to glucose
included anthropometric measurements, blood pressure, lipid profile and fasting
metabolism in the oxidative skeletal muscle. These adaptations are maintained
blood glucose analysis. The group was genotyped for FTO rs9939609
even after 4-week detraining.
polymorphism.
Results
DOI: 10.1530/endoabs.49.GP163
Mean BMI was 28.2G5.0 kg/m2 and was slightly higher in men. Prevalence of
obesity (BMI O30 kg/m2) was around 31% with no sex differences. Minor allele
frequency was 0.44. In whole study group, mean BMI was higher in risk allele
carriers (AA, AT) than TT homozygotes (AA - 28.45 kg/m2, AT - 28.41 kg/m2 vs
TT - 27.8 kg/m2), but the difference was not statistically significant. The
association between FTO polymorphism and obesity traits were stronger in men
GP164
than in women (p-values, respectively: for body weight 0.0005 vs O0.1, for BMI
miR-26b is decreased in obesity and is associated with insulin resistance
!0.01 vs O0.1, for waist circumference 0.0005 vs O0.1 in co-dominant model).
and visfatin levels
We did not observe any association between FTO polymorphism and
Mitra Nourbakhsh1, Atieh Hosnieh Farahan4, Farideh Yaghmaei4,
dyslipidaemia, hypertension or higher blood glucose concentration.
Saeedeh Moradgholi4, Fatemeh Ahmadpour1 & Maryam Razzaghy-Azar2,3
Conclusions
1Department of Biochemistry, Faculty of Medicine, Iran University of
FTO polymorphism is one of many factors influencing body mass in Polish
Meical Sciences, Tehran, Iran;2Metabolic Disorders Research Center,
population. The effect on other metabolic disturbances is not significant. The
Endocrinology and Metabolism Molecular-Cellular Sciences Institute,
reasons why the association between FTO and obesity were more pronounced in
Tehran University of Medical Sciences, Tehran, Iran;3H.Aliasghar
men than women remain unclear. Probably age, degree of obesity or other
Hospital, Iran University of Medical Sciences, Tehran, Iran;4Department of
hormonal factors modify the clinical presentation of genetic predisposition.
Biology, Science and Research Branch, Islamic Azad University, Tehran,
DOI: 10.1530/endoabs.49.GP165
Iran.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP166
altered sex steroid balance to WT mice, are needed to confirm the causality
between sex steroids, gut microbiota and metabolic disorders.
Role of Elovl6 in brown and beige adipose tissue during b3-adrenergic
receptor activation
DOI: 10.1530/endoabs.49.GP167
Rahul Sharma1, Takashi Matsuzaka1, Zao Hui1, Hiroshi Ohno1,
Yoshinori Takeuchi1, kaori Motomura1, Naoya Yahagi1, Motohiro Sekiya1,
Yoshimi Nakagawa1, Masafumi Muratani2 & Hitoshi Shimano1
1Department of Internal Medicine, Endocrinology and Metabolism, Faculty
of Medicine, University of Tsukuba, Tsukuba, Japan;2Department of
GP168
Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba,
Effects of short sleep duration on energy metabolism and energy
Japan.
balance in subjects with overweight and obesity
Eleonora Poggiogalle, Lorenzo Donini, Lucio Gnessi, Stefania Mariani,
Marianna Calabretto, Federica Luisi, Andrea Lenzi & Carla Lubrano
Anti-obesity therapeutics based on increasing the amount of brown fat have
received more attention from industry as the biology and regulation of brown fat
are better understood than that of beige fat. Cold exposure and treatment with b3
Introduction
adrenergic receptor agonist are known to activate brown/beige adipose tissue.
The chronic reduction of sleep duration is associated to an increased risk of
Many transcriptional pathways regulating brown/beige adipose tissue have been
weight gain, but mechanistic aspects remain to be fully elucidated. The aim of our
identified, the role of lipid biosynthetic enzymes in brown/beige adipose tissue
study was to examine the relationship between short sleep duration and energy
has been less investigated. In this study, we investigated the role of Elovl6, the
metabolism, fuel selection and energy balance in overweight and obesity.
enzyme responsible for converting C16 non-essential fatty acids (FAs) into C18
Methods: Inclusion criteria were: age 18-65 years, BMI R25 kg/m2. Use of any
species, in brown/beige adipose tissue. We have observed upregulation of Elovl3,
CNS medications, any psychiatric disorders and night shift work were considered
4, 6 and 7 in BAT and inguinal WAT of mice treated with b3-adrenergic receptor
as exclusion criteria. Body composition was evaluated by DXA. All participants
agonist CL-316243 as well as cold-expose. These elongases are responsible for
underwent indirect calorimetry. The respiratory quotient (RQ) was calculated
the conversion of C16 FAs into C30 saturated FAs, indicating the relevance of
from gas exchanges. The equations by Weir and by Frayn were used to calculate
very long chain FAs in the activation process of brown/beige adipose tissue. It
the resting energy expenditure
(REE), and carbohydrate and fat oxidation,
was reported that Elovl6 KO mice have impaired mitochondrial function and
respectively. Sleep duration, total daily energy expenditure (TDEE) and the level
hence impaired thermogenic capacity of BAT when exposed to cold temperature
of physical activity (METs/day) were objectively assessed (Sensewear Armband).
(Cell Rep. 13:2039, 2015). When exposed to chronic CL-316243 treatment we
A 3-day dietary record was administered. Participants were divided into two
observed that Elovl6
KO mice compensate its impaired BAT function by
groups,
“regular sleep”
(RS): O300 min/day or
“short sleep”(SS):
%300
increased development of functional beige fat contributing to its increased energy
min/day. Results: 88 women and 30 men were included (age:49.6G12.1 years),
expenditure. Interestingly, these metabolic changes are appearing to be mediated
of whom 30.5% exhibited a short sleep duration. BMI (39.7G7.1 vs. 36.2G
by increased type-2 cytokine signalling and macrophage polarization in the
5.0 kg/m2, PZ0.03) and truncal body fat (18.7G6.2 vs. 16.1G4.6 kg, PZ0.04)
inguinal WAT of Elovl6 KO mice, as per our preliminary results. We have
were higher in the SS group than the RS group. Subjects with short sleep had a
observed increased expressions of markers for cell proliferation
(Ki67),
lower RQ (0.71G0.12 vs. 0.76G0.12, PZ0.004) and oxidized more fat (113G55
macrophage (F4/80, CD68, Itgax-1, Arg-1, Clec-10) in the beige fat of Elovl6
vs. 95G56 g/min, PZ0.006) than regular sleepers. The METs/day were higher in
KO mice compared to WT mice stimulated with CL-316243. These results
the SS group compared to the RS group (1.56G0.55 vs. 1.35G1.24, PZ0.04).
suggest that Elovl6-regulated FA chain length is important for beiging and M2
RQ was positively associated to sleep duration (PZ0.04, adj. for age, sex, and
macrophages are playing a mediator role in beige adipogenesis.
body fat). No difference emerged in TDEE or energy intake (SS group: 23G10 vs.
DOI: 10.1530/endoabs.49.GP166
RS group: 25G6 kcal/kg/day, PO0.05).
Conclusion
Short sleep affects energy substrate metabolism and adiposity distribution in
overweight and obese subjects.
DOI: 10.1530/endoabs.49.GP168
GP167
A link between sex hormones, obesity and gut microbiota
Gabriela Martínez-Chacón1,2, Eveliina Munukka2, Himanshu Kumar1,
Sami Pietila4,5, Niina Saarinen2,3, Raine Toivonen2, Seppo Salminen1,
GP169
Arno Hänninen2, Leena Strauss2,3 & Sari Mäkelä1,2
Blood mercury concentration in relation to overweight or obese among
1Functional Foods Forum, University of Turku, Turku, Finland;2Institute of
Korean children and adolescents: KNHANES 2009-2013
Biomedicine, University of Turku, Turku, Finland;3Turku Center for
Kyung Hee Park1 & Jeong-Hyeon Kim2
Disease Modeling, Univesity of Turku, Turku, Finland;4Turku Centre for
Biotechnology, University of Turku, Turku, Finland;5
˚boAkademi,Turku,
1Hallym University Sacred Heart Hospital, Anyang, Republic of Korea;
2Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea.
Finland.
Background
Sex steroids are involved in the development of obesity and metabolic disorders.
Harmful effects of mercury on cardiovascular disease have been suggested in
The interrelationship between sex steroid balance and metabolism is complex,
many epidemiologic studies. However, reports on harmful effect of mercury in
and the underlying mechanisms are still unclear. The impact of gut microbiota in
relation to overweight or obesity have shown inconsistent findings.
development of obesity, inflammation and metabolic dysregulation has been
Methods
suggested in humans and demonstrated in mouse models. Less is known about the
A total of 1577 children and adolescents (10-18 years of age) from the Korean
interactions between sex steroids and gut microbiota. Based on available
National Health and Nutrition Examination Survey (KNHANES) 2009-2013.
evidence, it is, however, pertinent to ask if sex steroids participate in the
Overweight or obese group was defined as over the 85th percentile of the age- and
regulation of the composition or function of gut microbiota, or if gut microbes
sex-specific BMI norms or BMI over 25. Subjects were categorized into three groups
regulate sex steroid balance. The aim of the present study was to define the
by age and gender specific blood cadmium, lead, and mercury concentration.
interplay between sex steroid balance and gut microbiota, in the context of obesity
Multivariate logistic regression stratified by gender was performed to estimate the
and metabolic dysregulation. First, we showed that non-obese human aromatase
odd ratio (OR) and 95% confidence interval (CI) for investigate the association.
expressing
(AROMC) male mice, with increased circulating estradiol to
Results
testosterone ratio and impaired liver lipid metabolism, have a female-type
Compared to non-obese group, blood mercury concentration of was higher in obese
intestinal microbiota and higher ratio of Firmicutes to Bacteroidetes. Treatment
group. Blood levels of cadmium and lead were not significantly different according
with aromatase inhibitor restored estradiol/testosterone levels, followed by a
to obese status. After adjustment for confounders, subjects in the highest tertile
slight improvement in their microbiota ecology. Second, in a mouse model
group of blood mercury levels were more likely to have overweight or obesity (OR
reporting the expression of human aromatase (CYP19A1) gene (hARO-Luc
2.65, 95%CI 1.13-6.26) compared to subjects in the lowest tertile group in girls.
mouse), ovariectomy-induced obesity, accompanied with elevated Firmicutes to
No significant association was found in boys.
Bacteroidetes ratio, altered gut homeostasis and increased aromatase reporter
Conclusions
gene expression in the mammary adipose tissue. In conclusion, by applying two
Blood mercury concentration is positively associated with overweight or obesity
gene-modified mouse models, we showed that changes in sex steroid balance are
among Korean children and adolescents. Further longitudinal studies will be
linked to altered gut microbiota composition, and on the other hand, sex steroid -
needed to confirm the causality.
related obesity is linked to increased expression of human aromatase gene
DOI: 10.1530/endoabs.49.GP169
reporter. Further experiments, such as fecal transplantation from mice with
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP170
testosterone
(MDZ6.52, 95%CI (3.09, 9.94), PZ0.0002); estradiol (MDZ
K7.03, 95%CI (K11.05, K3.01), PZ0.0006); luteinizing hormone (MDZ0.92,
Association of the FTO gene rs9939609 polymorphism with obesity in
95%CI (0.64, 1.20), P!0.00001); follicle-stimulating hormone
(MDZ1.29,
the Republic of Tatarstan
95%CI (0.65, 1.94), P!0.0001); sex hormone-binding globulin (MDZ23.85,
Kamilya Khasanova1, Tatyana Kiseleva1, Sabina Bogdanova1,
95%CI (18.44, 29.26), P!0.00001). The changes of sex hormone levels in obese
Elena Valeeva1, Svetlana Gubaidullina2, Ildus Ahmetov1 & Farida Valeeva1
female patients before and after bariatric surgery as following: total testosterone
1Kazan State Medical University, Kazan/Republic of Tatarstan, Russia;
(MDZK0.78, 95%CI (K0.84, K0.71), P!0.00001); free testosterone
2Volga Region Academy of Physical Culture, Sport and Tourism,
(MDZK5.53, 95%CI (K10.47, K0.59), PZ0.03); estradiol (MDZK25.10,
Kazan/Republic of Tatarstan, Russia.
95%CI (K36.92, K13.27), P!0.0001); luteinizing hormone (MDZ4.50, 95%CI
(K1.04, 10.05), PZ0.11); follicle-stimulating hormone
(MDZ1.68, 95%CI
Aim
(0.50,
2.86), PZ0.005); sex hormone-binding globulin (MDZ34.79, 95%CI
To investigate the possible association of the rs9939609 polymorphism in the
(22.63, 46.96), P!0.00001).
FTO gene with obesity in the Republic of Tatarstan (RT).
Conclusion
Materials and methods
This meta-analysis indicates that bariatric surgery has a significant improvement
The study involved 63 adult patients (21 men and 42 women; 38-77 years old)
on the sexual function in both genders.
with overweight or obesity and 515 healthy young people (157 men and 358
DOI: 10.1530/endoabs.49.GP171
women; 16-35 years old) with normal weight. We assessed clinical and
biochemical parameters (blood lipid profile). The analysis of the rs9939609 T/A
polymorphism of the FTO gene in buccal cells was performed using Sintol kits
(Russia) for RT-PCR. All the patients were tested by bioelectrical impedance
analysis.
Results
The distribution of genotypes of the FTO gene polymorphism (TT - 11%, TA -
65% AA - 24%) and alleles (T - 44% A - 56%) in the group of patients with
GP172
overweight and obesity was significantly different from those of the control group
Lipolytic effects of endogenous 3-iodothyronamine (T1AM) and
(TT - 42,9%, TA - 45,4%, AA - 11,7%; T - 65,6%, A - 34,4%; ORZ2.43,
synthetic analog SG-2 in vivo and in cultured adipocytes
P!0.0001), confirming that the A allele is a risk factor for obesity. In the group of
Martina Sabatini1, Michael P Rogowski2, Ebru S Selen Alpergin3,
obese patients we found an additive effect of the A allele on the increase of the
Fariba Assadi-Porter3, Riccardo Zucchi1 & Grazia Chiellini1
average waist-hip ratio (lowest value in TT carriers, maximum value in AA
1Department of Pathology, University of Pisa, Pisa, Italy;2UAB School of
carriers). We found that the number of patients with arterial hypertension and
Medicine-Cardiovascular Disease, Birmingham, AL, USA;3Department of
dyslipidemia was higher in the group with AA and TA genotypes compared with
Zoology, University of Wisconsin-Madison, Madison, WI, USA.
group with TT genotype.
Conclusion
We found a significant association of the T/A polymorphism of the FTO gene
3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to
with the obesity. Obese patients with the risk allele of the rs9939609 FTO gene
TH, that has been reported to modulate energy metabolism by favoring lipid over
polymorphism have significantly higher values of absolute and relative body fat
glucose catabolism. To better understand the role played by T1AM on the
mass and BMI, total cholesterol, low-density lipoprotein, and triglycerides.
regulation of lipid metabolism, in the present study we administered
DOI: 10.1530/endoabs.49.GP170
spontaneously obese mice with T1AM at two different dosages
(10
and
25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid
profiles were examined. In addition a fluoro-labeled version of T1AM (FL-
T1AM) was synthesized and utilized to assess T1AM intracellular localization in
3T3-L1 mouse adipocytes.
Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or
18% of initial BW by day 7 of treatment. T1AM treatment at both dosages
produced a significant increase in total plasma triglycerides (P!0.05) and a
significant decrease in plasma cholesterol (P!0.05), without any significant
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change in glycaemia. At present, the specific mechanism of T1AM entry into the
cell, as well as its internal targets remains unknown. Cellular imaging revealed
Effect of bariatric surgery on sexual function and sex hormone levels in
rapid intercellular uptake of FL-T1AM without localization to the lipid droplet or
obese patients: a meta-analysis
nucleus of mature adipocytes. This rapid rate of uptake was further evaluated via
Junping Wen1,2, Lingying Wen2, Wei Lin1,2, Liantao Li1,2, Jixing Liang1,2,
flow cytometry, with peak detection of FL-T1AM steadily rising until reaching
Huibin Huang1,2 & Gang Chen1,2
peak signal and equilibrium at w20 min. We also observed that when 3T3-L1
1Fujian Provincial Hospital, Fuzhou, China;2Fujian Medical University,
adipocytes were treated with T1AM or its synthetic halogen free analog SG-2 (1-
Fuzhou, China.
10 mM), both compounds decreased lipid accumulation in mature adipocytes,
with SG-2 showing a potency significantly higher than T1AM (IC50SG-2Z5 mM;
Objective
IC50T1AMZ20 mM).
The aim of this meta-analysis is to evaluate the effect of bariatric surgery on
In conclusion T1AM and its synthetic analog show a significant lipolytic activity,
sexual function and sex hormone levels in obese patients.
both in cultured adipocytes and in vivo.
Methods
DOI: 10.1530/endoabs.49.GP172
Two independent investigators conducted a literature search of PubMed, Medline
and Cochrane databases using the terms bariatric surgery, sexual function and sex
hormone to identify appropriate human studies published in English about the
effect of bariatric surgery on sexual function and sex hormone levels in obese
patients. The search was restricted to data from January 1, 1990 to December 1,
2016. Bibliographies of recent review articles and systematic reviews were
searched to identify any additional trials. Two investigators according to the
Pituitary
inclusion and exclusion criteria independently select literature, extract data and
evaluate quality, then using RevMan 5.3.5 software for Meta analysis.
GP173
Results
A comparison of single-dose effects of short acting somatostatin analogs:
In all, 31 studies met all criteria, including 1150 patients. The types of bariatric
octreotide vs pasireotide in patients with active acromegaly after
surgery performed included laparoscopic Roux-en-Y gastric bypass, laparoscopic
surgical debulking
gastric banding surgery, laparoscopic adjustable gastric banding, laparoscopic
Agnieszka Majos, Maria Stelmachowska-Banas, Izabella Czajka-Oraniec &
sleeve gastrectomy, Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable
Wojciech Zgliczynski
gastric banding, vertical gastric banding, biliopancreatic diversion. The time to
Department of Endocrinology, Centre of Postgraduate Medical Education,
follow-up after surgery varied from 1 months to 115 months. Of the 31 studies, 5
Bielanski Hospital, Warsaw, Poland.
reported the IIEF in obese men in 154 of 1150 patients (MDZ4.84, 95%CI (2.92,
6.75), P!0.00001); 7 studies reported the FSFI in obese women in 369 of 1150
patients
(MDZ4.10, 95%CI (K0.28, 8.48), PZ0.07). The changes of sex
Acromegaly is a rare endocrine disorder caused by growth hormone (GH)
hormone levels in obese male patients before and after bariatric surgery as
secreting pituitary adenoma. The treatment of choice is transsphenoidal surgery.
following: total testosterone (MDZ8.55, 95%CI (6.59, 10.52), P!0.00001); free
In patients with persistent disease after surgery medical therapy is recommended.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
First-line medical treatment include first generation long-acting somatostatin
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analogs: octreotide LAR and lanreotide autogel. Recently, pasireotide - a second
Resistance to somatostatin analogues is associated with GSTP1 gene
generation somatostatin analog has been investigated in patients with acromegaly.
methylation and AHR rs2066853 variant in acromegaly patients
The aim of this study was to compare the effectiveness of the single-dose of short-
Francesco Ferraù1, Petronilla Daniela Romeo1, Soraya Puglisi1,
acting somatostatin analogs: octreotide vs pasireotide in patients with active
Marta Ragonese1, Federica Spagnolo1, Riccardo Ientile2, Isa Anna
acromegaly after surgical debulking who were resistant to first generation long-
Maria Picerno2, Monica Currò2, Giuseppa Visalli2, Angela Alibrandi3 &
acting somatostatin analogs.
Salvatore Cannavò4
Eighteen patients after debulking surgery without biochemical control of
1Department of Clinical and Experimental Medicine, University of Messina,
acromegaly on medical therapy were enrolled in the study. All patients had
Messina, Italy;2Department of Biomedical Sciences, Dental Sciences and
short-acting octreotide and pasireotide administered on different days. GH
Morpho-functional Imaging, Messina, Italy;3Department of Economics,
concentration was measured before and
60,
120
and
180 min after drug
Messina, Italy;4Department of Human Pathology of Adulthood and
administration. Nadir GH concentrations and decreases in GH concentrations
Childhood, Messina, Italy.
were compared.
Nadir GH values in octreotide test were reached 60 min after drug administration,
while in pasireotide test - 180 min after drug administration. The median nadir
Evidences suggest that environmental contaminants exposure and/or the
GH concentration was 2.765 mg/l (IQR: 1,885-4.07) vs 1.51 mg/l (IQR: 0.95-2.555)
impairment of intracellular xenobiotic metabolizing system could affect pituitary
respectively, P!0.001. The decrease in GH concentration was more significant
pathophysiology. Glutathione-S-transferase-P1 (GSTP1) gene encodes for an
after pasireotide administration compared to octreotide administration
enzyme that is involved in cellular detoxification mechanisms. GSTP1 altered
(P!0.001). The median decrease in GH concentration in octreotide test was
activity or expression has been reported in some tumours.
1.255 mg/l (IQR: 0.918-1.75) vs 2.805 mg/l (IQR: 1.523-5.043) after pasireotide
We aimed to assess the GSTP1 gene promoter methylation status in acromegaly
administration. Octreotide was generally better tolerated than pasireotide.
patients and its contribution to their clinical features.
Short-acting pasireotide is more effective than short-acting octreotide in GH
Seventy-seven WT AIP gene acromegaly patients (50 women) have been screened
supression in patients with uncontrolled acromegaly. Pasireotide may be a
for germline AHR rs2066853 variant and GSTP1 promoter methylation. Epide-
promising alternative for patients resistant to first-generation somatostatin
miologic, clinical, biochemical and radiological parameters at diagnosis have been
analogs.
compared after patients’ stratification according to GSTP1 methylation status and the
DOI: 10.1530/endoabs.49.GP173
presence of AHR rs2066853 variant. We also evaluated the response to somatostatin
analogues (SSA) administered either before or after surgery in 71 cases.
Seventeen patients were found to carry AHR rs2066853 variant and 26 methylated
GSTP1 (GSTP1met). GSTP1met patients showed a higher prevalence of diabetes
mellitus (PZ0.01), colonic polyps (PZ0.05), and were more resistant to SSA
(PZ0.02) as compared to GSTP1 unmethylated patients (GSTP1unmet).
On the basis of GSTP1 methylation status and the presence of AHR rs2066853
variant, we identified four groups: group 1, 40 patients GSTP1unmet and AHR
WT; group 2, 20 patients only GSTP1met; group 3, 12 patients carrying only AHR
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rs2066853 variant; group 4, five patients with both GSTP1 methylation and AHR
Efficacy and safety of switching to pasireotide LAR alone or in
rs2066853 variant. Group 1 patients were more sensitive to SSA than other groups
combination with pegvisomant in acromegaly patients controlled with
(PZ0.02). Patients of group 4 were more resistant to SSA (PZ0.02) and showed
combination treatment of first-generation somatostatin analogues and
higher GH (PZ0.03) and IGF1 (PZ0.04) levels and lower percentage of GH
weekly pegvisomant (PAPE study): a prospective open-label 48 week
decrease (PZ0.04) after SSA than other groups.
study, preliminary results 24 weeks
In conclusion, GSTP1 methylation and AHR rs2066853 variant associate with
Ammar Muhammad, Aart Jan van der Lely, Joop Janssen &
resistance to SSA in acromegaly patients.
Sebastian Neggers
DOI: 10.1530/endoabs.49.GP175
Erasmus MC, Rotterdam, The Netherlands.
Background
Efficacy and safety of combination treatment of pasireotide LAR with
pegvisomant (PEGV) has not been studied yet. Switching to Pasireotide LAR
GP176
in patients previously controlled with long-acting somatostatin analogues (LA-
Minimally Invasive Diagnosis and Direct Transnasal Surgery: a single
SSAs) and PEGV could reduce the required PEGV dose to normalize serum IGF1
centre series of 100 children with Cushing’s Disease with long term
levels, while the effect on glucose metabolism is unknown.
follow-up
Methods
Patricia Crock1,2, Dieter K Ludecke3, Ulrich Knappe4, Joerg Flitsch3 &
We enrolled 60 acromegaly patients O18 years with acromegaly who had normal
Wolfgang Saeger5
IGF1 levels (%1.2!Upper Limit of Normal (ULN)) using combination treatment
1Paediatric Endocrinology, John Hunter Children’s Hospital, Newcastle,
of high dose LA-SSAs and weekly PEGV for R6 months. After enrollment
NSW, Australia;2University of Newcastle, Newcastle, NSW, Australia;
LA-SSA treatment was continued, and the PEGV dose was reduced by 50% for 12
3Department Neurosurgery, University Hospital Eppendorf, Hamburg,
weeks. If IGF1 levels remained normal after 12 weeks, patients were switched to
Germany;4Neurosurgical Clinic, Minden, Germany;5Department
pasireotide LAR 60 mg monotherapy, every 4 weeks. If IGF1 levels O1.2!ULN
Neuropathology, University Clinic Eppendorf, Hamburg, Germany.
patients were switched to pasireotide LAR 60 mg and continued with the 50%
reduced PEGV dose. The primary endpoint was the percentage of patients
achieving normal IGF1 levels at 24 weeks. The key secondary endpoint was the
Introduction
frequency diabetes at 24 weeks.
Trans-sphenoidal surgery (TSS) with minimally invasive techniques is the first
Results
choice in the treatment of paediatric Cushing’s disease (CD). The question is how
At baseline, median IGF1 was 0.94!ULN with a median PEGV dose of
can high remission rates be achieved with less invasive investigations and TSS.
80 mg/week, and 30.6% of patients had pre-existing diabetes. After the 50% dose
The developments in our centre treating 100 pediatric Cushing patients with long-
reduction of PEGV, median IGF1 levels increased to 1.43 ULN, while IGF1
term follow-up may add some helpful ideas.
remained normal in 33% of patients. At 24 weeks, 73% of patients achieved
Material and methods
normal IGF1 levels with a median IGF1 0.98!ULN. Cumulative PEGV dose
Data from our first series 1 (nZ55) will be compared with new data from the
reduction between baseline and 24 weeks was 66%. At 24 weeks, IGF1 levels
recent series 2 (nZ45) until 2009. All patients were operated by one surgeon by
were normal in 88% of patients on pasireotide LAR monotherapy, and 68% of
direct transnasal microsurgery (TNS). Special diagnostic methods such as inferior
patients on combination treatment. Pasireotide LAR was well tolerated. At 24
petrosal sinus sampling (IPSS) were replaced by ACTH measurement from the
weeks, the most common adverse event was diabetes which occurred in 70.2% of
cavernous sinus (CSS) restricted to unclear cases without increase of salivary
patients. Two patients withdrew prematurely due to hyperglycemia requiring
cortisol in the CRH-test, difficult sella anatomy and/or negative MRI. Multiple
insulin treatment.
direct micro-cytology, micro-doppler and adequate visualization will be
Conclusion
described.
Pasireotide LAR alone or in combination with pegvisomant controls IGF1 in 73%
Results
of patients after 66% reduction in cumulative dose of weekly pegvisomant. The
In our first series of 55 cases, IPSS was performed in 13 (24%) of whom 46% had
frequency of diabetes was 70.2% and is in line with previous studies.
false adenoma lateralization. All adenomas could be removed with extensive
DOI: 10.1530/endoabs.49.GP174
pituitary exploration and all had intraoperative pathology. Two patients had early
successful re-surgery. Recurrence rate 15%. In the second series with more
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
refined MRI and endocrinology: easy repeat CRH saliva tests and CSS sampling
GP178
used in only 7 patients (15%), all micro-adenomas were initially detected. Early
Sleep patterns in patients with non-functional GHRH receptor
repeat-TNS was necessary and successful in three. Recurrence rate 11%. Side
Francielle T Oliveira1, Roberto Salvatori2, José Marcondes3,
effects of TNS were minimal, as such, children and parents readily accepted
Larissa B Macena1, Alecia A Oliveira-Santos1, Augusto C N Faro1,
re-TNS. Thus, including re-TNS in recurrences, 98 of 100 patients had long-term
Viviane C Campos1, Carla R P Oliveira1, Ursula M M Costa1 &
remission. TNS in recurrences had a better outcome in the last series with less
Manuel H Aguiar-Oliveira1
pituitary dysfunction using more intraoperative minute biopsies.
1Federal University of Sergipe, Aracaju/Sergipe, Brazil;2The Johns
Conclusions
Hopkins University School of Medicine, Baltimore, MD, USA;3Instituto do
Invasive pre-surgical investigations could be reduced. 98% remission rate could
Sono e Medicina Integrada, Aracaju/Sergipe, Brazil.
be achieved with advanced investigations, refined TNS, early re-TNS and re-TNS
in recurrences. Only two children (2%) were irradiated - only one was indicated
by the senior surgeon.
Hypothalamic GH releasing hormone (GHRH) has hypnotic actions by increasing
DOI: 10.1530/endoabs.49.GP176
slow wave sleep (SWS) (non-rapid eye movement sleep, non-REM), which
account for about 75% of sleep. Conversely, GH may stimulate the rapid eye
movement sleep (REM). Patients with GH deficiency (GHD) often exhibit sleep
problems leading to daytime fatigue and reduced quality of life (QoL). We have
described a cohort of patients with isolated GHD (IGHD) due to GHRH resistance
caused by a homozygous null mutation (c.57C1GOA) in the GHRH receptor
gene. They have normal QoL and no obvious complaints of chronic tiredness. The
aim of this study was to determine objectively and subjectively the sleep quality
in these subjects, who have never received GH therapy. A cross sectional study
was carried out on 21 adult IGHD subjects, and 21 matched controls. Objective
sleep assessment included polygraphic records of the stages wake (W), non-REM:
GP177
N1 (drowsiness), N2 and N3 (already sleeping) and R (REM). Subjective
Octreotide subcutaneous (s.c.) depot, a novel ready-to-use formulation,
evaluation included the Pittsburgh Sleep Quality Index, Insomnia Severity Index,
provides higher exposure and maintains response in patients with
and Epworth Sleepiness Scale. Compared to controls, IGHD subjects exhibited
acromegaly and functioning neuroendocrine tumours (NETs)
lower sleep efficiency (77.7 (27.5) vs 87.5 (10.1) %, PZ0.007), total sleep time
previously treated with long-acting octreotide: Results from a phase 2,
(330.0
(127.5) vs 385.5 (56.0) min, PZ0.028) and higher percentage of the non-
open-label, multicentre, randomized study
REM 1 stage (14.6 (18.9) vs 7.3 (8.1) %, PZ0.022). There was no difference
Diego Ferone1, Franc¸oise Borson-Chazot2, Anne Cailleux3, Dieter Horsch4,
between the groups in REM sleep and in quality questionnaires. These data show
Harald lahner5, Rosario Pivonello6, Libuse Tauchmanova7,
an extension of the drowsiness period, with a reduction in the total sleep time,
Christelle Darstein7, Håkan Olsson8, Fredrik Tiberg8,9 & Marianne Pavel10
suggesting a preponderant role of GHRH resistance over GHD in the sleep quality
1Endocrinology, DiMI, IRCCS AOU San Martino-IST, University of
of these IGHD subjects. The objective reduction in the sleep efficiency and total
Genoa, Genoa, Italy;2Fédération d’Endocrinologie, Hospices Civils de
sleep time seem have minimal subjective consequences, as it was not reflected in
Lyon and University Lyon1, Lyon, France;3CHU ouen, Hôpital Charles
differences of quality sleep questionnaires.
Nicolle, 1 rue de Germont, 76031 Rouen cedex, Rouen, France;
DOI: 10.1530/endoabs.49.GP178
4Department of Gastroenterology/Endocrinology, Center for Neuroendo-
crine Tumors Bad Berka - ENETS Center of Excellence, Zentralklinik Bad
Berka GmbH, Bad Berka, Germany;5Universitaetsklinikum Essen, Zentrum
f. Innere Medizin, Essen, Germany;6Dipartimento di Medicina Clinica e
Chirurgia, Università Federico II di Napoli, Naples, Italy;7Novartis Pharma
AG, Basel, Switzerland;8Camurus AB, Lund, Sweden;9Physical
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Chemistry, Lund University, Lund, Sweden;10Charité Universitatsmedizin
Correction of sustained hyponatremia secondary to SIAD by the use of
Berlin, Campus Virchow-Klinikum, Berlin, Germany.
chronic tolvaptan therapy is associated with a reduction in Emergency
Room visits, hospital admissions and days of hospitalization over a
3-year period
Background
Martín Cuesta Hernández1, Irene Crespo Hernández1, Pablo
Octreotide s.c. depot is a novel, ready-to-use formulation administered via a thin
Amich Alemany1, Emilia Gómez Hoyos2, Nancy Sánchez Gómez3,
needle, which may allow self-administration. In a phase 1 study in healthy
volunteers, octreotide s.c. depot provided greater bioavailability with faster onset
Alejandro Santiago1, Paz De Miguel Novoa1, Alfonso Luis Calle-Pascual1
and greater IGF1 suppression than long-acting octreotide. Here, we present data
& Isabelle Runkle de la Vega1
from a phase 2 study evaluating pharmacokinetics (PK), efficacy, safety, and
1Hospital Universitario Clínico San Carlos, Madrid, Spain;2Hospital
Universitario Clínico Universitario de Valladolid, Valladolid, Spain;
tolerability of octreotide s.c. depot in patients with acromegaly and neuroendo-
3Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
crine tumours (NETs).
Methods
Adult patients with acromegaly or functioning, well-differentiated NETs treated
Introduction
with long-acting octreotide 10 mg/20 mg/30 mg every 4 weeks (q4w) for R2
Hyponatremia (HN) is associated with worse clinical outcomes, and longer
months received the last dose of long-acting octreotide in period 0 (P0). Patients
hospital lengths-of-stay than seen in eunatremic patients. The Syndrome of
were randomized 28 days later to receive octreotide s.c. depot 10 mg q2w or
Inappropriate Antidiuresis (SIAD) is the most common cause of hyponatremia in
20 mg q4w for 3 months (period 1 [P1]).
hospitalization. We studied the relationship between correction of sustained
Results
SIAD-induced hyponatremia and visits to the Emergency Room (ERv) as well as
Twelve patients were randomized to receive octreotide s.c. depot 10 mg q2w
hospital admissions (HA) in a case series.
(acromegaly, nZ3; NET, nZ1) or 20 mg q4w (acromegaly, nZ4; NET, nZ4).
Methods
Acromegaly: steady state (SS) PK (for octreotide s.c. depot 10 mg, 20 mg vs long-
Retrospective, cross-sectional study of patients whose HN was corrected with
acting octreotide 10 mg, 30 mg, respectively) - AUC0-28d(day*ng/l): 95.6, 78.5 vs
chronic tolvaptan therapy (CTV) for a minimum of 3 years. Serum Sodium
6.23, 24.1; Cmax(ng/ml): 10.6, 11.3 vs 0.35, 1.41. NETs: SS PK (for octreotide s.c.
levels(SNa) in mmol/l. Descriptive statistics expressed as median (IQR). SPSS
depot 10 mg, 20 mg vs long-acting octreotide 20 mg, 30 mg, respectively) -
15, non-parametric tests (Wilcoxon for paired data), univariate analysis.
AUC0-28d(day*ng/l): 83.3, 135.0 vs 27.8, 39.9; Cmax(ng/ml): 5.61, 15.7 vs 1.68,
Results
2.48. In acromegaly, control of IGF-1 and GH levels was maintained or improved
16/25(64%) patients fulfilled inclusion criteria. Nine patients not completing
in P1 vs P0. In NETs, symptoms of carcinoid syndrome were similar or improved
1 year of follow-up were excluded. Median age: 82 (74-87). Women: 11/16(69%)
in P1 vs P0; symptoms disappeared in two patients in 20 mg group. Adverse
. HN was first detected a median of 51 months (IQR 29-56) prior to initiation of
events (all grade 1-2) were reported in six and eight patients during P0 and P1,
therapy. SIAD etiology: 9/16(56%) idiopathic, 3/16 (19%) drug-induced (19%),
respectively; most common in P1 were GI disorders.
2/16 (3%) respiratory, 1/16 (6%) abdominal, 1/16 (6%) cancer. The year before
Conclusions
HN correction, Nadir SNa:120(115-125) mmol/l, with a median of 2(1-4) ERv/
Octreotide s.c. depot provided higher exposure than long-acting octreotide,
patient, HA:1(1-2) with 18(10-32) days of hospitalization (DH). During year 1 of
maintained biochemical control in patients with acromegaly and symptom control
CTV, Nadir SNa rose to 136(133-137) mmol/l (PZ0.001), ERv dropped to
in patients with functioning NETs, and was well tolerated with a safety profile
1(0-3)(PZ0.03), HA to 0(0-0)(PZ0.003), DH to 0(0,0)(P!0.001). The benefits
consistent with long-acting octreotide.
were sustained when comparing the second and third years to the year prior to HN
DOI: 10.1530/endoabs.49.GP177
correction. Second year: ERv: 0(0-1)(PZ0.004), HA: 0(0-1)(PZ0.001), DH:
0(0-1)(P!0.001). Third year: ERv: 1(0-2)(PZ0.05), HA: 0(0-1)(PZ0.009), DH:
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
0
(0-4)(PZ0.01). Three years before start of therapy vs 3 years post: Total median
GP181
ERv/patient: 3(1-5), HA: 2(1-4), DH 18(10-34) vs total ERv: 2(1-4) (PZ0.03),
Targeting either GH or IGF-I levels during somatostatin analogue
HA: 1(0-2)(PZ0.006), DH 0(0-4)(PZ0.006). No patient developed hyperna-
treatment in patients with acromegaly: A randomized,
tremia. Tolvaptan doses were lowered if thirst developed or SNa reached
investigator-initiated multicenter study
141 mmol/l. Final weekly TV dose was 34 mg (23-105).
Jakob Dal1, Marianne Klose5, Ansgar Heck6, Marianne Andersen3,
Conclusions
Caroline Kistorp4, Eigil Husted Nielsen2, Jens Bollerslev6,
Correction of sustained hyponatremia secondary to SIADH with chronic TV
Ulla Feldt-Rasmussen5 & Jens Otto Lunde Jørgensen1
therapy was safe, and associated with a significant and sustained reduction in ER
1Aarhus University Hospital, Aarhus, Denmark;2Aalborg University
visits, hospital admissions, and days of hospitalization.
Hospital, Aalborg, Denmark;3Odense University Hospital, Odense,
DOI: 10.1530/endoabs.49.GP179
Denmark;4Herlev Hospital, Herlev, Denmark;5National University
Hospital, Copenhagen, Denmark;6Oslo University Hospital and Faculty of
Medicine, Oslo, Norway.
Context
Assessment of disease control in acromegaly depends on GH and IGF-I, but
discordant values frequently occur. Further, the role of OGTT-suppressed GH
(GHnadir) in somatostatin analogue (SA) treated patients is debated.
Objective
To evaluate the effect of targeting either IGF-I or GH during SA treatment.
Design
A randomized, investigator-initiated, multicentre trial.
Patients and methods
GP180
84 patients controlled with either SA (nZ61) or surgery-only (nZ23) underwent
Outcome of non-functioning pituitary adenomas that regrow after
a 3 h GH profile including a 2 h OGTT at baseline, after 6 months (SA treated
primary treatment: a study from two large specialist UK centers
patients only) and after
12 months together with IGF-I. SA patients were
Metaxia Tampourlou1,2, Georgia Ntali3, Shahzada Ahmed4, Wiebke Arlt1,2,
randomized to be monitored by either IGF-I (nZ33) or GHnadir (nZ28). SA dose
John Ayuk2, James Byrne5, Swarupsinh Chavda6, Simon Cudlip7,
increase were allowed at baseline and after 6 months. Symptoms and quality of
Neil Gittoes1,2, Ashley Grossman3, Rosalind Mitchell8, Michael O’Reilly1,2,
life
(QoL) were assessed by disease-specific questionnaires
(PAQ12 and
Alessandro Paluzzi8, Andrew Toogood2, John Wass3 & Niki Karavitaki1,2
AcroQoL).
1Institute of Metabolism and Systems Research, College of Medical and
Main outcome measures
Dental Sciences, University of Birmingham, Birmingham, UK;2Centre for
GH and IGF-I at baseline and 12 months, symptoms and QoL, and SA dose
Endocrinology, Diabetes and Metabolism, Birmingham Health Partners,
increases.
Birmingham, UK;3Oxford Centre for Diabetes, Endocrinology and
Results
Metabolism, Churchill Hospital, Oxford, UK;4Department of Ear, Nose and
IGF-I and fasting GH levels at baseline were comparable between the two groups,
whereas GHnadir (mg/l) was lower in the surgery group (GHnadir 0.7G0.1 (SA) vs
Throat, Queen Elizabeth Hospital, University Hospitals Birmingham NHS
0.3G0.1 (surgery), P!0.01). At baseline, 31% of SA patients had concordant
Foundation Trust, Birmingham, UK;5Department of Neuroradiology,
controlled GH and IGF-I,
43% had elevated GH and 3% elevated IGF-I.
John Radcliffe Hospital, Oxford, UK;6Department of Radiology, Queen
Significantly more patients in the surgery group had concordant controlled values
Elizabeth Hospital, University Hospitals Birmingham NHS Foundation
(65%), P !0.01. SA dose increase was performed in 20 patients in the GH target
Trust, Birmingham, UK;7Department of Neurosurgery, John Radcliffe
group as compared to eight patients in IGF-I target group (PZ0.02) and resulted
Hospital, Oxford, UK;8Department of Neurosurgery, Queen Elizabeth
in a higher proportion of controlled patients
(PZ0.01). SA patients had
Hospital, University Hospitals Birmingham NHS Foundation Trust,
suppressed insulin levels and elevated glucose and FFA levels during the
Birmingham, UK.
OGTT compared to surgery. QoL was only mildly affected at baseline and did not
change consistently.
Introduction
Conclusions
Despite the significant risk of regrowth of non-functioning pituitary adenomas
i) Discordance between GH and IGF-I is more prevalent during SA treatment
(NFAs) after primary treatment, systematic data on the probability of further
as compared to surgery, mainly due to elevated GHnadir levels, ii) targeting
tumour progression and the effectiveness of management approaches are lacking.
discordant GH or IGF-I levels in SA patients translates into SA dose increase and
Aims
a higher degree of concordance, iii) Our data suggest that a sizable proportion of
Assess the probability of further regrowth(s), predictive factors and outcomes of
SA patients are undertreated.
management approaches in patients with NFA diagnosed with adenoma regrowth
DOI: 10.1530/endoabs.49.GP181
after primary treatment (surgery combined or not with radiotherapy) in two UK
referral centers.
Methods
The records of the patients with NFA who during their follow-up had adenoma
regrowth were reviewed. The period covered for the primary NFA surgery was
between 1/1963 and 12/2011 and the follow-up period ended in 6/2016.
Results
We identified 237 patients (median follow-up after 1st regrowth of 5.9 years
(range 0.4-37.7)). The 5-year 2nd regrowth rate was 35.3% (36.2% after surgery;
GP182
12.5% after radiotherapy; 12.7% after surgery combined with radiotherapy;
Brain white matter damage and volumes of hippocampus and
63.4% with monitoring). Of those managed by monitoring, 34.8% eventually
hypothalamus correlates to cognitive function in craniopharyngioma
were offered intervention. Type of management and sex were risk factors for 2nd
Sigridur Fjalldal1, Daniel Svärd2, Cecilia Follin1, Danielle Van Westen2,
NFA regrowth, whereas age at diagnosis of primary NFA and type of adenoma
Sanaz Gabery3,
˚saPetersén3, Magdalena Jansson4, Pia Maly Sundgren2,5,
immunostaining were not. Amongst those with 2nd adenoma regrowth, the 5-year
Isabella Bjorkman-Burtscher2,5, Jimmy Lätt5, Peter Mannfolk5,
3rd regrowth rate was 26.4% (24.4% after surgery; 0.0% after radiotherapy; 0.0%
Carl-Henrik Nordstrom7, Lars Rylander8, Bertil Ekman9, Aki Johansson4 &
after surgery combined with radiotherapy; 48.3% with monitoring). Overall,
Eva-Marie Erfurth1
patients with a NFA regrowth had probability of a 3rd regrowth 4.4% at 5 years,
1Department of Endocrinology, Skåne University Hospital, Lund, Sweden;
and 10.0% at 10 years, and the type of management of the 1st regrowth was the
2Department of Diagnostic Radiology, Clinical Sciences, Lund University,
only risk factor. Malignant transformation was diagnosed in two of 237 patients
Lund, Sweden;3Translational Neuroendocrine Research Unit, Department
(one gonadotroph and one silent ACTH adenoma).
of Experimental Medical Science, Lund University, Lund, Sweden;
Conclusions
4Department of Psychology and Psychiatry, Skåne University Hospital,
Patients with regrown NFA after primary treatment continue to carry considerable
Lund, Sweden;5Department of Medical Imaging and Physiology, Skåne
risk of tumour progression necessitating long-term follow-up. Management
University Hospital, Lund, Sweden;6Lund University BioImaging Center,
approach of the regrowth is the major factor determining this risk; monitoring
Lund University, Lund, Sweden;7Department of Neurosurgery, Sk
˚ne
alone is associated with high progression rates and a substantial number of
University Hospital, Sweden, Lund, Sweden;8Division of Occupational and
patients will ultimately require intervention.
Environmental Medicine, Lund University, Lund, Sweden;9Department of
DOI: 10.1530/endoabs.49.GP180
Endocrinology and Medical and Health Sciences, Linkoping University,
Linkoping, Sweden.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
GP184
Adult patients with craniopharyngioma (CP) and hypothalamic (HT) damage
Hormonal and metabolic effects of long-term cabergoline withdrawal in
have impaired cognitive function. The white matter (WM) changes behind these
patients with hyperprolactinemia
findings remain to be elucidated. Diffusion tensor imaging (DTI) is a MRI
Renata Simona Auriemma, Chiara Blasio, Ludovica Francesca
technique that quantifies microstructural damage in the WM. This is the first study
Stella Grasso, Mariano Galdiero, Mariarosaria Negri, Claudia Pivonello,
of DTI, hippocampal (HC) and HT volume in relation to cognition in CP patients.
Luciana Granieri, Annamaria Colao & Rosario Pivonello
Methods
Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,
A cross-sectional study of childhood onset CP was performed at median 22 years
Università Federico II di Napoli, Naples, Italy.
after first operation. After exclusions, 36 patients and 31 controls remained in the
MRI study. Main outcome measures were comparison of cognitive tests, volume
measurements of HC and HT and the DTI parameters median diffusivity (MD)
Hyperprolactinemia is associated with abnormalities in glucose and lipid profile
and fractional anisotropy (FA) between patients and controls.
with development of insulin resistance and metabolic syndrome (MetS), which have
Results
been found to be improved by treatment with cabergoline (CAB). The current study
CP patients have WM damage in the left dorsal cingulum and right uncinate
aimed at investigating hormonal and metabolic effects of long-term CAB
fasciculus. No significant difference was found on DTI measurements of the HC.
withdrawal in patients with prolactinomas. In
46 patients (37 F, 9 M, aged
Correlations were found between DTI results from the right uncinated fasciculus
34.5G11.5 yrs,
36 microadenomas and
10 macroadenomas) anthropometric
(MD, PZ0.035 and FA, PZ0.005) and the left HC (MD, PZ0.035 and FA,
(weight, BMI, waist circumference (WC)) and metabolic (fasting glucose (FG)
PZ0.001) with long term memory reflecting general knowledge. DTI in the
and insulin (FI), total (TCHO), HDL and LDL cholesterol, triglycerides (TG),
cingulum correlated with visual memory (MD, P%0.04 and FA, P%0.04) and
HOMA-IR, HOMA-b, ISI0, VAI, and prevalence of MetS) parameters, and PRL
short term memory (MD, PZ0.004). DTI in the HC correlated with long term
levels were evaluated at baseline, at CAB withdrawal (TWD), and 12 (T12) and 60
memory (MD, PZ0.03 and FA, P%0.046) and short term memory (FA, PZ0.02).
(T60) months after CAB discontinuation. CAB treatment (median durationZ72
HT volume correlated negatively with MD of right uncinate fasciculus
months) induced PRL normalization in all patients, and a significant improvement
(PZ0.015). The CP patients had a smaller HC volume which correlated with
of BMI (P!0.0001), WC (P!0.0001), FI (PZ0.007), HDL (P!0.001), LDL
long term memory (PZ0.016).
(P!0.001), HOMA-IR (PZ0.012) and ISI0 (PZ0.05) compared to baseline. CAB
Conclusions
withdrawal resulted in prolonged and sustained normoprolactinemia, with only 8
A structure to function relationship is established between cognition and WM
(17.4%) patients requiring treatment restarting within 12 months. In 38 patients
damage detected with DTI in CP. CP patients have a smaller HC compared to
permanently discontinuing CAB, compared to TWD BMI (P!0.0001), WC
controls. Whether the cognitive deficits are a direct consequence of HT damage or
(P!0.0001), TCHO (P!0.001) and VAI (P!0.0001) significantly impaired at
an indirect effect on frontotemporal network remains to be elucidated.
T12, and similarly BMI (P!0.0001), WC (P!0.0001), TCHO (P!0.05) and VAI
(P!0.0001) at T60. Compared to TWD no further changes were seen in FI,
DOI: 10.1530/endoabs.49.GP182
HOMA-IR, HOMA-b, ISI0. MetS prevalence significantly increases from T0
(23.9%) to T60 (41.3%, P!0.0001), with 8 patients (17.4%) developing MetS after
CAB withdrawal. In conclusion, CAB discontinuation significantly worsens lipid
profile and MetS prevalence in patients with prolactinomas.
DOI: 10.1530/endoabs.49.GP184
GP183
Copeptin - a sensitive marker of an altered CRH-axis in
pituitary disease
Krzysztof Lewandowski1, Andrzej Lewinski1, Elzbieta Skowronska-
Jozwiak1, Katarzyna Malicka1, Wojciech Horzelski2 & Georg Brabant3
Pituitary & Endocrine Tumours
1Department of Endocrinology and Metabolic Diseases, “Polish Mother”
Memorial Research Institute and The Medical University of Lodz, Lodz,
GP185
Poland;2Faculty of Mathematics and Computer Science, University of
Localization of benign insulinomas using glucagon-like peptide-1
Lodz, Lodz, Poland;3Experimental and Clinical Endocrinology Med Clinic
receptor (GLP1-R) SPECT/CT and PET/CT and MRI in a prospective
I, University of Luebeck, Lubeck, Germany.
clinical study
Kwadwo Antwi1, Melpomeni Fani1, Tobias Heye1, Guillaume Nicolas1,
Elmar Merkle1, Jean Claude Reubi2, Beat Gloor3, Damian Wild1 &
Background
Copeptin (pre-proAVP) secreted in equimolar amounts with vasopressin (AVP)
Emanuel Christ1,4
closely reflects AVP release. Previously it was shown that copeptin is stimulated
1Clinic of Radiology and Nuclear Medicine, University of Basel Hospital,
in standard pituitary function tests acting through hypothalamic centres.
Basel, Switzerland;2Division of Experimental Pathology, Department of
Furthermore, copeptin has been shown to subtly mirror stress potentially
Pathology, University of Bern, Bern, Switzerland;3Department of Visceral
mediated via CRH. To further test a potential direct interaction of CRH with
Surgery, University Hospital of Bern, Inselspital, Bern, Switzerland;
copeptin release which could augment AVP effects on pituitary function, we
4Division of Endocrinology, Diabetology and Clinical Nutrition,
investigated copeptin response in a standard CRH test, both in healthy controls
University Hospital of Bern, Inselspital, Bern, Switzerland.
and patients with pituitary disease.
Patients and methods
Purpose
18 healthy controls and
29 subjects with history of pituitary disease were
We aim at prospectively comparing the detection rate of GLP1-R PET/CT vs
subjected to a standard CRH test and in addition to ACTH and cortisol we
GLP1-R SPECT/CT vs standardized contrast enhanced 3T-MRI in patients with
measured copeptin by standard assays (ThermoFisher).
suspected insulinoma.
Results
Methods
Patients with previous pituitary disease were subdivided in a group passing the test
40 patients with neuroglycopenic symptoms due to endogenous hyperinsulinemic
(P1) and failing (P2). The latter group included five patients with diabetes
hypoglycemia were enrolled.
insipidus. The overall copeptin response was higher in controls than in subjects
3T-MRI was performed. Afterwards patients received SPECT/CT after injection
with pituitary disease (area under the curve, PZ0.04 for P1CP2) with a maximum
of111In-DOTA-exendin-4 and PET/CT after injection of68Ga-DOTA-exendin-4
increase in controls from 3.84G2.86 pmol/l, to 12.65G24.87 pmol/l, PZ0.04, at
in a randomized order. Three blinded nuclear medicine physicians and three
30 min). In contrast, both groups of pituitary patients lacked a significant CRH
blinded radiologists reviewed the scans.
response. The mean increase in P2 was from 1.93G1.44 pmol/l to 3.37G
Standard of comparison was the histological diagnosis after surgery.
3.49 pmol/l, at 30 min, PZns, and even in P1 where ACTH concentrations
Results
increased four-fold (mean 21.48 vs. 91.53 pg/ml, P!0.01) copeptin did not
Previously performed cross-sectional imaging was negative or inconclusive in
respond (e.g. 4.35G5.81 pmol/l vs. 5.36G6.79 pmol/l, at 30 min, PZns).
27/40 patients. So far 29 patients have been operated. The histological diagnosis
Conclusions
of a benign insulinoma was confirmed in
25 patients, one patient had a
CRH is able to stimulate copeptin release in healthy controls suggesting a direct
nesidioblastosis. In one patient no lesion could be found intraoperatively. In two
interaction of CRH and AVP/vasopressin. Interestingly, this relation is altered
patient symptoms of endogenous hypoglycemia ceased postoperative but
already in the group of pituitary patients who pass the standard CRH test indicating
histological diagnosis did not confirm a benign insulinoma or nesidioblastosis.
i) that the CRH-ACTH-cortisol response is largely independent from the AVP
These two patients were excluded from evaluation as the final diagnosis remained
system, but ii) the CRH-AVP interaction reflected by copeptin may be much more
unclear. Two patients refused surgery. Three patients are awaiting surgery. In five
sensitive to reveal subtle alterations in the regulation of pituitary function.
patients all performed imaging modalities did not find any suspicious lesion and
DOI: 10.1530/endoabs.49.GP183
were thus not operated up to date. One patient showed signs of malignancy in
MRI, thus did not meet the inclusion criteria and was excluded. In this interim
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
analysis of 27 operated patients PET/CT showed an overall pooled sensitivity of
free cortisol (UFC) levels in some patients with Cushing’s disease (CD). Cabergoline is
92%, SPECT/CT at 72 h a sensitivity of 71% and 3T-MRI a sensitivity of 76%.
a dopamine D2 receptor agonist with efficacy in some patients with CD. Most
Conclusion
corticotropinomas co-express SSTR5 and D2, providing rationale for combination
1) These preliminary data suggest that PET/CT performs better as standardized
treatment with pasireotide and cabergoline. Results are reported from a Phase II
MRI imaging and SPECT/CT at lower irradiation dose and much shorter
study of pasireotide alone or combined with cabergoline in patients with CD.
investigation time than the latter.
Methods
2) GLP-1R PET/CT will be a useful diagnostic tool in patients where CT/MRI
Open-label, multicentre, non-comparative study. Patients with persistent/recur-
fails to localize the insulinoma.
rent or de novo (if not surgical candidates) CD who were pasireotide-untreated at
DOI: 10.1530/endoabs.49.GP185
screening were enrolled. Patients initiated treatment with pasireotide (subcutaneous)
0.6
mg bid. If mean UFC (mUFC; from two consecutive 24h collections)
remained OULN after 8 weeks, the pasireotide dose was increased, if tolerated, to
0.9 mg bid for 8 weeks. If mUFC remained elevated, cabergoline 0.5mg qd was
added for 8 weeks, increasing to 1.0mg qd for another 8 weeks if mUFCOULN.
Primary endpoint: proportion of patients with mUFC%ULN at week 35.
GP186
Results
24 hour urinary 5-hydroxyindoleacetic acid (5-HIAA) doubling-time
Sixty-six patients (median 40.5 years; 59 females) were enrolled. Twenty-seven
(DT) is associated with disease-specific mortality (DSM) and
patients received pasireotide monotherapy; 39 received combination therapy. At
progression-free survival (PFS) in patients with neuroendocrine
week 35, mUFC%ULN was achieved in 25 patients (37.9%, 95%CI 26.2-50.7),
tumors (NETs)
13 of whom received pasireotide monotherapy, with a further 12 achieving the
Amit Tirosh1,2, Naris Nilubol3, Dhaval Patel3 & Electron Kebebew3
primary endpoint after cabergoline addition. The most common (O20%) AEs
1National Institutes of Health, Bethesda, Maryland, USA;2Sackler Faculty
were hyperglycaemia (51.5%), nausea (47.0%), diarrhoea (45.5%), headache
of Medicine, Tel Aviv University, Tel Aviv, Israel;3Endocrine Oncology
(28.8%), dizziness (24.2%) and cholelithiasis (24.2%). Sixteen (24.2%) patients
Branch, National Cancer Institute, Bethesda, Maryland, USA.
discontinued before week 35 (10 on pasireotide monotherapy); seven (10.6%)
because of AEs (five on pasireotide monotherapy). Two on-treatment deaths
occurred, both unrelated to study treatment.
Background
Conclusions
Biochemical biomarker DT is used clinically for prognosis prediction in several
Pasireotide alone or combined with cabergoline effectively controlled mUFC.
solid malignancies. The aim of the current analysis was to determine whether
Results suggest that addition of cabergoline in patients with persistently elevated
biomarker DT has any prognostic utility in patients with NETs.
mUFC is an effective strategy to enhance the control of CD.
Methods
Patients with NETs
(nZ184) were enrolled in a prospective study with
DOI: 10.1530/endoabs.49.GP187
comprehensive biochemical analysis. The current analysis included subjects
with increasing 5-HIAA levels in at least two consecutive measurements. DTs for
each biomarker were calculated using the formula DT Z [log10(2)*(time interval
between tests)]/[log10(2nd value)-log10(1st value)]. Log-rank test was used to
assess differences in DSM or PFS risk by DT. The c-statistic of 5-HIAA predictive
GP188
utility for DSM was calculated using receiver operating characteristic (ROC)
Vertebral fractures are prevalent among patients with acromegaly in
curve analysis. DSM and PFS were compared by 5-HIAA DT using Kaplan-Meier
spite of normal bone mineral density reflecting overall duration of
survival analysis and multivariate analysis was performed using Cox regression.
disease regardless of biochemical control or cure
Results
Marko Stojanovic1,2, Dragana Miljic1,2, Sandra Pekic1,2, Mirjana Doknic1,2,
91 patients had increasing 5-HIAA levels. Four patients died during a median
Marina Nikolic Djurovic1,2, Zvezdana Jemuovic1, Vera Popovic2 &
follow-up of
8
months
(interquartile range,
12). The c-statistic for DSM
Milan Petakov1,2
prediction by 5-HIAA was 0.76 (95% CI 0.62-0.90), and 5-HIAA DT !434 days
1Clinic for Endocrinology, Diabetes and Metabolic Diseases,
had positive and negative predictive values for DSM of 75 and 76%, respectively.
Clinical Centre of Serbia, Belgrade, Serbia;2University of Belgrade,
Patients with a 5-HIAA DT !434 days had higher risk for DSM during follow-up
School of Medicine, Belgrade, Serbia.
(Log-Rank test, PZ0.02). In sub-group analysis this difference was found only
among patients with a non-pancreatic NET (PZ0.002). In the entire cohort, PFS
were comparable between patients with 5-HIAA DT longer vs. shorter than
Introduction
434 days. However, patients with small-intestine NET with 5-HIAA DT !
Skeletal complications of acromegaly are among its most persistent and
434 days had a higher risk for progression (PZ0.006), also in multivariate
invalidating impacts. Dual-X-ray absorptiometry
(DXA) alone might be
analysis (Hazard Ratio 15.3, 95% CI 1.01-232.6, PZ0.049).
insufficient or even misleading for bone health assessment in acromegaly.
Conclusions
Patients and methods
Short 5-HIAA DT is associated with increased DSM and lower PFS in patients
Patients with acromegaly
(NZ170) were classified as active
(NZ104),
with NET, and specifically among those with SINET, and can be used as a
operatively cured (NZ34) or medically controlled (NZ32). 57 males and 113
prognostic measure in NET patients.
females were included, 52.8 (22.0-78.5) years old. Bone mineral density (BMD)
DOI: 10.1530/endoabs.49.GP186
was assesed at L1-L4 and Femoral neck (FN) using DXA Hologic Discovery-W-
QDR. BMD results were expressed as Z score, accounting for age and gender.
Vertebral fracture assessment (VFA) on Th4-L4 was performed in 71 patients (24
male, 47 female) to identify number, type, location and degree of severity of
vertebral fractures (VFs).
GP187
Results
Pasireotide alone or in combination with cabergoline effectively
L1-L4 BMD was normal in all patients and not significantly different in active
controls urinary free cortisol levels: results from a prospective study in
(Zsc: 0.61G0.13) cured (Zsc: 0.32G0.25) or controlled acromegaly (Zsc: 0.17G
patients with Cushing’s disease (CAPACITY)
0.32). FN BMD was normal in all and not significantly different in active (Zsc:
Rosario Pivonello1, Pritam Kadioglu2, Marie Bex3, Deyanira
0.61G0.11) cured (Zsc: 0.59G0.19) or controlled acromegaly (Zsc: 0.49G0.22).
González Devia4, Cesar Boguszewski5, Dilek Gogas Yavuz6,
VFs were identified in 23.9% (17/71) of patients. Prevalence in males was
Heather Patino7, Federico Campigotto7, Alberto Pedroncelli8,
significantly higher than in females (33.3% vs. 19.2%; P!0.01). Patients with
Maria Fleseriu9, Beverly M K Biller10 & Richard Feelders11
and without VFs did not differ in BMD L1-L4 Zsc (0.98G0.06 vs. 1.04G0.02) or
1Università Federico II di Napoli, Naples, Italy;2Istanbul University,
FN Zsc (0.83G0.05 vs. 0.86G0.02). Duration of the disease in patients with VFs
Istanbul, Turkey;3University Hospitals Leuven, Leuven, Belgium;
was significantly longer (14.1G1.9 vs. 9.6G1.2yrs) then in those without VFs
4Hospital Universitario Fundación Santa Fé de Bogotá, Bogota, Colombia;
(P!0.05). Prevalence of VFs was significantly higher in controlled (62.5%) and
5Federal University of Paraná, Curitiba, Brazil;6Marmara University
cured (40.0%) compared to active (17.8%) acromegaly (P!0.01).
Medical School, Istanbul, Turkey;7Novartis Pharmaceuticals Corporation,
Conclusion
East Hanover, New Jersey, USA;8Novartis Pharma AG, Basel, Switzerland;
Considerable prevalence of vertebral fractures (24%) was identified in a large
9Oregon Health and Science University, Portland, Oregon, USA;
cohort of patients with acromegaly, irrespective of normal bone mineral density.
10Massachusetts General Hospital, Boston, Massachusetts, USA;11Erasmus
Duration of the disease was the main determinator of VFs prevalence, regardless
Medical Center, Rotterdam, The Netherlands.
of the biochemical control or cure. VFs are important, persistent and invalidating
Background
yet often under-recognized complication of acromegaly.
Pasireotide is a multireceptor-targeted somatostatin analogue that predominantly binds
DOI: 10.1530/endoabs.49.GP188
to somatostatin receptor subtype 5 (SSTR5) and provides sustained control of urinary
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP189
Objective and hypotheses
To describe and report safety data and incidence rates (IRs) (events/1000 patient-
Evaluation of pituitary toxicity after radiotherapy for cerebral
years) of adverse drug reactions (ADRs), serious adverse events (SAEs) and
chondrosarcomas in adult patients
serious ADRs (SADRs).
Suzanne Laroche1, Loïc Feuvret3,5, Alain Beauchet2, Rémi Dendale3,
Method
Philippe Chanson4, Eric Bruckert1 & Christel Jublanc1
Events were classified by MedDRA Preferred Term/System Organ Class (SOC).
1Endocrinologie, Hôpital Pitié Salpêtrière, APHP, Paris, France;2Unité de
IRs during GH treatment were calculated.
Recherche Clinique, Département de Santé Publique, Hôpital Ambroise
Results
Paré, APHP, Paris, France;3Centre de Protonthérapie d’Orsay, Institut
Data for 2438 patients (adult-onset, 90.1%; female 44.0%; mean (S.D.) age at
Curie, Orsay, France;4Endocrinologie, Hôpital Bicêtre, APHP, Le Kremlin
treatment start, 43.3 (17.8) years; duration of follow-up, 5.8 (4.7) years; GH dose,
Bicêtre, France;5Radiothérapie, Hôpital Pitié Salpêtrière, APHP, Paris,
0.41
(0.32) mg/day) were analysed. Overall, 197 adverse events (AEs) were
France.
reported in 150 patients. Among these patients, mean (S.D.) treatment duration to
first AE was 4.7 (4.1) years and GH dose at AE onset was 0.36 (0.31) mg/day.
Pituitary dysfunction can be a consequence of cranial radiotherapy. It usually occurs
After the first AE, GH dose was unchanged in 55.3%, discontinued in 26.4% and
years after the treatment. However little is known on risk factors for pituitary
decreased in 7.6% of patients (not reported/other for 10.7%). IRs were 11.91 for
dysfunction. The object of this study was to evaluate radiation induced pituitary
SAEs, 1.89 for SADRs and 5.52 for ADRs. Most frequently reported (nR10) AEs
toxicity of proton beam therapy in a cohort of adult chondrosarcoma patients.
by SOC (n, %) were nervous system disorders (nZ43, 21.8%), neoplasms
The files of 113 patients were reviewed. Mean age at the beginning of radiotherapy
(benign, malignant and unspecified)
(nZ35,
17.8%), musculoskeletal and
was 43 years old (18-76). Mean dose delivered to the tumor was 67 Gy and mean
connective tissue disorders
(nZ20; 10.2%); general disorders and adminis-
dose delivered to the pituitary gland was 59 Gy. Mean post-radiotherapy follow-up
tration-site conditions or infections and infestations (each nZ15, 7.6%); and
time was 7 years (4-17). Pituitary dysfunction was observed in 78 patients, within the
cardiac disorders (nZ14, 7.1%). Type 2 diabetes was reported as an AE in four
delay of 4 years after radiotherapy. The prevalence of hyperprolactinemia was of
patients. Twelve deaths (one possibly related) were reported.
40%, thyrotrophic insufficiency was 36%, corticotropic insufficiency 31%, and
Conclusions
gonadotropic insufficiency 25%. No significant differences were shown in the delay
IRs of SAEs, ADRs and SADRs were low. Data from NordiNetw IOS revealed no
of dysfunction between the pituitary axes. In multivariate analysis, risk factors
new safety signals, further supporting the favourable safety profile of GH
known to increase the risk of vascular side-effects of radiation (sex, age, smoking,
replacement in adults with GHD.
high blood pressure, dyslipidemia and diabetes mellitus) were not associated with an
DOI: 10.1530/endoabs.49.GP190
increase of pituitary dysfunction.
Conclusions
Pituitary toxicity of radiotherapy is frequent after 4 years. The high prevalence of
hyperprolactinemia pinpoints a possible hypothalamic origin of post radiotherapy
pituitary insufficiency. A prospective follow up is necessary to complete these
GP191
observations and propose relevant guidelines. Our study analyses the largest cohort
of patients with chondrosarcomas after proton beam therapy. Our results emphasize
GH and IGF-1 levels at 12 weeks predict long-term responses to
the importance of careful and long term endocrine follow-up of these patients.
lanreotide Autogel in treatment-naïve acromegalic patients: post-hoc
analyses from the PRIMARYS study
Philippe Caron1, Stephan Petersenn2, Aude Houchard3, Caroline Sert3 &
John S Bevan4
1
Department of Endocrinology, CHU Larrey, Toulouse, France;2ENDOC
Center for Endocrine Tumors, Hamburg, Germany;3Ipsen Pharma,
Boulogne-Billancourt, France;4Department of Endocrinology,
Aberdeen Royal Infirmary, Aberdeen, UK.
Background
In PRIMARYS, lanreotide Autogel (LAN) 120 mg/28 days reduced tumour
volume (TV), and GH/IGF-1 levels in patients with GH-secreting macro-
adenomas. In post-hoc analyses, we investigated predictive factors for treatment
responses.
Methods
PRIMARYS, a 48-week, international, open-label study, involved 90 treatment-
Figure: Kaplan-Meyer curve for pituitary dysfunction.
naïve patients with GH-secreting macroadenomas receiving LAN. Factors
predictive for hormonal control (HC; GH %2.5 mg/LC normal IGF-1) at last
DOI: 10.1530/endoabs.49.GP189
post-baseline value available (LVA) or R20% TV reduction (TVR) at week
48/LVA were investigated using univariate logistic regression. Week-12 GH,
IGF-1 and TV cut-off values for predicting responses were obtained from ROC
curves, maximising the Youden index. Analyses used intention-to-treat
populations and P!0.05 as significant.
Results
GP190
From univariate analyses, HC was more likely in women (odds ratio: 2.9 times
higher for women vs. men), and older patients (2.2 times higher for each 10-year
Safety of long-term growth hormone (GH) treatment in adults with GH
higher age), and with lower baseline IGF-1 (1.1 times higher for each 10% lower
deficiency (GHD): an analysis from the NordiNetw International
IGF-1 level [% upper limit of normal, ULN]), but no association with GH levels
Outcome Study
was shown. HC was determined by week-12 hormonal response: optimal cut-offs
Jens Otto Jørgensen1, Vera Popovic-Brkic2, Effie Pournara3,
were 1.19 mg/L for GH (sensitivity, 0.79; specificity, 0.89; area-under-the-curve
Birgitte Pedersen4, Anita Chudecka3 & Christian Strasburger5
[AUC] value, 0.87) and 110% ULN for IGF-1 (0.89, 0.85 and 0.93, respectively).
1Aarhus University Hospital, Aarhus, Denmark;2University of Belgrade,
Univariate analyses revealed no baseline factors influencing TVR. TVR was,
Belgrade, Serbia;3Novo Nordisk Health Care AG, Zurich, Switzerland;
however, determined by changes from baseline to week 12 in GH, IGF-1 and TV:
4Novo Nordisk A/S, Søborg, Denmark;5Charité Universitatsmedizin Berlin,
optimal cut-offs were K69% for GH (sensitivity, 0.74; specificity, 0.67; AUC,
Berlin, Germany.
0.74), K61% for IGF-1 (0.58, 0.80, 0.75), and K21% for TV (0.81, 0.97, 0.93).
Conclusions
Background
Based on post-hoc PRIMARYS data, treatment-naïve patients with GH-secreting
Long-term safety data (1998 to mid-2016) are reported for adult patients with
macroadenomas are more likely to achieve long-term hormonal control with LAN
GHD treated with GH (Norditropinw (somatropin), Novo Nordisk) as prescribed
120 mg/28 days if GH levels are !1.2 mg/L and IGF-1 levels !110% ULN at
by treating physicians in the real-life clinical setting and enrolled in NordiNetw
12 weeks, and more likely to achieve clinically significant long-term reductions in
International Outcome Study
(IOS)
(NCT00960128), a non-interventional,
TV with O60% reductions in GH/IGF-1 levels by week 12.
multicentre study.
DOI: 10.1530/endoabs.49.GP191
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP192
(68% women) but was also considered as climacteric and result of ageing.
Headache and visual impairment were common causes for referral later on, and
Long-term treatment with pegvisomant (Somavertw): Observations
hyperprolactinemia was found due to hormonal investigation after MR-visualiza-
from 2090 acromegaly patients followed in ACROSTUDY
tion of pituitary tumor. In some cases with prolactin levels 1300-1900 mMU/l,
Aart Jan vanderLely1, Beverly Biller2, Thierry Brue3, Michael Buchfelder5,
differential diagnosis was required between hyperprolactinemia due to pituitary
Ezio Ghigo4, kaijie Pan8, Peter Jonsson9, Joanne Lavenberg8, Christian
stalk compression and prolactinomas with moderate secreting activity (“hook”
J. Strasburger6, Susan Webb7, Cecilia Camacho-Hubner8
phenomena was excluded). However, significant tumor shrinkage and (in some
& Judith Hey-Hadavi8
cases) restoration of regular menstrual cycle after 3-6 months of cabergoline
1Erasmus University Medical Center, Rotterdam, The Netherlands;
treatment confirmed prolactinoma.
2Massachusetts General Hospital, Boston, MA, USA;3Universite de la
Conclusion
Mediterranee, Marseille, France;4Universita de Torino, Torino, Turin, Italy;
If a woman over 40 has menstrual irregularity or amenorrhea and does not
5University of Erlangen-Nurnberg, Erlangen, Germany;6Charite-Universi-
experience any vasomotor symptom, it is a reason to prove a natural menopause
tatsmedizin, Berlin, Germany;7Universitat Autonoma de Barcelona,
by measuring high FSH levels (O25 MU/l). In cases of lower FSH levels it is
Barcelona, Spain;8Pfizer Inc Endocrine Care, New York-Collegeville,
reasonable to consider pathological hyperprolactinemia.
USA;9Pfizer Inc ACROSTUDY Endocrine care, Sollentuna, Sweden.
DOI: 10.1530/endoabs.49.GP193
Introduction
Pegvisomant (PEGV) is approved for the treatment of acromegaly since 2003.
This is the second interim analysis of data from ACROSTUDY, with the majority
of patients treated for at least five years (yrs).
GP194
Methods/design
Serotonin, ATRX and DAXX as differential diagnostic markers of
ACROSTUDY is an international, open-label, prospective, non-interventional,
neuroendocrine tumours (NETs) in the sellar region. An
post-marketing surveillance study monitoring the long-term safety and efficacy of
immunohistochemical study in a large series of pituitary adenomas
PEGV. Patients were enrolled in the study on an ongoing basis.
and in a non-pituitary NET
Results
Olivera Casar-Borota1,2, Johan Botling1,2, Dan Granberg3,
As of May 31, 2016, data from 2090 patients (51% men) from 15 countries were
Johan Wikstrom4, Fredrik Pontén1,2 & Jacqueline Trouillas5,6
available. Mean treatment duration was 7.6 yrs (median 8.1 range: 0.0-19.1 yrs).
1Department of Immunology, Genetics and Pathology, Uppsala University,
Patients were followed in ACROSTUDY for a mean of 6.3 yrs (median 6.8, range
Uppsala, Sweden;2Department of Clinical Pathology, Uppsala University
0.1-12.1). At ACROSTUDY start, there were 12 patients in the 0-18 yrs category
Hospital, Uppsala, Sweden;3Department of Medical Sciences, Uppsala
and 203 patients in the O70 yrs category. At PEGV start, pituitary insufficiencies
University, Uppsala, Sweden;4Department of Surgical Sciences, Uppsala
were observed for gonadotrophins (37.9%), TSH (29.1%) and ACTH (28.3%).
University, Uppsala, Sweden;5Faculté de Médecine Lyon-Est, Université
54.4% of patients experienced adverse events (AEs) with most common AE being
Lyon 1, Lyon, France;6Centre de Pathologie et de Biologie Est,
IGF-I increased
(10.5% of patients), headache(4.9%), vitamin D defici-
Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, Lyon, France.
ency(4.6%) and arthralgia(3.7%). SAEs were experienced in 22% of patients
(2.3% were treatment related, while 7.0% of patients discontinued treatment due
to the SAE). A total of 78 deaths were reported (all non-treatment related).
We present a case of a patient with a locally invasive, serotonin- and ACTH-
Locally assessed MRIs showed that most patients (72.2%) had no change in
reactive tumour in the sellar region, filling the sphenoid sinus and expanding into
tumour size relative to last exam; 16.8% had decrease in tumour size, 6.8% had an
the epipharynx. Clinical examination completed by 68-Gallium-DOTA-TOC
increase, and 4.3% had both increase and decrease. Shift analysis demonstrated
PET revealed tracer uptake in the sellar tumour as well as in a 7 mm lesion in the
that of the
1245 with reported normal LFTs
(AST/ALT) at baseline,
3%
pancreatic tail. A differential diagnosis between silent corticotroph adenoma and
developed elevations O 3xULN. Administration site reactions were reported for
another primary or secondary neuroendocrine tumour
(NET) with ACTH-
3.4% of patients.
expression was difficult.
Conclusions
As serotonin was strongly positive in the tumour cells and its expression in
This second interim analysis of long-term follow up showed that PEGV is an
pituitary endocrine tumours has not been systematically studied, we performed
effective and safe treatment in patients with acromegaly. Data indicate low
immunohistochemical analysis of serotonin in a large series of pituitary adenomas
occurrence of reported pituitary tumor changes, liver test elevations and site
of different hormonal types from 246 patients. In addition, ATRX and DAXX,
administration reactions.
which mutations are associated with a subset of pancreatic NETs have been
DOI: 10.1530/endoabs.49.GP192
studied by using immunohistochemistry in the same cohort of pituitary tumours.
None of the examined pituitary tumours expressed serotonin. There was normal
expression of ATRX and DAXX corresponding to a lack of ATRX/DAXX
mutations in the pituitary tumours.
Thus, serotonin-immunolabelling tumours in the sellar region most probably
represent primary or secondary neuroendocrine tumours of non-pituitary origin.
GP193
ATRX and DAXX do not seem to be involved in the pathogenesis of pituitary
adenomas. Demonstration of ATRX or DAXX mutations in a neuroendocrine
Amenorrhea without vasomotor symptoms in women over 40: A sign of
tumour of the sellar region excludes pituitary adenoma and suggests a non-
pathological hyperprolactinemia?
pituitary NET, probably of pancreatic origin.
Irena Ilovayskaya, Alexader Dreval & Yulia Krivosheeva
Moscow Regional Research & Clinical Institute, Moscow, Russia.
DOI: 10.1530/endoabs.49.GP194
Background
Hyperprolactinemia is often seen in women of reproductive age (20-35 years),
most often due to microprolactinoma. However, prolactinomas do occur in older
GP195
women.
Long-term follow-up of a family with a large AIP gene deletion: variable
Objective
phenotypes and challenges in the management
To analyze clinical features of hyperprolactinemia in women O40 years
Pedro Marques1, Mary Dang1, Arla Ogilvie2, Helen Storr3, Michael Powell4,
Material and methods
Joan Grieve4, Jane Evason5, Ajith Kumar6 & Marta Korbonits1
Clinical and biochemical data of 185 women with pathological hyperprolacti-
1Centre for Endocrinology, William Harvey Research Institute, Barts and
nemia were analyzed.
the London School of Medicine and Dentistry, Queen Mary University of
Results
London, London, UK;2West Hertfordshire Hospitals NHS Trust, Watford,
Seventy
(37.8%) patients had microprolactinomas
(MI),
57
(30.8%)
-
UK;3Department of Paediatric Endocrinology, Royal London Hospital,
macroprolactinomas (MA), and 58 (31.4%) - non-tumoral hyperprolactinemia
Barts Health NHS Trust, London, UK;4The National Hospital for
(NT). Among them, 26(36.1% of corresponding subgroup) with MI, 27(46.6%)
Neurology and Neurosurgery, London, UK;5Department of Radiology
with NT and 37(64.9%) with MA were O40 years of age. Menstrual disturbances
Barts Health NHS Trust, London, UK;6North East Thames Regional
and infertility issues are key factors for prolactin measurement but among these
Genetics Service, Great Ormond Street Hospital, London, UK.
women, it was a reason to visit doctor only in few cases. In most cases with onset
of hyperprolactinemia within 40-50 years of age, women themselves or their
gynecologists considered amenorrhea as a natural postmenopause, missing the
Introduction
correct diagnosis. It was characteristic for hyperprolactinemic women that they
Germline aryl hydrocarbon receptor-interacting protein
(AIP) mutations are
did not experience vasomotor climacteric symptoms. Weight gain was common
responsible for 15-30% of familial isolated pituitary adenomas (FIPA). We report
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
a 4-generation FIPA kindred with a heterozygous AIP gene deletion in exon 2,
Thyroid 1
highlighting the benefits of genetic screening and management challenges in
GP197
affected subjects and asymptomatic carriers.
Patients
Cognitive functions in primary hypothyroidism on selenium
A 45y woman died of a spinal ependymoma (obligate carrier). Her 18y son
supplementation
showed lethargy over the following months attributed to grief. However,
Marina Nikolic-Djurovic1, Alberto Pereira2, Johannes Smit3,
investigations due to headache revealed hypopituitarism and a clinically non-
Olga Vasovic4, Zvezdana Jemuovic1, Svetozar Damjanovic1,
functioning PA was diagnosed. Two years later, his 185 cm 18y-brother was
Milika Asanin5, Dragan Pavlovic6, Dragana Jankovic1, Sandra Pekic1,
diagnosed with a sparsely-granulated PA co-expressing PRL&GH. Fourteen-
Dragana Miljic1, Marko Stojanovic1 & Milan Petakov1
years after operation his IGF-1 was repeatedly raised with small increase in his
1Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Clinical
tumour remnant. Lanreotide treatment was started and surgery is planned. A
Centre of Serbia, University of Belgrade, Belgrade, Serbia;2Department of
Rathke’s cyst was detected in a bulky gland in their eupituitary 17y mutation
Endocrinology and Metabolic Diseases Leiden University Medical Center,
carrier sister when she was first screened, which is now regressed. However, after
Leiden, The Netherlands;3Division of Endocrinology, Department of
8y follow-up a 4 mm-microadenoma became visible, with normal PRL, IGF-1
Internal Medicine, Radboud University Medical Centre, Nijmegen, The
and OGTT-GH nadir 0.38 mg/l. Their 27y second-cousin presented amenorrhoea
Netherlands;4Institute for Gerontology and Palliative Care, Belgrade,
after cessation of oral contraceptive, hyperprolactinaemia and 2xULN IGF-1. Her
Serbia;5Clinic for Cardiology, Clinical Centre of Serbia, University of
MRI showed 2 pituitary microadenomas, corresponding to a 6 mm-somato-
Belgrade, Belgrade, Serbia;6Faculty of Philosophy, University of Belgrade,
tropinoma on the right and a
4 mm-prolactinoma on the left, confirmed
Belgrade, Serbia.
histologically.
Discussion
Introduction
Of 14 subjects with AIP mutations, 4 have PA, 1 ependymoma and 7 are
Selenium (Se) is a trace element that plays key roles in thyroid pathology. In patients
asymptomatic (penetrance 29%). Ependymomas were described with loss of
with Hashimoto thyroiditis (HT), Se supplementation might reduce antibody levels
genetic material at 11q13-locus, but has not been described in patients with AIP
and may provide additional beneficial effects, such as on cognition.
mutations. The slow regrowth of the tumor in the brother suggests that long-term
Aim
follow-up is needed. Bulky pituitary and not fully suppressed GH on OGTT can
To evaluate cognitive function
(cognitive decline) in patients on long-term
represent challenges in AIP mutation carrier teenager females. Multiple PAs with
levothyroxine replacement for primary hypothyroidism with and without selenium
different secretory profiles may arise in the pituitary of these patients. Genetic
supplementation.
screening and baseline review with follow-up of younger subjects is
Design
recommended in AIP mutation-positive families.
Cross-sectional, case-control study.
DOI: 10.1530/endoabs.49.GP195
Patients and methods
Sixty nine patients with HT
(mean age
43.52G14.33
yrs) on long-term
levothyroxine replacement and 57 euthyroid healthy controls, matched for age,
sex, and educational level, were included. HT patients were divided into 2 groups,
25pts with (SeC) and 44pts without selenium supplementation(Se-). Neuropsy-
chological evaluation assessed general cognitive function(cognitive screening:
MMSE, Visual- and Digit Span), attention span in visual and verbal modality
(Numbers from WAIS and Visual span from WMS-R), conceptual tracking (TMT
A and B), verbal divergent thinking (Phonemic fluency test, Listing of animals from
BDEA, TMT B, Verbal fluency test).
Results
Selenium levels were within the normal range in all groups, but significantly higher
in HT(SeC)vs controls (94.88G20.63 vs 86.95G14.95 mcg/l, P!0.05). TSH
GP196
concentrations were higher in patients
(both HT(SeC) and HT(Se-)) when
Diagnosis of acromegaly: Sex and BMI are the major determinants of
compared to controls: (3.01G1.66 and 3.01G1.90 vs 1.77G0.88 mU/l, P!0.000),
growth hormone suppression during oral glucose tolerance test (OGTT)
but FT4 concentrations were not different: (12.81G4.01 vs 12.46G2.64 vs 12.93G
Katharina Schilbach, Shiva Sophia Nicolay, Michael Haenelt,
2.88 ng/l, PO0.05). TPOab concentrations were different, both between HT(SeC)
Andreas Lechner, Christina Gar, Jochen Schopohl, Sylvère Stormann,
and HT(Se-), as well as between patients and controls (1399.25G1968.30 vs
Rita Schwaiger & Martin Bidlingmaier
4290.96G3177.13 vs 20.48G30.73 U/ml, P!0.001). Global cognitive function
Medizinische Klinik und Poliklinik IV, Klinikum der Universitat Munchen,
(MMSE) was not different between groups (29.16G1.31 vs 29.16G1.61 vs
Munich, Germany.
29.54G0.93, PO0.05), but conceptual tracking and verbal divergent thinking was
different between all groups (TMTA:36.40G12.85 vs 40.89G21.89 vs 29.81G
GH suppression during OGTT is the gold-standard test in diagnosis and
11.57, P!0.001, TMTB:89.00G27.88
vs
103.93G48.81
vs
73.02G24.10,
monitoring of acromegaly. However, discrepancies between GH nadir and IGF-I
P!0.001, KF:21.88G5.61 vs 19.07G5.65 vs 21.44G5.11, P!0.05, FF:11.28G
have been described and have triggered search for factors modifying the extent
3.37 vs 9.22G3.69 vs 11.05G3.44, P!0.05).
of GH suppression. Cut-offs at 1.0 or 0.4 ng/ml are currently recommended with
Conclusion
modern, highly sensitive GH assays. To establish assay specific GH nadir cutoffs
Patients treated for primary hypothyroidism according to routine clinical care
for the 22kD GH specific IDS-iSYS assay, we examined 381 subjects (319
guidelines show persistent impairments in cognitive functioning which were, in
females, 62 males) with normal pituitary function. We analyzed the impact of
certain domains, improved with selenium supplementation. Future studies are still
age, body mass index (BMI), menstrual cycle and hormonal contraceptive
needed in order to provide reliable evidence to support selenium supplementation in
therapy.
a clinical practice.
In 96% of all subjects the GH nadir was !0.4 ng/ml (92% !0.3 ng/ml, 81%
DOI: 10.1530/endoabs.49.GP197
!0.2 ng/ml and 56% !0.1 ng/ml). In all sex- and age-groups BMI was the
major determinant, with lower GH nadirs in subjects with higher BMI. In 4
different BMI groups (A: !20 kg/m2, nZ30, B: 20-25 kg/m2, nZ174, C: 25-
30 kg/m2, nZ99 and D: O30 kg/m2, nZ77) mean GH nadirs were as follows:
A: 0.29 ng/ml, B: 0.15 ng/ml, C: 0.10 ng/ml and D: 0.07 ng/ml with significant
differences between all groups except group C vs. D (A vs. B: PZ0.0043, A
GP198
vs. C, A vs. D, B vs. C, B vs. D: P!0.0001, C vs D: PZ0.057). While age
had no impact, men exhibited significantly lower mean GH nadirs compared to
Which is the best tool to use when initiating the differential diagnosis of
women (0.09 vs 0.14 ng/ml, P!0.0001). Premenopausal women on estrogen
a thyrotoxic patient? A challenge to current guideline recommendations
containing oral contraception (OC) (nZ20) had significantly higher mean GH
Carolina Perdomo1, Elisa Gil Ramos1, Gala Gutiérrez Buey1,
nadirs (0.36 ng/ml) compared to women not taking estrogen containing OC
María Llavero1, Javier Gargallo1, Javier Arbizu2, Magdalena de la Higuera1
(nZ272, 0.13 ng/ml, P!0.044), while the phase of the menstrual cycle had no
& Juan C Galofré1
impact.
1Department of Endocrinology. University of Navarra, Pamplona, Spain;
Our findings confirm the need for lower cutoffs for the GH nadir if new
2Department of Nuclear Medicine. University of Navarra, Pamplona, Spain.
sensitive GH assays are used, but also suggest adjustment to sex- and BMI can
improve diagnostic sensitivity and specificity.
Aim
DOI: 10.1530/endoabs.49.GP196
Differential diagnosis (DD) of thyrotoxicosis is critical as the treatment of the
three main causes of this condition (Graves’ disease [GD], Toxic Multinodular
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Goitre [TMG], and Thyroiditis [TS]) differs substantially. Recently published
(rZ0.371, PZ0.004), LDL
(rZK0.325, PZ0.011), ApoB (rZK0.342,
diagnostic algorithms investigating hyperthyroidism embrace the presence of
PZ0.022) and lipoprotein(a)
(rZK0.470, PZ0.001) were revealed in the
thyrotropin receptor (TSH-R) antibodies (TRab) as the first and most cruicial
group TSH 2.5-5.0mUI/ml. Regarding the group TSHO5.0 mUI/ml, we found
diagnostic step. Although TRab measurement has important limitations (some
positive correlations between FT3 and HDL (rZ0.358, PZ0.030), vitamin B12
can block or be neutral to TSH-R, or pass undetected by the assay), Guidelines
(rZ0.398, PZ0.024) and HOMA-IR (rZ0,424, PZ0,031); and between anti-
recommend thyroid radionuclide scan
(TRS) when TRab are absent. Our
thyroglobulin and homocysteine (rZ0.383, PZ0.033).
objective was to compare the TRab vs. TRS values in the DD of hyperthyroidism.
Conclusion
We sought to analyse limitations of the current diagnostic Guidelines which could
We observed significant correlations between thyroid function, thyroid
lead to misdiagnosis and improper treatment of thyrotoxicosis.
autoimmunity, insulin resistance, lipid profile and homocysteine that may
Methods
contribute to an increased cardiovascular risk in AIT.
We conducted a retrospective study of 235 outpatients attended at our Centre
DOI: 10.1530/endoabs.49.GP199
from 2006 to 2016. Inclusion criteria were patients with overt or subclinical
hyperthyroidism from whom TRab and TRS levels were taken at the time of
diagnosis. SPSS 20.0 was used for statistical analysis. Pearson’s correlation was
applied to quantify the relationship between the two diagnostic tools.
Results
We grouped the sample in Gr. A: 89 (37.8%) those with positive TRab; Gr. B: 102
(43.4%) those with diffuse TRS uptake; and Gr. C: 146 (62.2%) those with
negative TRab. All groups were partially overlapped. In Gr. A, the TRS reported a
diffuse increase uptake (consistent with GD) in 63 (70.8%), heterogeneous uptake
GP200
consistent with TMG in 21 (3.6%), and absent or low uptake consistent with TRS
Evaluation of the effectiveness of personalized radioiodine treatment in
in 5 (5.6%). In Gr. B, only 63 (61.8%) had positive TRab. In Gr. C, up to 39
Graves’ disease
(26.7%) of individuals had a diffuse increased uptake in TRS. Pearson’s r analysis
Ana Fernandes1, Teresa Faria1, Ana Oliveira1, Jorge Pereira1 &
between positive TRab and diffuse increased uptake was: 0.431 (PZ!0.001).
Pedro Coelho2
Conclusions
1Centro Hospitalar são João, Porto, Portugal;2Universidade Fernando
Provided that a high diffuse uptake by TRS can only be associated with GD, our
Pessoa, Porto, Portugal.
study suggests that the DD of thyrotoxicosis should not rely initially on TRab, as
this approach may leave a third
(29%) of patients misdiagnosed, and
Aim
consequently, improperly treated. Our results support the value of thyroid
Radioiodine activities for the treatment of Graves’ disease hyperthyroidism are
scintigraphy as the first step in the DD of thyrotoxicosis.
still subject to discussion, as is the use of a fixed approach over a dosimetric one.
DOI: 10.1530/endoabs.49.GP198
We aimed to evaluate our success rate using a personalized dosimetric approach:
instead of the “(MBq I-131!g gland mass!100)/(percentage uptake at 24 h)”
activity calculation, we further adjusted for factors such as gender, age, diagnosis,
2 h and 4 h radioiodine uptake, previous medication, and clinical history.
Materials and methods
We reviewed data from all patients treated with radioiodine therapy (RIT) for
hyperthyroidism at our department (nZ179), from January 2008 to January 2016,
selected those with Graves’ disease (nZ118), and excluded the ones without
GP199
follow-up (nZ11). RIT was considered successful if either euthyroidism or
Cardiovascular risk factors in patients with autoimmune thyroiditis
hypothyroidism were achieved. We evaluated success rates differences between
Joa˜o Sérgio Neves2, Catarina Cunha1, Celestino Neves2, Sofia
lower and higher activities. All statistical analyses were carried out using IBM
Castro Oliveira2, Oksana Sokhatska3, Camila Dias4, César Esteves2,
SPSS version 21.0 for Mac. A type I error 0.05 was considered.
Miguel Pereira2, José Luís Medina1, Luís Delgado3 & Davide Carvalho1,5
Results
1Faculty of Medicine, University of Porto, Porto, Portugal;2Endocrinology
107 patients were included (44.346G13.07 years; 89 female). RIT was successful
Service, São Joa˜o Hospital, Faculty of Medicine, University of Porto, Porto,
in 91.6% (nZ98), while 8.4% (nZ9) remained hyperthyroid. If we consider the
Portugal;3Immunology Department, São João Hospital, Faculty of
success after the first RIT, 72.0% (nZ77) succeeded, while 28.0% (nZ30)
Medicine, University of Porto, Porto, Portugal;4Department of Biostatistics
remained hyperthyroid. 87 (81.3%) were submitted to a single therapy whereas 20
and Medical Informatics, Faculty of Medicine, Sa˜o João Hospital,
(18.7%) were submitted to multiple RIT. There were no significant outcome
University of Porto, Porto, Portugal;5Instituto de Investiga
¸a˜o e Inovação
differences between the lower and higher activities used (PZ0.061).
em Saúde, Faculty of Medicine, University of Porto, Porto, Portugal.
The used activities ranged between
148 MBq and 703 MBq (335.92G
101.60 MBq).
Conclusion
Background
Our results confirm RIT effectiveness in Graves’ disease hyperthyroidism
Overt thyroid dysfunction is associated with an increased cardiovascular risk. The
treatment. Although using inferior activities to those generally prescribed (200-
impact of subclinical hypothyroidism and autoimmunity in the increased
800 MBq), we achieved higher success rates - comparable to the best reposted in
cardiovascular risk remains controversial. Aim: To evaluate the interrelations
the literature. There were no statistically significant outcome differences between
between thyroid function, thyroid autoimmunity and cardiovascular risk factors,
the lower and higher activities used, highlighting the importance of tailored
in patients with autoimmune thyroiditis (AIT).
treatment approaches to warrant the best therapeutic outcome and while avoiding
Methods
unnecessary exposure.
353 subjects with AIT were evaluated. We defined three groups based on TSH
levels: TSH!2.5 mUI/ml, TSH
2.5-5.0 mUI/ml and TSHO5.0 mUI/ml. We
DOI: 10.1530/endoabs.49.GP200
recorded thyroid function tests, thyroid autoimmunity, insulin resistance markers
including Homeostasis Model Assessment for Insulin Resistance (HOMA-IR),
lipid profile, homocysteine, C-reactive protein (CRP) and vitamin B12 levels.
Statistical analysis was performed using Kruskal-Wallis test and Spearman
correlations.
Results
Our sample comprised 94% females with a mean age of 47G16.3 years. The group
TSHO5.0 mUI/ml presented higher levels of HOMA-IR when compared to the
other two groups [2.96(1.76-4.59) in TSHO5.0 mUI/ml vs 1.86(0.97-2.56) in
TSH 2.5-5.0 mUI/ml and 1.58(1.06-2.46) in TSH!2.5 mUI/ml, PZ0.002]. In the
total group we observed positive correlations between free T3 (FT3) and both HDL
GP201
(rZ0.118, PZ0.028) and ApoA1 (rZ0.129, PZ0.024); TSH was positively
correlated with HOMA-IR (rZ0.146, PZ0.018) while free T4 (FT4) was
negatively correlated with homocysteine (rZK0.119, PZ0.041). In the group
Abstract withdrawn.
TSH!2.5 mUI/ml, positive correlations were found between TSH and both HDL
(rZ0.136, PZ0.031) and homocysteine (rZ0.147, PZ0.028), FT4 and CRP (rZ
0.136, PZ0.037) and also anti-thyroglobulin and ApoB (rZ0.165, PZ0.013);
anti-thyroglobulin was negatively correlated with homocysteine (rZK0.186,
PZ0.006). Negative correlations between anti-thyroglobulin, total cholesterol
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP202
activity was mild (VISA %3/10) in 69% and severe in 16% (R7); severity mild
in 47.1% and severe in 20.2%. 1 year data (nZ36) showed mild activity at 1
Citrus flavanones naringenin and hesperetin induced mild functional
year in 95% (38.9% at referral) and 0% severe disease (33% at referral).
alteration in thyroids of old-aged Wistar rats
Intravenous methylprednisolone was administered to 30 patients; 47% required
Marko Miler1, Vladimir Ajdzanovic1, Natasa Ristic1, Branko Filipovic1,
%1.5 g total with use of SSAs: methotrexate (nZ30), azathioprine (nZ6),
Gordana Uscebrka2, Dragana Miljic3, Verica Milosevic1 &
ciclosporin (nZ10) and Rituximab (nZ8). Orbital decompression surgery was
Branka Sosic-Jurjevic1
performed in 12.5% (nZ13), squint surgery 12.5%, eyelid surgery 22% and
1Institute for Biological Research “Sinisa Stankovic”, University of
orbital radiotherapy 8%.
Belgrade, Belgrade, Serbia;2Department of Veterinary Medicine, Faculty of
Conclusion
Agriculture, University of Novi Sad, Novi Sad, Serbia;3Department of
Early use of SSAs has significantly reduced the overall steroid load in patients
Neuroendocrinology, Clinic for Endocrinology, Diabetes and Metabolic
when compared to established European guidance (EUGOGO). This regimen
Diseases, Clinical Center of Serbia, Belgrade, Serbia.
confers a low orbital decompression and orbital radiotherapy rate.
DOI: 10.1530/endoabs.49.GP203
Aging is a complex process characterized by a progressive decline in cellular
function, alterations of the endocrine system and the increased incidence of
thyroid diseases. Citrus flavanones naringenin (NAR) and hesperetin (HES) may
contribute to maintenance of health at old age however they may also affect
thyroid hormone economy. The aim of this study was to test weather NAR or HES
administration alter thyroid functioning. NAR or HES were administrated orally
(15 mg/kg) to male 24-month-old Wistar rats during 4 weeks. Control groups
GP204
received vehicle, sunflower oil. Immunohistochemical staining of thyroglobulin
24-month efficacy of a single radiofrequency ablation on autonomously
(Tg), thyroxine (T4) bound to Tg (T4-Tg) and sodium iodide sysmporter (NIS)
functioning thyroid nodules
were performed. Immunopositivity of Tg or T4-Tg in thyroid follicles were
Stella Bernardi1,2, Fulvio Stacul2, Andrea Michelli1, Veronica Calabrò2,
measured as intensity of optical density (OD) or relative intensity of fluorescence
Fabiola Giudici1, Chiara Dobrinja2 & Bruno Fabris1,2
(RIF). Thyroid stimulating hormone (TSH) and total T4 concentrations were
1Università degli Studi di Trieste, Trieste, Italy;2ASUITS, Trieste, Italy.
measured in serum. After citrus flavanones treatments, thyroids showed Tg and
T4-Tg immunopositivity mainly in the colloid of the follicles. The obtained
results showed increased (P ! 0.05) intensity of OD for Tg and T4-Tg RIF after
Background
both flavanones treatments, while NIS expression did not change. Serum TSH
Radiofrequency ablation has been advocated as an alternative to radioiodine
increased (P ! 0.05) only after NAR, although T4 remained unchanged after both
and/or surgery for the treatment of autonomously functioning benign thyroid
treatments. In conclusion, citrus flavanones induced stronger expression of
nodules. However, only a few studies have measured radiofrequency ablation
thyroid-specific proteins in gland of old-aged males. However, only NAR
efficacy on autonomously functioning benign thyroid nodules. The aim of this
elevated serum TSH, being more potent than HES. This alteration is in line with
work was to evaluate the 24-month efficacy of a single session of radiofrequency
preserved capacity of the thyroid to compensate the mild interference of
ablation (performed with the moving shot technique) on solitary autonomously
flavanones treatments with thyroid hormone production in old-aged males.
functioning benign thyroid nodules.
Methods
DOI: 10.1530/endoabs.49.GP202
Thirty patients with a single, benign autonomously functioning thyroid nodule,
who were either unwilling or ineligible to undergo surgery and radioiodine, were
treated with radiofrequency ablation between April 2012 and May 2015. All the
patients underwent a single radiofrequency ablation, performed with the 18-gauge
needle and the moving shot technique. Clinical, laboratory, and ultrasound
evaluations were scheduled at baseline, and after 1, 3, 6, 12, and 24 months from
the procedure.
Results
A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69,
75%, and 76% after 1, 3, 6,12, and 24 months, respectively. This was associated
with a significant improvement of local cervical discomfort and cosmetic score.
As for thyroid function, 33% of the patients went into remission after 3 months,
43% after 6 months, 50% after 12 months, and 70% after 24 months from the
procedure. This study demonstrates that a single radiofrequency ablation allowed
GP203
us to withdraw anti-thyroid medication in the majority of patients, who remained
The oxford multidisciplinary thyroid eye disease (TED) clinic; can short
euthyroid afterwards.
waiting times and use of steroid sparing agents (SSA) reduce total
Conclusions
steroid dose and requirement for surgery/radiotherapy?
This study shows that a single radiofrequency ablation was effective in 70% of
Helen Turner1, Joel David2 & Jonathan Norris3
patients with autonomously functioning benign thyroid nodules. Most
1Department of Endocrinology, Churchill Hospital, Oxford, UK;
importantly, patients responded gradually to the treatment, such that it is possible
2Department of Rheumatology, Nuffield Orthopaedic Hospital, Oxford, UK;
that longer follow-up studies might show greater response rates.
3Oxford Eye Hospital, Oxford, UK.
DOI: 10.1530/endoabs.49.GP204
Introduction
The Oxford multidisciplinary thyroid eye disease (TED) clinic comprising an
oculoplastic surgeon, rheumatologist and endocrinologist with access to
orthoptics, neuroradiology and radiotherapy was established in 2013. The aim
was to facilitate rapid referral and treatment in a specialist centre in keeping with
Amsterdam Declaration. Early use of steroid sparing agents (SSA) and recently
rituximab forms part of the treatment regimen.
Methods
A retrospective, 4-year, single-centre, consecutive case series of patients with
GP205
TED audited both outcomes (in terms of severity and activity) derived from
Association of vitamin D levels with thyroid function and
the VISA classification and treatment modalities, at presentation and 1 year
autoimmunity
follow-up.
Luis Raposo1,2, Sandra Martins3,4, Daniela Ferreira5, João
Results
Tiago Guimarães4,5 & Ana Cristina Santos2,5
104 patient records were analysed. Mean wait from referral to first review was 1
1Grupo de Estudo da Insulino-Resistência da Sociedade Portuguesa de
month with 42% of referrals originating from endocrinology departments. Mean
Endocrinologia, Diabetes e Metabolismo, Portugal, Portugal;2Instituto de
age was 51.2 years. 26.0% (nZ27) of patients were male and 35% were
Saúde Pública da Universidade do Porto - EPIUnit, Universidade do Porto,
current/ex-smokers. Where thyroid biochemistry was available at referral
Porto, Portugal;3Servic¸o de Patologia Clínica, Centro Hospitalar de S. João,
(nZ80): 51% were euthyroid, 45% hyperthyroid and 4% hypothyroid. TSHRAb
Porto, Portugal;4Departamento de Biomedicina, Faculdade de Medicina,
was positive in
85% of patients checked compared to
62% of TPO Ab.
Universidade do Porto, Porto, Portugal;5Departamento de Epidemiologia
Presenting signs included: ocular surface disease (68%), exophthalmos (53%),
Clínica, Medicina Preditiva e Saúde Pública, Faculdade de Medicina,
diplopia (45%), eyelid retraction (38%) and reduced vision (7%). Presenting
Universidade do Porto, Porto, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
TED. This approach results in a significant reduction in disease activity with
Vitamin D is a hormone that acts through the Vitamin D receptor (VDR) not only
reduced total steroid load.
on the skeletal system but on a great number of target tissues, including thyroid
DOI: 10.1530/endoabs.49.GP206
gland. In recent years the association of vitamin D with autoimmune thyroid
diseases (AITD), has been suggested.
VDR gene polymorphisms had been associated with an increased risk of AITD. In
addition a recent meta-analysis showed that AITD patients had lower level of
25-hydroxyvitamin D. However some studies have not confirmed the association
between vitamin D levels and AITD. Furthermore, data on the effects of vitamin
D in thyroid hormones and TSH serum levels are very poor.
The aim of our study was to evaluate the association of vitamin D levels with
GP207
thyroid function and positivity for thyroid antibodies.
Prediction of response to methimazole based on clinical symptoms in
Material and methods
new onset graves’ patients, using neural networks
PORMETS is a nationwide, cross-sectional study in Portugal comprising a
Hoon Sung Choi1 & Won Sang Yoo2
sample of 4095 adults. Five hundred participants were randomly selected to be
1Kangwon National University Hospital, Chuncheon-si, Republic of Korea;
included in the present study. A fasting venous sample was collected and serum
2Dankook University Hospital, Cheonan-si, Republic of Korea.
calcium, PTH, 25-hydroxyvitamin D [25(OH)D], TSH, FT4, FT3 and thyroid
antibodies were measured.
Introduction
Results
Anti-thyroidal drug (ATD) therapy is a treatment of choice for Graves’ disease
Our study included 286 women and 214 men with a mean age of 53.4 years.
because of its effectiveness and low rate of adverse effect. Response to ATD or
Free thyroxine (FT4), free triiodothyronine (FT3), TSH and thyroid antibody
remission rate varies among individuals, although there were few useful clues for
levels did not present any significant linear correlation with 25(OH)D levels.
prediction of treatment response. We applied neural network model to predict
After adjustment for sex and age, TSH, FT4 and FT3 levels did not present any
response to methimazole, based on clinical symptoms at initial clinical symptoms.
significant association with 25(OH)D levels or with low vitamin D status.
Methods & Design
Logistic regression analysis did not show any significant association of low
We reviewed 20 new onset Graves’ patients and used their symptoms at initial
vitamin D status with thyroid antibodies positivity, even after adjustment for
diagnosis. A total of 12 symptoms were classified into 5 categories (general,
several possible confounding variables.
cardiac, neuromuscular, psychologic, and gastrointestinal). In each category, the
Conclusion
number of positive symptoms was considered the score of the category. Response
Our results do not confirm the association of vitamin D levels with thyroid
to methimazole was defined as whether serum TSH normalized within 3 months.
function and positivity for thyroid antibodies.
A total of six variables, 5 symptom categories and sex, were used for a 2-layer
DOI: 10.1530/endoabs.49.GP205
neural network model. Among 20 subjects, 15 subjects used in training set, and
the other 5 subjects were use in model validation.
Results
The mean age of subjects was 49.3G12.2 years and male subjects were 6 (30%).
Our neural network model with 15 subjects as a training set showed sensitivity of
1.0 and specificity of 0.545 with AUC of 0.75 to predict normalization of serum
TSH within 3 months. With same model, the estimated scores of the other 5
subjects corresponded to their actual outcomes.
Conclusion
Thyroid 2
Despite the limitation of small sample size, our neural network model showed
GP206
promising performance to predict response to methimazole with patients’ clinical
symptoms in new onset Graves’ patients.
Early use of steroid-sparing agents in treatment of moderate-to-severely
active thyroid eye disease
DOI: 10.1530/endoabs.49.GP207
Zuzana Sipkova1, Joel David2, Helen Turner3 & Jonathan Norris1
1Oxford Eye Hospital, Oxford, UK;2Nuffield Orthopaedic Centre, Oxford,
UK;3Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford,
UK.
Introduction
The management of active thyroid eye disease (TED) remains controversial. High
GP208
dose intravenous methylprednisolone (IVMP) is the current recommended first-
Serum Interleukin-37 (IL-37) levels were increased and correlated with
line treatment based on EUGOGO guidance. Such therapy has the potential for
oxidative stress parameters in Hashimoto’s Thyroiditis (HT) patients
serious adverse effects. We present the outcomes of an alternative approach in the
Rosaria Maddalena Ruggeri1, Teresa Manuela Vicchio1, Angela Alibrandi2,
management of moderate-to-severely active TED, using steroid-sparing agents
Salvatore Giovinazzo1, Rosaria Certo1, Giuseppe Giuffrida1,
(SSAs) in conjunction with IVMP. Methotrexate is used as the first-line SSA
Francesco Trimarchi3, Sebastiano Gangemi4 & Mariateresa Cristani5
alongside ciclosporin and rituximab depending on activity score.
1Division of Endocrinology, Department of Clinical-Experimental Medicine
Methods
and Pharmacology, University of Messina, Messina, Italy;2Department of
Presented is a retrospective, 4-year, single-centre, consecutive case series of
Economy, University of Messina, Messina, Italy;3University of Messina,
patients with moderate-to-severe TED treated using the Oxford protocol.
Accademia Peloritana dei Pericolanti, Messina, Italy;4Division of Clinical
Treatment modality, disease activity (derived from the VISA classification) and
Immunology and Allergology, Department of Human Pathology, University
adverse effects are reported at initial presentation, 6- and 12-month follow-up.
of Messina, Messina, Italy;5Department of Pharmaceutical Sciences and
Results
Health Products (SCIFAR), University of Messina, Messina, Italy.
104 consecutive case notes were reviewed of TED patients treated by the TED
MDT. 24 patients with moderate-to-severely active disease were identified (mean
age 46.8 years; 12 female) with a mean pre-treatment VISA activity score of
Background
5.5/10 (S.D.Z1.98; range 1-9). IVMP and an SSA was commenced in all patients.
IL-37, member of the IL-1 family, is a natural suppressor of immune and
Mean total steroid dose was 2.72 g (S.D.Z1.4; 1.0-6.9). 38% of patients (nZ9)
inflammatory responses. Increased serum IL-37 levels were observed in several
received 1.5 g of IVMP or less. Only two patients required O4.5 g of IVMP
autoimmune diseases, including Graves’ disease. No data on TH are available
equating to the EUGOGO treatment protocol dose for this patient group. There
from the literature.
was significant improvement in VISA activity score both at the intermediate
Materials and methods
review (mean score 2.7; S.D.Z2.8; P!0.001; mean follow up 25.2 weeks) and at
We enrolled 45 euthyroid HT patients (5 M e 40 F, mean age 38.5G12.6) and
one year or last follow up (mean score 1.4; S.D.Z1.5; P!0.001; mean follow up
50
age- and sex-matched healthy controls. None was on LT-4
therapy.
48.0 weeks). Three patients stopped methotrexate due to a non-specific chronic
Smokers, subjects with kidney failure, history of cancer or autoimmune,
cough, deranged liver function or nausea. No serious or long-term adverse effects
inflammatory and infection comorbidities were excluded. Serum IL-37 levels
were reported.
were measured by ELISA (kit IL-37 DuoSet Elisa, R&D System, Minneapolis,
Conclusion
USA; minimum detectable dose
10 pg/ml). Specific serum tests, such as
Based on our experience and outcomes, the initiation of an SSA with limited
d-ROMs (derived Reactive Oxygen Metabolites) test and BAP (Biological
adjuvant IVMP is as an effective and safe therapy for moderate-to-severely active
Antioxidant Potential) test (Diacron International, Italy), were performed in all
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
subjects to investigate the changes in oxidative balance, and AGEs (Advanced
GP210
Glycation End Products) were determined as a specific marker of oxidative
Laser ablation of benign thyroid nodules without anesthesia: clinical
stress.
tolerance, hazards and complications
Results
Pablo Vidal-Ríos, Teresa Jiménez, Antonio Rodríguez, Laura Villas &
IL-37
levels were significantly higher in TH
(meanG S.D.:
999.59G
Sebastian Vidal-Ríos
1064.93 pg/ml) than in controls
(448.02G498.96 pg/ml; PZ0.018). In both
Coruna Endocrinology Center, La Coruna, Spain.
groups, these values correlated negatively with age
(TH, RSZK0.377
PZ0.016; controls, RSZK0.404; PZ0.06) and were tendentially higher in
men than in women (PZ0.063). Furthermore, there was a positive correlation
Laser ablation of thyroid nodules has been used for the last two decads (Pacella
between serum IL-37 levels and TSH, statistically significant in TH (RSZ
et al,
2000). Surprisingly, complications are less frequent in patients treated
0.412 PZ0.008; in controls, RSZ0.418; PZ0.053). The regression analysis
without anesthesia, probably because eventual pain is an useful alarm symptom,
showed a significant positive association between IL-37
and d-ROMs
leading the operator to repositioning the fiber during the procedure (Pacella et al.,
(PZ0.029) and AGEs
(PZ0.014): if serum d-ROMs and AGEs levels
2015).
increased, serum IL-37 levels also increased. A significant direct correlation
Material and methods
between serum IL-37
levels and AGEs was also observed
(RSZ0.578;
A total of 32 patients were included, without using local anesthesia. Nodules
PZ0.006).
were solid, 5-72 ml volume, age 36-84 years, gender female (84%). Procedure
Conclusion
included three phases:
(1) Preparation
30 min (informed consent and final
Serum IL-37 levels were significantly increased in TH patients and correlated
decision about anatomic approach); (2) Laser ablation 30 min (usually
3-8
with oxidative stress parameters. Given the anti-inflammatory properties, IL-37
paths, 3-5 illuminations each and total energy of 50-500 joules/cc); and (3)
could be an innovative research strategy for TH pathogenesis and therapy.
Observation
60 min
(with ice collar and vital constants monitoring). A
DOI: 10.1530/endoabs.49.GP208
1064 nm Nd-YAG laser from an EchoLaser generator (Elesta, Florencia-Italy)
was used. Triple thyroid image (Ultrasound, Doppler and Elastography) was
monitored using an Acusson
2000
Hellix platform
(Siemens, Forchheim-
Germany).
Results
30 of 32 patients (93.75%) would accept another ablation if necessary. Pain was
refered as 1-6 of 10 (arithmetic mean 3.5; median 2). Difficulties were: cervical
discomfort (4), excessive time of manipulation because short neck (1), transient
mild hypertension
(1), mild vasovagal reaction
(1), small intra-thyroid
hematoma (1) and a partial and transient Horner syndrome (1) resolved 3
months later.
Discussion
Clinical tolerance in general was spectacular. Major complaints were postural.
Complications were mild and transient, although potentially risky. No cases of
severe pain, voice change, fever, skin burn or cough were observed. In the future,
GP209
preventive specific strategies (like careful identification of risky patients, laser
cauterization of large feeding vessels or protective hydrodissection to protect vital
The increased immunohistochemical expression of IL-23 in Hashimo-
organs) will be considered before laser ablation.
to’s thyroiditis but not in Graves’ disease patients
Conclusions
Tatjana Zake1,3, Sandra Skuja3, Ieva Kalere2, Ilze Konrade1,2 &
Clinical tolerance was very good. Complications were few, mild and transient, but
Valerija Groma3
potentially risky. This highlights the importance of identifying properly risky
1Riga East University Hospital, Riga, Latvia;2Department of Internal
patients as well as the need of including preventive strategies.
Medicine, Riga Stradins University, Riga, Latvia;3Institute of Anatomy and
Anthropology, Riga Stradins University, Riga, Latvia.
DOI: 10.1530/endoabs.49.GP210
Introduction
Recently, Th17 cells and their cytokines were identified to play an important role
in the pathogenesis of thyroid autoimmunity. IL-23, produced by antigen
presenting cells, is required for survival and differentiation of Th17 cells, and is
known to guide T cells toward the Th17 phenotype. Its serum levels are increased
in several autoimmune diseases, including Hashimoto’s thyroiditis
(HT),
however, the expression level of IL-23
within thyroid tissue assessed by
immunohistochemistry has not been addressed thoroughly before. The aim of our
study was to estimate the levels of immunoexpression and distribution of IL-23
within thyroid tissue of patients with HT and Graves’ disease (GD) and compare
them with controls.
GP211
Materials and Methods
Forty seven adult patients presenting 21 cases of HT, 8 of GD, and 18 cases of
Orbital ectopic thyroid mistaken for mestastases
ordinary colloidal goiter without autoimmune component, which served as
Greta Jagucianskaite1,2, Agne Petrenaite1,2, Rasa Ziukaite2 &
control group, were enrolled in this study. Immunostaining was performed using
Zydrune Visockiene1,2
an anti-IL-23 antibody (Santa Cruz Biotechnology, CA, dilution 1:50). Levels of
1Vilnius University Faculty of Medicine, Vilnius, Lithuania;2Vilnius
immunopositivity for IL-23 were defined semiquantitatively.
University Hospital Santariskiu Klinikos, Centre of Endocrinology, Vilnius,
Results
Lithuania.
In HT patients the expression of IL-23 was detected both in the abundant
Introduction
inflammatory lymphocytic infiltrates characteristic of HT and follicular
Ectopic benign thyroid tissue outside the normal migration path of the thyroid is
epithelial cells, whereas tissues obtained from GD patients demonstrated the
an extremely rare condition that, to our knowledge, has never been described in
weak thyrocytic expression predominantly. Majority of patients in controls
the orbit.
showed negative or occasional expression of IL-23. The highest IL-23
Clinical case
immunopositivity was observed in HT patients, furthermore, it was significantly
75-year-old woman with nodular thyroid was referred to Vilnius University
higher compared to the control group and GD
(P!0.001; PZ0.043,
Hospital Santariskiu Klinikos for fine needle aspiration biopsy. Her complaints
respectively). No difference was found between the expression of IL-23 in
were palpitations, difficulty swallowing, diplopia, exophthalmos with medial and
GD patients and the control group (PZ0.324). Additionally, weak expression of
-superior dislocation. Symptoms were progressing for
2
years, although
IL-23 was observed in connective tissue septae and blood vessels in most HT
laboratory testing always showed euthyreosis. Her thyroid-stimulating hormone
patients.
(TSH) was 1.04 mU/l (normal 0.4-4.1 mU/l), anti-TPO antibodies - 1.9 kU/l
Conclusion
(!5.61 kU/l) on admission. Fine needle aspiration biopsy and histological
Overexpression of IL-23 might play a role in the pathogenesis of HT, guiding T
examination suggested diagnosis of Hurthle cell carcinoma and subject was
cells towards the Th17 phenotype and promoting the autoimmune inflammation
referred to surgery.
of the thyroid gland.
Management and Outcome
DOI: 10.1530/endoabs.49.GP209
After thyroidectomy histology revealed nodular thyroid hyperplasia and follicular
adenoma. To exlude orbital malignancy head MRI was performed. Imaging
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
showed 18!14 mm in size, non-homogenic, contrast accumulating mass with
higher in patients with AITD compared with controls (P!0.001) but TNF-a
well-defined margins in the inferior -lateral part of the orbit. Orbital tumor
levels were not significantly different in the groups of different genotypes of the
excision was performed and histological examination revealed tumor composed
selected polymorphism of the Period3 gene.
of micro-/macrofolicules with colloid. Folicular epithelium had no atypical
Conclusion
changes, as confirmed by three independed pathologists. These criteria supported
This study provides the first evidence for a genetic association between AITD and
diagnosis of ectopic thyroid tissue. Due to patients noncompliance further
the Period3 gene, highlighting the possible relevance of polymorphisms in clock
postoperative period is unknown. A 5-year follow-up showed normal TSH levels
genes in the etiopathogenesis of AITD.
of
3.07 mU/l, with 75 mcg/day levothyroxin therapy, anti-TPO antibodies -
DOI: 10.1530/endoabs.49.GP212
0.2 kU/l, thyroglobulin 0.91 mgk/l (normal 0.83-55 mgk/l). Once no primary or
secondary tumors were detected we concluded that the thyroid tissue in the orbit
of our patient was ectopic.
Conclusion
Ussualy ectopic benign thyroid tissue could be found in the normal migration path
of the thyroid. However, we are presenting the extremely rare case of benign
thyroid tissue located in the orbit, suggesting the extensive diagnostic approach in
unclear cases.
DOI: 10.1530/endoabs.49.GP211
GP213
IgG4-related fibrous variant of Hashimoto thyroiditis in a non-Asian
woman
Sónia do Vale1,2, Ana Filipa Martins1, Cristiana Costa1, Lucas Batista3 &
Margarida Mendes de Almeida4
1
Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital
Center, Lisbon, Portugal;2Endocrinology Department, Lisbon Medical
School, Lisbon, Portugal;3Surgery Department, Santa Maria Hospital,
North Lisbon Hospital Center, Lisbon, Portugal;4Pathology Department,
GP212
Santa Maria Hospital, North Lisbon Hospital Center, Lisbon, Portugal.
Association of the Period3 clock gene polymorphism with autoimmune
thyroid diseases
Nafiye Helvaci1, Seda Oguz1, Serkan Kabacam2, Erdem Karabulut3,
Introduction
Filiz Akbiyik4, Mehmet Alikasifoglu2 & Alper Gurlek1
First described in
2009, IgG4-related thyroid disease includes several
1Division of Endocrinology and Metabolism, Hacettepe University Faculty
subcategories: Riedel’s thyroiditis, fibrous variant of Hashimoto thyroiditis
of Medicine, Ankara, Turkey;2Department of Medical Genetics, Hacettepe
(FVHT), IgG4-related Hashimoto thyroiditis (HT) and Graves’ disease with
University Faculty of Medicine, Ankara, Turkey;3Department of
elevated IgG4. It is rare, with most cases described in Japan and characterized by
Biostatistics, Hacettepe University Faculty of Medicine, Ankara, Turkey;
increased IgG4 plasma cells at immunostaining.
4Department of Medical Biochemistry, Hacettepe University Faculty of
Case Report
Medicine, Ankara, Turkey.
A 59-year-old Caucasian women, without known Asian ancestry, was observed at
the endocrinology department due to neck swelling over the previous 4 months.
She reported dyspnea at some neck positions, fatigue and constipation. She
Background
presented a diffusely enlarged very hard thyroid, with some nodules and reduced
Circadian rhythmicity is generated by a set of genes including Period3. Changes
mobility. Laboratory evaluation revealed primary hypothyroidism, very elevated
in the expression of Period3 and other clock genes have been linked with
titles of anti-thyroglobulin and anti-peroxidase antibodies, elevated erythrocyte
regulation of the immune system. Period3 polymorphisms have been associated
sedimentation rate and G immunoglobulins (3400 mg/dl, reference range, RR:
with circadian disruption and so immune system dysregulation and altered
751-1560), elevated IgG4 (267 mg/dl, RR: 4-86) and k-dominant light chains.
secretion of several cytokines, which can lead to inflammatory and autoimmune
There was no monoclonal band; IgA and serum calcium levels were normal.
disorders.
Ultrasound confirmed an enlarged heterogeneous thyroid, with nodules and small
Aim
calcifications. Cytology was compatible with lymphocytic thyroiditis. The CT
To investigate the influence of a polymorphism in Period3 gene on susceptibility
scan additionally revealed multiple latero-cervical ganglia, esophageal diversion,
and severity of autoimmune thyroid diseases (AITD).
airway impression and reduction of the nasopharynx lumen. There was no
Methods
evidence of malignancy, infection, other autoimmune disorders or non-neck
A total of 125 unrelated patients (mean age 35.94G9.9 years) with AITD (GD,
involvement. Euthyroid state was obtained with levothyroxine reposition and
69; HT, 56) and 115 unrelated healthy controls (mean age 31.3G8.7 years) were
total thyroidectomy was performed. Histology revealed a FVHT with elevated
included. Serum levels of IL-6 (pg/ml) and TNF-a (pg/ml) were determined by
IgG4-positive plasma cells and IgG4/IgG ratio. After surgery, serum IgG levels
ELISA method. Period3 gene polymorphism rs2797685 was identified by PCR-
decreased and IgG4 levels became normal.
RFLP.
Discussion
Results
The very hard rapidly enlarging thyroid, short disease duration, high antibody
Subjects expressing the GACAA genotype of the selected polymorphism in
titers, hypothyroidism, diffuse thyroid involvement, no evident extrathyroidal
Period3 gene demonstrated a significantly higher risk of AITD compared to the
invasion, increased inflammatory parameters, IgG and k dominant profile and
population expressing the GG genotype (ORZ1.83, CI: 1.04-3.20; PZ0.033). No
elevated IgG4 that normalized after surgery, suggested a fibrous IgG4-HT.
significant associations of genotypes were detected with the age of onset of
Histology and immunostaining confirmed an IgG4-related FVHT. Although
disease, presence and severity of orbitopathy in GD and thyroid function status at
very rare in non-Asian countries, it is important to suspect and confirm an
diagnosis and daily dose of thyroxine per kg body weight in HT. AITD and
IgG4-related thyroid disease, allowing an adequate diagnosis, treatment and
control groups were similar in terms of mean IL-6 levels, but mean serum IL-6
follow-up.
level was significantly lower in the group with GA genotype than in the group
DOI: 10.1530/endoabs.49.GP213
with GG genotype in GD (PZ0.013). Mean level of TNF-a was significantly
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP214
Aim of the study
To evaluate the impact of HT on the progression of HF during a long-term
Thyroid hormones deficiencies and poor outcome in chronic heart
follow-up.
failure outpatients
Methods
Vincenzo Triggiani1, Brunella Licchelli1, P Terlizzese2, D Grande2,
From 2006 to 2015, we evaluated 675 consecutive CHF outpatients (523 males,
C Rizzo2, MS Lattarulo2, T Leopizzi2, I Gioia2, Vito Angelo Giagulli1,
64G13 years) in stable clinical conditions (O1 month) and in conventional
Edoardo Guastamacchia1 & Massimo Iacoviello3
therapy. They underwent a clinical evaluation, 12-lead ECG, echocardiogram,
1Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine
blood pressure measurement and a routine chemistry. They have been carefully
Department, University of Bari, Bari, Italy;2School of Cardiology,
evaluated for the presence of thyroid diseases. The follow-up was extended on a
University of Bari, Bari, Italy;3Cardiology Unit, Cardiothoracic
median value of 47 months, for a maximum of 123 months. Thyroid function has
Department, Polyclinic Hospital of Bari, Bari, Italy.
been evaluated every 4 months, more frequent (every 6 weeks) for patients
receiving levothyroxine. The onset of HT during follow-up was defined as
detection of TSH values above the upper limit. When HT was detected, thyroid
Background
replacement therapy was started according to guidelines. During follow-up were
Hypothyroidism and low T3 syndrome frequently occur in HF patients.
also evaluated hospitalizations related to exacerbation of HF and death.
Aim of the study
Results
To evaluate in a large sample of CHF patients the association between thyroid
Four hundred and fifty-five patients (67.7%) were euthyroid at the enrolment and
hormone deficiencies and poor outcome.
showed a normal thyroid function during the follow-up; in 80 patients (11.8%)
Methods and results
there was a previous diagnosis of HT; in 40 patients (5.9%) the HT was detected
From 2006 to 2015, we screened 712 consecutive CHF outpatients (551 males,
at the time of enrolment; 52 patients (7.7%) developed HT during the follow-up.
64G14 years, left ventricular ejection fraction (LVEF) 33G10%, NYHA class
To avoid confounding factors, we compared patients in euthyroid status at the
2.3G0.6, NTproBNP 2153G4696 pg/ml, GFR-EPI 71G25 ml/min*1.73 m2) in
enrolment and during follow-up and patients with HT at the enrolment. At
stable clinical conditions (O1 month) and in conventional therapy. All patients
univariate Cox regression analysis, a significant association between HT and the
underwent assessment of thyroid function. A total of 34 patients were excluded
events, i.e. mortality for all causes (HR: 1.60; 95% CI: 1.08-2.38; P:0.019) and
for hyperthyroidism; among the remaining 678, 58 (9%) showed a TSH level
hospitalization for HF worsening (HR: 2.13; 95% CI: 1.54-2.96; P:!0.001) was
above the upper normal limit, but below 10 microU/ml, 23 (3%) a TSH value
found. At multivariate Cox regression analyses, HT remained associated only
above 10 microU/mL, and 20 patients (3%) low fT3 (LT3) levels without changes
with HF hospitalization (HR: 1.58; 95% CI: 1.09-2.29; P:0.015), but not with
in TSH levels. During a mean follow-up of 38 months, 122 patients died (101 for
mortality (HR: 1.05;95% CI:0.67-1.65; P:0.819), after correction to LVEF!
cardiovascular causes) and 202 experienced at least one admission for acute
35%, GFR!60 ml/min/m2, NTproBNPO1000 pg/ml, NYHAIII, PA 95 mmHg.
decompensated heart failure. TSH O10 microU/mL (HR:2.96; 95%CI: 1.54-
Conclusion
5.68; P: 0.001) and LT3 (HR: 3.79; 95%CI: 1.91-7.54; P!0.001), but not high
In a long-term follow-up, HT is independently associated with hospitalization due
TSH!10 microU/mL (HR: 1.59; 95%CI: 0.871-2.91; P: 0.13), were associated
to HF worsening, but not with mortality. We hypothesise that HT is able to induce
with an increased risk of death at univariate analysis. At multivariate Cox
hemodynamic instability leading to hospitalization, but, probably, its correction
regression analysis, after correction for the presence of NYHA class 3, LVEF!
with thyroid hormone therapy could in part blunt its impact on patients’ survival.
35%, NTproBNP O1000, systolic arterial pressure !100 mm Hg and GFR-EPI
DOI: 10.1530/endoabs.49.GP215
!60 ml/min, only LT3 remained significantly associated with events (HR: 2.75;
95%CI:1.38-5.49; P: 0.004). When the occurrence of heart failure hospitalization
was considered, high TSH levels with a value !10 microU/ml (HR 1.82; 95% CI:
1.18-2.83; P!0.01), TSHO10 microU/ml
(HR 2.84;
95%CI:1.61-5.01;
P!0.001) and LT3 (HR:
3.33;
95%CI:
1.89-5.88; P!0.0001) were all
associated with events at univariate regression analysis. At multivariate
regression analysis TSHO10 microU/ml (HR: 1.91; 95%CI:1.06-3.46; P:0.03)
and LT3 (HR: 2.39; 95%CI: 1.36-4.24; P:0.002), but not high TSH with value
!10 microU/ml, remained associated with HF hospitalization.
Conclusions
GP216
In this observational study on a large cohort of CHF outpatients, we found
The correction of TSH with thyroid replacement therapy is associated
that impaired thyroid function, particularly when high levels of TSH
with a better outcome in chronic heart failure patients
(O10 microUI/ml) and low T3 levels are considered, has an independent adverse
V Triggiani1, B Licchelli1, D Grande2, C Rizzo2, P Terlizzese2,
impact on CHF events.
VA Giagulli1, M.S Lattarulo2, T Leopizzi2, I Gioia2, E Guastamacchia1 &
M Iacoviello3
1
Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine
Department, University of Bari, Bari, Italy;2School of Cardiology,
University of Bari, Bari, Italy;3Cardiology Unit, Cardiothoracic
Department, Polyclinic Hospital of Bari, Bari, Italy.
Background
It has been previously demonstrated that thyroid hormone deficiency is associated
with a worse outcome in patients affected by chronic heart failure
(CHF).
However, few data are available about the effects of thyroid replacement therapy
on the prognosis of patients.
DOI: 10.1530/endoabs.49.GP214
Aim of the study
The aim of the study was to evaluate the relationship among thyroid replacement
therapy, correction of thyroid stimulating hormone (TSH) serum levels and
outcome of a series of CHF outpatients.
Methods
We screened CHF outpatients in stable clinical conditions (O1 month) and in
conventional therapy. All patients underwent a baseline clinical evaluation, a
GP215
12-lead ECG, an echocardiogram and routine blood tests. Thyroid hormones were
Hypothyroidism and heart failure outcome: a study with a long-term follow-up
assessed at the enrolment and routinely during follow-up (every 3-4 months or
V Triggiani1, B Licchelli1, C Rizzo2, D Grande2, P Terlizzese2, T Leopizzi2,
every 6-8 weeks if TSH level was altered at the previous control). All patients
I Gioia2, VA Giagulli1, E Guastamacchia1 & M Iacoviello3
with history or newly diagnosed hypothyroidism were managed by endocrinol-
1Endocrinology and Metabolic Diseases Unit, Interdisciplinary Medicine
ogists. We considered hypothyroidism corrected when TSH serum levels were
Department, University of Bari, Bari, Italy;2School of Cardiology,
normalized by thyroid replacement therapy (levothyroxine).
University of Bari, Bari, Italy;3Cardiology Unit, Cardiothoracic
Results
Department, Polyclinic Hospital of Bari, Bari, Italy.
Hypothyroidism was diagnosed in 180 patients (121 males, 67G12 years, left
ventricular ejection fraction, LVEF,
33G10%, NYHA class 2.5G0.5,
Background
NTproBNP 2125G2975 pg/ml, GFR-EPI 64G22 ml/min*1.73 m2) out of 712
Hypothyroidism (HT) has been demonstrated to be associated to heart failure
patients. Twenty-four patients were excluded because they were lost at follow-up
(HF) progression.
or died within the first 3 months or because endocrinologists did not prescribe
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
levothyroxine for TSH values not high enough. Among the remaining 156
GP218
patients in which levothyroxine was prescribed, in 111 patients a normal TSH
STAT6 deficiency ameliorates Graves’ disease severity by suppressing
value was obtained. During a mean follow-up of 38 months, 29 patients died (25
thyroid epithelial cell hyperplasia
for cardiovascular causes) and 62 experienced at least one admission for acute
Bingbing Zha
decompensated heart failure. The failure in TSH correction was associated with
Department of Endocrinology, Fifth People’s Hospital of Shanghai Fudan
an increased risk of all cause of death (HR: 3.31; 95% CI: 1.59-6.86; P: 0.001)
University, Shanghai, China.
and of heart failure hospitalization (HR: 2.27; 95% CI: 1.36-3.79; P: 0.002). At
Cox multivariate analysis the failure in TSH correction remained associated with
all cause mortality (HR: 2.57; 95% CI: 1.20-5.51; P: 0.002) and with heart failure
hospitalization (HR: 1.78; 95% CI: 1.05-3.01; P: 0.03) after correction for NYHA
Signal transducer and activator of transcription 6(STAT6) is involved in
class 3, LVEF!35%, NTproBNPO1000, systolic blood pressure !100 mmHg
epithelial cell growth. However, little is known regarding the STAT6
and GFR-EPI!60.
phosphorylation status in Graves’ disease (GD) and its role in thyroid
Conclusion
epithelial cells (TECs). In this study, we found that STAT6 phosphorylation
Our results support the possibility that hypothyroidism correction could improve
(p-STAT6) was significantly increased in TECs from both GD patients and
the prognosis of CHF patients, although randomized controlled trials should be
experimental autoimmune Graves’ disease mice and that STAT6 deficiency
designed in order to demonstrate this hypothesis.
ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the
DOI: 10.1530/endoabs.49.GP216
phosphorylation of STAT6 via IL-4R engagement, and the downstream
targets of STAT6 were Bcl-xL and cyclin D1. Thus, the IL-4-STAT6-Bcl-
xL/cyclin D1 pathway is crucial for TEC hyperplasia, which aggravates GD.
More importantly, in vitro and in vivo experiments demonstrated that
STAT6 phosphorylation inhibited by AS1517499 decreased TEC hyper-
plasia, thereby reducing serum T3 and T4 and ameliorating GD. Thus, our
study reveals that in addition to the traditional pathogenesis of GD, in which
autoantibody TRAb stimulates thyroid-stimulating hormone receptors and
Thyroid 3
consequently produces T3, T4, TRAb could also trigger TECs producing IL-
GP217
4, and IL-4 then acts in an autocrine manner to activate p-STAT6 signalling
Thyroid function in heart failure with preserved ejection fraction
and stimulate unrestricted cell growth, thus aggravating GD. These findings
(HFpEF) - evaluation of serum and myocardial thyroid hormones in an
suggest that STAT6 inhibitors could be potent therapeutics for treating GD.
animal model of HFpEF
DOI: 10.1530/endoabs.49.GP218
Joa˜o Sérgio Neves1,2, Catarina Vale2, João Almeida-Coelho2,
Soledad Bárez-López3,4, Maria Jesus Obregon3, Ana Isabel Oliveira1,
André Lourenço2, Inês Falca˜o-Pires2, Davide Carvalho1,5 &
Adelino Leite-Moreira2
1Department of Endocrinology, Diabetes and Metabolism, São João
Hospital Center, Porto, Portugal;2Departamento de Cirurgia e Fisiologia,
Unidade de Investigac¸ão Cardiovascular, Faculdade de Medicina,
Universidade do Porto, Porto, Portugal;3Department of Endocrine and
Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas
Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC)-
Universidad Autónoma de Madrid, Madrid, Spain;4Department of
Endocrine, U-708, Center for Biomedical Research on Rare Diseases
(Ciberer), Instituto de Salud Carlos III, Madrid, Spain;5Instituto de
Investigação e Inova
¸a˜o em Saúde da Universidade do Porto, Faculdade de
GP219
Medicina, Universidade do Porto, Porto, Portugal.
Delayed TSH recovery after dose adjustment during TSH-suppressive
levothyroxine therapy in patients with differentiated thyroid cancer
Hye In Kim, Tae Hyuk Kim, Young Nam Kim, Hosu Kim, So Young Park,
Introduction
Yun Jae Chung, Jae Hoon Chung & Sun Wook Kim
Thyroid hormones play a central role in the regulation of the cardiovascular
1Samsung Medical Center, Seoul, Republic of Korea;2Chung-Ang
system. Heart failure with preserved ejection fraction (HFpEF) is responsible for
University Hospital, Seoul, Republic of Korea.
more than 50% of all heart failure cases and its main pathophysiological alteration
is diastolic dysfunction. Diminished thyroid function is known to predominantly
impair diastolic function, however the thyroid hormone status in HFpEF remains
Background
largely unknown.
Delayed thyroid-stimulating hormone
(TSH) recovery during treatment of
Methods
Graves’ disease is caused by long-term excessive thyroid hormone, which results
We evaluated an animal model of HFpEF, ZSF1 Obese rats (ZSF1-Ob, nZ13),
in down-regulation of pituitary thyrotropic cells. However, it is unknown whether
and their control group, ZSF1
Lean rats
(ZSF1-Ln, nZ11), with serial
delayed TSH recovery exists after levothyroxine
(LT4) dose adjustment in
echocardiography followed by invasive hemodynamic recordings and tissue
patients with differentiated thyroid cancer (DTC) who are taking a suppressive
collections at 20 weeks. Serum TSH was quantified by ELISA. Thyroxine (T4)
dose of LT4.
and triiodothyronine (T3) were quantified in serum, left ventricle and visceral
Methods
adipose tissue by radioimmunoassay (RIA).
We retrospectively reviewed 97 DTC patients who had a reduced LT4 dose while
Results
receiving excessive LT4 for TSH suppression. TSH levels at baseline (point 1),
At 20 weeks of age, ZSF1-Ob group developed HF with diastolic dysfunction, as
6 months (point 2), and 12-18 months (point 3) after LT4 dose adjustment were
shown by an increased E/E’ on echocardiography, a prolonged time constant of
compared with each other. A delayed TSH recovery group whose TSH levels
isovolumetric relaxation, an elevated end-diastolic pressure and upward shifted
exceeded target TSH levels (according to recent guidelines) between points 2 and
end-diastolic pressure-volume relationship on invasive hemodynamic evaluation.
3 was identified.
Serum levels of thyroid hormones were significantly decreased in ZSF1-Ob rats
Results
(T3: 5.96G4.65 vs 35.85G9.39 ng/dL in ZSF1-Ln, P!0.001; T4: 1.51G0.64 vs
In patients with LT4 reduction, the median TSH level at point 3 was significantly
3.49G1.35 mg/dl in ZSF1-Ln, P!0.001), while the levels of serum TSH were not
higher than that at point 2 [0.17 vs 0.09 mIU/ml; P!0.001). The delayed TSH
significantly different between the two groups (0.65G0.38 ng/ml in ZSF1-Ln vs
recovery group (44.3%, 43 of 97 patients) showed increased body weight during
0.79G0.57 ng/ml in ZSF1-Ob, PZ0.531). Left ventricle levels of thyroid
follow-up (60.84-62.73 kg; PZ0.01), although TSH levels remained in the target
hormones were significantly decreased in ZSF1-Ob rats (T3: 3.87G0.85 vs
range. A lower LT4 dose per body weight (LT4 dose/weight) after reduction [HR
10.51G7.91 ng/g in ZSF1-Ln, PZ0.012; T4: 0.99G0.43 vs 2.02G0.60 ng/g in
(95% CI), 0.01 (0.00-0.54); PZ0.03], greater changes in the LT4 dose/weight
ZSF1-Ln, PZ0.016). The levels of T3 and T4 in visceral adipose tissue were not
[1.10 (1.00-1.22); PZ0.04], and higher BMI before surgery [1.19 (1.03-1.38);
significantly different between the two groups.
PZ0.01] predicted the occurrence of delayed TSH recovery.
Conclusion
Conclusions
We observed a decrease in serum and myocardial thyroid hormone levels in an
Delayed TSH recovery was commonly observed after LT4 dose adjustment was
animal model of HFpEF. This may contribute to impaired diastolic function and,
performed as recommended by dynamic risk stratification. Six months may not be
therefore, may constitute an interesting therapeutic target in HFpEF.
enough time to evaluate real thyroid hormone status by TSH levels.
DOI: 10.1530/endoabs.49.GP217
DOI: 10.1530/endoabs.49.GP219
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP220
mediated by the autophagic/lysosomal pathway. The core autophagic machinery
is composed of ATG (autophagy-related) proteins. One ATG family member,
Analysis of a large cohort of subjects with thyroid hemiagenesis (THA)
Atg7, activates enzyme facilitating microtubule-associated protein-light-chain3
reveals random seasonality in the dates of birth
(LC3)-phosphatidylethanolamine conjugation. The presence of T3 was able to
Ewelina Szczepanek-Parulska1, Ariadna Zybek-Kocik1, Marek Niedziela2,
significantly reduce ATG7 mRNA expression, moreover the hormone signi-
Agata Czarnywojtek1 & Marek Ruchala1
ficantly reduces LC3II/LC3I protein expression, when compared to STV mice
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan
(P!0,05). On the whole our results suggest that T3 treatment can reduce fasting
University of Medical Sciences, Poznan, Poland;2Department of Paediatric
induced skeletal muscle atrophy by counteracting the autophagic process.
Endocrinology and Rheumatology, Poznan University of Medical Sciences,
Poznan, Poland.
DOI: 10.1530/endoabs.49.GP221
Introduction
In the etiology of thyroid dysgenesis (TD) an interplay between genetic and
environmental factors is thought to play a crucial role. Data from previous studies
on association between the season of birth and the incidence of TD causing
GP222
congenital hypothyroidism (mainly agenesis and ectopy) are conflicting. To date,
Will it be useful to measure PTH at 4 hours post thyroidectomy to
seasonality of births have not been analysed yet in regard to congenital absence of
decide for calcium replacement? 1st result of a prospective study
one thyroid lobe (thyroid hemiagenesis, THA).
Sílvia Silva1, Ana Rafael1, Ricardo Marques1, Luisa Moniz1, Carlos Costa1,
Patients and Methods
Ricardo Capita˜o2, Catarina Saraiva2, Clotilde Limbert2, Luis Fernandes1 &
Dates of birth of 102 patients diagnosed with THA were analysed and compared
Rogério Matias1
to 102 control subjects with no thyroid pathology matched for age and gender.
1Surgery, Egas Moniz Hospital, Lisboa, Portugal;2Endocrinology,
Both groups were subdivided according to the month of birth (I-XII), season of
Egas Moniz Hospital, Lisboa, Portugal.
birth
(spring, summer, autumn, winter) and quarter (1-4) of the year. The
differences were analysed statistically.
Introduction
Results
Calcium replacement after Thyroid surgery has been changing along times. The
Distribution of the months of birth in the group of patients with THA was
aim for this replacement is to avoid hypocalcaemia effects after thyroid surgery
asymmetric; smaller number of patients were born in the 4th (X-XII) quarter of
but not all the patients seem to need it. Parathyroid hormone (PTH) has a short
the year (19 patients) vs 1st (28 patients), 2nd (29 patients) and 3rd (26 patients).
half-life after its release into the bloodstream, making it a good marker of calcium
Similarly, smaller number of patients were born in autumn (IX-XI) - 19 patients if
metabolism in short time after surgery.
compared to other seasons of the year (winter - 27 patients, spring - 27 patients,
Method
summer - 29 patients). However, if the studied group was compared to the control
Prospective study of Endocrine Surgery Multidisciplinary group of one Centre
group, the difference in the distribution of the months of birth was at the border of
between March and December of 2016. Calcium replacement was done according
statistical significance (P!0.0923). Furthermore, if the studied and control group
to a protocol defined by multidisciplinary group after PTH measurement. PTH
were subdivided into four quarters or seasons, and then compared, the difference
values were considered normal above 15 pg/ml. Data were analyzed using SPSS.
was definitely not statistically significant.
Results
Conclusions
96 patients underwent total thyroidectomy vs totalization of thyroidectomy.
An analysis of the largest so far reported cohort of patients with THA indicate that
5 were excluded since they were admitted at ICU and protocol was not
environmental factors including intrauterine exposure to maternal seasonal viral
implemented. PTH was measured 4 hours after surgery.
infections or variable vitamin D availability seem not to play a significant role in
From the 91 patients, 74 had normal PTH levels. The remaining patients (17)
pathogenesis of THA.
started calcium replacement according to established protocol and showed no
DOI: 10.1530/endoabs.49.GP220
symptoms of hypocalcaemia.
Considering group with normal PTH, at day one after surgery, 41 had normal
calcium levels (P 0,01 on correlation analysis) and 33 had low levels. This last
group started the protocol of calcium replacement and at day two after surgery
were observed higher calcium levels (P 0,001 at linear analysis) and didn’t refer
hypocalcaemia symptoms.
GP221
Our Sample has a significance of 0.05 in the non-parametric, Q-square and
Thyroid hormone T3 protects mice from fasting induced skeletal muscle
Kolmogorov-Smirnov test.
atrophy by counteracting autophagy
Conclusion
Sarassunta Ucci1, Valentina Russi1, Maria Giulia Santaguida2,
Measuring PTH 4 hours after surgery is helpful to decide which patients should
Marco Centanni2, Viviana Moresi3 & Cecilia Verga Falzacappa1,2
start calcium replacement, using PTH value cut-off of 15 pg/ml.
1Pasteur Institute, Rome, Italy;2Sapienza, University of Rome, Medical
DOI: 10.1530/endoabs.49.GP222
Surgical Sciences and Biotechnologies Department, Rome, Italy;3Sapienza,
University of Rome, Department of Anatomy, Histology, Forensic Medicine
and Orthopedic, Section of Histology, Rome, Italy.
Purpose
GP223
Skeletal muscle has been recognized as a thyroid hormones (THs) target for
Endogenous TH metabolite 3-iodothyronamine (T1AM) and synthetic
contractile function, regeneration, metabolism and glucose disposal. Despite a
thyronamine-like analogues SG-1 and SG-2 induce autophagy in human
role in regulating muscle development has been described, little is known about
glioblastoma cells (U-87MG)
the role of THs in regulating muscle homeostasis in a pathological state such as
Lorenza Bellusci1, Martina Sabatini1, Giulia Nesi2, Simona Rapposelli2,
food deprivation induced atrophy. The purpose of this study is to evaluate whether
Leonardo Rossi3, Paola Lenzi4, Francesco Fornai4, Riccardo Zucchi1 &
thyroid hormones may hamper the fasting induced skeletal muscle atrophy and to
Grazia Chiellini1
investigate the mechanisms involved.
1Department of Pathology, University of Pisa, Pisa, Italy;2Department of
Methods
Pharmacy, Pisa, Italy;3Department of Clinical & Experimental Medicine,
Preliminary data on C2C12 myotubes have suggested that T3 could counteract the
Pisa, Italy;4Department of Translational Research and New Technologies in
starvation induced atrophy in vitro. Based on these results, BALB/C male mice
Medicine and Surgery, Pisa, Italy.
(8-10 weeks) were used for in vivo experiments. Animals were food-deprived
(STV) for
24 and 48 hours to induce muscle atrophy and daily injected
intraperitoneally with T3 (100 ug/kgBW) or vehicle (NaCl 0,95%) as controls.
Endogenous TH metabolite 3-iodothyronamine (T1AM) and recently developed
Tibialis anteriors were taken at the end of the experiments. Morphological
thyronamine-like synthetic analogues SG1
and SG2
have emerged as
analyses were performed on hematoxylin/eosin stained sections. ATG7-Mrna was
neuroprotective agents. Autophagy has proved to be an effective therapeutic
evaluated by Sybr-Green qRT-PCR and LC3II/Lc3I was evaluated by western
approach for neurodegenerative diseases. Therefore we investigated whether
blot.
these compounds can induce autophagy in human glioblastoma cells (U-87MG).
Results and conclusions
Cultured U-87MG cells were initially treated with 1 mM T1AM, SG-1, SG-2 or
As a sign of skeletal muscle atrophy, the STV group showed a significant
vehicle for 30’, 4, 8 and 24 h and autophagy was monitored morphologically by
(P!0.001) reduction in the Cross-Sectional-Area of the myofibers, compared to
assessing the presence of autophagic vacuoles and LC3-II puncta formation
the control group; on the contrary the T3 treated group (STVT3) ensures the
with transmission electron microscopy (TEM) and immunofluorescence (IF)
maintenance of the fiber size. Protein degradation in skeletal muscle cells is
microscopy, respectively. In addition, cellular lysates were subjected to western
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
blotting to assess the accumulation of microtubule-associated protein 1 light chain
Introduction
3
(LC3). This protein is widely used as a marker for autophagy because it is a
The aim of this study was to examine prognostic significance of patient-related,
structural protein vital in autophagosome formation. TEM and IF microscopy
tumor-related and treatment-related factors for intrathyroidal papillary thyroid
showed a significant time dependent increase of autophagy-like vacuoles density and
carcinomas (PTC), via multivariate analysis.
LC3 punta formation in U-87MG cells exposed to the treatment with test compounds,
Materials and methods
with T1AM and SG-1 being the most effective. Along with extensive cytoplasmic
This study included
153 patients with intrathyroidal PTCs
(pT1/pT2/pT3)
vacuolization, western blotting analysis revealed significant up regulation of LC3-II
surgically treated in our Institution during two-decade period. Patients with
expression (P!0.01). Finally, we extended our analysis to examine the role played
locally invasive tumors (pT4) and initial distant metastases (M1) were excluded.
by our test compounds on the PI3K-AKT-mTOR pathway that has been suggested
Parameters of interest were: gender (male; female), age (%45; O45 years), tumor
to play an important role in the regulation of autophagy in mammalian cells. We
size (pTNM classification WHO 1984), multifocality (no; yes), histological type
carried out WB for Akt, phosphorylated Akt (pAkt) and we calculated the ratio
of PTC (pure; microcarcinoma; follicular; poorly differentiated), presence of
pAkt/Akt in vehicle-treated cells following test compounds administration. We
lymphonodal metastases
(pN1a; ipsilateral-pN1b; contralateral-pN1b; total),
found that 1 mM T1AM, SG-1 and SG-2 decreased such a ratio after 30’ and 4 h
surgery extent
(total thyroidectomy; total thyroidectomy with lymphonodal
treatment, suggesting that they might induce autophagy through the modulation of
dissections). Univariate and multivariate analysis of all parameters was
pAkt level. In conclusion, T1AM and synthetic analogues induce autophagy in a
performed in order to distinguish factors of significance for disease-free (DFS)
glioblastoma cell line. The potential pathophysiological and/or therapeutic
and cancer-specific overall survival (cs-OS).
implications of this finding remain to be determined.
Results
DOI: 10.1530/endoabs.49.GP223
In the follow-up, 10% of patients had locoregional or distant relapse, while 5.2%
died due to PTC. Univariate analysis distinguished older age, male gender, tumors
over 4 cm in diameter, multifocality and poorly differentiated PTC-types as
unfavorable prognostic factors for cs-OS. DFS was significantly shorter in males
vs. females, as well as in patients with multifocal vs. solitary PTC. Tumor
multifocality was unfavorable prognostic factor for both DFS and cs-OS.
Independent prognostic factors for intrathyroidal PTCs, based on Cox multi-
variate analysis, were multifocality and gender for DFS, and multifocality and age
at diagnosis for cs-OS.
GP224
Conclusion
Prognostic factors define risk groups within population of differentiated PTCs
Impact of chronic high fat diet consumption on the expression of
providing timely, adequate treatment and opportunity for longer quality life of
organic nutrients carriers in the small intestine of mice: role of thyroid
patients with PTCs.
hormones in these processes
Mariana Losacco Cerqueira, Carolina Fernanda Theodora Almeida,
DOI: 10.1530/endoabs.49.GP225
Paula Bargi-Souza, Maria Tereza Nunes, Patricia Gama &
Francemilson Goulart-Silva
Institute of Biomedical Sciences - University of São Paulo, São Paulo-SP,
Brazil.
Products of carbohydrates, proteins and lipids hydrolysis are absorbed by specific
carriers located at the enterocytes apical membrane, but little is known about the
mechanisms related to their regulation by own nutrients, especially considering
the high consumption of fats. Carbohydrates are transported by SGLT1, GLUT5
GP226
and GLUT2 and peptides are transported by PEPT1. Cholesterol is transported by
NPC1L1 and long chain fatty acids occur through FAT-CD36 and FATP4.
Malignancy Rate in Thyroid Nodules: Cytology versus Histology in
Thyroid hormones have important effects on organic nutrients metabolism, but
challenging categories
little is known about their role on the intestine, which led us to evaluate thyroid
Catarina Silvestre, Rita Luís, Maria Joa˜o Bugalho, Margarida Mendes de
hormone effects on intestine organic nutrients carriers of mice fed high fat diet
Almeida & Raquel Carvalho
(HFD) or standard diet. C57BL/6 mice were fed standard diet (control) or high fat
Santa Maria Hospital, Lisbon, Portugal.
diet (HFD) for 12 weeks. Afterwards, both mice were treated with saline, PTU
(antithyroid drug) or T3 for 30 days. They were killed and the jejunum was
Background
removed for histological analysis or inverted for intestinal epithelium separation
To stratify the risk of malignancy, thyroid fine-needle aspiration cytology
from the mucosa for protein analysis by Western blotting technique. FAT-CD36,
(FNAC) is an important and cost-effective method to evaluate nodules. The
NPC1L1 and GLUT2 protein contents reduced in mice fed HFD compared to
Bethesda System for Reporting Thyroid Cytopathology III, IV and V categories
control mice. SGLT1, PEPT1
and FATP4
remained unchanged among
are diagnostic challenges, falling between benign and malignant.
experimental groups. On the other hand, NHE3
protein content, which is
Objective
important for sodium and peptides absorption, increased significantly in the small
Determinate the malignancy rates of thyroid nodules classified as Bethesda
intestine of mice fed HFD. PTU or T3 treatment did not affect these parameters.
Categories III-V.
High fat compared to standard diet did not show any alteration of the villus length,
Methods
but mice fed standard diet and treated with PTU or T3 showed an increased villus
Retrospective study of patients’ records with thyroid nodules classified as III-V
length compared to treated-vehicle mice, however this finding have no association
by the Bethesda system, between January 2014-June 2016.
with the changes of nutrient carriers described above. Thus, we can infer that HFD
Results
affects the expression of some organic nutrient carriers in the small intestine,
Of a total of 2791 cytologies, 176 (6%) were classified as III-V, with the following
independently of thyroid hormones treatment.
distribution: 93 (3%) atypia of undetermined significance (AUS, III); 50 (1,8%)
DOI: 10.1530/endoabs.49.GP224
suspicious for follicular neoplasm
(SFN, IV) and
33
(1%) suspicious for
malignancy (SM, V). Malignancy rates for IV and V FNAC diagnostic groups
were 27% (10/37) and 85% (22/26), respectively. Among patients in group III, 27
patients underwent surgery after a single AUS report
(final diagnosis of
malignancy
- 33%), 39 repeated the FNAC and the remaining are under
surveillance. The second cytology report was as follows: 24 benign, 9 AUS, 4
SM, 1 SFN and 1 unsatisfactory; surgery was performed in 9 patients (5AUSC
1SFNC3SM) and the final diagnosis of malignancy was 44%. The malignancy
Thyroid Cancer
rate based on histology was not statistically different between patients with one or
two cytologies (PZ0,693).
GP225
Conclusions
Prognostic factors for intrathyroidal papillary carcinomas - a
Incidences of III-V diagnostic categories in our study resemble the predicted by
multivariate analysis
the Bethesda System. The malignancy rate for the AUS category was higher than
Nada Santrac1, Ivan Markovic1,2, Merima Goran1, Marko Buta1,2,
expected and similar to the one found in SFN. Repeating the FNAC in the former
Igor Djurisic1 & Radan Dzodic1,2
group offered minimal additional benefit.
1Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia,
Belgrade, Serbia;2Medical Faculty, University of Belgrade, Belgrade,
DOI: 10.1530/endoabs.49.GP226
Serbia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
GP227
structural disease). Groups were compared for age at diagnosis, nodule
dimensions, multicentricity, capsule presence and extrathyroidal involvement
Fine needle aspiration biopsy in pediatric patients with thyroid nodules
as well as the presence of node or distant metastasis.
Maria Manuel Costa1,3, Rita Santos Silva2,4, Cintia Castro-Correia2,4,
Results
Maria Bom Sucesso2,4, Tiago Henriques Coelho2,4, Helena Barroca6 &
A total of 814 patients was included, 82.9% of which were female. The median
Manuel Fontoura2,4
age at diagnosis was 47 years old (min. 11; max. 89). Five hundred patients had
1Department of Endocrinology, Diabetes and Metabolism of Centro
criteria for remission (Group 1) and 314 didn’t (Group 2 [36 with cancer related
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of
death,
55 with persistent or recurrent disease and
223 with indeterminate
Porto, Porto, Portugal;3Instituto de Investiga
¸a˜o e Inovação da Saúde da
response]). Median follow up was 10 years (min. 3; max. 50) in Group 1and 9
Universidade do Porto, Porto, Portugal;4Department of Pediatrics of Centro
years (min. 3; max. 57) in Group 2. Patients in group 1 were significantly younger
Hospitalar de São Joa˜o, Porto, Portugal;5Department of Pediatric Surgery of
(median 44.5 vs 49.5; P!0.001) had more multicentricity (45,7% vs 37.7%;
Centro Hospitalar de São João, Porto, Portugal;6Department of Pathology,
PZ0,041) and less local (22.7 vs 30.6%; PZ0,016) and distant metastasis (0.4%
Centro Hospitalar de São João, Porto, Portugal.
vs 5.7%; P!0,001). No differences were found in nodule dimensions, capsule
presence or extrathyroidal involvement.
Introduction
Conclusion
Although thyroid nodules (TN) are less common in children than in adults, the
Among patients with differentiated thyroid cancer, the older ones, with unicentric
risk of malignancy is much higher in pediatric age and therefore representing
tumours, local or distant metastasis at presentation seem to have worst outcome.
greater concern in this age group.
DOI: 10.1530/endoabs.49.GP228
Objective
Evaluate a cohort of pediatric patients with TN and search differences between
subjects with malignant and benign TN regarding sex, age, compressive
symptoms, cervical ultrasound characteristics, family history of differentiated
thyroid cancer (FHDTC), radiation exposure and previous/coexisting thyroid
GP229
disease.
Methods
Trends in papillary microcarcinoma prevalence in North of Portugal
Retrospective review of patients under 18 years of age with the diagnosis of TN
Teresa Alves Pereira1, Ana Amado1, Patrícia Gouveia2, Rosa Castro2,
submitted to fine needle aspiration biopsy (FNAB) from 2010 to 2016.
António Moreira da Costa3, André Couto de Carvalho1, Cláudia Freitas1 &
Results
Fátima Borges1
Seventy-three patients [21% males; mean age 13.8(3.2) years] were included.
1Endocrinology Department, Centro Hospitalar e Universitário do Porto,
46.6% had palpable nodules. 84.9% were euthyroid and 12.3% had hypothyroid-
Porto, Portugal;2Nuclear Medicine Department, Centro Hospitalar e
ism.
31.5% of the patients had positive anti-thyroid antibodies. Ultrasound
Universitário do Porto, Porto, Portugal;3Surgery Department,
showed that TN had a diameter range of 15.9G9.8 mm, 47.9% patients had a
Centro Hospitalar e Universitário do Porto, Porto, Portugal.
solitary nodule, 31.5% TN were hypoechoic, 5.5% had increased intranodular
flow, 10.9% had microcalcifications and 5.5% had irregular margins. We found
Introduction and Objectives
that 5.5% of patients had undergone previous cervical irradiation and 12.3% had
The incidence of thyroid cancer has increased worldwide. This increase has been
FHDTC. 84.9% of the patients had a conclusive FNAB at first: benign in 39
attributed to more diagnosed papillary thyroid microcarcinomas. The purpose of
(colloid
(nZ25), chronic lymphocytic thyroiditis
(nZ12), granulomatous
this study was to analyse the growing trend of first appointments in our Thyroid
thyroiditis
(nZ1), thymus tissue
(nZ1)), FLUS in 4, suspected follicular
Cancer Unit, namely patients with papillary microcarcinomas.
neoplasia in 3, suspected malignancy in 1 and papilar carcinoma in 15 patients.
Methods
Thyroidectomy was performed in 43.8% of the patients. In histology, 71.9% were
We performed a retrospective study based on the patients diagnosed with thyroid
diagnosed as malignant. One patient developed permanent hypoparathyroidism
cancer between 1960 and 2016. We divided these patients into groups, based on
after surgery. We verified that the FHDTC was more frequently present in the
the year of first surgical treatment: 1960 to 1996, 1997 to 2001, 2002 to 2006,
malignant nodules (26% vs 6%, PZ0.024), while for the other factors mentioned
2007 to 2011 and 2012 to 2016. We calculated the relative frequency of papillary
above there were no statistically significant differences.
microcarcinomas comparing to the total cancer diagnostics in each group.
Conclusion
Results
In most patients a conclusive diagnosis was achieved with FNAB. The high
The total count of patients with registered thyroid cancer dimensions was 1146.
prevalence of malignancy was similar to that described in the literature. FHDTC
The mean age was 48.2G15.3 years old. 81.9% were female. We have found that
was the only factor found associated with an increased risk of malignancy.
papillary microcarcinoma frequency increased steeply from 11.2% [35/313, 95%
DOI: 10.1530/endoabs.49.GP227
confidence interval (CI) 8.2-15.2%] in 1960-1996 to 30.9% (42/136, 95% CI
23.7-39.1%) in 1997-2001. From that time onwards it stabilised around 1/3 of
thyroid cancer cases evaluated - 34.0% (54/159, 95% CI 27.1-41.6) in 2002-
2006; 34,6% (93/269, 95% CI 29.1-40.4%) in 2007-2011 and 30.5% (82/269,
95% CI 25.3-36.2%) in 2012-2016.
Conclusions
GP228
The prevalence of papillary microcarcinomas has increased until the end of the
Differentiated thyroid cancer - comparison between patients with and
last century. After 2002 our data showed a somewhat stabilised rate of 1/3 of all
without remission
diagnosed thyroid cancers.
Ana Amado1, Patrícia Gouveia2, Teresa Alves Pereira1, Rosa Castro2,
DOI: 10.1530/endoabs.49.GP229
António Moreira da Costa3, André Carvalho1, Cláudia Freitas1 &
Fátima Borges1
1Endocrinology Department, Centro Hospitalar e Universitário do Porto,
Porto, Portugal;2Nuclear Medicine Department, Centro Hospitalar e
Universitário do Porto, Porto, Portugal;3Surgery Department,
Centro Hospitalar e Universitário do Porto, Porto, Portugal.
GP230
Radioiodine (RAI) refractory differentiated thyroid cancer (DTC):
outcome and prognostic factors for DISEASE progression
Introduction
Katerina Saltiki, George Simeakis, Elli Anagnostou, Michalis Apostolakis,
Differentiated thyroid cancer
(DTC) is one of the most frequent forms of
Evangelia Zapanti, Eleni Anastasiou & Maria Alevizaki
malignancy. Because of its favourable outcome and low mortality rates,
Endocrine Unit, Department Medical Therapeutics, Alexandra Hospital,
identifying prognostic factors has been a challenge. Several risk stratification
Athens University School of Medicine, Athens, Greece.
systems have been developed. Most of them include demographic and tumour
specific features, as well as extrathyroidal extension. Our objective was to
compare clinical characteristics between DTC patients with and without
Introduction
remission.
Patients diagnosed with DTC have excellent prognosis. A small percentage of
Methods
patients with disease persistence do not respond to treatment with RAI (RAI-
Data from patients followed for DTC between 1956 and 2016 was retrieved.
refractory DTC) and have low median survival (3.5 years). We investigated the
Patients with less than
2 years of follow up, those submitted to subtotal
prognostic factors and the disease course in patients with RAI-refractory DTC.
thyroidectomy or with positive antithyroglobulin antibodies were excluded. They
Methods
were divided in two groups, according to the presence or absence of remission
Of all DTC patients (nZ1160) followed-up in our department in recent years, 800
criteria (undetectable TSH-suppressed thyroglobulin levels and no evidence of
received RAI treatment and were classified in 2 groups: RAI-refractory DTC
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(5.8%) and RAI responsive DTC (94.2%). Clinical and histological charac-
in the real life, the use of bone active drugs is currently limited to zoledronate in
teristics were compared between the 2 groups.
patients with pre-existing SREs. In this specific clinical setting, RAI therapy, but
Results
not zoledronate, prevented progression of SREs and mortality. Future studies are
The incidence of RAI-refractory DTC was higher in patients R45yrs and
needed to clarify the effectiveness of anti-resorptive drugs in primary prevention
particularly in those R65yrs (3% vs 7.4% vs 17.4%, PZ0.001). Men had RAI-
of SREs and possible advantages of denosumab versus zoledronate in the
refractory DTC more frequently than women (PZ0.02). RAI-refractory DTC
treatment of BM from DTC.
patients presented higher incidence of capsular, lymph node and extra-thyroid
DOI: 10.1530/endoabs.49.GP231
invasion (P!0.004), larger size (P!0.001), worse histological type (high risk
papillary:
34.9% vs 12% and features of poor differentiation:
14%vs0.6%
respectively, P!0.001,). They presented more frequently distant metastases at
follow-up (73.3% vs 1.5%, P!0.001). 12 RAI-refractory patients had local
persistence. 5/12 had no distant metastasis; all underwent multiple surgeries and 3
locoregional external radiation therapy. The
10-year probability of lack of
GP232
progression of disease was
27.9% vs 98.8% (x2Z297, P!0.001). In Cox
Germ-line mutations in RET-790 and RET-791 codons (exon 13) among
proportional hazard analysis, the only predictor for disease progression was
subjects with sporadic medullary thyroid cancer
resistance to RAI (HR 0.032, 95% CI 0.007-0.146, P!0.001). Within the RAI-
Darko Katalinic1, Miljenko Solter2 & Nora Nikolac2
refractory DTC subgroup, when age at diagnosis, gender, tumor size, histological
1Department of Internal Medicine, Faculty of Medicine, Josip Juraj
type, lymph node, capsular and tissue invasion were taken into account, the only
Strossmayer University of Osijek, Osijek, Croatia;2UHC Sisters of Charity,
predictor for disease progression and occurrence of distant metastases was tumor
Faculty of Medicine, University of Zagreb, Zagreb, Croatia.
size (PZ0.008 and PZ0.015 respectively).
Conclusions
Background
Patients with RAI-refractory DTC present disease progression at high percentage
Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendo-
(72.7%). In these patients, tumor size is the most important unfavorable factor
crine tumour that originates from parafollicular C-cells of the thyroid gland. RET
predicting disease progression and occurrence of distant metastases. These data
proto-oncogene germline mutations are crucial for the onset and the progression
may be useful in designing treatment strategy.
of MTC, and the occurrence of single nucleotide polymorphisms could predispose
DOI: 10.1530/endoabs.49.GP230
the clinical course of disease. The objective of this study was to evaluate possible
differences in clinical presentation among patients with/without RET codon 790
and codon 791 (exon 13) mutations.
Methods
A non-isotopic polymerase chain reaction based single strand confirmation
GP231
polymorphism analysis and heteroduplex gel electrophoresis method was used to
screen tumour DNA extracted from
132
formaldehyde fixed and paraffin
Management and outcome of bone metastasis from differentiated
embedded MTC specimens. We analysed clinical data from
69
patients
thyroid carcinoma in the real life: the M.OS.CA.TI. study
harbouring RET codon 790 and codon 791 mutations (exon 13) (group A)
Gherardo Mazziotti1, Maria Beatrice Panarotto2,3, Emanuela Arvat5,
compared with 63 patients with “wild-type” genotype (group B). The study was
Arturo Chiti6, Alberto Cuocolo7, Massimo Dottorini8, Rossella Elisei10,
conducted according to the Declaration of Helsinki, the protocol was reviewed
Sebastiano Filetti9, Angelina Filice11, Anna Maria Formenti2,12,
and approved by the institutional independent ethics committee. All patients were
Leonardo Pace13, Teresa Pellegrino14, Marcello Nodari6,
provided with written informed consent.
Massimo Salvatori15, Cristina Tranfaglia8, Annibale Versari11,
Results
Stefano Frara16, Alfredo Berruti4, Andrea Giustina16 & Raffaele Giubbini2,3
Mean age for the group A was 56.2G11.4 years (range, 44.8-67.6) vrs. 49.4G9.7
1Endocrine Unit, ASST Carlo Poma, Mantua, Italy;2Nuclear Medicine,
(range 39.7-59.1) for the group B. Lymph node metastases were found in all
ASST Spedali Civili of Brescia, Brescia, Italy;3Nuclear Medicine,
patients (group A, nZ46 vrs. group B, nZ31; P!0.001), and distant metastases
University of Brescia, Brescia, Italy;4Clinical Oncology, University of
in 11 patients (group A, nZ7 vrs. group B, nZ4; PO0.001). Postoperatively,
Brescia, Brescia, Italy;5Oncological Endocrinology, University of Turin,
62% of patients in group A vrs. 78% of patients in group B were biochemically
Turin, Italy;6Nuclear Medicine, Humanitas, Milan, Italy;7Nuclear
cure (P!0.001). In the group A, pT-category was: T0, nZ21; T1, nZ16; and T2,
Medicine, University Federico II of Naples, Naples, Italy;8Nuclear
nZ9. In the group B, pT-category was: T0, nZ22; T1, nZ7; and T2, nZ2
Medicine, “Maria della Misericordia” Hospital, Perugia, Italy;9Internal
(P!0.001).
Medicine, University Sapienza of Rome, Rome, Italy;10Endocrinology,
Conclusions
University of Pisa, Pisa, Italy;11Nuclear Medicine, Arcispedale S. Maria
Nuova A.O. Reggio Emilia, Reggio Emilia, Italy;12Department of
Patients with RET codon 790/791 (exon13) mutations have a more aggressive
clinical course and lower biochemic cure rate in comparison with patients with
Molecular and Translational Medicine, University of Brescia, Brescia, Italy;
‘wild-type’ genotype. This information should be considered by genetic
13Department of Medicine and Surgery, University of Salerno, Salerno,
counseling or by operative therapy and could have clinical importance when
Italy;14Institute of Biostructure and Bioimaging of the National Research
specific targeted therapy is discussed.
Council of Italy - CNR, Naples, Italy;15Nuclear Medicine, Catholic
University of Rome, Italy, Rome, Italy;16Endocrinology, San Raffaele
DOI: 10.1530/endoabs.49.GP232
Vita-Salute University, Milan, Italy.
Although differentiated thyroid cancer (DTC) has the third highest propensity to
spread to the bone after breast and prostate cancer, there is a paucity of data
concerning the treatment of bone metastasis (BM) in this setting. The MOSCATI
GP233
(Metastasi OSsee da Carcinoma TIroideo) was a multicenter, retrospective study
Comparison of clinicopathological features in patients with familial and
investigating the real-life outcome and management of BM in 143 patients (80 F,
sporadic papillary thyroid cancer
63 M; median age 60 years) with DTC involving 10 specialized centers in Italy.
Fatma Dilek Dellal1, Didem Ozdemir1,2, Cevdet Aydin1,2, Berna Ogmen1,
One or more skeletal related events (SREs) were diagnosed in 58% of patients in
Aydan Kilicarslan1,2, Mehmet Kilic1,2, Reyhan Ersoy1,2 & Bekir Cakir1,2
significant association with more aggressive tumor histotype (OR 5.39), higher
1Ataturk Training and Research Hospital, Ankara, Turkey;2Yildirim
number of BM (OR 1.36), localization of BM to thoracic spine (OR 2.7), cervical
Beyazit University, Ankara, Turkey.
spine (OR 7.47) or skull (OR 2.28), and lack of radio-iodine (RAI) uptake (OR
6.03). RAI treatment was performed in 93% of patients. Bone active drugs were
Introduction
used in 32 patients with SRE (22.4%; zoledronate in 31 and denosumab in one).
Although, familial medullary thyroid cancer is a known condition, familial
Bone active drugs were used more frequently in patients with more aggressive
papillary thyroid cancer (PTC) is a rare and less well described clinical entity.
histotype of DTC (P!0.001), with RAI-refractory BM (P!0.001) who did not
While some studies suggest more aggressive features in familial PTC, some do
receive RAI therapy (P!0.001) and/or in those with multiple BM (PZ0.006),
not support these findings. We aimed to compare ultrasonographical,
malignant hypercalcemia (PZ0.001), pathological fractures (PZ0.02) and in
cytopathological and histopathological results of patients with familial and
those undergoing radiotherapy (P!0.001). After treatment, 13.5% of patients
sporadic PTC.
developed new SREs and 39 patients (27.3%) died. RAI treatment significantly
Methods
prevented the second SRE (HR 0.01) and decreased mortality (HR 0.12) as
Data of 194 patients diagnosed with PTC histopathologically between 2007-2016
compared to patients treated with anti-resorptive drugs alone. Patients treated
were retrospectively reviewed. PTC in R2 members of the family was defined
with RAI plus anti-resoptive drugs showed less efficacy in preventing second SRE
as familial PTC. Thyroid functions, ultrasonography features, cytological and
and decreasing mortality as compared to treatment with RAI alone. In conclusion,
histopathological findings were compared in familial and sporadic PTC.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
retrospective multicenter study of
871 patients at 11 centers in Spain with
There were 35 tumor foci in 20 familial and 253 foci in 174 sporadic PTC
papillary thyroid cancer followed after total thyroidectomy and radioactive iodine
patients. Gender, thyroid functions, thyroid autoantibody positivity, mean nodule
remnant ablation. 685 patients were re-stratified during the first year of follow-up
number, thyroidectomy indications and surgical approach were similar in two
based on response to therapy: excellent (73% of the patients), indeterminate (8%),
groups. Preoperative ultrasonography features were available in 20 familial and
biochemical incomplete (6%) and structural incomplete (13%). Clinical outcomes
112 sporadic nodules. There was not any difference in mean nodule diameter,
were obtained in each group and no evidence of disease (NED) was seen in 95%,
echogenity, texture, microcalcification, macrocalcification, presence of hypo-
47%, 32% and 24% respectively for a median follow-up of 57 months. BRAF
echoic halo, taller than wide shape, margin irregularity and vascularization
mutation prevalence was 51% and was significantly associated with patients who
pattern. Cytological results were distributed similarly in two groups (PZ0.433).
had no excellent response (31.4% vs 22.9%; HR 1.53 (95% CI, 1.080 a 2.188)).
In histopathological examination, mean tumor number was 1.79G0.98 in familial
This association remained significant with biochemical incomplete response but
and 1.46G0.77 in sporadic patients (PZ0.09). Mean tumor diameters were
not with structural incomplete response. Moreover, BRAF positive tumors were
6.26G4.10 mm and 9.87G11.62 mm in familial and sporadic tumors, respect-
less likely to have distant metastasis compared with BRAF negative tumors.
ively (PZ0.074). Multifocality, microcarcinoma rate, variants of PTC, vascular
Patients with excellent response and BRAF negative tumors, almost 100% had
invasion and extracapsular extension were similar
(PZ0.155, PZ0.239,
NED at the end of follow-up. Patients with indeterminate and biochemical
PZ0.094, PZ0.617 and PZ0.743, respectively). Capsular invasion was
incomplete response and BRAF positive tumors, were less likely to have NED
significantly increased in sporadic group (19.8% vs 5.9%, PZ0.049).
compared with BRAF negative, although the difference was not significant due to
Conclusion
the small number of patients in each group. Our data show that indeterminate and
Whether familial PTC is more aggressive than the sporadic form of the disease
biochemical incomplete response may not have such favourable clinical outcome
is controversial. Clinical, ultrasonographical, cytological and most of the
as previously shown. In addition, BRAF status informs about the way papillary
histopathological features of familial and sporadic PTC were identical in our
carcinomas disseminate (locoregional vs distant metastasis) and may help to
study. Early detection of cases other than index patients might cause diagnosis at
better assess risk estimates that change over time based on response to therapy.
an earlier stage of the disease in familial form.
DOI: 10.1530/endoabs.49.GP235
DOI: 10.1530/endoabs.49.GP233
Thyroid Cancer & Thyroid Case Reports
GP234
GP236
Lobectomy as a treatment option for well differentiated thyroid cancer
A rare case of medullary thyroid cancer, mesothelioma and
(WDTC) between 1-4 cm: which results should we expect?
meningioma, due to APC and RASAL1 mutations
Ana Fareleira, Patrícia Andrea Ferreira, L Matos Lima & J Costa Maia
Charalampos Lyssikatos1, Martha M Quezado2, Fabio R Faucz3,
Centro Hospitalar S. João, E.P.E., Porto, Portugal.
Anna Angelousi1,4, Narjes Nasiri-Ansari5, Constantine A Stratakis1 &
5,6
Eva Kassi
Introduction
1Section on Endocrinology and Genetics, Eunice Kennedy Shriver National
The ATA guidelines 2015 suggests lobectomy as an option for low risk thyroid
Institute of Child Health and Human Development (NICHD), National
tumors between 1-4 cm, although there remains some controversy once some
Institutes of Health (NIH), Bethesda, MD, USA;2Laboratory of Pathology,
characteristics become apparent only on pathologic examination.
National Cancer Institute, Bethesda, MD, USA;3Section on Endocrinology
Objective/methods
& Genetics, NICHD, National Institute of Health, Bethesda, MD, USA;
Retrospective analysis of patients who underwent thyroid surgery in 2014 and
4Department of Pathophysiology, Unit of Endocrinology, Kapodistrian
2015, with a histologic diagnosis of WDTC 1-4 cm in size and revision of the
University of Athens, Athens, Greece;5Laboratory of Biochemistry,
proportion of patients eligible for lobectomy with indication for completion
National and Kapodistrian University of Athens, Athens, Greece;
thyroidectomy according to the ATA guidelines 2015.
6Endocrine Unit of Clinical and Translational Research, National and
Results
Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Three hundred and eighty eight patients who underwent thyroidectomy were
analysed. Of these, 85 (21,9%) were include for final analysis. Exclusion criteria:
Introduction
history of cervical radiation, tumors !1 and O4 cm, macroscopic extrathyroidal
Patients with “mixed” phenotypes are common among patients with multiple
extension (ETE), cNC, and bilateral thyroid nodules.
endocrine and non-endocrine neoplasias. Their diagnoses do not fit a given
The mean age of the cohort was 49 years, 83,5% are females, none had an
pattern making ge netic counseling difficult and testing impossible to guide. Most
aggressive histology, 12 (14,1%) had vascular invasion, 5 (5,9%) had microscopic
of these patients end up getting genome-wide studies for the identification of any
ETE, 3 (3,5%) had positive margins and 1 (1,2%) patient had positive lymph node
predisposing genetic defect. We present a rare case of a 57 year old female who
metastasis.
presented clinically with medullary thyroid cancer (MTC), mesothelioma and
Conclusion
meningioma. As part of our diagnostic work-up for this category of patients, we
(20%) of the patients with apparently ‘low risk’ WDTC who are eligible for
performed a SNP microarray (comparative genomic hybridization; CGH) and
lobectomy would have indication for completion total thyroidectomy according
whole exome sequencing (WES). CGH did not reveal any abnormalities; WES
to the ATA guidelines 2015.
revealed two variants of unknown significance (VUS) in two separate genes,
DOI: 10.1530/endoabs.49.GP234
namely APC and RASAL1.
Case presentation
The patient, a 57 year old female patient, was diagnosed with AML at 41y old,
peritoneal mesothelioma at 43y old, meningioma at 53y old and medullary
thyroid cancer with lymph node metastasis at 53y old. She also suffers from
GP235
autoimmune atrophic gastritis, alopecia universalis and relapsing perichondritis
of the ear.
Clinical Utility of response to therapy in combination with BRAF in risk
Results
assessment of thyroid cancer
WES was performed by DNA extracted from blood and revealed two specific VUS,
Laura Pérez Fernández1, Antonio De la Vieja Escolar2, Carles Zafón3, Juan
in the APC gene: p.R1103W, c.3307 AOT and in the RASAL1 gene: p.R538H,
Carlos Galofré4, Garcilaso Riesco-Eizaguirre5 & Spanish Task Force for the
c.1613 GOA. The APC gene (OMIM #17500) is a tumor suppressor gene involved
study of BRAF SEEN4,5
in Wnt / b catenin signaling pathway; mutations have been reported in Familial
1Hospital del Tajo, Aranjuez, Madrid, Spain;2Instituto de Salud Carlos III,
Adenomatous Polyposis (FAP), brain tumors and Turcot syndrome. Mutations in
Majadahonda, Madrid, Spain;3Hospital Universitari Vall d’Hebron,
the RASAL1 gene (OMIM#604118) have been found in thyroid cancer (both
Barcelona, Catalun˜ a, Spain;4Clinica Universitaria de Navarra, Pamplona,
papillary and medullary) and Cowden syndrome. The above two variants found in
Navarra, Spain;5Hospital Universitario de Móstoles, Móstoles, Madrid,
this patient have not been reported previously as pathogenic. The mutations in the
Spain.
APC and RASAL1 genes are probably involved in thyroid cancer development. In
addition, the mesothelioma and meningioma are likely related to mutations in the
Response to therapy re-stratification approach has been recently included in the
APC gene. This unique clinical presentation has not been reported before and is
2015 ATA guidelines as a risk-adapted approach to management of thyroid
being proven by additional immunostaining and molecular studies.
cancer. Our aim was to investigate the clinical utility of response to therapy
Conclusion
variables obtained during early follow-up in combination with BRAF, a
Patients with unique phenotypes may present with a list of clinical manife stations
prominent oncogene in thyroid cancer with prognostic value. This was a
that do not fit any given diagnosis. These patients deserve genome-wide testing
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
that is often rewarding but also complex. In our patient with MTC, mesothelioma
undertreated AH (TSH 31.4 mU/mL, fT4L 0.97 ng/dL) and Levothyroxine dose was
and meningioma two new gene defects were identified that are probable
increased. At 24th GW, blood tests showed a mild hyperthyroidism (TSH 0.05 mU/mL,
responsible for the phenotype.
fT4 1.53 ng/dL) and LT4 dose was reduced. Fetal ultrasound (US) at 25th GW showed
DOI: 10.1530/endoabs.49.GP236
a male fetus with bilateral cerebral ventriculomegaly without other alterations.
TORCH serologies were negative, amniocentesis revealed a normal karyotype and
fetal MRI showed bilateral cerebral ventriculomegaly and fetal goiter.
To study the fetal thyroid function a blood sample by cordocentesis was obtained
and a maternal blood test to examine TSH-R-ABs levels was performed.
Meanwhile, fetal US at 26th GW showed tachycardia, mild pericardial effusion,
GP237
hydrothorax, cardiomegaly, hepatomegaly and splenomegaly. Fetal blood sample
Thyrotoxic Periodic Paralysis due to Graves’ disease: a mandatory
showed fetal hyperthyroidism (TSH!0.008, fT4 4.03, fT3 9.92) while maternal
differential diagnosis in Asian patients presenting with paralysis and
TSH-R-ABs were elevated (O40 mUI/mL). Unfortunately, fetal death occurred
hypokalemia
before knowing the results and antithyroid drugs could not be started. As far as we
David Barbosa1, Carolina Faria1, Ana Sofia Osório1, Ema Nobre1,
know, this is the second reported case of TSH-R-ABs-induced fetal thyrotoxicosis
Ana Paula Vilas2 & Maria Joa˜o Bugalho1
in an AH woman.
1CHLN - Hospital de Santa Maria, Endocrinology, Diabetes and
Conclusion
Metabolism Department, Lisbon, Portugal;2CHLN - Hospital de Santa
TSH-R-ABs plasma determination should be mandatory in pregnant women with
Maria, Medicina 2B, Lisbon, Portugal.
any previous autoimmune thyroid disease and fetal goiter or thyrotoxicosis.
Antithyroid drugs should be started as soon as fetal hyperthyroidism is suspected.
Introduction
DOI: 10.1530/endoabs.49.GP238
Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication
of hyperthyroidism that is underdiagnosed and frequently missed. It is relatively
common in Asian men with Graves’ disease. TPP attacks are frequently
associated with hypokalemia.
Case presentation
GP239
We describe a 26-year-old Asian male with an unremarkable past medical history
Renal cell carcinoma metastasis to thyroid tumor: a case report
who was admitted following sudden onset of flaccid paralysis of the lower
Carolina Faria, David Barbosa, Ana Sofia Osório, Ema Nobre &
extremities. Signs and symptoms such as weight loss, diaphoresis, palpitations
Maria Joa˜o Bugalho
and mild diffuse goitre were present. The electrocardiogram showed a sinus
Hospital de Santa Maria, Lisboa, Portugal.
tachycardia and the laboratory evaluation revealed markedly low potassium and
phosphorus levels (KC1.5 mmol/l; PO3K 1.8 mg/dl). The patient was managed
with intravenous potassium chloride with markedly improvement of the
Introduction
neurological deficits, despite a rebound hyperkalemia shortly after replacement.
Subacute thyroiditis (SAT) association with papillary thyroid carcinoma (PTC)
A thyroid profile was taken due to the suspicion of TPP in the context of Graves’
has been rarely reported in the literature. Metastatic neoplasms to the thyroid are
disease, and the diagnosis was made (TSH 0.01 mU/ml; free T4 5.21 ng/dl; free
rare in clinical practice. Renal cell carcinomas (RCC) are the most frequent site of
T3 15,64 pg/ml; TRABs 37,64 U/l). The patient then started on oral propranolol
origin of thyroid metastases (12 to 34%). Tumor-to-tumor metastases, in which a
and tiamazol, with complete remission of the symptoms and sustained
thyroid neoplasm is the recipient of a metastasis, are exceedingly rare. Tuberous
normalization of serum potassium.
sclerosis (TS) is associated with several renal manifestations (80-85% of the
Conclusion
patients) including angiomyolipomas (AMLs) (80%), renal cysts (30%) and RCC
TPP is an alarming and potentially lethal complication of hyperthyroidism
(2-4%)
characterized by muscle paralysis and hypokalemia due to a massive shift of
Case report
potassium into cells. This condition mainly affects male patients of Asian descent.
A 19-year-old male, with personal history of TS, presented in the emergency
With increasing population mobility and admixture, TPP as the presenting feature
department complaining of edema, jitteriness and pain in cervical region. SAT
of hyperthyroidism is now more common in Western countries. Early diagnosis
diagnosis was established based on complaints, physical examination and
not only aids in definitive management with nonselective beta-blockers and
laboratory results. After the resolution of SAT, thyroid ultrasonography (US)
correction of hyperthyroidism, but also prevents the risk of rebound hyperkalemia
revealed 2 suspicious nodules. The major nodule was submitted to fine needle
due to excessive potassium replacement. We report this case to emphasize the
aspiration cytology and the report was suspected of malignancy. Total
importance of recognizing TPP to avoid missing a treatable and curable condition.
thyroidectomy was performed. Postsurgical pathology evaluation showed a
DOI: 10.1530/endoabs.49.GP237
bilateral PTC/follicular variant (pT3N0). Within the PTC were a few nests of a
morphologically distinct neoplasm. Immunoperoxidase stains of these cells were
positive for CK8/18 and CK7 and were negative for thyroglobulin, calcitonin,
vimentin, CK20, CD10 and racemase thus suggesting metastases of RCC. The
body CT showed bilateral renal lesions likely to be angiolipomas without
distinctive criteria. Suspicious lesions in the liver, lungs and bones were also
GP238
reported without uptake in a 18F-FDG PET-CT.
A fatal case of fetal goiter: autoimmunity is the key
Conclusion
Irene Berges-Raso1, Lara Albert1, Assumpta Caixàs1, Ismael Capel1,
This case illustrates an extremely rare occurrence of tumor-to-tumor metastasis
Albert Cano1, Isabel Mazarico1, Laura Serra2, Manuel Corona2,
where the recipient was a PTC and the donor likely to be an occult RCC.
Cesar Martín Martínez3 & Mercedes Rigla1
DOI: 10.1530/endoabs.49.GP239
1Endocrinology and Nutrition Department. Parc Taulí Hospital Universitari.
Institut d’Investigació i Innovació Parc Taulí I3PT. Universitat Autònoma
de Barcelona., Sabadell, Barcelona, Spain;2Obstetrics and Gynecology
Department. Parc Taulí Hospital Universitari. Institut d’Investigació i
Innovació Parc Taulí I3PT. Universitat Autònoma de Barcelona., Sabadell,
Barcelona, Spain;3SDI-UDIAT. Parc Taulí Hospital Universitari. Institut
GP240
d’Investigació i Innovació Parc Taulí I3PT. Universitat Autònoma de
Giant goiter with intrathyroid arteriovenous fistula as a cause of severe
Barcelona, Sabadell, Barcelona, Spain.
pulmonary hypertension
Elena Márquez Mesa, Estefanía González Melo, Cristina Lorenzo González,
Pilar Olvera Márquez, Ricardo Darias Garzón, María Teresa
Introduction
Herrera Arranz, Bruno Francisco García Bray, Yolanda Zambrano Huerta &
Fetal goiter is an infrequent and potentially life-threating condition derived from
Enrique Palacio Abizanda
either fetal hypothyroidism or hyperthyroidism. TSH-receptor stimulating
Hospital Universitario Nuestra Sen˜ora de la Candelaria,
antibodies (TSH-R-ABs) can cross the placenta and induce fetal hyperthyroidism
Santa Cruz de Tenerife, Spain.
and goiter. We describe a rare case of TSH-R-ABs-induced hyperthyroidism in a
woman with autoimmune hypothyroidism (AH) without previous hyperthyroidism.
Case Report
Introduction
A 28 years old pregnant woman under treatment with Levothyroxine (LT4) for
Hyperthyroidism has been described as a rare cause of pulmonary hypertension
6 years because of AH was referred during pregnancy. She had history of
(PH) as well as systemic arteriovenous fistulas. However, we describe a case of
2 miscarriages: fetal death at 28th gestational week (GW) two years before and
pulmonary hypertension secondary to an intrathyroid arteriovenous fistula, not
fetal loss in 2015 because of corioamnionitis. Blood tests at 12th GW showed
previously described in the literature.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Case report
GP242
A 56 year old woman followed in our consultations with multinodular goiter and
False negative fine needle aspiration thyroid cytology: an institutional
a long standing hyperthyroidism, secondary to Graves Basedow disease with
experience
difficult management. She required methimazole and low doses of levothyroxine
Anabela Martins, Evelina Mendonc¸a, António Garrão, Hugo Marques,
simultaneously to achieve hormonal control, needing multiple admissions for
Maria Cid, Francisco Rosário, Ricardo Veiga & Ana Catarino
heart failure (HF). In her last admission to Cardiology, she had right HF stage III-
Hospital da Luz, Lisbon, Portugal.
IV of NYHA, and physical examination revealed grade III goiter with murmur
auscultation and thrill palpation. The blood tests revealed that she was euthyroid.
The echocardiogram showed dilatation of both ventricles, ejection fraction 57%,
Introduction
moderate-severe biauricular dilatation, moderate mitral and tricuspid insuffi-
Fine needle aspiration cytology (FNA) is the most accurate diagnostic method for
ciency, PAPs 73 mmHg. Cervical thoracic CT evidenced large multinodular
thyroid malignant nodule diagnosis. According to the literature, the percentage of
goiter with intrathoracic extension and tracheal compression, multiple hypervas-
false negative results (FN-FNA) is less than 1.5%, in tertiary health care centers.
cular nodules and cervico-vascular venous congestion. Right cardiac catheteriza-
In this study we describe the cases reported in this Hospital, between 2014 and
tion showed moderate precapillary PH with high saturations in the venous
2016, of benign cytology, histologically characterized as malignant. All
territory explored and cardiac output 8.1 l/m. These findings were consistent with
pathologic specimens were reviewed.
the diagnosis of PH secondary to intrathyroid arteriovenous fistula. Definitive
Results
treatment was made by performing total thyroidectomy. The pathologic study of
From a total of 299 benign FNA cases submitted to surgery, 6 cases with
the piece was reported as multinodular thyroid goiter (12!13!5 centimeters and
malignant histopathology were detected (2.0%). FN-FNA was identified in 5
140 grams) with signs of diffuse hyperplasia and arteriovenous fistula. Two
males and 2 females, with ages ranging from 42 to 72 years old. The nodules size
months after surgery the patient had improved her functional class and the PAPs
varied between 41 to 95 mm.
had decreased to 30 mmHg.
The ultrasound malignancy risk was between 5 and 20% (ATA 2015 Risk
Conclusions
Stratification System).
This is the first case described in which pulmonary hypertension is secondary to
The benign FNA were described as hyperplasic nodule in 3 cases, cystic
an arteriovenous fistula in a giant goiter. Surgery was a successful treatment, and
hyperplasic nodule in 1 case, cystic colloid nodule in 1 case and colloid nodule in
one year after, the patient has a disease free survival.
the remaining.
DOI: 10.1530/endoabs.49.GP240
In all the cases the histological diagnosis was of follicular variant of papillary
carcinoma, with macrofollicular areas, either predominant or focally, and with a
heterogeneous distribution of the distinctive nuclear features of papillary
carcinoma.
Four patients were recommended for radioiodine therapy. One of these patients
was diagnosed with pulmonary and bone metastases.
Four patients were available for follow-up (mean time Z1.5 years; 9-24 months).
GP241
There is no imaging evidence of disease in any of the patients.
Thyroid-related adverse events in patients treated with Nivolumab
Conclusions
I Peiró1, L San Martín2, A Simó-Servat2, J Otero2, JC Ruffinelli3, E Nadal3,
In our institution, the percentage of FN-FNA was 2.0%, in accordance with that
P Iglesias4, JJ Díez4 & C Villabona2
described in the literature.
1Clinical Nutrition Unit, Institut Català d’Oncologia (ICO), Hospitalet de
The ultrasound risk assessment did not significantly change the risk assessed
Llobregat, Spain;2Department of Endocrinology, Hospital Universitari de
by FNA.
Bellvitge, Hospitalet de Llobregat, Spain;3Department of Oncology, ICO,
In all the cases the histological diagnosis was follicular variant of papillary
Hospitalet de Llobregat, Spain;4Department of Endocrinology, Hospital
carcinoma. The presence of macrofollicular areas, cystic areas and a
Ramón y Cajal, Madrid, Spain.
heterogeneous expression of the typical nuclear features of papillary carcinoma
may explain the occurrence of FN-FNA.
DOI: 10.1530/endoabs.49.GP242
Introduction
Nivolumab is an antibody that binds to and blocks the activation of programmed-
death-receptor 1(PD-1), promoting the activation of T-cells against tumor cells.
Thyroid dysfunction (TD) is one of the most common immuno-related adverse
events, with incidence up to 10% in patients treated with PD-1/PD-L1 blockade.
Objective
To report our experience of Nivolumab-TD in patients with advanced cancer.
Methods
All patients diagnosed of nivolumab-induced TD during 2016 were included.
GP243
Data from thyroid function tests, autoimmunity and imaging study before and
during nivolumab therapy were recorded.
Risk factors associated with malignancy in thyroid nodules classified as
Results
Bethesda category IV (follicular neoplasm/suspicious for follicular
Twelve cancer patients (5 lung, 4 melanoma, 3 Hodgkin lymphoma) were
neoplasm)
evaluated. 75% women, mean age: 56.7 year (19-77). Ten patients were treated
Bekir Kuru & Mehmet Kefeli
with nivolumab 3 mg/kg (with or without chemotherapy) every 15 days, 2
Ondokuz Mayis University School of Medicine, Samsun, Turkey.
patients received combined immunotherapy (nivolumab 1 mg/kg plus ipilimumab
3 mg/kg). Three patients had previously well-controlled thyroid disease (1 overt
Background
primary hypothyroidism, 2 subclinical hypothyroidism). Baseline serum TSH and
Thyroid nodules diagnosed as Bethesda category IV (follicular neoplasm/suspi-
free thyroxine were evaluated in eleven patients, being normal in ten whereas one
cious for follicular neoplasm (FN/SFN)) are recommended for surgery. However,
showed minimal subclinical hypothyroidism. During follow-up,
7
patients
only 25% of these nodules turn to be malignant on histopathology. Therefore,
(58.3%) developed hyperthyroidism (4 overt and 3 subclinical). Six of them
selection of nodules for surgery diagnosed as Bethesda category IV is important.
after cycle(C) 2, and 1 after C3. Thyroid antibodies were positive in 3 patients.
We aimed at to define the predictive factors for malignancy and predictive risk
One overt hyperthyroidism was treated with high dose steroids (prednisone
indices for selection of surgery.
0.8 mg/kg per day) and nivolumab was temporarily withdrawn. Four of seven
Method
hyperthyroid patients became hypothyroid later, needing levothyroxine. Primary
The records of all patients with nodules that underwent fine needle aspiration
hypothyroidism occurred in 5 patients (41.7%) (3 overt and 2 subclinical),
biopsy (FNA) and classified by Bethesda reporting system as FN/SFN between
between C4-C7. Autoimmunity was positive in 3 hypothyroid patients. No patient
2011 and 2017 at our institution were reviewed. Univariate and multivariate
discontinued nivolumab due to hypothyroidism.
analysis were performed to select independent factors associated with thyroid
Conclusions
cancer. Using independent risk factors for malignancy predictive indices were
In our series, hyperthyroidism is more frequent and appears earlier than
created.
hypothyroidism. A pattern consistent with a transient thyroiditis followed by
Results
hypothyroidism is seen in one-third of patients. Monitoring thyroid function at
Among 6,217 nodules which underwent FNA, 163 (2.6%) were diagnosed as
baseline and before each therapeutic cycle is warranted to detect and treat TD
FN/SFN. Of the 163 patients classified as FN/SFN, 126 underwent surgery with
promptly.
an associated malignancy rate of 36% (45/126). Age under 45, solid structure,
DOI: 10.1530/endoabs.49.GP241
microcalcification, hypoechogenicity and increased vascularization were found to
be significant and independent risk factors associated for malignancy. The risk
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
indices were created by classifying nodules with 0, 1, 2, 3, and R4 risk factors as
(57.9%) were shown to be positive. Subsequently, DNA samples from Rc-PTC
risk indices 0, 1, 2, 3, and 4. There were 17 (14%), 41 (33%), 27 (21%), 22 (17%),
and NR-PTC groups were analysed for BRAFV600E mutation and this mutation
and 19 (15%) patients in risk indices 0, 1, 2, 3, and 4, respectively. The estimated
was found in 54.8% (17/31) of Rc-PTC samples and 59.0% (49/83) of NR-PTC
malignancy risk in patients with 0, 1, 2, 3, and 4 risk indices were 0% (0/17), 12%
samples. There was no signifficant difference between these groups (PZ0.686).
(5/41), 26% (7/27), 64% (14/22), and 100% (19/19), respectively.
Conclusion
Conclusions
These results suggest that miRNA-21, miRNA-222, miRNA-146b might be
Using predictive factors for malignancy in Bethesda IV category a small, but
potential biomarkers for PTC recurrence. BRAF mutation is not associated with
important proportion of patients 14% who had nodules without any risk factors
PTC recurrence.
could be spared unnecessary surgery. Predictive indices should be considered for
DOI: 10.1530/endoabs.49.GP244
informing the patients about the malignancy risk and for selection of surgery in
Bethesda IV category.
DOI: 10.1530/endoabs.49.GP243
GP245
A statistical, in silico model predicts polygenic thyroid cancer risk
Livio Casarini1,2, Marco Marino1,2, Federico Nuzzo1, Manuela Simoni1,3 &
Giulia Brigante1,3
1
Unit of Endocrinology, Department Biomedical, Metabolic and Neural
GP244
Sciences, University of Modena and Reggio Emilia, Modena, Italy;2Center
Expressions of miRNAs and BRAFV600E mutation detection in papillary
for the Genomic Research, University of Modena and Reggio Emilia,
thyroid carcinoma
Modena, Italy;3Azienda Ospedaliero-Universitaria di Modena, Modena,
Vaida Simanaviciene1, Aiste Kondrotiene2, Daina Pamedytyte1,
Italy.
Valdas Sarauskas3, Dalia Dauksiene4, Albertas Dauksa5,
Aurelija Zvirbliene1 & Birute Zilaitiene1
1Institute of Biotechnology, Vilnius University, Vilnius, Lithuania;
Introduction
2Lithuanian University of Health Sciences, Medical Academy, Kaunas,
The detection of a unique genetic marker is not possible for multifactorial
Lithuania;3Department of Pathological Anatomy, Lithuanian University of
diseases, such as thyroid cancer (TC), where the pathological phenotype is given
Health Sciences, Kaunas, Lithuania;4Institute of Endocrinology, Medical
by the contribution of multiple genes, environmental factors and lifestyle. We
Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania;
found a mathematical model for inferring the risk of thyroid cancer, an example of
5Institute of Digestive Research, Medical Academy, Faculty of Medicine,
multifactorial disease.
Lithuanian University of Health Sciences, Kaunas, Lithuania.
Methods
Genetic data represented by 184 SNPs associated to thyroid tumors were used for
Bayesian clustering of 2504 individuals from the 1000 Genomes database, by
Introduction
STRUCTURE software. Numerical values representing the inferred genetic
Papillary thyroid carcinoma
(PTC) is the most common type of thyroid
structure of each individual is provided in the output file of the software and were
malignancy. For the majority of patients with PTC, the prognosis is very good;
matched with environmental and lifestyle parameters associated to thyroid
however, up to 20% of patients suffer disease recurrence. Currently, the risk
functions, i.e. iodine exposure and obesity, by principal component analysis
stratification for PTC recurrence is based on clinicopathological features which
(PCA). Data analysis was performed using labels such as geographic origin of
have limited prognostic value. Identification of molecular biomarkers of PTC
individuals, population, sex and thyroid cancer incidence.
recurrence such as protooncogene BRAF and miRNAs may help to improve risk-
Results
stratified patient management.
We found that seven thyroid tumor-related genetic clusters are differently
Objective
represented among human populations. The matching of genotype, iodine and
The aim of this study was to detect BRAFV600E mutation and identify miRNA
obesity data resulted in individuals’ gradient distribution by thyroid cancer
biomarkers for PTC recurrence.
incidence, revealing that all these components are required to infer the disease
Methods
risk. Genetic background and, to a lesser extent, environmental factors and
We selected 3 miRNA (miRNA- 146b, -222 and -21) and measured the expresion
lifestyle, are not related per se to a specific range value of cancer risk. An
levels of these miRNAs in patients with recurrent PTC (Rc-PTC) and without
exception is provided by individuals from Tuscany, Italy, which deviates from the
recurrence
(NRc-PTC). 106 NR-PTC and 60 Rc-PTC FFPE samples were
overall distribution, preserving high cancer risk independently from obesity or
analysed for selected miRNAs. 114 FFPE PTC samples (31 Rc-PTC and 83
iodine. This could result from a peculiar genetic setting or from the exposure to
NR-PTC) were analysed for BRAFV600E mutation.
environmental factors not considered in the analysis.
Results
Discussion
The expression levels of all three miRNAs were significantly increased in PTC
We demonstrated that TC risk may be detected a priori by applying polygenic
when compared to healthy thyroid tissue. miRNA-146b expresion was extremely
model to specific population or individuals.
elevated with 55.6-fold over-expression in PTC (P!0.001). miRNA-222 and -21
Conclusion
were over-expressed 13.8-fold and 3.7-fold, respectively (PZ0.001 and PZ0.16).
This study provides a novel mathematical approach to infer the polygenic disease
In Rc-PTC and NRc-PTC groups miRNA-21, -146b and -222 were significantly
risk, as a promising diagnostic tool for personalized medicine.
differently expressed with 1.4- fold (PZ0.006), 1.8-fold (PZ0.007) and 2.1-fold
DOI: 10.1530/endoabs.49.GP245
(P!0.001) higher expresion in NRc-PTC compared with Rc-PTC tissues. 114
FFPE PTC samples were analysed for BRAFV600E mutation and 66 of them
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations:
Adrenal and Neuroendocrine
Tumours
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Adrenal Cortex (to include Cushing’s)
Conclusions
In our study we found a correlation between salivary and serum cortisol values in
EP1
both samples, at the morning and at the midnight to all participants; in healthy
Confirmatory tests for diagnosis of primary aldosteronism among
people, patients with Cushing’s disease.
Chinese hypertensives
Keywords: salivary cortisol; serum cortisol; correlation
Minchun Jiang1, Dujuan Ma2, Hailun Lin1, Ying Lin1, Yajuan Deng3,
DOI: 10.1530/endoabs.49.EP2
Juying Tang1, Shaoling Zhang1 & Ying Guo1
1Department of Endocrinology and Metabolism, Sun Yat-sen Memorial
Hospital, Sun Yat-sen University, Guangzhou, China;2Department of
Endocrinology and Metabolism, Guangzhou Panyu Central Hospital,
Guangzhou, China;3Shenzhen Hospital of Southern Medical University,
Shenzhen, China.
EP3
Adrenocortical virilizing tumor in an adult woman in remission after
surgical therapy performed more than 12 years ago
Objective
Terroba Larumbe, Crespo Soto, Citores Pascual, Benito Fernandez,
Primary aldosteronism (PA) has emerged as the most frequent form of secondary
Calero Aguilar, Anacabe Goyogana, Urbon Lopez De Linares,
hypertension. For the diagnosis of PA, confirmatory testing is indispensable and
Ventosa Vin˜ a, Cuellar Olmedo & Palacio Mures
different tests are recommended by guidelines, including captopril challenge test
Hospital Universitario Rio Hortega, Valladolid, Spain.
(CCT) and saline infusion test (SIT). However, there are sparse studies evaluating
and comparing CCT and SIT in Chinese population. Hence, we investigate the
diagnostic efficiency of CCT and SIT for PA in Chinese hypertensives in our study.
Introduction
Methods
Adrenocortical carcinomas (ACCs) are rare, frequently aggressive tumors. Pure
In total, 183 patients with essential hypertension and 105 patients with PA were
virilizing carcinomas are infrequent, constituting 5 to 10% in most series.
recruited in the study, and their clinical data were analyzed by constructing the
Clinical case
receiver operating characteristics (ROC) curve to compare the accuracy of CCT
A 36-year-old female consults for 5 years evolution of amenorrhea associated
and SIT.
with hirsutism attributed to polycistic ovary syndrome (PCOS) and treated with
Results
oral contraceptives during the previous 2 years. There was no other data on
(1) A total of 277 patients underwent CCT. The AUC of post-CCT aldosterone,
virilization, changes in body weight, hypertension or gastrointestinal symptoms.
aldosterone suppression rate and post-CCT aldosterone/renin ratio (ARR) were
In the biochemical exam the following were observed: total testosterone 405 ng/dl
0.877
(95% CI 0.833 to 0.921, P!0.001), 0.683 (95% CI 0.617 to 0.748,
(15-110), free testosterone 26.9 pmol/l (0.19-8.9), DHEA-sulphate 1000 mg/dl
P!0.001) and 0.929 (95% CI 0.896 to 0.963, P!0.001), and accuracy of ARR
(35-430), FSH 2.9 mU/ml and LH 11.4 mU/ml. Basal and urinary cortisol,
post-CCT is highest (P!0.001). For post-CCT ARR, at the optimal cut-off value
prolactin, beta-estradiol,
17-OH-progesterone, thyroid, hepatic and renal
of 30 ng†dl-1/ng†ml-1†h-1, the sensitivity and specificity were 67.6% and
function, ions, were normal. The response to LHRH and ACTH and ovarian
96.2% respectively. (2) The SIT was performed in 116 patients. The AUC of post-
ultrasound were compatible with PCOS and ruled out late onset congenital
SIT aldosterone and post-SIT ARR were
0.829
(95% CI 0.731 to 0.928,
adrenal hyperplasia. The imaging tests showed a solid adrenal mass in the left
P!0.001) and 0.923 (95%CI 0.860 to 0.985, P!0.001), and post-SIT ARR has
10!13!14 cm, with prominent vascular structures inside it, which were
higher accuracy
(P!0.05). The best cut-off value of post-SIT ARR for
embolized prior to surgical excision performed by bilateral subcostal laparotomy.
identifying PA was 60 ng†dl-1/ng†ml-1†h-1, with sensitivity and specificity of
The histological diagnosis of the tumor which weighed 1.152 kg and measured
81.8% and 95.2%, respectively. (3) 110 patients underwent both CCT and SIT. In
20!12.5!8.5 cm, proved to be an adrenocortical tumor of low degree
the consistency check of CCT and SIT, kappa value was 0.714, P!0.001. The
malignancy, without invasion of the capsule or adjacent tissues. Menstruation,
AUC of post-CCT ARR, post-SIT ARR, serial test of post-CCT ARR and post-
hormonal tests and ovarian ultrasound became normal after surgery. The patient
SIT ARR were 0.937 (95% CI 0.885 to 0.990, P!0.001), 0.921 (95% CI 0.858 to
did not receive any therapy and the follow-up has not shown recurrence.
0.984, P!0.001) and 0.939 (95% CI 0.881 to 0.881, P!0.001), there is no
Discussion
statistical difference among the three indices.
Overall, survival is poor for ACC. Five-year survival is approximately 45-60%
Conclusions
for early stage disease, and 10-25% for advanced stage disease. For patients with
With a good consistency, CCT and SIT are both efficient confirmatory tests for
stage I to III disease, complete surgical resection as initial therapy is the only
PA, and applying ARR post-CCT or ARR post-SIT make it feasible to diagnose
potentially curative treatment and open surgery remains the standard approach.
PA more accurately. However, combining two tests fails to further improve the
Despite the large tumor size, the patient had a good prognosis based on the
accuracy for diagnosis of PA.
absence of invasion of the surrounding tissues, the histological grade of
DOI: 10.1530/endoabs.49.EP1
differentiation and the complete tumor resection. The interest of her case is due
not only to the prolonged survival with an optimal quality of life, but also is a
representative example of PCOS secondary to hyperandrogenism that disappears
from the functional and morphological point of view after the suppression of its
cause.
DOI: 10.1530/endoabs.49.EP3
EP2
The correlation of salivary cortisol values with serum cortisol values
Blertina Dyrmishi1, Taulant Olldashi1, Ema Lumi3, Entela Puca4,
Emirvina Kolici4, Dorina Ylli2 & Thanas Fureraj2
1Hygeia Hospital Tirana, Tirana, Albania;2UHC Mother Teresa, Tirana,
Albania;3Regional Hospital Korca, Korca, Albania;4Neo Style Clinic,
EP4
Tirana, Albania.
Investigation of atrophic adrenal glands in Cushing’s syndrome model
rats induced by the administration of dexamethasone
Toshiro Seki1, Atsushi Yasuda1, Natsumi Kitajima1, Masami Seki2,
Aim
Masayuki Oki1, Atsushi Takagi1 & Masafumi Fukagawa1
The aim of the study was to evaluate the correlation between salivary and serum
1Tokai University School of Medicine, Isehara-shi, Kanagawa, Japan;
cortisol values to the healthy people and patients with Cushing’s syndrome.
2Seirei Numazu Hospital, Numazu-shi, Shizuoka, Japan.
Methods
33 cases: 21 healthy people aged 22 to 53 years old; 12 patients with Cushing’s
syndrome values were included to our study. All the participiants of control group
Cushing’s syndrome is a disease caused by excessive glucocorticoids from
were healthy without known disease. Two samples of salivary and serum cortisol
adrenocortical tumors. In most cases, impaired adrenocortical function is likely
was taken to all the participiants of the study in the morning and in the midnight.
caused by atrophy of the normal adrenal tissue as a result of chronic suppression
All the subject respect the rolls of salivary collected samples.
by the low ACTH levels in the hypercortisolism state. Secondary adrenal
Results
insufficiency causes with surgical resection of cortisol-secreting tumors.
The mean age of the healthy subjects was 31G4.8 years old. Basal salivary
Therefore, we thought that it was necessary to prepare Cushing’s syndrome
cortisol was significantly correlated with serum salivary cortisol in the morning
model rats for establishment of a new treatment method to promote improvement
and at the midnight; P!0.05 in the morning and PZ0.052 at the midnight.
of the function of the remaining adrenal glands after adrenalectomy. Cushing’s
Pearson coefficients were 0.45 in the morning and 0.42 at the midnight (2300 h).
syndrome model rats have already been published and they describe changes in
The sensitivity of salivary cortisol values in diagnoses of Cushing’s syndrome
blood pressure and body weight. Regarding atrophy of tissues, it is considered that
was 100% for cut off values 2.18 ng/dl and for cut off values 3.14 ng/dl the
the atrophy of cells and the appearance of apoptosis are observed in such tissues.
sensitivity was 100% and specificity 83%. ACU 0.97.
However, the weight and histological changes of the adrenal glands are not
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
described. In this study, we investigate ACTH, the ratio of adrenal cortex to
stimulates the adrenal gland and induces the release of glucocorticoids. Many
medulla and number of apoptotic cells as evaluation of atrophic adrenal glands in
studies have shown their effects on several physiological functions such as
dexamethasone-treated rats (nZ5) compared to control rats (nZ5). In the group
immunity, inflammation as well as the cardiovascular system whose action is
treated with dexamethasone, an increase in blood pressure (135G24 mmHg),
controlled by ACTH. For this purpose, the study carried out in the wistar rat
suppression of plasma ACTH (20G12 pg/ml) and the low serum corticosterone
revealed the effects of a treatment with Cortrosyn (ACTH of synthesis) on the
levels (7.5G1.1 ng/ml) were observed as compared with the control group. In
weight and the adrenal structure in the wistar rat. The work was carried out on a
addition, adrenal gland weight decreased (13.6G1.2 mg), and the low ratio of
lot of rat wistar divided into two lots: one batch of control rat (T) and one batch of
adrenal cortex to medulla and an increase of apoptotic cells were observed.
treated rat (S) receiving a daily intramuscular injection of Cortrosyn at the rate of
Compared with control rats, dexamethasone-treated rats showed a significant
0.01 mg/100 g of weight Body for 20 days. After sacrifice of the animals, the
decrease in hormonal secretory ability both endocrinologically and histologically.
adrenals are taken, weighed and immediately immersed in the fixing liquid in
Our group is currently conducting experiments to investigate the levels of
order to carry out the histological techniques. The results show that the
mRNAs for c-fos in adrenal glands as assessment of the recovery of adrenal
intramuscular injection of Cortrosyn resulted in a very significant increase in
atrophy.
absolute and relative adrenal weights in treated rats as compared to controls as
DOI: 10.1530/endoabs.49.EP4
well as an increase in the number of cells
(hyperplasia), a different cell
distribution and The appearance of optically empty space. These results to be
investigated and could explain why the activation of the adrenal cortex during
20 days by the Cortrosyn would be in favor of an important structural and
functional modification of the adrenal gland whose indirect trophic effect of this
hormone could be regulated by several factors.
EP5
Keywords: Cortosyn; adrenal; ACTH
Long-term assessment of AddiQoL and patient diaries may identify
DOI: 10.1530/endoabs.49.EP6
Addison patients at high risk for adrenal crises
Maike Koch1, Klaus Badenhoop1, Eva Herrmann2 & Gesine Meyer1
1Department of Internal Medicine 1, Endocrinology, Goethe-University
Hospital, Frankfurt, Germany,2Institute for Biostatistics, Goethe-University
Hospital, Frankfurt, Germany.
Introduction
Several studies have shown a reduced quality of life (QoL) in patients with
Addison’s disease (AD). However, by now there are no data investigating the
changes of QoL over a long-term course. Adrenal crises (AC) are frequent and
potentially life-threatening complications in patients with AD. Since no reliable
laboratory indicator can predict impending crises it is difficult to detect patients at
EP7
increased risk. The purpose of this study was to test whether the repeated use of
questionnaires for self-assessment over longer periods can detect possible
Molecular variability determines subtle adrenal biosynthetic defect in
prodromal periods of an AC.
non-classical congenital adrenal hyperplasia due to 21-hydroxylase
Methods
deficiency
137 patients with AD were included. They were asked to complete the disease
Livia Mermejo1, Fernanda Coeli-Lacchini1, Wendy Turatti1,
specific-quality of life questionnaire AddiQoL once monthly over a period of ten
Marcia Elamid2, Renata Parente2, Carlos Martinelli2, Sonir Antonini2,
months. In addition they also completed a short questionnaire about adverse
Margaret Castro1 & Ayrton Moreira1
events during the last month. AC was defined if at least two of the following
1Department of Internal Medicine Ribeirao Preto Medical School,
symptoms were reported: a) hypotension, b) nausea or vomiting, c) severe fatigue,
University of Sao Paulo, Brazil, Ribeirao Preto/SP, Brazil;2Department of
d) documented hyponatremia, hyperkalemia, or hypoglycemia, and subsequent
Pediatrics Ribeirao Preto Medical School, University of Sao Paulo, Brazil,
parenteral glucocorticoid administration was carried out.
Ribeirao Preto/SP, Brazil.
Results
110 patients completed the study by fulfilling at least 9 of the 10 required sets of
There is a clinical spectrum of non-classical congenital adrenal hyperplasia due to
questionnaires and not exceeding a time-lag over more than three months. Seven
21-hydroxylase deficiency (NC-CAH). In addition, CYP21A2 gene mutations
patients suffered an AC, resulting in 7.6 crises/100 patient years. AddiQoL scores
analysis present in homozygosis or as compound heterozygosis.
in patients with adrenal crises showed a trend (PZ0.058) to a wider fluctuation
Objectives
over the ten months. 19 Patients reported about severe adverse events not
To evaluate the relationship between the genotype and biochemical profiles and
fulfilling the named criteria of AC. In these patients we found a significantly
also compare with clinical severity in NC-CAH.
lower median (PZ0.017) of the AddiQoL scores compared to patients not
Patients and methods
suffering a pre-crisis.
Clinical, hormonal and molecular data of 57 patients (47 female,10 male; 47
Conclusions
children,10 adults) with NC-CAH were retrospectively analyzed.
These are the first data showing the course of QoL during a period of ten months
Results
in patients with AD. Prevalence of AC lay by 7.6 per 100 patient years, in
The majority of children
(76%) presented with premature pubarche at the
accordance with previous data. Our data show, that relevant medical adverse
diagnosis and 12% showed clitoromegaly. Among adult patients, hirsutism (90%)
events in patients with AD are associated with a lower QoL. Furthermore, such
and menstrual abnormalities (66%) were observed at diagnosis. The basal and
events affect intraindividual AddiQol-scores over time with a trend to a stronger
ACTH-stimulated 17OHP mean levels were 1115G919 (97-4125) and 4245G
fluctuation. Long-term assessment of AddiQol and assessment of adverse events,
2059
(1115-10648) ng/dl. The most frequent mutation was p.V281L (68% of
e.g. via patient diaries, may be applied as an additional clinical tool to identify
alleles) being 42% in homozygosis and 39% of the patients were compound
patients at risk for critical events.
heterozygotes for one classic and one non-classical mutation (C/NC).The severe
DOI: 10.1530/endoabs.49.EP5
mutations were p.I172N, IVS2-13A/COG, D8, CL6, p.Q318X, p.R356W and
LGC. Basal and ACTH-stimulated 17OHP values were higher in patients carrying
the C/NC genotype group compared to NC/NC genotype (1549G250 vs 806G
162; PZ0.01
and
4740G577 vs 3355G345 ng/dl; PZ0.04, respectively).
Moreover, ROC curve analyses showed that the basal and ACTH-stimulated
17OHP levels of 610 and 3,913 ng/dl were the best cutoffs to identify NC-CAH
patients carrying compound heterozygosis with severe mutations. We observed a
EP6
higher DHEAS
(182G150
vs
85G69 mg/dl, PZ0.03) and a bone age
advancement trend (PZ0.05) in C/NC genotype group compared to NC/NC.
Impact of Cortrosyn treatment on weight and adrenal structure in the
There were no differences in age, height, weight, androstenedione and
wistar rat
testosterone levels at diagnosis.
Samira Akdader-Oudahmane, Zohra Hamouli-Said &
Conclusion
Fatma Hadj-Bekkouche
Although no phenotype difference was observed between NC/NC and C/NC
University of Algiers, Algiers, Algeria.
genotypes, the present study showed graded severities of adrenal biosynthetic
defect reflecting the molecular variability in NC-CAH.
The corticotropic hormone (ACTH) mainly secreted by the anterior lobe of the
DOI: 10.1530/endoabs.49.EP7
pituitary gland which, following a physiological or psychological stress situation,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP8
Discussion
The presence and type of hyperlipemia prior to therapy is likely to affect the
Corticoids-therapy related complications in patients with primary
adverse effects of mitotane on lipids and in this patient, TG levels have varied
adrenal insufficiency
according to mitotane doses and levels despite lipid-lowering therapy. On the
Juan Carlos Romero Rodríguez, María Calatayud Gutiérrez, Laura
other hand, dyslipidemia may induce an overestimation of plasma mitotane
Mola Reyes, Carlos Silva Vaca, Sonsoles Guadalix Iglesias & Guillermo
measurements, so it is necessary to closely monitor the lipid profile in all patients
Martínez Díaz-Guerra
treated with this drug.
Hospital Universitario 12 de Octubre, Madrid, Madrid, Spain.
DOI: 10.1530/endoabs.49.EP9
Introduction
Patients with primary adrenal insufficiency
(PAI) require lifelong corticoids
replacement and they are at risk of therapy-related osteoporosis and cardiovascular
complications.
Objectives
EP10
Determine the prevalence of cardiovascular risk factors, osteoporosis, and other
Addison’s disease presenting as severe hypoglycaemia and cachexia
toxicities related with corticoids treatment.
Ana Cláudia Martins, Paula Bogalho & Ana Agapito
Material and methods
Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,
Retrospective, descriptive study in patients with PAI follow up in our service
Portugal.
during the last 30 years. Information was collected from clinical histories.
Results
Addison’s disease (AD), also known as primary adrenal insufficiency, is caused
Identified 30 patients with PAI. Clinical characteristics: 21 were women, mean
by destruction or dysfunction of the adrenal cortex, resulting in hypocortisolism.
age at diagnosis of 36.72G5.3 years and mean time since diagnosis 263.8G57.5
The usual clinical features of chronic AD are non-specific and include fatigue,
months. Etiology: 15 (50%) autoimmune disease; 7 (23.3%) post-surgery; 5
nausea, vomiting and hyperpigmentation. We describe the case of a 58-year-old
(16.6%) congenital adrenal hyperplasia; 2 (6.7%) tuberculosis and 1 (3.3%)
African black male with AD presenting with recurring severe hypoglycaemia.
metastatic disease.
The patient was admitted several times to the emergency department with
Steroid replacement: 26 (86.7%) used hidrocortisone (HC), 3 (10%) dexameta-
hypoglycaemia
(blood glucose between
26
and
50 mg/dl) and loss of
sone, 1 (3.3%) prednisone. 25 patients were on treatment with fludrocortisone.
consciousness, managed with intravenous dextrose. These episodes were
Mean glucocorticoid dose
(HC or equivalent):
20.58G1.5 mg/day, mean
associated with anorexia, dizziness, fatigue and progressive weight loss over
fludrocortisone dose 0.066G0.008 mg/day.
two years prior to presentation. His past history was significant for pulmonary
Possible therapy-related complications: 23(76.7%) patients developed at least
tuberculosis, and there was no family history of note. Physical examination
1complication during follow-up: osteoporosis
11(36.7%), dyslipidemia
10
revealed a cachectic habitus, depressed mood and hyperpigmentation of palmar
(33.3%), prediabetes 8(26.6%), hypertension 7(23.3%), type 2 diabetes 6(20%),
creases and oral mucosa. He had a body mass index of 14.9, blood pressure
1(3.3%) cardiovascular event.
88% patients with osteoporosis,
78.6% with
98/57 mmHg and regular pulse of 64 bpm, with no other remarks on systemic
diabetes or prediabetes, 85.7% hypertension and 70% with dyslipidemia used HC
examination. Biochemical analysis revealed Hb
11 g/dl, mild hyponatremia
dose R20 mg/d.
(134 meq/l), normokalemia (4.1 meq/l), hypoalbuminemia (32.4 g/l), and normal
Conclusions
renal and hepatic function tests. Morning serum cortisol level was 2.3 mg/dl and
Osteoporosis and cardiovascular complications are frequents in patients with PAI.
ACTH 52.2 pg/ml, with normal levels of other pituitary hormones. ACTH
Patients on treatment with higher corticoid dose are at risk of development
stimulation test was performed and confirmed adrenal insufficiency. Compu-
therapy-related complication. Adjustment in corticoid to minimal necessary dose
terised tomography scan of the abdomen showed normal shaped and sized adrenal
could prevent these complications.
glands. HIV screening was negative and there were no clinical or radiological
DOI: 10.1530/endoabs.49.EP8
signs of active tuberculosis. He started treatment with hydrocortisone and
fludrocortisone, and his symptoms readily improved. This case illustrates an
unusual presentation of Addison’s disease and points out the need for a high index
of suspicion so that morbidity and mortality can be decreased by a prompt
EP9
diagnosis.
Severe hypertriglyceridemia in relation to toxic levels of mitotane in a
DOI: 10.1530/endoabs.49.EP10
patient with stage IV adrenocortical carcinoma (ACC)
Terroba Larumbe, Crespo Soto, Anacabe Goyogana, Urbon López De
Linares, Amon Sesmero, Ventosa Vin˜ a, Cuellar Olmedo, Marcos García,
Otero Roussel & Almendros Mu
˜ oz
H. U. Rio Hortega, Valladolid, Spain.
EP11
Posterior reversible encephalopathy syndrome (PRES) in a patient with
Introduction
primary aldosteronism
The use of mitotane as ACC therapy is associated with multiple adverse effects
Julia Silva-Fernández1, Florentino Del Val-Zaballos1, Francisco
including hypercholesterolemia due to increased levels of LDL cholesterol. There
Javier Gómez-Alfonso1, Paloma González-Lázaro1, Belvís Torres-Arroyo1,
are no reported cases of severe hypertriglyceridemia (HTG).
Rafael García-Ruiz2, Álvaro García-Manzanares Vázquez de Agredos1,
Clinical case
María López-Iglesias1 & Inés Gómez-García1
A 59-year-old male with a personal history of dyslipidemia phenotype IV and
1Endocrinology Service, Hospital La Mancha Centro, Alcázar de San Juan,
pulmonary emphysema, former smoker and drinker was diagnosed with non-
Spain;2Neurology Service, Hospital La Mancha Centro, Alcázar de San
functioning left-sided ACC. Left adrenalectomy C left nephrectomy and
Juan, Spain.
subsequently right adrenalectomy and atypical segmentectomy of the upper
right lung lobe due to the presence of metastases was performed. One month later,
low-dose
(2 g/day) mitotane therapy was initiated in combination with
Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder
hydrocortisone and oral fludrocortisone replacement therapy. In the first post-
characterized by varied neurological symptoms. There are two leading theories
mitotane control, triglycerides
(TG) level which previously was
325 mg/dl
regarding the pathophysiology: hypertension crisis and endothelial dysfunction.
increased to 953 mg/dl, coinciding with serum mitotane of 13.8 mg/l. Other
Case report
factors that could increase it were overruled. Fenofibrate
145 mg/day was
We report the case of a 42-year-old patient with history of hypertension. She
prescribed but in the following control TG were 880 mg/dl with serum mitotane
presented to the emergency department with headache and bilateral loss of vision.
of 14.3 mg/l. The dose of mitotane was then reduced to 1 g/day, its level dropped
She described one previous episode of witnessed generalised tonic-clonic seizure
to 10.5 mg/l and TG were 939 mg/dl. Consequently ezetimibe 10 mg/day was
at home. She was found to have an elevated blood pressure (BP) of 210/105 mm
added to the therapy and the mitotane dose was increased to 1.5 g/day and
Hg. An ocular examination revealed a diminished vision and perception of hand
subsequently to 2 g/day because the level was very low and a 4.5 cm unresectable
movement on both eyes. Laboratory findings were within normal range except for
metastatic adenopathy that received radiotherapy appeared in the mediastinum.
potassium, which was 2.7 mEq/l (normal range 3.5-5). Brain MRI showed
Coinciding with a mitotane level of 33.8 mg/l, the patient presented severe
bilateral posterior parietooccipital hyper densities in the cortex and subcortical
asthenia attributable to mitotane toxicity and TG of 1,528 mg/dl, without data of
white matter consistent with PRES. Antihypertensive therapy was started. The
pancreatitis, what required a drastic decrease in the dose of drug. In the last
patient’s headache rapidly resolved and her vision improved. The patient was
review, the mitotane level was 6.7 mg/l, TG were 344 mg/dl, the symptoms
discharged symptom-free on potassium supplements and antihypertensive
disappeared and the mitotane dose was again raised while those of fenofibrate,
therapy. After discharge the patient was referred to the Endocrinology service.
ezetimibe, hydrocortisone and fludrocortisone remained the same.
Aldosterone concentration/plasma renin activity ratio was positive and the saline
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
infusion test confirmed the diagnosis of hyperaldosteronism. Abdominal MRI
Methods
revealed a two-centimetre adenoma of the left adrenal gland. The patient
Hair samples were collected from 12 study subjects (four with PA, two with PA
underwent surgery to remove the adenoma. After surgery, hypokalemia and
and cortisol co-secretion, and six controls), with mean age 40.1G21.4 years,
hypertension resolved.
mean BMI 28.1G5.3 kg/m2. Diurnal serum cortisol and ACTH measurements,
Conclusions
24-h-urinary free cortisol corrected by body surface area
(UFC/BSA) and
Although primary aldosteronism (PA) is not included among the reported causes
17-hydroxysteroids, corrected for creatinine (17OHS/Cr) were measured. Patients
of PRES, it is important to consider its existence in PRES patients, particularly in
underwent step-wise diagnosis, with measurement of serum aldosterone and
those with hypokalemia. The occurrence of PRES in patients with PA might be
plasma renin activity followed by saline suppression and/or oral salt loading tests.
independent of hypertension since the direct action of aldosterone on the
Patients without PA or CS were excluded as controls, if midnight serum cortisol
mineralocorticoid receptor may cause endothelial dysfunction.
O1.8 mg/dl. Segmental hair samples from each patient were processed and
DOI: 10.1530/endoabs.49.EP11
analysed for cortisol according to the methods described by Meyer et al. (2014).
Results
Age, blood pressure, urinary and midnight cortisol levels were higher (P!0.05)
in the PA group compared to the controls. Average hair cortisol values in the
groups with PA and controls were 30.0G31.0 pg cortisol/mg hair (median:
EP12
16.3 pg/mg; interquartile range: 12.6-37.4 pg/mg) and 22.9G27.6 pg cortisol/mg
hair
(median:
11.3 pg/mg; interquartile range
7.9-26.6 pg/mg), respectively
Evaluation of cardiovascular risk in patients with adrenal
(PO0.05). No correlation between hair cortisol and serum and urinary markers of
incidentaloma
hypercortisolemia was seen in the six patients with PA.
Goknur Yorulmaz1, Aysen Akalin1 & Burcu Yagiz2
Discussion
1Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey;
We found that no statistically significant difference in hair cortisol between
2Uludag University School of Medicine, Bursa, Turkey.
groups and no significant correlation of hair cortisol with urinary or serum cortisol
evaluations. We speculate that the lack of correlation may be due to insufficient
Introduction
power. More research is needed on the use of hair cortisol in patients with PA.
Recent studies indicate that patients diagnosed with adrenal incidentaloma may
DOI: 10.1530/endoabs.49.EP13
present with cardiovascular disease. The aim of this study was to investigate
markers of subclinical cardiovascular disease in patients with adrenal
incidentaloma and healthy control group.
Methods
This study included 50 patients with non-functional adrenal adenoma and 30
EP14
healthy controls. BMI and waist circumference of the patients were measured.
The lipid parameters, glucose, insulin, C-peptide, erythrocyte sedimentation rate,
Salivary steroid levels during diagnostic tests for adrenal insufficiency
fibrinogen, homocysteine, hsCRP levels and carotid intima media thickness were
Michaela Dušková1, Kateřina
ˇ im
˚ nková1,2, Jana Vítk
˚1,
measured. HOMA levels of the patients were calculated.
Lucie Kolátorová1, Hana Jandíková1, Hana Pospíšilová1,
Results
Monika Sˇ rámková1, Mikuláš Kosák2 & Luboslav Stárka1
Patients with non-functional adrenal adenomas were compared with obese and
1Institute of Endocrinology, Praha, Czech Republic;2Third Department of
non-obese control groups. Carotid intima media thickness and erythrocyte
Medicine, General University Hospital and First Faculty of Medicine,
sedimentation rate levels of the patients with adrenal incidentaloma were
Charles University, Praha, Czech Republic.
significantly higher than the healthy controls. There was not statistically
significant difference between lipid parameters, glucose, insulin, C-peptide,
Diagnostic tests of the hypothalamic-pituitary-adrenal axis
(HPA axis),
fibrinogen, homocysteine, hsCRP levels of the patients and control group.
measuring of free cortisol and use of other adrenal steroids are the subject of debate.
Conclusion
We investigated 15 healthy men with mean/median age 27.4/26 (G4.8) years, and
In patients with nonfunctional adrenal adenomas the carotid intima media
mean/median BMI 25.38/24.82 (G3.2) kg/m2. All subjects underwent four
thickness, which is a cardiovascular risk indicator, was found to be thicker than
dynamic tests of the HPA axis, specifically 1, 10, and 250 mg synacthen tests and an
the normal population. At the same time, erythrocyte sedimentation rate, another
insulin tolerance test (ITT). Salivary cortisol, cortisone, pregnenolone, and DHEA
indicator of cardiovascular risk, was also higher in the adrenal incidentaloma
were analysed using liquid chromatography-tandem mass spectrometry.
group. These findings suggest that patients with adrenal adenomas have a higher
During the ITT maximum salivary cortisol levels of over 12.5 nmol/l were found at
risk for subclinical cardiovascular disease and close follow-up may be necessary.
60 min. Maximum cortisol levels in all of the Synacthen tests were higher than
DOI: 10.1530/endoabs.49.EP12
stimulation in the ITT. Cortisone reacted similarly as cortisol, i.e. we did not find
any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were
higher during the ITT, and their peaks preceded the cortisol peak. There was no
increase of pregnenolone or DHEA in any of the Synacthen tests.
Our results indicate that a 10 mg Synacthen dose is a safe and cost-effective choice.
EP13
This study was supported by the project MZCR for conceptual development of
Hair cortisol in patients with primary aldosteronism
research organization 00023761 Institute of Endocrinology and grant 17-28692A.
Aaron Hodes1,3, Maya Lodish1, Amit Tirosh1,3, Jerrold Meyer5,
DOI: 10.1530/endoabs.49.EP14
Elena Belyavskaya1, Charalampos Lyssikatos1, Kendra Rosenberg5,
Andrew Demidowich1, Jeremy Swan1, Nichole Jonas1,
Constantine Stratakis1 & Mihail Zilbermint1,2
1Section on Endocrinology and Genetics, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland, USA;2Johns Hopkins University School of
EP15
Medicine, Division of Endocrinology, Diabetes, and Metabolism, Balti-
Assessment of quality of life of patients with Cushing’s syndrome
more, Maryland, USA;3Sackler Faculty of Medicine, Tel Aviv University,
depending on the disease course
Tel Aviv, Israel;4Albert Einstein College of Medicine, Department of
Gulchekhra Narimova, Zamira Yusupovna, Ravshan Fayzullaev &
Radiology, Jacobi Medical Center, Bronx, New York, USA;5Department of
Iskandar Arifjanov
Psychological and Brain Sciences, University of Massachusetts, Amherst,
Republican Specialized Scientific and Practical Medical Center of
Massachusetts, USA.
Endocrinology Uzbekistan, Tashkent, Uzbekistan.
Context
Aim of the study
Primary aldosteronism (PA) is a common cause of secondary hypertension, and
To evaluate effectiveness of pituitary transsphenoidal surgery (TSS) in patients
some PA adrenal tumors co-secrete glucocorticoids, causing subclinical or overt
with ACTH-dependent Cushing’s syndrome
(ACTH-DCS) in Republic of
Cushing syndrome (CS). We recently reported correlations between hair cortisol
Uzbekistan (RUZ).
concentration (HCC) and serum and urinary levels of cortisol in patients with CS.
Materials and methods
Objective
Patients who included in CS register monitored in 2015. All data from 2000 to
To determine correlations of segmental hair cortisol and biochemical markers of a
2015 analyzed including outpatient, inpatient examines, tests and treatment. To
referred cohort of patients for the evaluation of PA and to compare to patients
present, 158 patients with ACTH-DCS registered and monitored. Of these 158
with normal cortisol secretion. This pilot study was conducted at the National
patients, 41 males (26%) and 117 females (74%). Mean age of patient varied from
Institutes of Health Clinical Center.
12 to 38 years old. Mean age was 26.38G3.4 and 27.58G3.4 years old for males
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
and females respectively. Duration of the condition varied from 4 months to 25
EP17
years. 73 patients who had TSS were evaluated in 1, 3, 6 and 12 months period of
Frequancy of diabetes and prediabetes in patients with adrenal
time and the every 3 months for the follow-up period. TSS was performed initially
incidentaloma without hormonal activity
in 73 patients and in ten patients it was carried out after medical treatment.
Elzbieta Bandurska-Stankiewicz, Katarzyna Myszka-Podgórska,
Results
Joanna Rutkowska & Wojciech Matuszewski
Of 158 patients, 86 patients (54%) had surgery including 73 cases who underwent
Endocrinology, Diabetology and Internal Diseases Clinic, University of
TSS. Pituitary surgery performed as a monotherapy in 32 patients (44%) and in 41
Warmia and Mazury in Olsztyn, Olsztyn, Poland.
cases
(56%) patients received combination therapy. Of
73
patients who
underwent TSS, in 60 cases (82%) patients had cured, while repeat surgery
performed in ten cases (13.7%). After repeat surgery all ten patients (13.7%) had
Aim of the study
remission, however, four of them relapsed in 15 months in average. After TSS
Estimation of the frequancy of diabetes and prediabetes in patients with adrenal
remission was achieved in 82% of patients who included 62 patients with
incidentaloma (AI) without hormonal activity.
microadenomas (84.9%) and 12 cases with macroadenimas (16.6%). After 3 years
Material and methods
of follow-up five patients (6.8%) who had total hypophisisectomy procedure
The study comprised patients with AI without hormonal activity, verified by CT.
developed no relapse, whereas of
62
patients
(84.9%) with selective
The hormonal function of adrenal glands was determined according to the
adenomectomy and of six patients (6.8%) who had hemihypophysisectomy
circadian rhythm of cortisol and/or dexametasone suppression test, ACTH,
recurrent disease observed in 5 (8.1%) and 1 (16.7%) cases respectively while
aldosterone, plasma renin activity, DHEAS, androstenedione,
17hydroxy
remission has not developed in 6 (9.7%) and 1 (16.7%) respectively (PZ0.03).
progesterone, metanephrines in urine.
Conclusion
Physical examination included: the BMI, the waist circumference (norm !80 cm
Of 73 patients with CS who had pituitary surgery, remission observed in 60
women, !94 cm men), blood pressure. The biochemical assays: fasting
patients (82%), whereas six patients (8.2%) relapsed and in seven cases (9.6%)
glycemia, OGTT (excluded patients with diabetes), fasting insulin and lipids
remission has not developed. TSS remains as first treatment choice in CS and
level (total, HDL and LDL cholesterol, triglycerides).
contributes to a steady remission in 82% according to our results.
Results
DOI: 10.1530/endoabs.49.EP15
125 patients were examined, aged 61.3G8.8 years, 72 (57.6%) women. Size of
tumors were 27.6 mm G15 mm. Carbohydrates disorders were observed in 62
(49.6%) persons aged 62.9G7.5 years, including 32 (25.6%) women. Abdominal
obesity was diagnosed in 87 (69.6%), 56 (44.8%) women and 31 (24.8%) men.
Diabetes was regonised in 16 (13%) patients, IFG in 24 (19.2%), IGT in 34
(27.6%). The concentration of fasting insulin was 8.9C/K5.5 mU/ml, higher in
men then in women
(9.16C/K5.65
vs
8.71C/K4.70; PO0.01). The
concentration of total cholesterol was 218G49.7 mg/dl, HDL-cholesterol 59G
21.1 mg/dl, LDL cholesterol 134G44.1 mg/dl, triglycerides 116G60 mg/dl; 83
(66.6%) of the patients had been diagnosed positive for dyslipidemia or were
administered hypolipemic medications. Additionaly arterial hypertension was
diagnosed in 99 (79.2%) patients, with the arterial systolic BP 131G15 mmHg,
diastolic BP 80G9 mmHg.
EP16
Conclusions
1) Diabetes was observed more often in patients with AI without hormonal
Paraneoplastic Cushing’s syndrome and nephrotic syndrome in a
activity then in the entire Polish population.
patient with bronchial carcinoid
Patients with AI without hormonal activity are a risk group of prediabetes and
Daniel Grigorie1,2, Andra Caragheorghopol2, Carmen Iordachescu2,
diabetes.
Dan Hortopan2, Ionela Pascanu3, Livia Hara4, Iulian Brezean1,
Nicolae Galie1, Florina Vasilescu5, Eugen Mandache6 & Alina Sucaliuc1,2
DOI: 10.1530/endoabs.49.EP17
1Carol Davila University of Medicine, Bucharest, Romania;2National
Institute of Endocrinology, Bucharest, Romania;3University of Medicine,
Targu Mures, Romania;4Matei Bals Hospital, Bucharest, Romania;5Central
Military Hospital, Bucharest, Romania;6Carol Davila Nephrology Hospital,
Bucharest, Romania.
Introduction
We report a case of Cushing’s syndrome association with nephrotic syndrome in a
EP18
patient with occult ectopic ACTH (EAS) secretion by a bronchial carcinoid and
To big to work! Lymphoma presenting with primary adrenal
resolution of both disorders after bilateral adrenalectomy.
insufficiency
Case report
Joel Capraro, Hanna Giessen & Beat Muller
A 42-year-old man was admitted to our department with the suspicion of EAS. He
Division of Endocrinology, Diabetes and Metabolism, Kantonsspital Aarau,
was in a very good health until several months ago when he developed suddenly
Aarau, Switzerland.
nephrotic syndrome, severe hypertension, severe hypokalemia, hyperglicemia
and rapidly progressive the full blown picture of severe hypercortisolism: severe
mental changes, muscle weakness, bruising, pigmented moon facies, no striae,
Background
distal muscular atrophy and weight loss. A renal biopsy showed podocyte foot
Primary adrenal lymphoma (PAL) is a rare cause of primary adrenal insufficiency
process effacement and no inflammation/sclerosis; renal function was normal.
(PAI). Most often patients present with unspecific symptoms. Bilateral adrenal
Serum cortisol was frankly elevated and variable (21-97 mg/dl), because of the
enlargement with signs and symptoms of PAI are clues, percutaneous biopsy after
heavy and variable proteinuria
(1.7-7.5 g/24 h), urinary free cortisol
having excluded pheochromocytoma in a situation of high suspicion is diagnostic.
37.071 nmol/24 h. Serum cortisol did not supress with both low -dose and
Most of PAL are highly malignant B-cell lymphomas with a bad prognosis.
high-dose dexamethasone and serum ACTH was high (238 pg/ml). A pituitary
Case
MRI was normal. Chest CT scan revealed a round subpleural nodule 8-9 mm in
A 71-year-old patient was sent for endocrine workup because of a 2-month history
the right lung. SRS (111-indium-pentetreotide) and 18-FDG-PET CT scans were
of intermittent dyspnea, thoracic discomfort, weight loss and abdominal pain. An
negative. Bilateral laparoscopic adrenalectomy was performed. Postoperative
ambulant CT scan to exclude pulmonary embolism showed bilateral adrenal
course was marked by sepsis and he was treated with antibiotics for three months.
enlargement (right 77!31!55 mm, left 63!38!41 mm, native 25-29HE),
All the sign and symptoms of hypercortisolism gradually disappeared but the
which were new compared to a CT scan done one year earlier. On clinical
pigmentation remained; surprisingly the resolution of the nephrotic syndrome was
examination, the patient was orthostatic and in an im-paired general condition. He
noted. One year later he was in good clinical condition with adrenal replacement
had hyperpigmented hand lines. Laboratory evaluation showed a slight
therapy. Chest CT scan confirmed the presence of a stable pulmonary nodule and
hyponatremia (131 mmol/), potassium in the upper normal range (4.2 mmol/l),
he underwent thoracic surgery. A bronchial typical carcinoid tumour with positive
pathologic ACTH-stimulation test (peak cortisol level: 153 nmol/l) and elevated
immunostaining for ACTH was diagnosed. Postoperative course was uneventful.
ACTH levels (231 ng/l, normal range !46 ng/l). Antibodies for 21-hydroxylase
Conclusion
were negative, as well as free metanephrines in plasma, aldosterone-renin ratio
This is a rare case of the association of severe occult EAS with nephrotic
was decreased (aldosterone 122 pmol/l, renin 39 mU/l). 17-hydroxyprogesterone
syndrome, which has been cured by the resolution of the severe hypercortisolism.
was low
(3.3 nmol/l, normal range
1.9-6.5 nmol/l). Quantiferon test was
DOI: 10.1530/endoabs.49.EP16
negative, and the CT scan did not raise suspicion for tuberculosis. We diagnosed
PAI and started substitution with hydrocortisone
(initial dose
50 mg/d) and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
fludrocortisone (0.1 mg/d). Histology of a CT-guided needle biopsy revealed
EP20
infiltration of a highly malignant B-cell lymphoma. The patient was sent for
Cofilin is a cAMP effector in mediating actin cytoskeleton reorgan-
oncological evaluation and start of chemotherapy with rituximab, cyclopho-
ization and steroidogenesis in mouse and human adrenocortical
sphamide, doxorubicin, vincristine and prednisone (R-CHOP).
tumor cells
Discussion
Rosa Catalano1,2, Erika Peverelli1,2, Elena Giardino1,2,
PAL is a rare manifestation of primary extranodal lymphomas (1/3 of all lymph
Donatella Treppiedi1,2, Valentina Morelli1,2, Iacopo Chiodini1,2,
node neoplasms, PAL!1% of all extranodal lymphomas). Only about 100 cases
Lorenzo Marcon1,2, Cristina L Ronchi3, Jérôme Bertherat4,
are published in the literature worldwide. Conversely, secondary spreading of a
Felix Beuschlein5, Maura Arosio1,2, Anna Spada1,2 & Giovanna Mantovani.
lymphoma to the adrenals is quite common (in autopsy studies up to 25%). Other
1Endocrine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
reasons for bilateral adrenal enlargement are adrenal hyperplasia (any cause),
Policlinico;2Department of Clinical Sciences and Community Health,
metastasis of lung, breast and stomach
(O50% of metastasis), bilateral
University of Milan, Milan, Italy;3Department of Internal Medicine I,
pheochromocytoma, adrenal hemorrhage, adrenal involvement with granuloma-
Division of Endocrinology and Diabetes, University Hospital, University of
tous diseases, histicytosis and primary pigmented nodular adrenal dysplasia
Wuerzburg, Wuerzburg, Germany;4Institut Cochin, Inserm U1016, CNRS
(PPNAD). Symptoms of PAL are unspecific (asthenia, weight loss, vague
UMR8104, Descartes University, Department of Endocrinology, Reference
abdominal pain, fever). Diagnosis is made by percutaneous biopsy. In nearly 70%
Center for Rare Adrenal Diseases, Hôpital Cochin, Paris, France;
of cases PAL are bilateral, causing primary adrenal insufficiency. Average age of
5Medizinische Klinik und Poliklinik IV, Endocrine Research Unit,
affected patients is around
70 years. Most of PAL are diffuse large B-cell
Klinikum der Universitat Munchen, LMU, Munich, Germany.
lymphomas with BCL6 gene rearrangement and poor prognosis, as in our case.
Therapy consists of R-CHOP.
Conclusion
The cAMP signaling pathway plays a major role in the pathogenesis of cortisol-
Patients with bilateral adrenal enlargement and PAI need immediate replacement
producing adrenocortical adenomas (CPA). In adrenocortical cells cAMP induces
of glucocorticoid (including instructions about dosing in stressful situations) and
dramatic changes in cell morphology accompanied by actin cytoskeleton
mineralocorticoid hormones. While PAL is rare, it has a poor prognosis, thus
rearrangements that precede steroidogenesis, the causal relationship between
rapid induction of treatment is necessary.
these events being still undefined. In this study we investigated cAMP effects on
DOI: 10.1530/endoabs.49.EP18
cytoskeleton rearrangements and steroidogenic response in mouse (Y1) and
human adrenocortical tumor cells, focusing on the role of the actin-severing
protein cofilin, whose inactivation is regulated by phosphorylation on Ser3.
Moreover, we tested possible alterations in cofilin phosphorylation status and
expression in human CPA vs endocrine inactive adrenocortical adenomas (EIA).
We demonstrated that forskolin induced cell rounding and reduced phosphory-
lated (P)-cofilin/total cofilin ratio in Y1 (K52G16%, P!0.001) and primary
human CPA cells (K53G18%, P!0.05). Cofilin silencing in Y1 cells reduced
both forskolin-induced morphological changes (37G8% rounded cells vs 63G
7% in control cells, P!0.05) and progesterone production (1.3-fold increase in
EP19
silenced cells vs 1.8-fold in control cells, P!0.05), whereas transfection of wild
type or S3A (active) cofilin, but not S3D (inactive) cofilin, potentiated forskolin
Specificity of the posture test for subtyping of primary aldosteronism, a
effects on cell rounding (80G6% and 85G14% rounded cells, respectively, vs
10 year nationwide summary in Iceland
69G6% in control cells) and increased about threefold progesterone synthesis
Hrafnhildur Gunnarsdottir1, Gudbjorg Jonsdottir1,2, Jon Gudmundsson3,
with respect to control cells (P!0.05). Furthermore, cofilin dephosphorylation by
Gudjon Birgisson4 & Helga Sigurjonsdottir1,5
Y27632, a selective inhibitor of ROCK, the kinase that phosphorylates cofilin,
1Faculty of Medicine, University of Iceland, Reykjavik, Iceland;
potentiated forskolin induced cell rounding
(about
90% rounded cells) and
2Department of Internal Medicine, University of Iowa Hospitals and Clinics,
steroidogenesis (about twofold increase vs forskolin alone).
Iowa City, Iowa, USA;3Department of Radiology, Landspitali University
Finally, western blot analysis showed a reduced P-cofilin/total cofilin ratio and an
Hospital, Reykjavik, Iceland;4Department of Surgery, Landspitali
increased total cofilin expression in CPA vs EIA (P-cofilin/total cofilin ratio 0.76
University Hospital, Reykjavik, Iceland;5Department of Endocrinology,
and 2.44 respectively, P!0.05, total cofilin/GAPDH 1.20 and 0.54, respectively,
Landspitali University Hospital, Reykjavik, Iceland.
P!0.01).
Overall, these data identified cofilin as a mediator of cAMP effects on both
Introduction
morphological changes and steroidogenesis in mouse and human adrenocortical
The posture test (PT), developed to distinguish idiopathic adrenal hyperplasia
tumor cells.
(IAH) from aldosterone producing adenoma (APA), has been postulated as
DOI: 10.1530/endoabs.49.EP20
inaccurate. In
2007, standardized diagnostic methods, including PT for
subclassification, were introduced in Landspitali University Hospital (LUH),
housing the only endocrine department in Iceland. The aim of this study is to
review the results of PT performed in LUH in 2007-2016.
Methods
Charts for all patients R18 years old, diagnosed with primary aldosteronism (PA)
during 2007-2016 in LUH, were retrospectively reviewed. After screening,
verification of PA was made with saline infusion test. During PT, s-aldosterone,
EP21
s-renin and s-potassium were measured after a 10-h bed-rest and again after
Primary Aldosteronism in Iceland, nationwide results from 2012-2016
subsequent 4-h upright-position. If s-aldosterone increased by O50%, the test
Hrafnhildur Gunnarsdottir1, Jon Gudmundsson2, Gudjon Birgisson3 &
was considered positive. Thereafter, patients underwent a CT-scan and adrenal
Helga Sigurjonsdottir1,4
venous sampling (AVS). Adrenalectomy was offered if PA was found unilateral
1Faculty of Medicine, University of Iceland, Reykjavik, Iceland;2Depart-
by AVS.
ment of Radiology, Landspitali University Hospital, Reykjavik, Iceland;
Results
3Department of Surgery, Landspitali University Hospital, Reykjavik,
Out of 49 PA-patients undergoing PT during the period, 22 had unilateral disease
Iceland;4Department of Endocrinology, Landspitali University Hospital,
and 27 bilateral. The unilateral group (UG) consisted of 14 patients with APA and
Reykjavik, Iceland.
4 with IAH. Three are awaiting surgery and one histopathological examination
was inconclusive. Average increase of s-aldosterone during PT in the bilateral
group (BG) was 217G127%, significantly higher than 88G26% in the UG
Introduction
(PZ0.008). A greater proportion of the BG had a positive PT, 81% (22/27) versus
Primary aldosteronism
(PA) is an important, potentially curable cause of
55% (12/22) of the UG, PZ0.04. Positive predictive value of the PT with regards
hypertension (HT) with higher risk of cardiovascular events than essential HT. In
to bilateral disease was 0.65 (22/34), sensitivity 0.81 (22/27) and specificity 0.45
2007, a standardized PA work-up protocol was introduced in Landspitali
(10/22).
University Hospital (LUH), housing the only endocrine department in Iceland.
Conclusions
The aim of this study is to review characteristics, test results and histopathology
In this nationwide study we found the PT to have fairly high sensitivity but low
for patients diagnosed with PA in 2012-2016 in LUH.
specificity in subclassifying PA, supporting previous reports of inaccuracy.
Methods
Although the PT is not conclusive, it could be informative in addition to CT-scan
Charts for PA-patients aged R18, diagnosed in 2012-2016 in LUH, were
for treatment decision if a patient is unable to undergo AVS for practical reasons.
retrospectively reviewed. Screening was considered positive if s-aldosterone
DOI: 10.1530/endoabs.49.EP19
and/or 24-h urinary aldosterone excretion was increased and s-renin decreased.
Diagnosis was confirmed if s-aldosterone increased by O140 pmol/l on saline
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
infusion test (SIT) performed by a 4-hour intravenous infusion of isotonic saline,
EP23
500 ml/h. Thereafter, patients underwent a CT-scan and adrenal venous sampling
Bilateral adrenal incidentaloma: a diagnostical and therapeutical
(AVS) for distinguishing unilateral
(UD) from bilateral disease
(BD).
challenge
Adrenalectomy was offered if UD was diagnosed.
Ines Bilic-Curcic1,2, Tatjana Bacun1,2, Marija Tripolski2 & Biljana Zulj2
Results
1Faculty of Medicine, University J.J. Strossmayer, Osijek, Croatia;2Clinical
Thirty-six patients were diagnosed with PA during the period; 19 males and 17
Hospital Center, Osijek, Croatia.
females. All had s-aldosterone O300 pmol/l on morning screening and 12 had an
elevated 24-h urinary aldosterone (nZ23). Median (range) s-aldosterone after
SIT was 311 pmol/l (202-1715). By the end of 2016, 10 had a confirmed UD
Incidentally discovered adrenal masses (incidentalomas) present challenges both
(32%), 21 BD (68%) and 5 were awaiting AVS. Six out of 10 UD underwent
in diagnosis and management. The bilateral adrenal mass carries a risk of
adrenalectomy by the end of
2016
and all had a cortical adenoma on
hormone hypersecretion, but it could also present a metastasis from another
histopathological examination. CT-scan showed unilateral adrenal nodule in 15
primary carcinoma or be a part of genetic syndrome.
patients, 8 of whom had UD by AVS on that same side (positive predictive value
We report a 68 year old patient with bilateral adrenal incidentalomas (revealed
0.53).
accidentally on US, confirmed by abdominal CT in 2015.) left 29 mm, right
Conclusions
33 mm in diameter, radiological characteristics indicating adenoma. Initial
This study indicates that PA is an important cause of HT in Iceland with equal
diagnostical work up showed subclinical Cushing syndrome with osteoporosis
gender distribution. Bilateral hyperplasia proved to be a more frequent cause than
and arterial hypertension as part of clinical presentation. One year later,
cortical adenoma which is consistent with prior Icelandic results from 2007-2011.
abdominal CT showed significant enlargement of both adrenal masses (left
Interestingly, no-one was diagnosed with unilateral hyperplasia during the study
50 mm, right 45 mm), still adenomas according to CT characteristics, but post
period.
contrast imaging could not be performed due to chronic renal impairment. Her
DOI: 10.1530/endoabs.49.EP21
laboratory results were still consistent with subclinical Cushing syndrome, now
presenting with osteoporosis, hypertension and glucose impairment with no signs
of other excessive hormone secretion but now her chest x-Ray revealed a lesion in
her left lung 27 mm in diameter of unknown etiology (although she mentioned
lung tuberculosis in her youth). As she did not have any signs of metastatic
disease and her tumor markers were normal we decided to perform left
adrenalectomy to provide definite diagnosis. Histological finding confirmed
adrenal adenoma and hormone reevaluation showed possible excessive cortisol
secretion with osteoporosis, but now blood glucose was normal, and anti-
hypertensive agents were discontinued due to normal blood pressure. There was
no change in the size of the lung lesion on her chest X ray (6 months after) and no
signs of metastatic lesions. Thoracic CT and bronchoscopy are planned.
While the initial diagnostic approach is similar to the unilateral incidentaloma,
additional testing should be considered in the case of the bilateral adrenal mass
and as oppose to unilateral incindentalomas surgery remains the mainstay of
treatment in most cases.
EP22
DOI: 10.1530/endoabs.49.EP23
Cardiovascular risk factors do not play a role in the risk factor profile of
adrenal crisis
Marcus Quinkler1, Robert D. Murray2, Pinggao Zhang3, Pierre Zelissen4 &
Bertil Ekman5
1Endocrinology in Charlottenburg, Berlin, Germany;2St James’s University
EP24
Hospital, Leeds, UK;3Shire, Lexington, MA, USA;4University Medical
Are we missing patients with primary aldosteronism (PA) if we require
Center Utrecht, Utrecht, The Netherlands;5Linkoping University, Linkop-
both elevated aldosterone: renin ratio (ARR) and elevated aldosterone
ing, Sweden.
levels?
Troy Puar, Joan Khoo & Meifen Zhang
Changi General Hospital, Singapore, Singapore.
Introduction
Adrenal crises (ACs) are life-threatening events in patients with primary (PAI) or
secondary (SAI) adrenal insufficiency, occurring w4-10 times per 100 patient-
Introduction
years. Major causes of ACs are infections, especially gastroenteritis and
Although the Endocrine Society guidelines recommend using aldosterone: renin
tonsillitis/laryngitis. Risk factors for ACs remain ill defined, but could include
ratio (ARR) to screen patients for primary aldosteronism (PA), whether to include
concomitant endocrine diseases (diabetes mellitus, premature ovarian failure) in
a cut-off for aldosterone levels remains controversial. In Singapore, most centres
PAI, diabetes insipidus in SAI, and concomitant non-endocrine diseases (obesity,
require both an ARR O550 (ng/dl)/(ng/ml per h) and aldosterone R15 ng/dl.
asthma, cancer, and cardiac and neurological diseases) in both groups.
However, it has been shown that patients with PA may have aldosterone
Design
levels!15 ng/dl, and also respond well to mineralocorticoid antagonists. We
We analysed data from the European Adrenal Insufficiency Registry (EU-AIR;
examined the prevalence of Asian patients with high ARR, and influence of
NCT01661387) with centres across Germany, the Netherlands, Sweden and the
including patients with unsuppressed aldosterone levels O5 ng/dl.
UK. Clinical and biochemical data at enrolment were compared for patients with
Methods
frequent (nR2) and infrequent ACs (n!2) in each AI subset; 1969 patients were
We determined the prevalence of patients with high ARR O550 (aldosterone,
included (727 PAI, 1172 SAI) in the current analysis. Patients with congenital
ng/dl; plasma renin activity, ng/ml per hr) in a multi-ethnic Asian population with
adrenal hyperplasia or tertiary AI were excluded.
hypertension being screened for PA in a single tertiary centre, and stratified them
Results
by aldosterone levels.
To November 2016, 27 patients with frequent ACs were identified (19 PAI, 8
Results
SAI). The number of adverse events/patient was significantly higher in the
A total of 786 patients were screened for PA from 2015-2016, with 219 of 786
frequent than the infrequent AC group in both subsets (PAI, 15.3G14.0 vs 3.9G
(27.8%) patients having a high ARR. Amongst these 219 patients with a high
6.5; SAI,
19.6G18.5 vs
2.2G4.3, respectively; PZ0.0024). Patients with
ARR, 68 of 219 (31.1%) had an aldosterone levels R15 ng/dl, 51 (23.3%) had
frequent ACs were more likely to be female (PAI, 78.9% vs 65.1%; SAI, 75.0%
aldosterone levels
10-14.9 ng/dl,
60
(27.4%) had an aldosterone levels
5-
vs 47.9%), and less likely to have hypertension (PAI, 5.3% vs 21.0%; SAI, 25.0%
9.9 ng/dl, and 40 (18.3%) had aldosterone levels !5 ng/dl. When both ARRO
vs 34.4%), with a lower BMI (PAI, 24.2G4.7 vs 26.2G4.9 kg/m2; SAI, 26.0G
550 and aldosterone R15 ng/dl are required, only 68 of 786 (8.6%) patients will
5.7 vs 28.7G5.1 kg/m2). There were no differences in daily glucocorticoid dose,
proceed for confirmatory tests as per current practice. However, if all patients
frequency of diabetes mellitus, HbA1c levels, lipid profiles or use of statins.
with ARRO550 and unsuppressed aldosterone levels R5 ng/dl are included, then
Interestingly, disease duration was shorter in patients with frequent compared
179 of 786 (22.8%) of patients should be considered for the diagnosis of PA.
with infrequent ACs in PAI (12.8G13.2 vs 18.9G14.5 years), whereas the
Conclusion
opposite was true in SAI (15.6G12.3 vs 13.8G11.2 years).
Current practice of requiring a high aldosterone level in addition to a high ARR
Conclusions
may underdiagnose patients with PA. However, potential benefit of working-up
Data suggest that known cardiovascular risk factors appear not to feature in the
all patients with a high ARR has to be weighed against increased cost. A possible
AC risk profile.
alternative would be a trial of mineralocorticoid therapy in these patients.
DOI: 10.1530/endoabs.49.EP22
DOI: 10.1530/endoabs.49.EP24
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP25
in the Addison group than in ACC patients, both in baseline conditions
(PZ0.036) than following CRH (PZ0.041).
Severe hypoglycaemic ketoacidosis in a patient with adrenal crisis
In conclusion, measurement of salivary cortisol did not add useful information for
Azmi Mohammed, Giridhar Tarigopula, Paul Peter, Praveen Partha &
assessing AI in mitotane-treated ACC patients. Assessment of ACTH levels may be
Shafie Kamaruddin
of some aid, since levels that are not frankly elevated may herald over-replacement.
Darlington Memorial Hospital, Darlington, UK.
The observation of lower ACTH levels in ACC patients than in patients with
Addison, both in basal conditions and after CRH stimulation, suggests that
We present a case of a 26 years old female who was rushed to hospital with 4 days
mitotane may play an inhibitory effect on ACTH secretion at the pituitary level.
history of abdominal pain, vomiting and dizziness. She also had one episode of
However, an effect of high-dose cortisol replacement should not be ruled out.
diarrhoea. Further history revealed that she had lost 32 kilograms of weight over
DOI: 10.1530/endoabs.49.EP26
the last 18 months through diet and exercise. There were no signs suggestive of an
eating disorder.
On examination she was peripherally cold, tachycardic (117/min), hypotensive
(86/50 mmHg) and sweaty. Her Glasgow Coma Scale was 15. Her chest was clear
and she had mild epigastric tenderness. She was fluid resuscitated with 0.9%
sodium chloride. Blood test results: pH 7.01, pCO2 (3.2), pO2 (14.6), blood
EP27
glucose (2.1 mmol/l), HCO3 (12), Na (126), K (5.6), ketones (7.6 mmol/l), urea
Extra-gastrointestinal stromal tumor in the retroperitomeum which
15.1 mmol/l and creatinine (79) and CRP (76). 10% Dextrose infusion was started.
had difficulty in differential diagnosis with adrenal cancer
An adrenal crisis was suspected and she was commenced on IV hydrocortisone.
Naotetsu Kanamoto, Makiko Nagatsuji, Keiko Yamagami,
A possible trigger was thought to be gastroenteritis. Her serum cortisol was
Shinya Tokunaga & Masayuki Hosoi
13 mmol/l, no baseline ACTH was checked. She remained hypotensive despite
Osaka City General Hospital, Osaka, Japan.
aggressive fluids and was subsequently transferred to ITU. Over the next 24 hours
her blood pressure was maintained on inotropes however her acidosis was
Extra-gastrointestinal stromal tumors
(EGISTs) in the retroperitomeum are
refractory to treatment (pH!7.2 after 8 hours). She was started on sodium
extremely rare. A 44-year-old man was referred from a private clinic suspicious
bicarbonate 1.26%; however, the effect was not sustained as her pH continued to
of an adrenal tumor that was incidentally detected by abdominal ultrasound.
drop. Her ketones also remained high (5-6 mmol/l) despite a normal glucose
Computed tomography (CT) scan showed a retroperitoneal mass of
12 cm
(4-7 mmol/l). She was subsequently commenced on 5%Dextrose infusion to halt
harboring a feeding artery from the left adrenal gland contiguous with the left
ketogenesis. Her HbA1c was 35 mmol/mol. Following 5% Dextrose infusions, her
adrenal gland, which enhanced heterogeneously on post-contrast imaging. By
acidosis started to improve with normalisation of ketones. Learning points:
magnetic resonance imaging, the tumor demonstrated heterogeneous low intensity
1. Adrenal crisis should be treated promptly
in T1 weighted images and an extremely heterogeneous lesion composed of high
2. Euglycaemic or hypoglycemic ketosis can complicate prolonged starvation,
and low signal intensity in T2 weighted images. PET CT imaging with fluorine-
vomiting and eating disorders, so detailed and collateral history is important
18-fluorodeoxyglucose (18F-FDG) demonstrated18F-FDG accumulation in the
3. Although very rare, type 1 diabetes can be masked by adrenal insufficiency and
tumor in the early and late phase. Iodine-123-metaiodobenzylguanidine and iodine-
present with euglycemic ketoacidosis. It should be considered in similar scenarios.
131-adosterol scintigram did not detect any accumulation in the tumor. The results
DOI: 10.1530/endoabs.49.EP25
of all conducted serum and urinary examinations of adrenocortical hormone and
catecholamine were within the normal range. Adrenalectomy was performed.
Histopathological diagnosis of the tumor was GIST. Immunohistochemical findings
revealed that the neoplastic cells were positive for c-kit and CD34 and negative for
S100 protein, alpha-SMA, and desmin. Mitotic activity (2-3/50 high power field)
and the labeling index for MIB-1 (about 3.2%) were low. The GIST was diagnosed
EP26
as a high-risk tumor because its diameter was over 5 cm. We started imatinib
Assessment of the hypothalamic pituitary adrenal axis in patients
400 mg/day according to the Japan GIST guideline 1 month after operation.
receiving adjuvant mitotane treatment after radical resection of
DOI: 10.1530/endoabs.49.EP27
adrenocortical carcinoma
Giuseppe Reimondo1, Soraya Puglisi2, Barbara Zaggia1, Vittoria Basile1,
Laura Saba1, Paola Perotti1, Silvia De Francia3, Maria Chiara Zatelli4,
Salvatore Cannavo2 & Massimo Terzolo1
1Internal Medicine 1, Department of Clinical and Biological Sciences,
University of Turin, Orbassano, Italy;2Endocrinology Unit, Department of
EP28
Clinical and Experimental Medicine, University of Messina, Messina, Italy;
Perceptions of medical practitioners’ management of addison’s disease
3Pharmacology, Department of Clinical and Biological Sciences, University
across Africa: an on-line survey
of Turin, Orbassano, Italy;4Section of Endocrinology and Internal
Ian Louis Ross1, Thabiso RP Mofokeng2, Fazleh Mahomed2 &
Medicine, Department of Medical Sciences, University of Ferrara,
Salem Beshyah3
Ferrara, Italy.
1University of Cape Town, Cape Town, South Africa;2University of the
Free State, Bloemfontein, South Africa;3Sheikh Khalifa Medical City,
Abu Dhabi, United Arab Emirates.
Mitotane, used in the treatment of adrenocortical cancer (ACC), is able to inhibit
multiple enzymatic steps of adrenocortical steroid biosynthesis, potentially
causing adrenal insufficiency (AI). Recent studies in vitro have also documented a
Objectives
direct inhibitory effect of mitotane at the pituitary level.
Addison’s disease diagnostic and management challenges in Africa are not well
The aim of the study was to assess the hypothalamic pituitary adrenal (HPA) axis
documented. We aimed to identify the specific needs of patients with established
in patients receiving mitotane as adjuvant treatment after radical resection of
Addison’s disease, across Africa.
ACC getting insights on how mitotane affects the HPA axis and looking for
Methods
markers to assessing AI.
An online survey of a large pool of medical practitioners was undertaken. The
We prospectively enrolled 16 patients on adjuvant treatment with mitotane after
questionnaire covered patient demographics, aetiology, therapy and limitations of
radical surgical removal of ACC, who were on stable mitotane dose and cortisol
diagnosis and treatment.
replacement therapy for at least 6 months and were disease free at the time of
Results
evaluation. Patients underwent standard hormone evaluation and stimulation test
Of the 36,203 recipients; 661 responded; 246 completed the questionnaire. 151
with h-CRH. A group of 10 patients with Addison’s disease served as controls for
were actively treating Addison’s disease. The total number of patients identified
the h-CRH test.
with Addison’s disease in this study was 1134 (530 males; 604 females). The
At the time of the study, six patients had mitotane levels within the therapeutic
highest number were reported from South Africa (748; 66%). Majority of patients
range, one had levels O20 mg/l, while nine had levels !14 mg/l. The median
were in the age groups of 16-60 years with a slight excess of females (334 vs 403).
dose of cortisone acetate was 62.5 mg daily. Basal serum cortisol was reduced in
Associations were reported with hypothyroidism in 15.3%, type 1 diabetes in
14 patients, being undetectable in 7 of them, and in the normal range in only two
11.6%, pernicious anaemia in 6.5%, premature ovarian insufficiency in 4.6% and
patients (12.5%); one of them had low mitotane concentrations. Only a non-
Graves’ disease in 3.0%. Presentation in crisis was reported in 12.1% of cases,
significant trend between mitotane dose and either serum or salivary cortisol was
otherwise classical symptoms were seen fairly consistently. Over 60% of patients
evident. We demonstrated a close correlation between CBG levels and plasma
received hydrocortisone only and the remainder received combination of
mitotane levels
(PZ0.003) and between serum cortisol levels and salivary
hydrocortisone and fludrocortisone. Fixed doses of steroid replacement were
cortisol levels (PZ0.005), while ACTH levels were inversely correlated with the
used by 35.3% of physicians, whereas 57.9% of respondents adjust doses on basis
daily dose of cortone acetate (PZ0.006). ACTH levels were significantly higher
of body weight. Appropriate diagnostic investigations, proved to be the greatest
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
limitation in making the diagnosis, with 73.2% of responders relying on the
aldosterone to renin ratio was compatible with diagnosis. A CT scan revealed a
combination of clinical grounds and compatible electrolytes alone and only 27.9%
right adrenal nodule suggestive of adenoma (21!19 mm). He was submitted to
having access to an ACTH stimulation test. There were few therapeutic options
laparoscopic unilateral adrenalectomy. Pathology confirmed an adrenal adenoma.
available to the responders outside of South Africa, with overall, 53% indicating
At discharge, all anti-hypertensive drugs were suspended.
non-availability of medication and 58% not having access to a CT scan.
3 weeks after surgery he complained of asthenia, anorexia and diarrhea. Blood
Conclusions
tests showed severe hyperkalaemia (7.8 meq/l), metabolic acidosis and acute renal
This first continent-wide survey highlighted some challenges in diagnosis and
failure (creatinine 4.2 mg/dl). The serum aldosterone was low (43 ng/dl) and renin
treatment of Addison’s disease. Awareness and resources are required for timely
(4.7 pg/ml) normal. We assume the diagnosis of hyporeninemic hypoaldosteron-
recognition and optimal management of Addison’s disease in Africa.
ism and he was treated with fludrocortisone (0.1 mg id), sodium bicarbonate and
DOI: 10.1530/endoabs.49.EP28
fluids, with improvement in serum creatinine and normalization of potassium
levels. 3 months after discharge he remained asymptomatic but fludrocortisone
dependent, with stable potassium and creatinine levels and mild hypertension.
Conclusion
Despite uncommon, hypoaldosteronism after unilateral adrenalectomy is known
to occur. Usually mild and transitory, it can also be severe, persistent and life-
EP29
threatening. Long term hypertension and impaired renal function, both present in
Improved metabolic outcomes for patients with subclinical Cushing’s
our patient, are associated with persistent disease. A close and regular follow-up
syndrome treated with surgery: Ten year experience in a tertiary centre
is essential for earlier detection, especially in high risk patients.
Lih Ming Loh, Du Soon Swee, Wei Lin Tay & Peng Chin Kek
DOI: 10.1530/endoabs.49.EP30
Department of Endocrinology, Singapore General Hospital, Singapore,
Singapore.
Introduction
Subclinical Cushing’s syndrome (SCS) occurs in up to 12% of patients with
EP31
incidentally found adrenal masses. Optimal management remains controversial.
The role of CYP11B2 polymorphism in the pathogenesis of
We report our experience of nine patients with SCS managed at our institution
hypertension in patients with adrenal incidentaloma
from 2007 to 2016.
Lukasz Zukowski1,2, Natalia Wawrusiewicz-Kurylonek1,
Methods
Janusz Mysliwiec2 & Maria Gorska1
All patients were referred for adrenal incidentalomas
(AI) and had no
1Department of the Endocrinology, Diabetology and Internal Medicine,
discriminatory clinical features of Cushing’s syndrome. SCS was defined using
Medical University of Białystok, Poland;2Department of Nuclear Medicine,
cortisol levels O 138 nmol/l after overnight 1-mg dexamethasone suppression
Medical University of Białystok, Poland.
test and one additional abnormal biochemical test. ACTH was suppressed in all.
Urinary free cortisol measurements were normal in the majority.
Patients and results
Background
The median age of our patients was 53 years (range 36-63) and all but one were
Significant prevalence of hypertension in the world’s population and its
female. Mean size of the adenomas was 2.65C0.52 cm. Majority of our patients
consequences tend to an intensive search for pathogenesis and etiology of this
had metabolic comorbidities of overweight, hypertension, glucose intolerance or
disease. Epidemic of hypertension is accompanied by an epidemic of adrenal
diabetes and dyslipidemia. One patient initially followed up as a non-functioning
incidentaloma and grows in direct proportion to patients age. Polymorphism of
AI developed SCS over 8 years of surveillance as her adenoma grew. Another
aldosterone synthase (CYP11B2) in -344th region of promoter seems to have
patient had bilateral adrenal adenomas. All our patients underwent surgical
much in common with hypertension and adrenal incidentaloma.
resection. The patient with bilateral nodules underwent bilateral subtotal
Aim
adrenalectomy. All but one required a period of postoperative corticosteroid
The aim of this study was to assess what role may play CYP11B2 polymorphism
support. Following withdrawal of steroids, there was observable median weight
in the phenotype of hypertension with associated adrenal incidentaloma. In this study,
loss of 3.85 kg (0.5-10.7) compared to presurgical weight. Four patients had an
the analysis of alleles and genotypes focused on incidence of adrenal tumour and
improvement of their BMI category from overweight to normal. All six patients
impact on the number of antihypertensive medications required to proper control.
with hypertension had sustained improvement in their blood pressure: two
Subjects and methods
became normotensive and the remainder had reduction of doses of antihyperten-
Study was performed on 106
hypertensive patients with diagnosed adrenal
sives. However there was no change to glycemic and lipid status.
incidentaloma (HAI), on 44 hypertensive patients without adrenal incidentaloma
Conclusions
(HWAI) and on 63 healthy individuals forming control group. Groups matched to
In our small series of patients with SCS, surgical intervention resulted in
each other in terms of age, gender. Related patients and those who suffered from
improved metabolic outcomes. We therefore suggest that if patients are surgically
disease that may falsely affect the results were excluded. Severity of hypertension
fit, surgery should be considered for SCS.
was determined by number of antihypertensive medications used to control. The
DOI: 10.1530/endoabs.49.EP29
significance of differences between the groups was evaluated through chi-square
and Student’s t-test.
Results
TT genotype and T allel occurred significantly less frequently in HAI in comparison
with Control Group (respectively: PZ0.049; PZ0.04). Patients with TT genotype
needed more medication to control hypertension in comparison with CC genotype
EP30
(3,080 vs 2,361, PZ0.0439). Lack of significant differences between HWAI to the
Severe hypoaldosteronism after unilateral adrenalectomy for primary
rest groups.
hyperaldosteronism
Conclusions
Joa˜o Ananias Gonçalves1, Rui Barrros1, Betânia Ferreira1 &
Cláudia Amaral1,2
† The presence of the C allele in the region of -344 aldosterone synthase
1Hospital da Luz Arrábida, Vila Nova de Gaia, Portugal;2Centro Hospitalar
promoter predisposes to adrenal tumour, the TT genotype reduced that risk.
do Porto - Hospital de Santo António, Porto, Portugal.
† Hypertension in patients with CC genotype is less severe, regardless of its
phenotype.
Introduction
DOI: 10.1530/endoabs.49.EP31
Primary hyperaldosteronism is a known cause of arterial hypertension, classically
with hypokalaemia. About
30-40% of the cases are caused by unilateral
aldosterone-producing adenoma, and the recommended treatment is adrenalect-
omy. Hypoaldestoronism is an uncommon complication of unilateral adrena-
lectomy, but it can be life-threatening. We present a case of severe
hypoaldosteronism after unilateral adrenalectomy for the treatment of primary
EP32
aldosteronism.
Case presentation
Primary aldosteronism: more common than once thought:
A 66 years old male with long term hypertension on triple drug therapy, chronic
Two clinical cases
kidney disease and persistent hypokalaemia was diagnosed with primary
Nadine Monteiro, Eduarda Comenda, Joana Costa, Helena Vitorino,
hyperaldesteronism. He had increased aldosterone - 3426 pg/ml (normal 34.7-
Sofia Santos, Filipa Moleiro, Claúdia Jesus, Ana Afonso & Helena Cantante
275 pg/ml) and low renin - 4 uUI/l (normal 4.4-46.1 uUI/l). An elevated plasma
Lusiadas, Lisboa, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
EP34
Estimated prevalence of hypertension (HT) in Portugal is 42%. It is a major risk
The treatment with dual release hydrocortisone in patients with adrenal
factor for coronary heart disease and cerebrovascular disease, the leading
insufficiency: correlation between change of the evening cortisol
mortality cause in Portugal. Primary aldosteronism (PA) was once recognized as
exposure time profile and change in metabolic profile, depression status
rare cause of secondary hypertension and hypokalemia a condition present in all
and quality of life
cases. Nowadays, prevalence of this condition is about 10% in HT patients, being
Chiara Simeoli, Rosario Ferrigno, Claudia Pivonello, Renata
the commonest form of secondary HT. Secondary forms of HT should be
Simona Auriemma, Mariarosaria Negri, Gilda Di Gennaro,
excluded in young patients, severe increase in blood pressure, sudden onset or
Davide Iacuaniello, Maria Cristina De Martino, Annamaria Colao &
worsening of HT, poor blood pressure response to drugs and organ damage
Rosario Pivonello
disproportionate to the duration of hypertension.
Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia,
Case 1
Università Federico Ii Di Napoli, Naples, Italy.
A 69 years old female with a past medical history of HT for the last 20 years,
presented with poor blood pressure control on bisoprolol 10 mg id perindopril
10 mg id and nifedipine 30 mg ER id at outpatient department. She had normal
Conventional glucocorticoids (CGCs) are unable to mimic physiological cortisol
electrolytes. Screening tests for PA revealed high plasmatic aldosterone and
rhythm in adrenal insufficiency (AI), resulting in increased metabolic morbidity
suppressed renin plasmatic activity with a ratioO25 ng/ml per h. Diagnosis was
and impaired quality of life
(QoL). Non-physiological cortisol pattern and
confirmed after saline infusion test. CT adrenal scan suggested left adrenal diffuse
elevated evening cortisol levels may be responsible for the increased risk of
hyperplasia.
metabolic disorders observed in AI patients under CGCs. Once daily dual-release-
Case 2
hydrocortisone (DR-HC), which better reproduces physiological daily cortisol
A 48 years old female presented at the emergency room complaining of severe
profile, significantly improves metabolic parameters and QoL in primary AI (PAI)
headache and four limbs’ muscle weakness. There was a past medical history of
and secondary AI (SAI) patients. The aim of the current study was to evaluate
eclampsia and hypertension diagnosed at the age of
30, and euthyroid
cortisol profile and its impact on metabolism, depression status and QoL in PAI
multinodular goiter. Labs revealed hypokalemia and she was started on oral
and SAI patients switched from CGCs, including cortisone acetate and
KCl 600 mg bid. After electrolytes correction, she was screened for PA. High
immediate-release hydrocortisone, to DR-HC. Fourteen AI patients underwent
plasmatic aldosterone and low renin plasmatic concentration with a ratioO3.8
daily cortisol sampling, at 3 h intervals, at baseline (CGCS treatment) and 12
was detected. Diagnosis was confirmed after saline infusion test.
months after switching to DR-HC. Mean cortisol (24 h, 7-7am) AUC was 15.61%
Conclusion
lower with DR-HC than with CGCs. In particular, mean (7am-1pm) and (1-7am)
PA is an important cause of secondary hypertension, with a higher cardiovascular
were 15.61% and 2.1% higher whereas mean (1-7pm), (7pm-1am) and (7pm-
event rate than essential hypertension. It is frequently underdiagnosed and a
7am) AUC were 18.8% (PZ0.057), 58.39% (P!0.001) and 41.87% (PZ0.004)
potentially curable form of hypertension.
lower with DR-HC than with CGCs, respectively. After 12 months of treatment,
DR-HC induced a significant improvement in waist circumference (PZ0.002),
DOI: 10.1530/endoabs.49.EP32
depression status (PZ0.05) and QoL (PZ0.05). Moreover, the change (D) in
cortisol 7pm-1am and 7pm-7am AUC appeared significantly correlated with the
change (D) in glucose 120’ after load (P!0.005), depression score (P!0.05) and
QoL score (P!0.05). The change (D) in cortisol 7pm-1am AUC appeared also
significantly correlated with the change (D in fasting insulin (PZ0.045) and
HOMA index (PZ0.045). In conclusion, the switch from CGCs to DR-HC in AI
EP33
patients induces a significant improvement of waist circumference, depression
Rapid reduction in left ventricular mass in primary aldosteronism after
status and QoL, and a significant decrease of late afternoon, evening and night GC
treatment; a prospective cardiac MRI study
overexposure; this reduction is significantly correlated with the improvement in
Marianne Aardal Grytaas1,2, Kjersti Sellevåg1, Hrafnkell
metabolic profile, depression status and QoL.
Baldur Thordarson1,2, Eystein Sverre Husebye2,1, Kristian Løvås1,2 &
DOI: 10.1530/endoabs.49.EP34
Terje Hjalmar Larsen1,2
1Haukeland University Hospital, Bergen, Norway;2University of Bergen,
Bergen, Norway.
Background
EP35
Primary aldosteronism (PA) patients have increased left ventricular mass (LVM)
and increased cardiovascular morbidity compared with those with essential
Treatment of adrenal insufficiency with hydrocortisone dual-release
hypertension. Echocardiographic studies have demonstrated that adrenalectomy
formulation: glycometabolic profile and health-related quality of life
or spironolactone decreases LVM. The aim of the present study was to use MRI to
Laura Maria Mongioì, Rosita Angela Condorelli, Laura Cimino,
Sandro La Vignera & Aldo Eugenio Calogero
assess both LVM and cardiac function before and during stress testing, at baseline
Unit of Andrology and Endocrinology, Department of Clinical and
and after treatment with adrenalectomy or spironolactone, compared with healthy
Experimental Medicine, University of Catania, Catania, Sicily, Italy.
subjects (HS).
Material and methods
Fifteen recently diagnosed PA patients and
24 age- and sex-matched HS
Introduction
performed a baseline cardiac MRI with a 3.0 Tesla scanner. Imaging was
Treatment of adrenal insufficiency (AI) in the last years has been object of
performed at rest and during stress-testing with adenosine 140 mg/kg per min.
important changes due to the development of a dual-release preparation of
Short-axis images were used for quantifications of LVM and left ventricular
hydrocortisone (Plenadrenw). Hydrocortisone dual-release therapy contemplates
volumes. A follow-up MRI was performed in 20 of the HS and 14 of the PA
a once-daily tablet that allows more closely mimicking the physiological
patients, at least one year after starting specific treatment.
circadian rhythm cortisol, thus avoiding overexposure.
Results
Objective
Nine patients (60%) had unilateral PA, the remaining bilateral (nZ5, 33%) or not
The aim of the study was to value effects of Plenadren administration on the 24-h
representative (nZ1, 7%) adrenal vein sampling. The PA and HS did not differ in
urinary free cortisol (UFC), the glycometabolic profile and health-related quality
age or sex. PA patients had higher baseline blood pressure (BP) than the HS
of life of patients with AI.
(median BP
138/90
vs
118/75, P!0.001). At follow-up,
8/14
PA were
Methods and materials
adrenalectomized (median 18 months). The remaining 6/14 were on spirono-
We enrolled seven adults with secondary AI caused by panhypopituitarism
lactone (median 21 months). LVM at baseline differed significantly between the
(55.9G3.6 years) and seven adults with primary AI
(36G6.2 years). We
PA and HS groups (median 145 vs 97 g; P!0.001). At follow-up, the PA group
evaluated BMI, UFC levels, the glycometabolic profile and health-related quality
had a significant reduction in LVM (median -18 g, P!0.001), but no difference in
of life (estimated by AddiQol questionnaire) before and 3, 6, 9 and 12 months
cardiac output (CO) response to stress compared with baseline (follow-up PA
after Plenadren administration. One patient dropped out the study for personal
median stress CO/rest CO 1.4 vs baseline 1.5, PZns).
reasons.
Conclusion
Results
Cardiac MRI showed rapid reduction in LVM in PA after treatment with
All patients, except one, reported a significant improvement of the quality of life
adrenalectomy or spironolactone. CO response to stress remained unchanged after
after 3 months of treatment, whereas after 1 year everyone reported individual
treatment. Our results underline the importance of early diagnosis and treatment
wellness. After 12 months of treatment, all parameters evaluated improved,
of PA.
though not in statistically significantly manner. The parameters for which there
DOI: 10.1530/endoabs.49.EP33
was evidence of a greater improvement were total cholesterol, low-density
cholesterol and glycosylated hemoglobin levels.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
Transduction of HAC15
cells with shRNA for Vsnl1
that reduced Vsnl1
The once-daily oral hydrocortisone dual-release therapy is a valid option for the
expression decreased their basal and A-II stimulated aldosterone synthesis. The
treatment of patients with AI. It allows a good glycometabolic balance in the
Vsnl1 has a myristoylation consensus sequence at the N-terminal domain. Site
absence of side effects and improving compliance.
directed mutagenesis of Vsnl1 at the 2 position (G2A) lentivirus transduced in
DOI: 10.1530/endoabs.49.EP35
HAC15 cells resulted in a significant decrease in the aldosterone response to A-II.
In summary, the Vsnl1 is a zona glomerulosa protein that participates in calcium
mobilization and increases the various secretagogue-induced aldosterone synthesis.
DOI: 10.1530/endoabs.49.EP37
EP36
Transformation from Addison’s disease to adrenocortical carcinoma
presented as Cushing’s syndrome with androgenisation
Antonela Sabati Rajic, Kristina Groti Resman, Tomaž Kocjan &
EP38
Marija Pfeifer
Metabolic syndrome is common among patients with adrenal
Department of Endocrinology, University Medical Centre Ljubljana,
incidentalomas, but not associated with functional adrenal status
Ljubljana, Slovenia.
Charalampos Tsentidis, Andreas Bampilis, Vasiliki Ntova, Grigoria Betsi &
Georgia Kassi
Department of Endocrinology, Metabolism and Diabetes, Nikaia General
We present a female patient 56 years old, who was treated at the endocrinology
Hospital ‘Ag. Panteleimon’, Athens, Greece.
department from the year
2006. The diagnosis of Addison’s disease was
established and she was properly treated. At the same time primary
hypothyroidism was diagnosed, also started treating it properly. She was
Background
regularly controlled more often at the first time, than yearly at outpatient clinic. In
Adrenal incidentalomas (AI) have an increasing prevalence during last decades,
September 2015 she was in menopause. A few months before she noticed
probably due to the extended use of new imaging techniques and longer life
oedematous legs and arms and diffuse bruising. Hypertension was also noticed for
expectancy. Adrenal hormonal hypersecretion, even subclinical, is probably
the first time and needed therapy. Her voice was different (became deep), she
related to cardiovascular disease (CVD).
noticed hair loss and hirsutism, as well. She thought it was all in correlation with
Methods
menopause. At the control examination she had hypokalemia, hypernatremia,
We evaluated 100 patients with adrenal masses, incidentally discovered in
hypertension, osteopenia with clear clinical aspect of Cushing. The abdominal
imaging techniques performed for non adrenal disorders (67 Female, 33 Male,
ultrasound, CT scan and FDG-PET scan showed huge (13.8 cm in diameter)
mean 58.1G12.9 years, median 60.5y), according to NIH criteria of 2002 and
heterogeneous tumour mass in the right adrenal gland. The tumour infiltrates
ESE 2016. IDF 2006 criteria were used for metabolic syndrome (MS) definition.
inferior vena cava and liver. Pelvic bone metastases were diagnosed also. CT
Results
angiography showed tumour thrombus and pulmonary embolism. Tumour biopsy
Mean incidentaloma size was 35.5G20 mm. 20% were bilateral, while 41% were
showed adrenocortical carcinoma. The hormonal tests showed co-secretion of
located to the right and 39% to the left adrenal. The majority (70%) was found to
cortisol and androgens (Cushing’s syndrome and androgenisation). Tumour was
be non functional and 30% to be functional. Autonomous cortisol secretion (ACS)
inoperable so tumour arterial embolisation was performed with idea of debulking.
was found in 15%, pheochromocytoma (Ph) in 7% and hyperaldosteronism (HA)
The patient was treated with mitotane in combination with systemic
in 8% of all cases. Non functioning lesions were defined as non functioning
chemotherapy (EDP regiment: etoposide, doxorubicin), antiandrogen therapy
adenomas (62%), non malignant cysts (2%), myelolipomas (2%), metastases
per os and metirapon. Because of the important hepatotoxicity mitotane was
(1%) and bilateral teratoma (1%). MS prevalence was higher in study group
discontinued soon. She needed also hydrocortisone supplementation transitory,
compared with general population (65% vs 23%, P!0.001). There was no
for the short time. The patient died due to the disease progression after one year.
difference in MS prevalence between patients with functional and non functional
DOI: 10.1530/endoabs.49.EP36
tumors (63.3% vs 64.7%, PZ0.53), while no difference was found between
functional tumors (ACS60% vs Ph57% vs HA75%, PZ0.78). Hypertension had
the greatest proportion in cases with hyperaldosteronism, while no difference in
central obesity, hyperlipidemia and abnormal glucose metabolism was found
between functional tumors.
EP37
Conclusions
Visinin-Like Protein-1 in the regulation of aldosterone biosynthesis
The prevalence of metabolic syndrome was found to be high in patients with AI.
Celso Gomez-Sanchez1, Maniselvan Kuppusamy1, Jeanne Ishimwe1,
A common pathophysiologic pathway (probably hyperinsulinaemia) must be the
Tracy Williams2, Paolo Mulatero2 & Elise Gomez-Sanchez1
underlying mechanism between AI and MS, associated with an increased risk for
1University of Mississippi Med Center, Jackson, MS, USA;2University of
CVD.
Turin, Turin, Italy.
DOI: 10.1530/endoabs.49.EP38
Visinin-Like Protein-1 (Vsnl1) is a member of the EF-hand calcium sensor
protein family that is expressed in the zona glomerulosa of the rat and human
adrenal and upregulated in aldosterone-producing adenomas.
We studied the expression pattern of Vsnl1
and co-localization with the
EP39
CYP11B2 enzyme and the zona glomerulosa (ZG) marker Dlk1 (ZOG) using
The clinical course of patients with adrenal incidentaloma: Ba¸kent
double and triple immunofluorescence in the adrenal of rats on a normal, high and
University experience
low sodium diets. We also studied the role Vsnl1 in aldosterone biosynthesis and
Nazli Gulsoy Kirnap1, Ozlem Turhan Iyidir1, Yusuf Bozkus1,
calcium in the HAC15 cell.
Lala Ramazanova1, Asli Nar1, Altug Kut2 & Neslihan Tutuncu1
In the rat adrenal, Vsnl1 was expressed only in cells of the ZG and in cells
1Department of Endocrinology, Baskent University Hospital, Ankara,
expressing Dlk1, including undifferentiated cells between the ZG and zona
Turkey;2Department of Family Medicine, Baskent University Hospital,
fasciculata. Nearly all of the ZG cells from adrenals of rats on a low sodium diet
Ankara, Turkey.
expressed both Vsnl1 and CYP11B2. However in adrenals of rats on a normal and
high sodium diet the staining for Vsnl1 was in many more ZG cells than those
expressing CYP11B2. Vsnl1 and Dlk1 immunoreactivity was found not only cells
The prevalance of incidentally discovered adrenal masses increased in last three
that are steroidogenically active and producing aldosterone, but also in ZG and
decades. The major clinical concern is the risk of malignancy and hormone
undifferentiated cells in the rat adrenal subcapsular area.
overproduction but most of them are non-fonctional and benign. Current practices
Human adrenal cortical carcinoma cell line HAC15 was transduced with a
in the management of adrenal incidentalomas reevaluated the follow-up
lentivirus carrying Vsnl1. Three days after transduction cells were incubated with
suggestions considering low probability of the transformation of a benign and
vehicle, angiotensin II (A-II) 10 nM, Forskolin 10 mM and potassium 16 mM and
non-functional adrenal mass to a malignant or functional one. Therefore, in the
compared with control cells transduced with an empty lentivirus. Aldosterone and
present study we analysed the clinical course of patients with adrenal
cortisol were measured after 24 h. The basal secretion of aldosterone was not
incidentaloma. We evaluated
203
consecutive patients
(139
females,
64
increased, but that of cortisol was. Aldosterone and cortisol secretion were greater
males:mean age 55.8G0.8 years) who were referred to the Department of
after A-II, forskolin and potassium stimulation in cells overexpressing Vsnl1.
Endocrinology, Ba¸kent University Hospital, between January 2007 and 2017.
Proliferation of the HAC15 cells measured by the XXT and crystal violet methods
Among the 203 patients examined 171 had unilateral, 32 had bilateral adrenal
and intracellular calcium, as measured by the Fluo-4 AM dye, were also increased
masses. Mean size of tumors was 22.7G10.8 mm. In 157 (%77.3) patients’
after transduction with Vsnl1.
adrenal mass was benign and non-functional, 21 (%10.3) had autonomous cortisol
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
secretion, 9 (%4,4) had Cushing syndrome, 5(%2.5) had pheochromocytoma, 9
Introduction
(%4,4) had primary hyperaldosteronism and,
2(%1) had adrenocortical
Pheochromocytomas are rare tumors arising from adrenomedullary chromaffin
carcinoma. Twentyone patients went adrenelectomy. Median follow up time
cells. Pheochromocytomas are a serious clinical condition and undiagnosed cases
was 3 (1-10) years. During the follow up the change in the size of adrenal mass
are associated with increased unexpected cardiovascular mortality.
was non significant (PZ0.12) and there were no changes either in metanephrines
Case report
and normetanephrines or in the activity of renin-aldosterone axis. There was a
A female Caucasian patient aged 52-year-old was referred to the endocrine
significant correlation between adenom size and cortisol levels after dexametha-
department of a public central hospital because of an incidental right adrenal mass
sone supression test in patients with autonomous cortisol secretion. As a result our
first found 3 years before during the work out of non specific tiredness. Annual CT
study suggests that the risk of an adrenal adenoma initially diagnosed as benign or
CT scans documented significant growth (34, 40 and 62 mm) of a hypodense
non-functional becoming malignant or hormonally active is low.
lesion (less than 10 Housefield units). Presently the patient denied gastrointestinal
DOI: 10.1530/endoabs.49.EP39
or abdominal complaints and did not present clinical evidence for hypercorti-
solism, hyperaldosteronism, hyperandrogenism or for excessive catecolamine
production. Past medical history revealed chronic gastritis treated with
omeprazole daily. She reported three uneventful pregnancies 25, 20 and 19
years ago. Physical examination was unremarkable, with normal blood pressure
and no orthostatic hypotension. Analytic evaluation excluded hypercortisolism
EP40
and hyperaldosteronism. Urinary metanephrine and normetanephrine were high
Predictive baseline morning P-cortisol levels for the response to a
(12 and 16 times higher than the upper limit of the reference range) and dopamine
Synacthen test in prednisolone treated patients
1.5 times over the upper limit. Serum calcium and calcitonin were in the reference
Stina Willemoes Borresen1, Marianne Klose1, Henning Locht3,
range.
123I-MIBG scintigraphy presented increased right adrenal uptake.
Toke Laursen3, Bente Jensen3, Linda Hilsted6, Bo Baslund2,
˚se
Uneventful laparoscopic right adrenalectomy was performed after preoperative
Krogh Rasmussen1, Lennart Friis-Hansen7, Annette Hansen4, Merete
treatment with doxazosin 8 mg, 2 l normal saline ev and propranolol 30 mg daily.
Lund Hetland5 & Ulla Feldt-Rasmussen1
Histologic evaluation confirmed a 55 mm pheochromocitoma, with no signs of
1Department of Medical Endocrinology, Copenhagen University Hospital,
malignancy. No genetic study was conducted.
Rigshospitalet, Copenhagen, Denmark;2Center of Rheumatology and Joint
Discussion and conclusion
Diseases, Copenhagen University Hospital, Rigshospitalet Blegdamsvej,
About 7% of adrenal incidentalomas are pheochromocytomas. Although rare,
Copenhagen, Denmark;3Center of Rheumatology and Joint Diseases,
clinically silent pheocromocytomas are recognized. Possible mechanisms may
Copenhagen University Hospital, Frederiksberg Hospital, Frederiksberg,
include
1) vasodilator peptides co-secreted by pheochromocytomas such as
Denmark;4Center of Rheumatology and Joint Diseases, Copenhagen
dopamine; 2) desensitization of target organs due to high catecholamine long-
University Hospital, Gentofte Hospital, Gentofte, Denmark;5Center of
term exposure, 3) low circulatory volume in these patients and 4) malignancy with
Rheumatology and Joint Diseases, Copenhagen University Hospital,
undifferentiation and minimal catecholamine production. This case highlights the
Rigshospitalet Glostrup, Glostrup, Denmark;6Department of Clinical
need to exclude catecholamine producing tumors in all adrenal incidentalomas,
Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenha-
even if they are asymptomatic.
gen, Denmark;7Department of Clinical Biochemistry, Copenhagen
DOI: 10.1530/endoabs.49.EP41
University Hospital, Nordsjællands Hospital Hillerød, Hillerød, Denmark.
Introduction
Evaluation of glucocorticoid production generally requires a dynamic test. Cut-
off levels for baseline cortisol concentrations predicting the outcome of a
Synacthen test have been proposed for different cortisol assays. With introduction
of the new Roche Elecsys Cortisol II assay, P-cortisol concentrations are expected
to decrease by 20%. We have investigated cut-off levels for baseline P-cortisol
concentrations measured with the Roche Elecsys Cortisol II assay that could
EP42
predict the response to a Synacthen test in patients at risk of glucocorticoid-
induced adrenal insufficiency.
LH and adrenal tumor size correlate with insulin resistance in
Methods
menopausal patients with adrenal incidentalomas and (possible)
In a cross-sectional study, 110 prednisolone treated rheumatologic patients had a
autonomous cortisol secretion
250 mg Synacthen test performed, fasting, in the morning, starting between 0800
Ljiljana Marina1,2, Miomira Ivovic1,2, Milina Tancic-Gajic1,2,
and 1030 h, 36-48 h after the last prednisolone dose. P-cortisol was measured
Zorana Arizanovic1, Dragana Rakovic1, Jelena Milin-Lazovic1,2,
before and 30 min after Synacthen injection. The locally validated assay specific
Aleksandra Kendereski1,2, Dragan Micic1,2, Srdjan Pandurevic2 &
cut-off for normal adrenal function was 30 min P-cortisol R420 nmol/l.
Svetlana Vujovic1,2
Results
1Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical
Forty-six patients
(42%) had an insufficient response to the Synacthen test.
Centre of Serbia, Belgrade, Serbia;2Faculty of Medicine, University of
Baseline and
30 min P-cortisol correlated positively
(P!0.0001, rZ0.86).
Belgrade, Belgrade, Serbia;3Institute of Medical Statistics and Informatics,
Receiver-operator curve analysis showed an area under the curve of 0.94 (95%
Belgrade, Serbia.
CI: 0.90-0.98). All patients with baseline P-cortisol !139 nmol/l also failed the
Synacthen test (positive predictive valueZ100%). All patients with baseline
High prevalence of insulin resistance (IR) has been shown in patients with adrenal
P-cortisol O310 nmol/l had a normal response to the Synacthen test (negative
incidentalomas (AI) and it has been demonstrated that an increase in IR is related
predictive value Z100%). Applying these cut-off values baseline P-cortisol
to the adrenal tumor size (ATS). Also, responsive adrenal pathologies are well
measurements predicted the response to the Synacthen test in 58/110 (53%) of
documented in patients with chronically elevated LH. The aim was to investigate
cases; P-cortisol O310 nmol/l (33%); P-cortisol !139 nmol/l (20%).
the association between LH and IR and ATS and IR in AI patients. The case-
Conclusion
control study was conducted in Clinic for endocrinology, diabetes and metabolic
We have presented assay specific baseline P-cortisol concentrations that could
diseases, Belgrade, Serbia. The total studied group consisted of 105 menopausal
predict the response to a Synacthen test in half of patients at risk of
women: 75 AI patients (mean age 60.13G7.28 years, mean BMI 27.60G
glucocorticoid-induced adrenal insufficiency and potentially reduce the number
4.66 kg/m2, mean menopause duration 10.86G7.79 years, mean LH 31.82G
of needed Synacthen tests in the worldwide many glucocorticoid treated patients.
14.17 IU/l and mean ATS 31.25G10.72 mm) and 30 age, BMI, menopause
Baseline morning cortisol measurements might become a valid diagnostic
duration and LH matched healthy control (HC) women. Based on level of cortisol
screening tool in the future.
after
1 mg-dexamethasone suppression test AI patients were divided in two
DOI: 10.1530/endoabs.49.EP40
groups: !50 nmol/L, 27 with nonfunctional AI (NAI) and O50 mmol/l, 48 with
(possible) autonomous cortisol secretion ((P)ACS). To estimate IR we used
homeostasis model assessment (HOMA-IR). There was no significant difference
between AI subgroups in terms of age, BMI, menopause duration, LH and
HOMA-IR. HC subjects had significantly lower HOMA-IR when compared to
EP41
NAI (PZ0.017). There was a significant positive correlation between LH and
HOMA-IR in AI group (rZ0.230; PZ0.047) and in (P)ACS subgroup (rZ0.353;
Silent pheochromocitoma - a rare case of adrenal incidentaloma
PZ0.017), but not in patients with NAI (rZK0.097, PZ0.623). The correlation
Ana Filipa Martins1, Sónia do Vale1,2 & João Martin Martins1,2
of ATS and HOMA-IR was significant in AI group (rZ0.341; PZ0.003) and both
1Hospital de Santa Maria-CHLN, Lisboa, Portugal;2Faculdade de Medicina
NAI (PZ0.018, rZ0.445) and (P)ACS (PZ0.012, rZ0.362). After adjusting
de Lisboa, Lisboa, Portugal.
for age and BMI both LH and ATS were significant predictors of HOMA-IR,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(r2Z0.196, PZ0.004). There was no significant correlation between LH and
Methods
HOMA-IR in HC. Our data suggest that not only insulin, but also the interplay
Three group of subjects were studied: healthy volunteers, suspected CS and
between LH and insulin may contribute to the adrenal tumorigenesis.
proven CS. All patients collected saliva at 23.00 h using a Salivette. Salivary
DOI: 10.1530/endoabs.49.EP42
Cortisol was measured using an automated electrochemiluminescence assay -
Elecsys 2010-Roche. The functional sensitivity of the assays is 0.018 mg/dl.
Diagnostic cut-off level was defined by Receiver operating characteristic (ROC)
curve and Youden’s J index.
Results
We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected CS
and 31 with proven CS (ACTH-dependent: 22 pituitary, two ectopic; ACTH-
independent: two adrenal adenoma, five adrenal carcinoma).
EP43
The 2.5th-97.5th percentile of the LNSC concentrations in normal subjects was
A case of recurrent Cushing’s disease after total bilateral
0.054-0.1827 mg/dl, respectively. The meanGS.D. LNSC concentration in
adrenalectomy
patients with proven CS (0.6798G0.52 mg/dl) was significantly higher than
Ivan Vicic1, Ivan Kruljac2, Miroslav Cacic2, Bozidar Peric2,
those in normal subjects (0.0642G0.03 mg/dl; P!0.0001) and suspected CS
Maja Filipovic-Grcic2, Gorana Mirosevic2, Vatroslav Cerina3,
group (0.1803G0.19 mg/dl; P!0.0001).
Leo Pazanin4 & Milan Vrkljan2
ROC curve analysis showed an AUC of 0.9881 (P!0.0001) and a cut-off point of
1University of Zagreb School of Medicine, Zagreb, Croatia;2Department of
0.1 mg/dl provides a sensibility
(S) of
96.77% (95%CI 83.3-99.92%) and
Endocrinology, Diabetes and Metabolic Diseases ‘Mladen Sekso’,
specificity (E) of 91.23% (95%CI 80.7-97.09%).
University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia;
There were significant correlations between LNSC and late-night serum cortisol
3Department of Neurosurgery, University Hospital Center ‘Sestre Milosrd-
(LNSeC) levels (rZ0.6977; P!0.0001) as well as with Urinary Free Cortisol
nice’, Zagreb, Croatia;4Department of Pathology ‘Ljudevit Jurak‘,
(UFC) levels (rZ0.5404; P 0.0025) in proven CS group.
University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.
Conclusion
Our results give to LNSC an excellent accuracy and reaffirm that can be used as a
Bilateral adrenalectomy usually results in lifelong primary adrenal insufficiency.
highly reliable noninvasive screening tool for outpatient assessment. In our
Evidence exists that up to 34% of patients with Cushing’s disease (CD) have some
population, the LNSC reference cut-off was 0.1 mg/dl with S 96.77% and E
degree of endogenous cortisol secretion after bilateral adrenalectomy due to
91.23% for CS diagnosis. Given its convenience and diagnostic accuracy, LNSC
ACTH driven hyperplasia of residual cortical tissue. We present a case of a
may profitably be added to traditional screening tests such as LNSeC and UFC.
patient with atypical corticotropinoma/carcinoma and recurrence of CD after
DOI: 10.1530/endoabs.49.EP44
bilateral adrenalectomy.
A 59-year-old man presented with Cushing’s disease (CD) in 2010. An MRI
revealed intrasellar mass 8!8 mm suggestive of a microadenoma. After the
surgery pathohistological evaluation was suggestive of atypical corticotropinoma
(Ki-67 proliferation index 7%, positive nuclear staining for p53). CD recurred
eight months after the surgery. Total hypophysectomy led to complete remission,
followed by recurrence 5 months later. We performed radiosurgical treatment of
EP45
the remnant tumor mass, along with bilateral two-stage adrenalectomy.
Pathohistological evaluation confirmed complete removal of the left adrenal
Adrenal involvement in MEN1 families
gland, and was inconlusive about the right one. Postoperatively, patient required
Mara Ventura, Miguel Melo, Leonor Gomes, Joana Saraiva, Luisa Barros,
replacement therapy. Two years after the adrenalectomy patient was diagnosed
Dírcea Rodrigues, Diana Oliveira, Diana Martins, Adriana Lages,
with Nelson’s syndrome due to enlargement of the pituitary mass. Fractionated
Nelson Cunha & Francisco Carrilho
radiotherapy was performed, after which ACTH slightly decreased, but UFC
University and Hospital Center of Coimbra, Coimbra, Portugal.
levels continued to increase, while taking hydrocortisone replacement.
Replacement therapy was stopped, but urinary free cortisol increased to
Introduction
1400 nmol/24 h 3 years after the bilateral adrenalectomy, accompanied by the
MEN1 is a rare autosomal dominant syndrome typically characterized by
recurrence of signs and symptoms of CD. Computed tomography showed 4-cm
neoplastic lesions of parathyroid glands, anterior pituitary gland and endocrine
large mass in the left adrenal bed suggestive of an adrenal tissue, along with the
pancreas. Several other tumours are associated with this syndrome, including
multiple liver lesions and without the signs of another primary tumor. Patient died
adrenal lesions, but their prevalence and clinical characteristics
(endocrine
five years after the initial diagnosis and his family refused an autopsy.
secretion and aggressiveness) are largely unknown.
This is the first case of a recurrent CD after bilateral adrenalectomy. This report
Objective
highlights the importance of long-term monitoring of the patient and individual
To determine the prevalence, clinical characteristics and the possible
dosing of replacement therapy.
genotype/phenotype association of adrenal lesions in MEN1 patients, as well as
DOI: 10.1530/endoabs.49.EP43
their global impact on patients’ outcome.
Material and methods
We retrospectively studied 16 patients belonging to six families of individuals
with MEN1. Adrenal involvement was evaluated clinically, biochemically and
imagiologically based on clinical records.
Results
Adrenal lesions were identified in 9 of 16 (56.3%) patients. This group comprises
seven women and two men with a mean age of 55.6 years. The mean age at
diagnosis of MEN1 was 46.3 years (18-68) and adrenal involvement was detected
EP44
between 0 and 16 years after the syndrome was diagnosed. Among the 16 patients
Late-night salivary cortisol: cut-off definition and diagnostic value in
evaluated, a total of nine adrenal nodules were founded, with a median of two
Cushing’s syndrome
nodules per patient. Only three patients had unilateral involvement. The mean
Adriana Lages1, João Frade1, Isabel Paiva1, Patrícia Oliveira1,
adrenal lesion diameter at diagnosis was
17.5 mm (6-30 mm). Hormonal
Diana Oliveira1, Diana Martins1, Mara Ventura1, Nelson Cunha1,
hypersecretion - autonomous cortisol secretion - was founded in one patient.
Alexandre Rebelo-Marques2, Susana Antunes1, Fátima Leitão1 &
None of the patients was submitted to adrenalectomy. Adrenal lesions were
Francisco Carrilho1
evenly distributed between the different germline mutations.
1Coimbra Hospital and University Center, Coimbra, Portugal;2Faculty of
Conclusion
Medicine University of Coimbra, Coimbra, Portugal.
Adrenal tumours are a common feature of MEN1 that can affect more than half of
the patients. Most of the tumours are bilateral non-functional lesions, but
Background
hormonal secretion may occur and should be promptly identified in order to
The diagnosis of Cushing’s syndrome (CS) remains a challenge in clinical
reduce the morbidity/mortality of the syndrome. Adrenal evaluation should be
endocrinology. Several screening tests have been proposed to establish
considered in patients with MEN1.
hypercortisolism. Late-night salivary cortisol (LNSC) is used as screening tool,
DOI: 10.1530/endoabs.49.EP45
however, individualized cut-off levels for each population must be defined.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP46
Comment
In the case of Cushing’s syndrome, the adrenal glands on one side or on both
Differential effects of aldosterone excess on potassium homeostasis and
adrenal glands are not diagnostic in terms of diagnosis.
blood pressure in Asian subjects
Du Soon Swee, Peng Chin Kek & Lih Ming Loh
Department of Endocrinology, Singapore General Hospital, Singapore,
Table 1
Singapore.
Cushing’s
Unilateral mass
Bilateral Masses
Syndrome
(n:20)
(n:15)
P
Introduction
Hypokalemia is considered as a late manifestation of primary aldosteronism (PA),
Age
58.2G2.4
63.5G2.5
0.7
long preceded by hypertension. However, there have been reports of
1 mg DST
5.9G1.6
5.8G1.8
0.9
normotensive PA patients presenting with hypokalemia. This study aims to
(median:3.3)
(median:3.1)
examine the relationship of hypokalemia and blood pressure in patients with
Liddle test
4.8G1
4.2G0.7
0.2
hyperaldosteronism.
24 h urine cortisol
138.2G28.8
184G26.5
0.5
Methods
A retrospective review of patients who underwent saline infusion test (SIT) from
2014 to 2016 was conducted. All patients had screening plasma aldosterone
DOI: 10.1530/endoabs.49.EP47
concentration (PAC): plasma renin activity (PRA) ratio of O20. Postinfusion
PAC level !5 ng/dl (139 pmol/l) indicated normal aldosterone suppression, PAC
O10 ng/dl
(277 pmol/l) confirmed PA, whereas PAC
5-10 ng/dl
(139-
277 pmol/l) was regarded as indeterminate. Hypokalemia was defined as serum
potassium !3.5 mmol/l.
Results
EP48
Over a 3-year period, 52 patients referred for hypokalemia had non-suppressible
Late night salivary cortisol measurement may help in excluding
postinfusion PAC (O5 ng/dl). They comprised of 36 men and 16 women, with a
Cushing’s syndrome in patients with chronic kidney disease
mean age of 58.4G9.1 and 57.3G13.2 years respectively.
Urszula Ambroziak1, Agnieszka Kondracka1, Jadwiga Rojek-Tre˛bicka2,
In the PA group consisting of 26 men and 11 women, the mean serum potassium
Paweł Gajkowski1, Agnieszka Stan´ czyk1, Malwina Stępor1 &
were 2.9G0.3 mmol/l and 2.7G0.5 mmol/l respectively. Eighteen (69.2%) men
Tomasz Bednarczuk1
and 10 (90.9%) women were on %2 antihypertensive agents, including two
1Department of Internal Medicine and Endocrinology, Medical University
women (age 48 and 51) with severe hypokalemia (!2.5 mmol/l) who were
of Warsaw, Warsaw, Poland;2Department of Internal Medicine and
normotensive and rendered normokalemic after adrenalectomy and spironolac-
Nephrology, Medical University of Warsaw, Warsaw, Poland.
tone treatment separately.
In the indeterminate group comprising of ten men and five women, the mean
serum potassium were 3.1G0.2 mmol/l and 3.0G0.2 mmol/l respectively. Five
Objective
(50%) men and 4 (80%) women were on %2 antihypertensive agents.
The diagnosis of Cushing’s syndrome may be challenging, especially in cases of
In all patients with moderate to severe hypokalemia (%2.9 mmol/l), 7/11 (63.6%)
patients with chronic kidney disease (CKD).
men and 8/9 (88.9%) women were on %2 antihypertensive agents.
Aim
Conclusion
The assessment of late night salivary cortisol concentration, serum and salivary
In our cohort of Asian patients, majority with hypokalemia secondary to
concentration in overnight dexamethasone suppression test in patients with CKD
autonomous aldosterone production required only 0-2 antihypertensive agents,
stage III-V and a control group.
even in those with more severe degree of hypokalemia. This suggests possible
Patients and methods
differential effects of aldosterone excess on potassium homeostasis and blood
37 patients mean age 66G12 (MZ13) with CKD stage III-V according to
pressure.
KDIGO and 28 controls mean age 45.3G15 years (MZ6) were enrolled to the
study. Patients were recruited in the nephrology clinic during their routine control
DOI: 10.1530/endoabs.49.EP46
visits. Serum and salivary cortisol were measured by Roche ECLIA cortisol test
(Cobas E411). Two samples of late night salivary cortisol (LNSC) from each
subject were obtained from home. 1 mg dexamethasone suppression test (DST)
was done in patients and controls with serum and saliva measurement at 0800 h.
Serum creatinine assessment was done no longer than 1 week prior to cortisol
measurement. GFR was obtained from the CockcroftKGault calculator.
EP47
Results
The mean GFR in patients was
33.89 ml/min
(8.4-54) while in controls
Effect of adrenal mass lateralization on diagnostic tests in patients with
125 ml/min (73-230) (P!0.0001). The mean serum DST cortisol in patients
Cushing
was 2.62 mg/dl (0.46-7.42). In 19 (51.4%) patients serum DST cortisol was
Ozlem Ustay Tarcin, Emre Pehlevan, Eren Imre, Melin Uygur,
O1.8 mg/dl. In all controls serum DST cortisol was !1.8 mg/dl (mean, min-max
Oguzhan Deyneli & Dilek Gogas Yavuz
0.70, 0.36-1.48). The mean DST salivary cortisol in patients was 0.88 mg/dl
Marmara University Pendik Hospital, Endocrinology and Metabolism,
(0.11-0.88) while in controls 0.18 mg/dl (0.02-0.69) mg/dl. Although there was a
Istanbul, Turkey.
significant difference between controls’ and patients’ salivary cortisol concen-
tration in DST (PZ0.01), all but one patient’s salivary measurement were within
The frequency of adrenal masses is increasing in parallel with the progress of the
control ranges. The mean LNSC in patients was 0.26 mg/dl (0.10-0.65) while in
technology. Most of these masses, which are detected by chance, are not
controls 0.29 mg/dl (0.04-0.80), PZ0.4. All patients’ LNSC measurements were
functional, and only a part of them are exposed to an excess of hormone. The most
within control ranges. In the patients’ group the negative correlation between
common dysfunction in masses with hormonal activity is hypercortisolism.
GFR and DST serum cortisol was detected, rZK0.6, PZ0.001 (the higher
However, the diagnosis of Cushing’s disease is based on more than one test. In this
cortisol the lower GFR).
study, we intended to compare the values of screening tests to determine whether
Conclusion
the presence of a unilateral mass or bilateral mass would help in the diagnosis.
LNSC may be helpful in excluding Cushing’s syndrome in patients with CKD.
Materials and methods
DOI: 10.1530/endoabs.49.EP48
Adrenal masses were detected in our clinic and 143 patients who were followed
up were evaluated. 112 of these patients have unilateral adrenal mass, 31 have
bilateral adrenal masses. Twenty (17.8%) of 112 unilateral adrenal masses and 15
(51.6%) of the patients with bilateral adrenal masses were diagnosed as Cushing.
The 1 mg overnight dexametasone suppression test
(DST),
2
days
2 mg
EP49
dexametasone suppression test (Liddle test), and 24-h urine cortisol levels used
for diagnosis in these patients were compared. Averages of tests were taken
The short Synacthen test revisited - reevaluation of the normal
multiple times.
reference range using LCMSMS
Conclusion
Grethe
˚strømUeland1,2, Paal Methlie1,2, Marianne Øksnes1,2,
The mean age of the patients with bilateral and unilateral adrenal masses was
Kristian Løva˚s1,2, Hrafnkell Thordarson2 & Eystein Husebye1,2
around 60. When the mean values of 1 mg DST, Liddle test and 24 h urine were
1Department of Clinical Science, University of Bergen, Bergen, Norway;
compared, no statistically significant difference was found between the two
2Department of Endocrinology, Haukeland University Hospital, Bergen,
groups.
Norway.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
EP51
The Synachten test is used to diagnose for adrenal insufficiency (AI) and non-
Education sessions in patients with adrenal insufficiency
classical congenital adrenal hyperplasia (CAH). The cut-off levels for s-cortisol
Aldora Távora, Ema Lemos, Isaura Duarte, Joaquim Sobral,
and s-17-hydroxyprogesterone are derived from immunoassays that were not well
Catarina Machado, Patrícia Tavares, Gustavo Rocha, Sara Monteiro,
standardized and are no longer in use. Introduction of liquid chromatography
Ana Sousa, Pedro Rodrigues & Maria Joa˜o Oliveira
tandem mass spectrometry (LCMSMS) could resolve the lack of standardization
Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.
of steroid hormone assays and enable increased diagnostic accuracy.
Aim
Define cut-off values for s-cortisol and s-17OH-progesterone by LCMSMS after
Introduction
intravenous administration of 250 mg tetracosactide acetate (Synachten).
Adrenal insufficiency (AI) is a rare and potentially life-threatening disease. The
Methods
most common causes are primary adrenal insufficiency (Addison’s Disease), due
The Synachten test was performed in healthy individuals (nZ60) and patients
to an adrenocortical disease, and secondary insufficiency, due to disorders of the
referred for evaluation of adrenocortical function (nZ42). Steroids were assayed
pituitary gland. Chronic glucocorticoid replacement is vital and patients should be
by LCMSMS. Cut-off level for s-cortisol was defined as the 2.5% percentile in
educated about how to act in acute stress situations, in order to avoid adrenal
healthy subjects not using oral estrogens (nZ55), and for 17-OH-progesterone as
crisis. Taking this into account, we organized education sessions, aimed at
the 97.5% percentile in the healthy women.
patients with AI.
Results
Discussion
Cortisol cut-off levels were 415 and 493 nmol/l at 30 and 60 min, respectively.
We realized group sessions of about 90 minutes duration each, with maximum 8
All controls had higher cortisol at 60 compared to 30 min. Applying the current
patients with AI; the presence of a family member or caregiver was strongly
cut-off of 550 nmol/l, 27 healthy controls would have had a false negative test at
advised. A multimedia presentation was performed, focusing on basic knowledge
30 min, and six at 60 min. For s-17-OH-progesterone the cut-off levels were 10.5
on adrenal insufficiency, management of the disease during stress situations and
and 11.1 nmol/l at 30 and 60 min, respectively. Forty-two patients performed the
early recognition of signs and symptoms of an adrenal crisis. At the end of each
test for suspected AI or non-classic CAH. Applying the new cut-offs, seven who
session, patients were given an emergency hydrocortisone kit and taught how and
had AI according to old criteria, now scored normal.
when to use it. In addition, three brochures with written information with general
Conclusions
information about the disease, specials situations and how to prepare and
Cut-off levels for s-cortisol after Synacthen test are lower than the commonly
administer emergency medication were available to take home. The identification
recommended discriminating levels when cortisol is analyzed by LCMSMS.
card of disease carrier (European Society of Endocrinology) was also provided to
When applied, a significant proportion of patients can be re-categorized from
those who didn’t have it. Patient adherence was 100% and a second session will
adrenal insufficiency to healthy. We recommend using the 60 min value as
be scheduled in order to access the effectiveness of the first session and to
standard, as cortisol increased from 30 to 60 min in all controls.
reinforce patient education.
Conclusions
DOI: 10.1530/endoabs.49.EP49
AI is a chronic disease with a significant burden in both patients and its partners.
A careful and repeated education is the best strategy to avoid life-threatening
emergencies.
DOI: 10.1530/endoabs.49.EP51
EP50
Cushing’s syndrome in pregnant woman
Anastasiia Chekanova, Irina Komerdus, Tatiana Shestakova,
EP52
Fatima Burumkulova, Timur Britvin & Alexander Dreval
Characteristics of aldosterone-producing adenomas: a tissue
Moscow Regional Research Clinical Institute n.a. M.F.Vladimirsky,
microarray study
Moscow, Russia.
Yara Rhayem1, Annette Feuchtinger2, Christine Woischke3,
Philippe Ludwig1, Thomas Kunzke2, Thomas Schwarzmayr4,
Background
Stefanie Hahner5, Celso E. Gomez-Sanchez6, Tim M. Strom4,
Pregnancy occurs rarely in Cushing’s syndrome (CS), slightly over 150 cases
Thomas Kirchner3, Martin Reincke1, Axel Walch2 & Felix Beuschlein1
have been reported in the literature. The risk of maternal morbidity and a poor
1Department of Endocrine Research, Klinikum der Universitat Munchen,
fetal outcome is significant when CS coexists with pregnancy. CS may be difficult
Ludwig-Maximilians University, Munich, Germany;2Research Unit of
to detect clinically and laboratory because of the hormonal changes and
Analytical Pathology, Institute of Pathology, Helmholtz Zentrum Munchen,
pathological comorbidities associated with normal pregnancy.
Neuherberg, Germany;3Institute of Pathology, Klinikum der Universitat
Material and methods
Munchen, Ludwig-Maximilian University, Munich, Germany;4Institute of
A case of CS that was diagnosed and treated during pregnancy.
Human Genetics, Helmholtz Zentrum Munchen and Technische Universitat
Case
Munchen, Munich, Germany;5Endocrinology and Diabetes Unit, Depart-
Woman Y., 30y.o., since she was 18 had menstrual irregularities and since she
ment of Medicine I, University Hospital Wurzburg and Comprehensive
was 28 an arterial hypertension, type
2 DM. She was on supervision of
Heart Failure Center, University of Wurzburg, Wurzburg, Germany;
therapeutist and take metformin for her DM and hypotensive medication.
6Division of Endocrinology, G.V.(Sonny) Montgomery VA Medical Center
Unexpected pregnancy occurs in December 2016. She was referred in our clinic in
and Department of Medicine-Endocrinology, University of Mississippi
15 weeks of her pregnancy because of uncontrolled DM and hypertension.
Medical Center, Jackson, MS, USA.
Examination revealed increased blood pressure, fatigue, easy bruising, excessive
hair growth on the face and body, swelling and rounding of the face, edema of legs
Background
and feet. Laboratory evaluation: UFC-1475.0 and 1511.0 nmol/24 h (N 138.0-
Sporadic aldosterone-producing adenomas (APA) are relevant cause of endocrine
524.4), serum cortisol
- at
0800 h K868 nmol/l
(190-650), at
2300 h
related hypertension in Primary Aldosteronism (PA). Next generation sequencing
K995 nmol/l (50-350)), suppressed ACTH level. HbA1c-7.7%. Insulin therapy
techniques have identified somatic mutations in APA harbored in KCNJ5,
initiated to treat DM. MRI data: adenoma in left adrenal (32!30 mm). 13.05.16.-
ATP1A1, ATP2B3, CACNA1D, CTNNB1 and PRKACA genes. Yet, a number
unilateral adrenalectomy was done. Adrenal insufficiency developed post-
of APA harbor no mutations in candidate genes (designated as wild type, WT) and
operatively and glucocorticoid therapy was started. She was under close
little is known about genotype/phenotype correlation.
supervision of gynecologist. At 38 weeks gestation surgical delivery performed
Objectives
(boy,
1900 g, 44 cm, 7/8 Apgar score, with three degrees of fetal growth
We investigated the tissue-based molecular and histopathological characteristics
retardation and two degrees of malnutrition). Insulin was cancelled after delivery,
of 132 APAs after laparoscopic unilateral adrenalectomy in PA-patients and
and hydrocortisone and antihypertensive therapy cancelled 2 months postpartum.
studied genotype/morphometry and histopathology correlation.
Conclusion
Methods
High clinical suspicion of the CS during pregnancy can help for the diagnosis and
Tumor-DNA was screened for somatic mutations in candidate genes by targeted
leads to better outcomes for the mother and the fetus. Multidisciplinary approach
(nZ84) or whole-exome (nZ48) sequencing. Accurate characterization of 179
needs for these patients with careful supervision during pregnancy and
morphometric parameters and of immunohistochemistry
(IHC) results for
postpartum.
steroidogenic enzymes CYP11B1, CYP11B2, CYP17, HSD3B1 and HSD3B2
DOI: 10.1530/endoabs.49.EP50
was performed on tumor tissue microarrays from all samples by digital image
analysis.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
1Department of Endocrinology, Diabetes and Metabolism, São João
Prevalence of WT APA in our cohort was 34% and affected men more frequently. In
Hospital Center, Porto, Portugal;2Departamento de Cirurgia e Fisiologia,
8/48 APA, non-recurrent somatic mutations (NR) were identified. H&E analysis
Unidade de Investiga
¸a˜o Cardiovascular, Faculdade de Medicina, Uni-
demonstrated that 6 morphometric parameters correlated negatively with WT status
versidade do Porto, Porto, Portugal;3Faculty of Medicine University of
whereas those same parameters correlated positively with the presence of KCNJ5 or
Porto, Porto, Portugal;4Department of Medical Oncology, São Jo
˜o
NR (P!0.01). The same reversed pattern between WT and KCNJ5 mutated APA was
Hospital Center, Porto, Portugal;5Instituto de Investigac¸ão e Inovação em
found in
10 cytoplasmic parameters, including mainly color-based features
Saúde da Universidade do Porto, Porto, Portugal;6Department of Infectious
(P!0.01). KCNJ5 mutation status was negatively correlated with CYP11B1 and
Diseases, São Jo
˜o Hospital Center, Porto, Portugal;7Servic¸o de Medicina
HSD3B1 expression (P!0.01). On the contrary, WT, CACNA1D and NR APA
Interna. Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira,
significantly correlated positively with CYP11B1. ATP1A1 mutated APA correlated
Portugal.
positively with CYP11B2 (P!0.01) and not with CYP11B1 or HSD3B2.
Conclusion
Introduction
Our findings in NR APA point towards a KCNJ5-like morphometric pattern
Adrenal tumors are usually detected due to clinical manifestations of hormonal
associated with a WT-like steroidogenic enzymes expression pattern. WT APA
hypersecretion or incidental findings on imaging evaluation. Although most
presented an opposed morphometric pattern in comparison to mutated APA,
incidentalomas are non-functioning adenomas, it is important to appropriately
indicating that in absence of detectable somatic mutations APA cells are driven
evaluate such masses to exclude hormonal excess or malignancy.
towards a different cellular fate.
Case description
DOI: 10.1530/endoabs.49.EP52
An 81-year old male was admitted to our hospital for fever with 15 days of
evolution. The patient also presented chills and loss of 3 kg in the last 4 weeks.
Regarding past medical history, the patient had type 2 diabetes, hypertension,
coronary artery disease, heart failure, cerebrovascular disease (stroke 8 years
before), vertebral fractures (3 years before), deep vein thrombosis (3 months
EP53
before), renal lithiasis and a right adrenal mass
(3 cm in the abdominal
Adrenal cushing’s syndrome surprisingly unveiling breast cancer
tomography 16 months before; no functional study available). An elevated
Joa˜o Sérgio Neves1,2, Ana Isabel Oliveira1, Pedro Souteiro1,3, Sofia
C-reactive protein (142 mg/l) was observed, with negative blood and urinary
Castro Oliveira1,3, Helena Baldaia4, Daniel Melo4, Celestino Neves1,3,
cultures and no other signs of infection. The abdominal ultrasound shown a right
Paula Freitas1,5 & Davide Carvalho1,5
adrenal mass of 13 cm. On magnetic resonance, the mass was heterogenous with
1Department of Endocrinology, Diabetes and Metabolism, Sa˜o João
invasion of inferior vena cava. The patient had no stigmas of Cushing’s syndrome.
Hospital Center, Porto, Portugal;2Departamento de Cirurgia e Fisiologia,
Plasma catecholamines, urinary catecholamines and metanephrines, and renin
Unidade de Investigac¸ão Cardiovascular, Faculdade de Medicina, Uni-
and aldosterone levels were normal. The midnight salivary cortisol was normal
versidade do Porto, Porto, Portugal;3Faculty of Medicine University of
and the plasma cortisol level after 1 mg overnight dexamethasone suppression test
Porto, Porto, Portugal;4Department of Pathology, São João Hospital Center,
was 3.7 mg/dl. Given the risk for a surgical approach, the fast growth of the tumor
Porto, Portugal;5Instituto de Investiga
¸
˜o e Inova
¸a˜o em Saúde da
and the imaging characteristics suggestive of adrenal carcinoma, a decision to
Universidade do Porto, Porto, Portugal.
preclude biopsy was made. The patient started mitotane and two months later the
mass has 15 cm and the patient is still on follow-up in outpatient setting.
Conclusions
Introduction
The authors present a case of adrenal carcinoma in a patient with previous adrenal
Cushing’s syndrome is an endocrinopathy characterized by glucocorticoids
mass not completely studied at presentation. Adrenal incidentalomas are frequent.
excess. Adrenalectomy is the recommend treatment for unilateral adrenal
This case highlights the importance of prompt evaluation of adrenal
Cushing’s syndrome and is usually associated with resolution of the disease.
incidentalomas to early recognize rapidly growing adrenal carcinomas.
Clinical Case
DOI: 10.1530/endoabs.49.EP54
A 54-year old woman with central obesity (BMI 34.3 kg/m2), diabetes and
hypertension had a left adrenal mass of 15 mm and characteristics suggestive of
adenoma (Hounsfield unit of !10). On CT reevaluation, five years later, there
was evidence of mass growth (28 mm) and the characteristics were suspicious of
malignant lesion (Hounsfield unit of 38 and absolute contrast washout of 35%).
She was then referred to our department for evaluation. Urinary catecholamines
EP55
and metanephrines were normal, ACTH level was 4.2 pg/ml and the cortisol
The relative risk of developing Addison’s disease among patients
following 1 mg overnight dexamethasone suppression test was 11.0 mg/dl. The
with type 1 diabetes mellitus: a nationwide, matched, observational
24 h urinary-free cortisol, late-night salivary cortisol and two-day low-dose
cohort study
dexamethasone suppression test were consistent with ACTH-independent
Dimitrios Chantzichristos1,2, Anders Persson3, Bjorn Eliasson1,2,
Cushing’s syndrome. A left adrenalectomy was performed. At pathological
Mervete Miftaraj3, Stefan Franzén3, Ann-Marie Svensson3 &
evaluation, there was a neoplasm of solid pattern, with vascular invasion and a
Gudmundur Johannsson1,2
immunohistochemical pattern suggestive of a breast carcinoma metastasis.
1Department of Internal Medicine and Clinical Nutrition, Institute of
Mammography revealed a 15 mm nodule with spiculated contours that on breast
Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg,
biopsy revealed a NST (no special type) breast carcinoma. The patient was
Sweden;2Department of Endocrinology-Diabetes-Metabolism, Sahlgrenska
submitted to neoadjuvant chemotherapy and surgical tumorectomy. Five months
University Hospital, Gothenburg, Sweden;3Department of Medicine,
after surgery she was admitted in Endocrine department for adrenal insufficiency.
National Diabetes Register, Centre of Registers, University of Gothenburg,
Ten months after the adrenalectomy, the patient presents an adrenal insufficiency
Gothenburg, Sweden.
(compensated with replacement therapy) and maintains follow-up on endo-
crinology and multidisciplinary breast cancer appointments.
Background
Conclusion
Both prevalence and incidence of type 1 diabetes (T1DM) is increasing. T1DM is
The authors present a case of Cushing’s syndrome of adrenal origin, with a
associated with other autoimmune diseases, such as Addison’s disease (AD). This
concomitant metastasis of a breast carcinoma. The find of a metastasis in an
combination is rare, with estimated prevalence in Norway 20 per million. Having
adrenal mass, is consistent with a tumor-to-tumor metastasis, a rare finding in
both DM & AD is associated with marked excess mortality.
adrenal masses that, in this case, allowed the diagnosis of a previously unknown
Objectives
breast cancer.
To study prevalence and incidence of AD among patients with and without
DOI: 10.1530/endoabs.49.EP53
T1DM.
Methods
Nationwide, observational study cross-referencing the Swedish National Diabetes
Register with Inpatient Register in patients with T1DM & AD and matched
controls from the general population (matched 1:5 for age, sex and country).
EP54
Demographics at baseline, group proportions and time to AD diagnosis using a
Giant adrenal tumor in a patient admitted for fever
Cox proportional hazards model were assessed.
Joa˜o Sérgio Neves1,2, Luís Teles7, Pedro Souteiro1,3, Sofia
Results
Castro Oliveira1,3, Ana Isabel Oliveira1,3, Ana Catarina Fernandes4,
Prevalence: Between 1987-2012, 105 subjects were diagnosed with AD among
Margarida Damasceno4, Luísa Grac¸a6, Elisabete Rodrigues1,3,
30,685 patients with T1DM, while 32 among 153,918 controls. The odds ratio
Celestino Neves1,3, Paula Freitas1,5 & Davide Carvalho1,5
for AD in T1DM patients vs controls was therefore 16.5 (95% CI 11.1-24.5).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
The prevalence of AD in patients with and without T1DM was 3400 and 200 per
Introduction
million, respectively. Incidence: Between 1998-2013, 67 subjects were diagnosed
Primary adrenal insufficiency (PAI) is a rare but severe and potentially life-
with AD at a mean age of 36.7 years (SD 13.1) among 36,705 patients with
threatening condition. There are no studies characterizing portuguese patients
T1DM, while 33 were diagnosed with AD at a mean age of 43.1 (SD 15.1) among
with PAI.
184,304 controls. The estimated relative risk increase to develop AD in T1DM
Aims
patients was therefore 10.7 (95% CI 7.0-16.2). The incidence of AD for a patient
To characterize the clinical presentation, diagnostic workup, treatment and
with and without T1DM was 195 and 18 per million patient-years, respectively.
follow-up of patients with confirmed PAI.
Conclusion
Methods
This nationwide study shows that prevalence of AD is higher than previously
A multicentre retrospective study of PAI patients followed in 12 portuguese
reported and that the incidence of AD for a patient with T1DM is 195 per million
hospitals.
patient-years. T1DM patients have a more than 10-fold higher risk of developing
Results
AD than matched controls and their AD develops at a younger age.
We investigated 278 patients with PAI (55.8% were females) with mean age of
DOI: 10.1530/endoabs.49.EP55
diagnosis of 33.6G19.3 years, 7.3 years after the beginning of the symptom
presentation. The most frequently reported symptoms and signs were asthenia
(60.1%), hyperpigmentation (55.0%), weight loss (43.2%), hypotension (42.8%)
and hypoglycaemia (8.6%). Hyponatremia was documented in 36.3% of cases
and hyperkalaemia in 25.9%; 29.1% of patients were diagnosed in adrenal crisis.
In 122 patients the diagnosis was established using morning cortisol !5 g/dl and
plasma ACTH 2-fold the upper limit of the reference range and in 39 cases by the
corticotropin stimulation test. The main causes were autoimmune adrenalitis (140
EP56
cases), idiopathic
(48 cases), congenital adrenal hyperplasia
(27 cases) and
The frequency of incidental liver and renal masses in patients with
tuberculosis (17 cases). Concerning associated autoimmune diseases, the most
adrenal incidentalomas
common were autoimmune thyroiditis (81 patients) and type 1 diabetes mellitus
Narin Nasiroglu Imga, Yasemin Tutuncu, Mustafa Unal, Mazhar
(25 patients). Seventy-nine percent were treated with hydrocortisone (mean dose
Muslum Tuna, Bercem Aycicek, Serhat Isik, Dilek Berker & Serdar Guler
26.3G8.3 mg/day) in three (57.5%), two (37.4%), one (3.7%) or four (0.5%)
Department of Endocrinology and Metabolism, Ankara Numune Education
daily doses; the remainder with prednisolone (10.1%), dexamethasone (6.2%) and
and Research Hospital, Ankara, Turkey.
methylprednisolone (0.7%); 66.2% were medicated with fludrocortisone (median
dose of 100 mg/day). Since diagnosis 33.5% have been hospitalized due to disease
Purpose
decompensation. At the last consultation, 17.2% of the patients had complaints
Adrenal incidentalomas (AIs) are adrenal masses, which are found on imaging
(7.6% asthenia and
6.5% depression) and
9.7% presented changes in the
ionogram.
studies not performed related to an adrenal problem. Hepatic incidental masses
Conclusion
and renal incidental masses are usually seen in abdominal imaging methods. We
This is the first multicentre Portuguese study about PAI. As described in
aim to investigate the frequency and the kind of hepatic and renal incidental
international studies a significant number of PAI patients continue to have
masses in patients with AIs.
symptoms of over or under-substitution despite optimal steroid replacement.
Methods
Retrospective evaluation of 381 (245 female and 136 male) AI patients and 285
DOI: 10.1530/endoabs.49.EP57
(168 female and 117 male) controls were done. Adrenal masses were divided into
two groups according to Hounsfield Units (HU) %10 and O10, also classified as
right, left and bilateral sided. The comparisons were made between hepatic and
renal and both hepatic and renal incidental masses in AIs patients.
Results
Renal incidental mass and both hepatic and renal mass frequency were found
higher in AIs group than controls. InAIs patients who had left sided
unilateraladrenal mass HU O10, the frequency of both hepatic and renal
incidental mass was found more than left sided unilateral adrenalHU %10 group
EP58
(PZ0.001). Also in patients who had bilateral sided adrenal mass HU O10 the
Adrenal incidentaloma: a challenging dilemma!
frequency of both hepatic and renal incidental mass was found more than bilateral
Caoimhe Bonner, Usman Shah, Anna Hawkins, Anthony Pittathankal,
sided unilateral adrenal HU %10 group (PZ0.049).
Imran Syed, Edel Casey & Khash Nikookam
Conclusions
King George Hospital, London, UK.
Increased incidence of both hepatic and renal incidental masses were detected in
AIs patients which adrenal mass HU greater than 10. We consider that the
physicians should carefully evaluate these cases. Large studies are needed to
The prevalence of adrenal incidentaloma on abdominal Computed Tomography
define the incidence and follow-up of AIs patients with hepatic and renal
(CT) is around 4.4%. This prevalence is increased in obese, diabetic, hypertensive
incidentalomas.
patients, and could be as high as 10% in older patients. Unilateral adrenal masses
larger than 4 cm should be considered for surgical removal to avoid missing
DOI: 10.1530/endoabs.49.EP56
adrenal carcinoma, particularly in younger patients.
This is the case of a 67 year old gentleman with Type 2 diabetes mellitus, known
to have hypertension, hypercholesterolaemia, ischaemic heart disease with six
coronary stents, and iron deficiency anaemia. He was on polypharmacy including
aspirin, clopidogrel, bisoprolol, amlodipine, oral hypoglycaemic agents, insulin
and iron supplementation. He presented with increased urinary frequency and
pain in the right flank. Urinalysis and examination of all systems were
unremarkable.
EP57
An ultrasound of kidney, ureter, and bladder (KUB) was performed showed a
Primary adrenal insufficiency: a Portuguese multicentre study by the
well-defined solid echogenic mass superior to the right kidney measuring 98!
adrenal tumour study group
76!85 mm with no vascularity. CT of the adrenals and abdomen revealed a 7 cm
Lia Ferreira1, João Silva2, Ana Martins3, Carlos Belo4, Diana Oliveira5,
right adrenal mass, most likely myelolipoma, multiple bilateral small renal cysts,
Hélder Simo˜ es6, Isabel Paiva5, Joana Guimarães7, Marta Ferreira8,
and an extensively calcified atherosclerotic abdominal aorta. Phaeochromocy-
Rita Silva9, Susana Garrido10, Tiago Silva11, Vera Fernandes12 & Maria
toma and Conn’s syndrome were ruled out following normal 24 hour urinary
Lopes Pereira12
metanephrines and normal renin aldosterone ratio. It was rather unlikely for
1Centro Hospitalar do Porto, Porto, Portugal;2Hospital das Forças Armadas,
Cushing’s in view of normal 24 hour urinary cortisol and lack of the clinical
Lisboa, Portugal;3Centro Hospitalar Lisboa Norte, Lisboa, Portugal;
stigmata of excess cortisol.
4Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal;5Centro Hospitalar e
Conclusion
Universitário de Coimbra, Coimbra, Portugal;6Instituto Português de
Is it best to leave it alone, bearing in mind his multiple co morbidities or to operate
Oncologia Lisboa, Lisboa, Portugal;7Centro Hospitalar do Baixo Vouga,
in view of right flank pain, the size of tumour, and the risk of bleeding in this type
Aveiro, Portugal;8Centro Hospitalar Leiria, Leiria, Portugal;9Centro
of tumour?
Hospitalar São João, Porto, Portugal;10Hospital Tâmega e Sousa, Penafiel,
Portugal;11Hospital Garcia da Orta, Lisboa, Portugal;12Hospital de Braga,
DOI: 10.1530/endoabs.49.EP58
Braga, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP59
between conventional therapy and Plenadren. Currently, the median follow-up is
9 months (range 3-24 months). In one obese and diabetic patient body weight
Assay of steroids with Liquid chromatography tandem mass
decreased as well as fat mass while lean mass increased and HbA1c improved. In
spectrometry is superior to immunoassays in monitoring patients
one patient with osteoporosis T score improved and accordingly cross laps
with 21-hydroxylase deficiency
decreased and BAP increased. All study parameters did not show significantly
Ingrid Nermoen1,2, Sandra Rinne Dahl1, Ingeborg Brøndstad1,3, Eystein
changes in the remaining patients.
S Husebye3,4, Per M Thorsby1 & Kristian Løvås3,4
Conclusions
1Oslo University HospitalHrmone Laboratory, Oslo, Norway;2Akershus
Treatment with Plenadren provides a more physiological cortisol profile and in
University Hospital, Lørenskog, Norway;3University of Bergen, Bergen,
some patients shows a beneficial effect on glucose metabolism and bone and body
Norway;4Haukeland University Hospital University, Bergen, Norway.
composition without increasing adrenal crisis and/or infections.
DOI: 10.1530/endoabs.49.EP60
Objective
Immunoassays of steroids are still used in the diagnosis and biochemical
monitoring of patients with congenital adrenal hyperplasia due to 21-hydroxylase
deficiency (21 OHD). However, high levels of steroid intermediates can promote
cross-reactivity between steroids giving rise to falsely elevated levels.
Design
Fifty-nine patients with classic 21OHD (38 women) were studied. Blood samples
EP61
were collected in the morning after overnight medication fasting. Immunoassay
Autoimmune Addison disease - data from long-term follow-up of
and liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitation
patients from a tertiary hospital’s Endocrinology Department
of the following steroids were performed:
17OH-progesterone
(17OH),
Diana Oliveira, Isabel Paiva, Adriana Lages, Diana Martins, Mara Ventura,
21-deoxycortisol (21DF, an 11-hydroxylated derivative of 17OHP), 11-deox-
Nelson Cunha, Sandra Paiva & Francisco Carrilho
ycortisol, testosterone and androstenedione.
Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital
Results
and University Center, Coimbra, Portugal.
Concentrations of testosterone, androstenedione and 17OHP were lower when
measured with LC-MS/MS compared with immunoassays, with exception of
testosterone levels in men. Testosterone results differed by 30.0% in females and
Introduction
only a small difference in men (C1.1%). The difference was even larger for
Autoimmune Addison disease requires lifelong glucocorticoid and mineralo-
androstenedione (31.3%) and 17OHP (57.0%).
corticoid replacement. Optimal therapy is not standardized and must balance
The correlation between 21DF and 17OHP was good (rZ0.87), but three patients
adequate hormone substitution with prevention of treatment-related compli-
did not have measurable 21DF which indicate that 21DF is not superior to 17OHP
cations.
to monitor replacement therapy. Subjects with no enzyme activity had
Objective
significantly lower mean 11-deoxycortisol concentrations compared with subjects
Assessment of patients followed at our department: epidemiology, associated
with severe enzyme failure, analyzed by LC-MS/MS. Levels of other steroid
conditions, treatment, cumulative hydrocortisone dose and comorbidities.
hormones did not differ significantly between the genotypes and methods.
Methods
Conclusions
Review of clinical records of patients currently followed at our department,
LC-MS/MS is superior to immunoassays in monitoring patients with 21-OHD on
diagnosed from 1975 until 2015. Statistical analysis using SPSS v. 23.0.
corticosteroid replacement therapy as they are more specific and can be
Results
multiplexed. Immunoassays seems to overestimate high levels of 17OHP and
A total of 27 records were evaluated, 17 were women, 10 men. Mean age at
androstenedione considerably.
diagnosis was 32G9.7 years, mean follow-up 19.7G13.8 years. Disease duration
DOI: 10.1530/endoabs.49.EP59
was 20 or more years in 55.6%. Mean current age 51G13 years. The most
frequently associated immune system disorder was autoimmune thyroiditis
(42.3%). Regarding glucocorticoid replacement,
92.6% were treated with
hydrocortisone (HC), 2 patients with prednisolone. Mean daily dose of HC
31.2G10.0 mg
(range
5.0-47.5 mg). Mineralocorticoid replacement with
fludrocortisone, mostly 0.1 mg/d. Osteoporosis/osteopenia was found in 33.3%
EP60
(nZ9), hypertension (HT) in 25.9% (nZ7), diabetes in 14.8% (nZ4), treatment
for depression or anxiety in 40.7% (nZ11) and dyslipidemia in 51.9% (nZ14).
Treatment of patients with primary and secondary adrenal insufficiency
Mean cumulative HC dose was higher in patients with osteoporosis/osteopenia
with hydrocortisone modified-release (Plenadrenw)
and in those with HT, dyslipidemia and diabetes, although not reaching statistical
Tania Pilli, Raffaella Forleo, Sandro Cardinale, Valeria Cenci &
significance. Tendency remained when adjusted for age.
Furio Pacini
Discussion and conclusion
Section of Endocrinology, Department of Clinical&Surgical Sciences and
Our sample shows a long follow-up time, associated with lifelong need of
Neurosciences, University of Siena, Siena, Italy.
Endocrinology assessment. A significant number of patients developed
comorbidities possibly related to long-term glucocorticoid therapy (osteoporosis,
Introduction
HT, dyslipidemia and diabetes). All of these were related to higher cumulative
Adrenal insufficiency is a life-threatening disease. Conventional treatment
HC dose. Absence of statistical significance was likely due to sample size. To
requires multiple daily doses of immediate-release hydrocortisone or cortisone
reduce the risk of complications, replacement therapy in autoimmune Addison
acetate causing non-physiological peaks and nadir of cortisol and it has been also
disease should be individually adjusted and overtreatment avoided.
associated with premature mortality, high frequency of infections, reduced quality
DOI: 10.1530/endoabs.49.EP61
of life, altered metabolic profile and reduced bone mineral density. A modified-
release hydrocortisone
(Plenadrenw, Shire) by combining a rapid with an
extended-release of the hormone can mimic the normal circadian rhythm of
cortisol and may be administered as a single daily dose. Plenadren has been also
associated with a reduction of body weight and blood pressure and improvement
of the glyco-metabolic parameters.
Purpose
EP62
The study objectives are: (1) to compare the area underr the curve (AUC) of
Effect of GH treatment on coagulation and fibrinolysis parameters in
cortisol under conventional therapy and Plenadren and (2) to evaluate clinical
prepubertal children with growth hormone deficiency
(body weight, body composition, blood pressure), glyco-metabolic (HbA1c)) and
Feneli Karachaliou1, Maria Kafetzi2, Maria Drakopoulou3,
bone (T score, BMD, serum bone alkaline phosphatase (BAP) and cross laps)
Elpis Vlachopapadopoulou4, Sofia Leka-Emiris4, Aspasia Fotinou2 &
parameters at 3, 6 and 12 months of treatment with Plenadren.
Stefanos Michalakos4
Materals and Methods
1Pediatric Endocrinology Unit, 3rd Department of Pediatrics, University
Thirteen patients
(7
M/6 F; age 53G17 (mG S.D.)) with primary adrenal
General Hospital Attikon, Athens, Greece;2Biochemistry-Hormonology
insufficiency in seven subjects and secondary in six cases were prospectively
Department, P & A Kyriakou Children’s Hospital, Athens, Greece;
enrolled in the study.
3Endocrine Unit, Choremis Research Laboratory, A Pediatric Department,
Results
Athens University Medical School, Aghia Sophia Children’s Hospital,
Daily cortisol profiles were more physiological on Plenadren and body exposure
Athens, Greece;4Endocrinology Department, ‘P. & A. Kyriakou’ Children’s
to cortisol, calculated as area under the curve, was not statistically significant
Hospital, Athens, Greece.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
EP64
Increased fibrinogen levels have been reported in prepubertal children and
Cushing’s Syndrome During Pregnancy mimicking preeclampsia -
adolescents with growth hormone deficiency (GHD), which were reduced after
case report
rhGH treatment. rhGH treatment has also been shown to exert a beneficial effect
Danijela Radojkovic1,2, Milan Radojkovic1,3, Milica Pesic1,2,
on the amount of aPAI-1 in children with GHD.
Slobodan Antic1,2, Sonja Kostic2, Sanja Curkovic2, Vojislav Ciric2 &
Aim
Ivan Ilic1,4
Of the study was to evaluate whether prepubertal GH deficient (GHD) children
1Medical Faculty, University of Nis, Nis, Serbia;2Clinic of Endocrinology,
showed any impairment in coagulation- and fibrinolysis-related parameters and
Diabetes and Metabolic Disorders, Clinical Center Nis, Nis, Serbia;
the effect of GH therapy on these parameters.
3Surgery Clinic, Clinical Center Nis, Nis, Serbia;4Pathology Institute,
Patients and methods
Clinical Center Nis, Nis, Serbia.
Fifteen prepubertal children (10 girls and five boys) of a mean (S.D.) age of 9.8
(0.4) years with GH deficiency were included in this hospital based prospective
study. Serum levels of PT, APTT, fibrinogen, VII, VIII, AT, PC, D-dimers, Plg,
Introduction
and PAI-1 were measured before and after 6-12 months of GH treatment.
Physiological changes of pregnancy could be similar with classical presentation
Results
and biological confirmation of Cushing’s Syndrome (CS). To diagnose CS in
At baseline all studied parameters were within normal ranges. A significant
pregnancy is very difficult especially in previously healthy women. Since the
increase in PT values was noted after a mean (S.D.) interval of 9.3 (0.4) months of
hypercortisolemia in the pregnancy increase maternal and foetal morbidity it is a
treatment: 12.46 (0.2) s vs 12.1(0.15) s, PZ0.045. A significant decrease in PAI-1
concern for endocrinologists, gynaecologists, and paediatricians.
levels (3.04 (0.1) U/ml vs 2.28 (0.3) U/ml, PZ0.018) was noted at the same time.
Patient case report
No significant changes in the rest of parameters were found during the study
Herein, we present young woman (23 years old) admitted to the Genecology
period.
Clinic, with uncontrolled hypertension and gestational diabetes. The pregnancy
Conclusion
was terminated with an emergency caesarean section at 28 weeks of gestation due
GH replacement therapy for 6-12 months led to a significant increase in PT
to sever preeclampsia. Five months after delivery hypertension, weight gain, poor
values, while fibrinogen levels did not change. Moreover, GH treatment reduced
glycaemic control, irregular menstrual cycles and cushingoid features persisted.
PAI-1 levels in GHD children, suggesting a beneficial effect of GH treatment on
She was admitted to the Endocrinology Clinic for further evaluation. Computed
possible risk of future atherothrombosis. Further evaluation of the clinical
tomography revealed right adrenal adenoma, size
32!41 mm. Endocrine
significance of these changes is needed.
evaluation verified increased cortisol and decreased ACTH. There was no plasma
cortisol suppression after low- and high-dose dexamethasone suppression tests.
DOI: 10.1530/endoabs.49.EP62
Vanillylmandelic acid in 24 h diuresis, plasma catecholamine and chromogranin
serum level, were normal. Potassium was decreased, but other electrolytes
(sodium, calcium, phosphorus, magnesium) were in normal range. After
adequately preoperative preparation, right adrenalectomy was performed. The
procedure and postoperative course were uneventful. The histopathological
examination confirmed a benign adrenocortical adenoma.
Conclusion
Even though CS in pregnancy is very rare, it is worthy to be considered when
pregnant women develop hypertension and gestational diabetes. Delayed
diagnosis and treatment could lead to maternal-foetal complications.
EP63
DOI: 10.1530/endoabs.49.EP64
Treatment with modified-release hydrocortisone for 6 months: A
clinical audit in 15 patients with adrenal insufficiency
Charlotte Steffensen1, Marianne Andersen2, Ulla Feldt-Rasmussen3,
Caroline Kistorp4 & Jens Otto L Jørgensen1
1Department of Endocrinology and Internal Medicine, Aarhus University
Hospital, Aarhus, Denmark;2Department of Endocrinology and Internal
Medicine, Odense, Denmark;3Department of Endocrinology and
Metabolism, Rigshospitalet, Copenhagen, Denmark;4Deparment of
Endocrinology and Internal Medicine, Herlev, Denmark.
EP65
Potentially aggressive adrenal oncocytoma during pregnancy: about
Background
one case
Patients with adrenal insufficiency (AI) exhibit increased morbidity, mortality and
Mouna Mezoued1,2, Maissa Smaili1 & Djamila Meskine1,2
impaired quality of life (QoL) and conventional hydrocortisone replacement does
1Laboratoire Endocrinologie et Metabolisme, Algiers, Algeria;2EPH
not mimic the endogenous circadian pattern and may compromise adherence. A
Bologhine, Algiers, Algeria.
modified - release hydrocortisone formulation (Plenadren) for once-daily use is
licensed in order to meet these needs.
Objective
Oncocytary cells adrenal adenoma or adrenal oncocytoma is an extremely rare
To audit the effects of treatment change from HC to Plenadren in an out-patient,
tumor, mainly composed by oncocytomes. The diagnosis is exclusively confirmed
daily-life clinical setting.
on histological findings. There are about 50 cases published in the scientific
Patients and methods
reviews, of which only one case described a pregnant woman.
Fifteen consecutive patients with AI and problems with adherence and/or QoL
We report an observation about a 31 years old patient, with no personal
were shifted from HC to Plenadren treatment. The effect of treatment was
antecedent, explored in our unit for an adrenal masse, measuring 71!58!46 mm
assessed by clinical biochemistry, DEXA scanning and QoL (AddiQol) before
discovered during an abdominal CT scan done for low back pain.
and after 6 months.
Patient did not present obvious signs of adrenal hypersecrtion at clinical exam, we
Results
noticed some sympathic signs associated to an amenorrhea, and a pregnancy of 8
Fifteen patients (10F/5M) were included in the audit of whom 8 had primary AI
weeks of amenorrhea was then diagnosed. At CT scan the adrenal masse did not
with a mean age of 49.5 years. The mean daily HC dose was 21.4 mg and the
match with the characteristics of an adenomatous one, having a spontaneous
mean daily plenadren dose was 20 mg. No significant changes were recorded in
density of 40 HU, and an absolute washout up to 33%.
fasting lipid levels, morning salivary cortisol, serum electrolytes, HbA1c, or CRP
Methoxylated drift and hormonal exploration were normal.
before and after plenadren treatment. Likewise, body composition and BMD were
Regarding to the size of this mass and its radiological characteristics with a strong
unchanged. The AddiQol questionnaire showed a trend towards improved sleep,
suspicion of malignancy, Surgical management was decides, and patient was
less muscle pain and better concentration at 6 months. Fourteen of the 15 patients
treated at 12 weeks of amenorrhea with simple post-operative issues. Histological
continued on Plenadren after 6 months.
findings concluded to an adrenal adenoma with oncocytary cells presenting
Conclusion
malignant potential (according to BISCEGLIA criteria).
Plenadren treatment for 6 months in patients with AI was well received but did not
Pregnancy was leaded to its term, with birth of a healthy new-born. The patient
translate into detectable changes in clinical biochemistry or body composition.
was followed for more than one year without recurrence.
Longer treatment duration and a larger patient group are needed to evaluate the
Treatment of adrenal oncocytoma should always be surgical, with an exert as
long term benefit of plenadren.
large as possible.
DOI: 10.1530/endoabs.49.EP63
DOI: 10.1530/endoabs.49.EP65
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP66
sample of patients the over-substitution of these patients should be reconsidered
regarding the consequences.
Primary hyperparathyroidism associated with Cushing syndrome and
primary hyperaldosteronism
DOI: 10.1530/endoabs.49.EP67
Fatma Mnif, Hamza Elfekih, Mouna Elleuch, Faten Hadjkacem,
Dorra Ghorbel, Nabila Rekik, Mouna Ammar, Mouna Mnif &
Mohamed Abid
Hedi-Chaker University Hospital, Sfax, Sfax, Tunisia.
Introduction
EP68
The simultaneous occurrence in the same patient of more than one
endocrinological condition is rare and was described in the multiple endocrine
The role of dehydroepiandrosterone sulphate (DHEAS) in the
neoplasia (MEN). Here, we report a patient with an unusual combination of
evaluation of autonomous cortisol secretion in adrenal incidentalomas
primary-hyperparathyroidism, papillary thyroid microcarcinoma, primary-hyper-
Fotini Adamidou, Thomas Georgiou, Gesthimani Mintziori, Efrosini Tsirou,
aldosteronism and ACTH-independent Cushing’s syndrome.
Panagiotis Anagnostis, Athanasios Panagiotou & Marina Kita
Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece.
Case description
A 54-year-old women with a primary-hyperparathyroidism was admitted to our
hospital to undergo a parathyroidectomy for a single adenoma and total
Introduction
thyroidectomy for suspicious nodules in which one of it was confirmed
Subclinical hypercortisolism (SH) has been reported in 5-20% of patients with
histopathologically to be a
3 mm papillary thyroid microcarcinoma. An
adrenal incidentalomas (AIs), with various cardiometabolic consequences. We
exploration of a resistant hypertension associated with hypokalaemia was done
intended to investigate the contribution of DHEAS to standard testing, as another
and the co-secretion excess of aldosterone (aldosterone-renin ratio O23 ng/ng
indicator of autonomous cortisol secretion in AIs.
twice) and cortisol (negative overnight and low-dose Dexamethasone suppression
Materials and methods
with low ACTH level) was confirmed with an abdominal CT-scan showing a
Ninety consecutive patients (nZ90) with AIs were included in a prospective
19 mm left adrenal adenoma. The patient has also multiple lipomas.
cohort study. SH was diagnosed if R2 criteria were fulfilled: an overnight
Conclusion
dexamethasone suppression test (DST) R1.8 mg/dl, a 24 h urinary free cortisol
The multiple endocrine hypersecretion exists and the MEN1 should be considered
(UFC) above the upper limit of normal, midnight/morning serum cortisol R0.5
since there is a considerable number of atypical MEN1 syndrome thus the DNA
and plasma ACTH !10 pg/ml. Age- and sex-specific DHEAS ratios were
testing is scheduled.
calculated and a ratio of 1.25 was considered the cut off. Data are expressed as
DOI: 10.1530/endoabs.49.EP66
median (interquartile range).
Results
Ten cases of SH were found among the 90 patients (11%), harboring 112 AIs.
DHEAS ratio in patients with SH was 1.55 (2.5) and 1.85 (2.67) in non-functional
AIs. A DHEAS ratio %1.25 was not predictive of SH.
Conclusion
DHEAS failed to prove a useful screening tool for SH in patients with AIs in this
study. Further study is needed to evaluate its potential as an adjunct to DST.
DOI: 10.1530/endoabs.49.EP68
EP67
Comparison of biochemical and hormonal parameters in patients with
primary adrenal insufficiency of autoimmune and no-autoimmune
cause
Anna Angelousi, Aggeliki Karapanagioti, Giorgos Nikolopoulos,
Panagiotis Moschouris, Marina Tsoli, Vasiliki Mavroeidi,
EP69
Michalis Kokkinos, Nikolaos Assonitis, Fotini Petychaki, Gregory Kaltsas
& Eva Kassi
Adrenocortical carcinoma in pregnancy
Kapodistrian University of Athens, Athens, Greece.
Goknur Yorulmaz1, Nur Kebapci1, Funda Canaz2, Betul Aydin Buyruk1,
Sevil Alaguney1, Bartu Badak3 & Mahmut Kebapci4
1Division of Endocrinology, Eskisehir Osmangazi University School of
Introduction
Medicine, Eskisehir, Turkey;2Department of Pathology, Eskisehir
Primary adrenal insufficiency (PAI) can be of autoimmune origin (AI), non-
Osmangazi University School of Medicine, Eskisehir, Turkey;3Department
autoimmune origin (bilateral adrenalectomy, acute hemorrhage, infection) (NAI)
of General Surgery, Eskisehir Osmangazi University School of Medicine,
or pharmaceutical (mitotane) origin. Studies have shown that these patients
Eskisehir, Turkey;4Department of Radiology, Eskisehir Osmangazi
develop long-term morbidities and increased mortality due to excessive
University School of Medicine, Eskisehir, Turkey.
glucocorticoid tissue exposure. Data about differences concerning hydrocortisone
(HC) needs, cortisol hormonal levels and metabolic parameters in these patients
are scarce.
Introduction
Methods
Adrenocortical carcinoma (ACC) is a very rare tumor. The mean age at onset is
This retrospective analysis included patients with PAI with follow-up more than
between 40 and 50 years. Patients with nonfunctioning ACC report symptoms of
5 years (mean follow-up: 9G6.9 years). Patients had two different day curves of
abdominal discomfort or back pain due to the large tumor size. Surgery for ACC
cortisol (F) measurements and 24 h urinary cortisol levels (UFC) and were on oral
should be performed by an expert surgeon.
HC replacement treatment (total mg/day).
Case
Results
A 29-year-old patient with 25 weeks of pregnancy admitted at our clinic with
We included 12 patients with Addison disease (AD), 8 patients under therapeutic
right side pain. 10!11 cm solid mass on right adrenal gland was detected by
mitotane levels (O13 mg/l) and six patients with PAI of other causes (NAI). BMI
ultrasonography. The lactate dehydrogenase level of the patient was 10 times
increases in all groups in the follow up and it is positively correlated with daily
higher than normal ranges. The urinary metabolits were within normal limits.
HC substitution (PZ0.017, rZ0.5). Mitotane group had statistical significant
Because of the increase in the size of the mass, the patient underwent operation
higher BMI at diagnosis compared to the two other groups (PZ0.015). This
urgently. The histopathological report indicates an adrenocortical carcinoma and
difference among groups in the BMI disappears in the follow-up thus probably
tumor weighting 376 g and measuring 10!9!7 cm. The patient gave birth on
due to ‘Cushing effect’. NAI group had higher HC substitution compared to AD
the 32nd gestational week. The patient was evaluated after delivery and liver,
group (PZ0.01) and higher Hb1Ac and cholesterol levels during follow up
pulmonary and brain metastases were detected. One week after delivery patient
compared to AD group (PZ0.02) and mitotane group (PZ0.05). As expected HC
was died in intensive care unit.
substitution as well as UFC levels were significant higher in the mitotane group
Conclusion
compared to the two other groups (PZ0.0014, PZ0.05 respectively). Median F
Several clinical data shown that the secretion and or proliferation of
levels were positively correlated with HC substitution (PZ0.027) (mitotane
adrenocortical tumors may have be affected by the hormonal context of
group was excluded).
pregnancy. Most of patients present with excess steroid hormone or abdominal
Conclusion
mass effects. In our patient, a mass was detected in the ultrasonography performed
Patients with NAI had statistically higher HC substitution as well as Hb1Ac and
with the cause of side pain. In pregnancy treatment procedure was not still
cholesterol levels in the follow up compared to AD group. Despite the small
standardized in ACC, but ACC was an aggressive malignant tumor, so our patient
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
was operated urgently. Because of her pregnancy chemotheraphy was planned
ACC size was 9 cm (P!0.05). In the ACC group, NLRO5 was found in 26.3%
after birth. But one week after delivery patient was died.
(5/19) patients which was higher compared to 9% (2/22) of the patients with
DOI: 10.1530/endoabs.49.EP69
NLRO5 in the adenoma group. PLRO190 was found in 36.8% (7/19) of ACC
patients compared to 18.2% (4/22) in the adenoma group. Mean NLRs in the ACC
and in the adenoma group were 3.6 and 3.1, respectively (PZ0.886) and mean
PLRs were 219.1 and 143.3, respectively (PZ0.026). Our results indicate that in
addition to tumor size, PLR might potentially serve as biomarker of malignant
tumor behavior.
DOI: 10.1530/endoabs.49.EP71
EP70
Abnormal aldosterone/renin ratio is common in patients of African
compared to European origin, is associated with hypokalaemia, and left
ventricular hypertrophy, but is rarely associated with abnormal
adrenal imaging characteristics
KS Ahmed, D Bogdanet, S Heshe, G Boran, LA Behan, M Sherlock &
J Gibney
EP72
Departments of Endocrinology, Cardiology and Chemical Pathology,
Adrenal involvement of Non-Hodgkin’s lymphoma: a case report
The Adelaide and Meath Hospital, Incorporating the National Children’s
Ozen Oz Gul, Soner Cander, Erdinc Erturk & Canan Ersoy
Hospital, Tallaght, Dublin 24, Dublin, Ireland.
Uludag University Medical School, Department of Endocrinology and
Metabolism, Bursa, Turkey.
Adrenal mineralocorticoid biochemistry differs between people of African and
European ancestry. The aldosterone/renin ratio (ARR) is the initial screening test
Introduction
for primary hyperaldosteronism (PHA), but little data exists regarding ethnic
The involvement of certain organs such as the adrenal gland is rare in non-
variations in this.
Hodgkin’s lymphoma (NHL). Although lymphomas can involve virtually all
Following clinical observation of a high prevalence of abnormal ARR in patients
extranodal organs, different organs show different frequency of involvement.
of African origin, we retrospectively reviewed all ARR measurements in a single
Adrenal gland involvement is usually bilateral. We report that a rare case of
centre over 10 years. Rates of hypokalaemia and intraventricular septal thickness
unilateral adrenal involvement of diffuse large B-cell lymphoma presenting with
(IVS, by echocardiography) were studied as end-points of PHA, and adrenal
abdominal pain.
imaging was reviewed. Data were analysed using Student’s t-test, c-square test
Case
and Mann-Whitney-Wilcoxon test as appropriate.
A 64-year-old-man presented with abdominal pain, weakness, weight loss.
ARR was available in 1,473 patients, and abnormal in 374 (25.4%). Abnormal
Abdominal computed tomography (CT) revealed 59!53 mm right adrenal mass,
ARR occurred in 305/1473 (20.7%) of European and 69/124 (55.6%) of African
40!25 mm paraaortic lymphadenopathy, multiple solid mass lesions in the
patients
(P!0.001). Among those with abnormal ARR, hypokalaemia
spleen and malignant infiltrating mass lesions in the perineal vascular structures.
(!3.5 mmol/l) was documented on at least one occasion in 171/305 (56.1%)
Surgical lymph node biopsy demonstrated a diffuse large B cell lymphoma. The
European and
43/69
(62.3%) African patients. Median
(range) IVS was
pathology specimens showed neoplastic infiltration of pleomorphic lymphoid
1.57(0.78-2.80) cm in African-origin and
1.2
(0.69-2.18) cm in European
cells with scanty cytoplasm, irregular nuclear contour, large nuclei, with one to
patients (P!0.002). Adrenal adenoma was identified in 2/69 (2.8%) African and
three peripherally positioned nucleoli. He was treated with rituximab, cyclopho-
41/305 (13.4%) of European patients (P!0.005).
sphamide, doxorubicin and vincristine (R-CHOP). The patient tolerated treatment
In summary, ARR was abnormal in 55.6% of African-origin patients screened at
well without significant side effects. After the six courses chemotherapy, the
an Irish hospital, but only 2.8% had demonstrable adrenal pathology. Rates of
patient’s systemic symptoms were improved.
hypokalaemia were similar between European-origin and African-origin patients,
Conclusion
while cardiac hypertrophy was more marked in African-origin patients. These
Extranodal organ involvement is more common in non-Hodgkin’s lymphoma
findings have implications for the use of current screening guidelines for ARR in
than in Hodgkin’s lymphoma. Systemic chemotherapy has been regarded as the
African-origin patients and also for the mechanistic role of aldosterone in
best therapeutic approach for NHL involving rare extranodal sites. Adrenal
hypertensive complications in African-origin patients.
involvement of systemic lymphoma should be considered when evaluated the
DOI: 10.1530/endoabs.49.EP70
adrenal masses.
DOI: 10.1530/endoabs.49.EP72
EP71
Neutrophil-lymphocyte and platelet-lymphocyte ratios as biomarkers in
distinguishing adrenocortical adenomas and carcinomas
EP73
Mirsala Solak1, Ivana Kraljevic1, Marko Kastelan1, Luka Kakarigi1,
Challenges in differential diagnosis of adrenal incidentaloma or clinical
Tina Dusek1, Tanja Skoric Polovina1, Annemarie Balasko1,
case of multiple myeloma
Nikola Knezevic2 & Darko Kastelan1
Natalia Volkova1, Maria Porksheyan1, Ilya Davidenko1, Kit Oleg2 &
1Department of Endocrinology, University Hospital Center Zagreb, Zagreb,
Dimitriadi Serguey2
Croatia;2Department of Urology, University Hospital Center Zagreb,
1Rostov Sate Medical University, Rostov On Don, Russia;2Rostov Research
Zagreb, Croatia.
Institute of Oncology, Rostov On Don, Russia.
The role of systemic inflammation in promoting tumor progression has been a
Adrenal incidentaloma (AI) in patients with cancer poses diagnostic challenge for
topic of increasing interest. Neutrophil-lymphocyte ratio (NLR) O5 and platelet-
doctors. We present clinical case of generalised metastatic bone diseases and
lymphocyte ratio (PLR) O190 used as indicators of inflammation have been
adrenal mass.
reported to have prognostic value in numerous solid tumors. The aim of this
Male 59 years old asked the second opinion about incidental adrenal mass, which
retrospective study was to investigate NLR and PLR as biomarkers in
was suspected for adrenal cancer by urologist. His medical anamnesis began in
distinguishing between adrenocortical adenomas and adrenocortical carcinomas
April of 2015 with severe generalised bone pain. The whole body MRI/CT
(ACC). Nineteen patients with ACC (mean age 54 years, range 24-75; eight male,
detected multiple bone lesions, adrenal mass (57!45!56 mm, 37 HU) and
11 female) and 22 patients with adrenal adenomas (mean age 47 years, range 28-
prostate mass. Urologist studied PSA and carried out prostate biopsy, the results
71; six male, 16 female) were enrolled in the study. In the ACC group, only one
excluded prostate cancer. Basing on size and CT dencity of adrenal mass, the
patient presented with functional tumor (excess estradiol), whereas all the others
urologist suspected adrenal cancer and prepared to perform adrenal biopsy. First,
were discovered incidentally. Eleven out of 19 patients with ACC were operated
he decided to get an endocrinologist consultation to exclude pheochromocytoma
laparoscopically, while the open approach was used in eight of them. In the
and ask the second opinion about suspected adrenal cancer. There were excluded
adenoma group, the first presentation of the disease was hyperandrogenemia in
pheochromocytoma, subclinical Cushing and adrenal insuficiency. Taking into
one patient, and in the rest of the group, adenoma was discovered incidentally.
accout the fact that adrenal cancer metastasis affect liver and lung first, which
Open surgical approach was used in one patient with adenoma and the others were
were abcent in this case, lack of rapid growth of adrenal mass, the suspected
operated laparoscopically. The mean size of adenoma was 5.8 cm while the mean
diagnosis of adrenal cancer was hardly probable. The suggestion for adrenal
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
biopsy was refused because of hematologic disturbances and potential
study was to analyze differences in adipose tissue distribution in women with
hemorrhage. Also there was made an offer to perform the bone lesion biopsy,
Cushing’s disease and Cushing’s syndrome due to adrenal adenoma.
which is easier and safer to perform. The results were consistent with multiple
Method
myeloma. Patient was seen by hematologist, the appropriate treatment assigned.
We evaluated 12 women with Cushing’s syndrome, six with ACTH secreting
The interesting fact was that the hematologic, bony and urinary signs, which are
pituitary adenomas (Group A) and six with adrenal adenomas (Group B). In all
typical for myeloma, were abcent. Unfortunately, patient died after second cource
subjects BMI was calculated and body composition assessed by dual energy
of chemotherapy.
X-ray absorptiometry. Basal values of serum cortisol, ACTH and DHEA-S were
This case illustrates as diagnostic as administrative issues. First, the urologist did
determined at admission to the hospital.
not follow the diagnostic protocol for adrenal incidentalomas, which would have
Results
been fatal. Secondly, the management of AI in cancer or suspeceted cancer
Mean age was comparable between Group A and Group B (44.5C/K14.7 years
patients should be absolutely multidisciplinary. Thirdly, untypical signs of the
vs. 52.7C/K5.6 years, PZ0.23) while BMI was significantly higher in Group B
disease requires doctors to be more educated in edjacent specialities.
(32.7C/K5.5 kg/m2 vs. 25.6C/K4.3 kg/m2, PZ0.034). Group B had signi-
DOI: 10.1530/endoabs.49.EP73
ficantly higher percent of total body fat (45.4C/K4.3% vs. 34.5C/K8.4%,
PZ0.021) but borderline difference in trunk fat percentage (Group B 44.3C/K
6.8% vs. Group A 32.6C/K10.7%, PZ0.055). Main difference in adipose tissue
percentage was found on arms and legs, which was higher in Group B (arms
53.6C/K8.8% vs. 38.5C/K11.9%, PZ0.037; legs 47.6C/K4.4% vs. 39.0C/K
5.9%, PZ0.022). There was no significant difference in lean body mass or bone
mineral density between these two groups. As expected, ACTH was significantly
higher in group A (74.3C/K16.4 ng/l vs. 14.7C/K7.6 ng/l, PZ0.040), but with
EP74
no significant differences in morning cortisol concentrations (Group A 664.2C/K
Iatrogenic Cushing syndrome and suprarenal secondary insufficiency
210.4 nmol/l vs. Group B 432.8C/K146 nmol/l, PZ0.060), midnight cortisol
due to interaction between fluticasone and ritonavir
concentrations
(Group A 461.3C/K236.2 nmol/l vs. Group B
330.3C/K
Suarez Gutierrez Lorena1, Veiguela Blanco Brenda2, Dieguez
203.6 nmol/l, PZ0.410) or DHEA-S concentrations (4.9C/K5.4 nmol/l vs.
Felechosa Lorena2, Manjon Miguelez Laura1, Riestra Gonzalez Maria2,
2.8C/K3.8 nmol/l, PZ0.564) between groups.
Antun˜a García Nuria2, Diaz Fernandez Maria Jesus2 &
Conclusion
Casal Alvarez Florentino2
Our group of women with Cushing’s syndrome due to adrenal adenoma had
1Hospital Universitario Central De Asturias, Oviedo, Spain;2Hospital De
higher BMI and increased total fat adiposity. It was not determined yet if the
Cabuen˜es, Gijon, Spain.
origin of hypercortisolism, or derangements in other related hormones or
metabolic pathways, could possibly influence body composition in those patients.
Introduction
DOI: 10.1530/endoabs.49.EP75
The interaction between corticosteroids and protease inhibitors (PIs) is a clearly
described drug interaction.
Case report
A 44-year-old woman diagnosed with HIV category B3 diagnosed in 1989; severe
lipodystrophy. In addition , HCV genotype IA. Bronchial asthma since 2000.
Treatment with fluticasone
1 inh/24 h, salbutamol on demand, darunavir
800 mg/day and ritonavir 100 mg/day. He had known lipodystrophy since 2001
and the abdominal perimeter was monitored, aiming to increase it. Likewise, it
EP76
presented progressive proximal weakness in lower limbs, with increased hair, hair
Clinical course of patients with adrenal incidentaloma: retrospective
fragility and alopecia reason why it is referred to Endocrinology. Moderate
analysis of a single center
hirsutism, muscular atrophy and in the analytical study: normal FSH and LH are
Ana Carolina Ruiz Serrano1, Ana Megia Colet1,2, Silvia Näf Cortes1,2,
objectified. Testosterone
0.05 ng/ml
(0.1-0.9), ACTH
1.0 pg/ml
(7.2-63.3),
Joan Vendrell Ortega1,2, Inmaculada Simon Muela1,2, Esther Solano Fraile1
Cortisol am 0.65 mg/dl (4.30-22.40) urinary free cortisol 3.74 mg/24 h (36-137).
& Theodora Michalopoulou Alevras1
A Synacten test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1
1Endocrinology and Nutrition Service University Hospital of Tarragona
and was diagnosed as having an independent iatrogenic Cushing ACTH syndrome
Joan XXIII, Tarragona, Spain;2CIBERDEM, Tarragona, Spain.
associated with secondary adrenal insufficiency. With this diagnosis he is referred
to the pulmonology department for corticosteroid replacement. Inhaled and
substitution treatment was initiated with hydrocortisone and went home with a
In the adrenal incidentaloma (AI) it is fundamental to determine functionality and
new antiretroviral regimen (raltegravir, tenofovir and abacavir)
benignity. The aim of this study was to evaluated the clinical, radiological and
Discussion
hormonal evolution of AI and compare the frequency of autonomous cortisol
Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 CYP3A4
secretion (ACS) between American and European Guidelines.
enzyme, which is inhibited or potentiated by a multitude of drugs, including
Methods
ritonavir. As it is not metabolized, an increase in circulating levels leads to a
Retrospective evaluation of patients with AI referred to our service in the last
decrease in the secretion of ACTH and therefore a suppression of the adrenal
5 years.
gland with insufficiency of the same and cushing syndrome.
Results
The options are the substitution of Fluticasone by a non-substrate of CYP3A4
140 patients were included, 50.9% were men. At diagnostic, the media of age was
such as beclomethasone and the substitution of ritonavir for another antiretroviral.
66G11.2 years and the median of size was 20 mm. CT detected the 95% of AI
Most cases resolve in about 9-12 months.
and 80% had an adenoma-like appearance (49.3% left). Hormonal evaluation
DOI: 10.1530/endoabs.49.EP74
revealed that
54.3% were nonfunctional (NF), 38.6% possible autonomous
cortisol secretion (PACS), 5.7% ACS, 5% Cushing’s syndrome (CS) and 1.4%
pheochromocytoma (PCC). Considering American guidelines: 87.9% were NF,
9.3% subclinical Cushing’s syndrome and 0.7% CS. The majority of patients
remained stable. None developed overt CS. The 13.6% showed growth, with a
median of 6 mm. Median follow-up: 30 months. There were significant statistical
differences (P!0.05) between the group of NF and PACS/CS in terms of size and
EP75
between NF and CS in terms of growth. No differences were observed in terms of
Body composition in women with Cushing’s syndrome of different
sex, age or cortisol-related comorbidities. Seven patients underwent surgery: one
etiology
PACS, three ACS, two PCC and one adrenal carcinoma. The 4.3% died due to
Dusan Ilic, Djuro Macut, Ivana Bozic Antic, Bojana Popovic,
unrelated adrenal disease.
Tamara Bogavac, Tatjana Isailovic, Valentina Elezovic, Sanja Ognjanovic
Conclusions
& Svetozar Damjanovic
The AI’s are predominantly small, benign, nonfunctioning; stable in time, tumor
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Belgrade,
size and hormonal production. The use of the diagnostic criteria for ASC
Serbia.
according to European guidelines shows an increase in the frequency of
PACS/ACS, therefore, ACTH determination should be considered in the
diagnosis.
Introduction
Cortisol has important roles in the regulation of body composition and
DOI: 10.1530/endoabs.49.EP76
hypercortisolaemia have major impact on body fat distribution. The aim of this
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP77
In everyday PHA diagnostics practice there is still lack of “game changer”
bringing the final conclusion for diagnostic and profilactic strategies for the whole
Malignant androgen-secreting adrenocortical carcinoma with adrenal
hypertensive population.
insufficiency: a case report
Fatma Mnif, Mehdi Kalthoum, Mona Elleuch, Saafi Wajdi, Nadia Charfi,
DOI: 10.1530/endoabs.49.EP78
Mouna Ammar, Hamza Feki, Mona Mnif & Mohamed Abid
Endocrinology-diabetelogy Departement CHU Hedi Cheker, Sfax Tunisia,
Tunisia.
Adrenocortical carcinoma (ACC) is a rare malignancy, accounting for 0.02% of
all annual cancer. The majority of these tumors are benign, non-functioning
EP79
adenomas that are incidentally discovered on abdominal image studies. Others are
functional adenomas secreting cortisol, aldosterone, or less commonly androgens
Clinical, laboratorial and densitometric evaluation of adult women with
or estrogens. Pure androgen-secreting adrenal tumors are very rare.
congenital adrenal hyperplasia
Case report
Leilane Vensa˜o, Victoria Borba & Adriane Rodrigues
SEMPR, Curitiba, Paraná, Brazil.
A 34-year-old female patient presented with pain in the left upper abdomen. A
multiphasique CT scan abdomen was done, which revealed large adrenal mass
measuring 18!14!14 mm in dimension with central hemorrage. Patient gave
Introduction
history of amenorrhea since 6 months associated with increased hair growth of
There is paucity of data comparing bone densitometry and body composition in
chest, lower abdomen, and face. Moreover the patient declare recent weight loss
adult women with congenital adrenal hyperplasia
(CAH) treated with
(11 kg in 2 months) with asthenia, anorexia, and melanoderma.
glucocorticoids since childhood and the same parameters in healthy women of
On examination, heart rate was 84/min, blood pressure 120/70 mm of Hg.
the same age and BMI.
Hirsutism was evaluated based on Ferriman-Gallwey score
(result Z
13).
Methods
Biochemical screening showed a total testosteroneZ8 ng/ml (0.06-0.82), DHEA
20 women with classical CAH (35% simple virilizing, 65% salt losing), aged 16-
sulfate Z3.27 mg/ml
(0.4-2.17 mg/ml),
17-hydroxyprogesterone O20 ng/ml
45 years, had anthropometric, laboratorial and densitometry exam (DXA) for
(0.1-0.8 ng/ml), LHZ0.83 mUI/l and FSHZ0.1 mUI/l. The diagnosis of
bone mineral density (BMD) (L1-L4, total femur and femoral neck). Laboratory
Addison’s disease was confirmed by basal serum ACTHZ125.82 ng/l and
determinations during follow-up were recorded and expressed as average levels.
serum cortisolZ135 mg/l after ACTH test; serum aldosterone and 24 h urinary
18 control women of the same age and BMI as patients realized densitometric
VMA were normal. A diagnosis of androgen-secreting adrenocortical cancer with
evaluation for mineral density and body composition.
adrenal insufficiency was made.
Results
Patient underwent exploratory laparotomy with excision of large adrenal tumor
BMI ranged from16 to 41 kg/m2 (average 26.3; 25% overweight and 30% obese),
without any complication. The histopathological examination described a mass
whereas height varied from136 to167 cm (average 151 cm). During follow-up,
21!18!12 mm with microscopique features of tumor cells sharing mild nuclear
35% patients were treated with prednisone as the sole glucocorticoid type, 50%
atypia and rare mitotic figures: histological and immunohistochmical aspect of
used prednisone and dexamethasone and 15% other combinations. Average daily
adrenocortical carcinoma (Weiss scoreZ3, Ki67Z10).
dose of prednisone was 7.5 mg (hydrocortisone equivalent dose 37 mg/day) and
On follow-up after 6 months, patient was comfortable, and no longer had
70% used fludrocortisone (average 0.1 mg/day). Combined oral contraceptives
amenorrhea or hursitism. Total testosterone was 0.03 ng/ml (0.06-0.82), DHEA-
were taken by 65% women. Half of women were not controlled based on average
sulfate was 0.174 mg/ml (0.4-2.17 mg/dl) and CT scan abdomen was normale.
testosterone and androstenedione levels, 40% presented altered glycemic status,
DOI: 10.1530/endoabs.49.EP77
26% elevated LDL cholesterol, 21% elevated triglycerides, 68% low HDL-
cholesterol levels. No patient presented low BMD according to Z-score and
compared to control group. Fat-free mass was considerably lower in patients than
controls (33.726 vs 40.637 kg) and it correlated positively with testosterone levels
(R 0.52, P 0.027). Women using fludrocortisone had lower body fat mass than
women who used only glucocorticoids (34.3C12.3% vs 44.9C3.8%).
Conclusion
Adult women treated for classical congenital adrenal hyperplasia had important
metabolic disturbances and alterations in body composition. Nevertheless bone
EP78
mass was preserved, possibly because hyperandrogenism was not controlled most
Hyperaldosteronism screening in Hypertensiologists experience -
of the time.
epidemiological review of over 800 cases
DOI: 10.1530/endoabs.49.EP79
Weronika Korzynska, Anna Jodkowska & Grzegorz Mazur
Department and Clinic of Internal and Occupational Diseases, Hypertension
and Clinical Oncology, Wrocław Medical University, Wroclaw, Poland.
Primary aldosteronism (PHA) is one of the most common cause of secondary
hypertension. It can possibly concern over 10% of hypertensive patients, but often
is being under-recognised. The basic tool of case PHA detection is aldosterone to
EP80
renin ratio (ARR). Appropriate cutoff value of ARR is still under discussion.
The effect of subclinical hypercortisolism on bone mineral density in
We review occurrence of CT/MRI detectable adrenal gland laesions according to
female patients with adrenal incidentalomas
assigned ARR cutoff value. Retrospective data from
833
consecutive
Sanja Ognjanovic, Djuro Macut, Milan Petakov, Valentina
hypertensive patients of average age 39.85 (S.D.:C/K15), 449 men and 384
Kovacevic Elezovic, Tatjana Isailovic, Ivana Bozic Antic, Dusan Ilic,
women was analized. ARRO20, 30, 40 concerned respectively: 12.7%, 7.6%,
Bojana Popovic, Tamara Bogavac, Jadranka Antic & Svetozar Damjanovic
4.7%. CT/MRI was performed respectively in patients with ARRO20, 30, 40 in
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Belgrade,
55.7%, 66.7%, 69.2%. Laesions in adrenal glands in groups of ARRO20, 30, 40
Serbia.
concerned respectively: 47%, 52.4%, 56%. The most common CT/MRI findings
were adenomas: respectively: 37.3%, 42.9%, 44.4% in groups of ARRO20, 30
and 40. Less common was nodular hypertrophia: respectively: 10.2%, 9.5%,
To investigate the prevalence of SH and osteoporosis in female patients with
14.8% in groups O20, 30, and 40. The average potassium level in a group of
unilateral AIs (UAIs) and bilateral AIs (BAIs).
ARRO20 was 4.05 (mmol/l) (S.D.:C/K0.46), O30 3.94 (S.D.:C/K0.50), O40
We enrolled 106 female patients, 68 (64.2%) with UAIs and 47 (35.8%) with
3.93
(S.D.:C/K0.55).
BAIs. SH was diagnosed in the presence of serum cortisol levels after 2-day low-
Average concentration of urine aldosterone in a group O20 was 14.36 (mg/24 h)
dose dexamethasone suppression test (LDDST) O50 nmol/l with at least one of
(reference value 2.1-18.0 mg/24 h) (S.D.:C/K10.88), O30 15.72 (S.D.:C/K
the following parameter (midnight serum cortisol O208 nmol/L, 24-h urinary
12.33), O40 17.71 (S.D.:C/K14.08).
free cortisol O245 nmol/24 h, or ACTH !10 ng/l). BMD was measured with
Adrenal lesions in enlarged ARR group were notably more often than adrenal
dual-energy X-ray absorptiometry at lumbar spine (LS), femoral neck (FN), and
incidentalomas occurrence reported in population (47% vs 2-3%). Higher cutoff
total skeleton.
ARR value is more specific and allows to reduce costs of confirmative tests. If the
No difference was noted in age, BMI, percent of postmenopausal women and
ARR over O40 group we miss 16.95%, in ARR O30 group we miss 6.78% in
years since menopause. The overall prevalence of SH was 20.2%, and was more
compare to ARRO20. Can we afford missing them considering its’ increased
prevalent in BAIs than UAIs patients (36.1% vs 11.8%, respectively, PZ0.003).
cardiovascular risk?
The largest tumor diameter was similar in patients with UAI and BAI (PZ0.254).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
After adjustment for BMI, waist, and presence of BAIs, SH were associated with
Introduction
adrenal mass size (odds ratio (OR)Z1.101, 95% CI 1.041-1.166, PZ0.001) and
Adrenocortical carcinomas are rare neoplasms with an incidence of 0.7 to 1.5 per
age (ORZ1.086, 95% CI 1.021-1.155, PZ0.009). LS-BMD and total-BMD were
million/year. Diagnosis often requires a multidisciplinary approach. When the
lower in BAIs than in UAIs patients (0.94G0.13 vs 0.86G0.17, PZ0.015, and
disease is confined to the adrenal gland, absolute criteria defining malignancy,
1.08G0.18 vs 1.02G0.14, PZ0.029). There were no differences in FN-BMD.
do not exist, however a score of WeissO or Za 3 is considered diagnosis. The
Patients with BAIs had an increased frequency of osteoporosis (46.41% vs 23.5%,
prognosis is usually reserved and conventional chemotherapy is not curative.
respectively, PZ0.036). The presence of osteoporosis was associated with
Material and Methods
SH (ORZ5.775, 95%CI 1.423-23.426, PZ0.014) and lower BMI (ORZ1.226,
Retrospective analysis of the clinical and demographic characteristics, review of
95%CI 1.071-1.405, PZ0.003), after adjusting for age, menopause and
the anatomopathological and therapeutic criteria of patients with adrenocortical
vitamin-D.
carcinoma treated at our Institution between 1999 and 2015.
This study suggests significantly higher prevalence of SH in patients with BAIs
Results
than in patients with UAIs. Tumor mass could be of importance for the amount of
Twenty-two patients with a mean age of 56 years were evaluated, 50% of cases
autonomous cortisol production. The prevalence of osteoporosis was higher in
were male. The majority of patients (63.6%) were symptomatic and pain was the
patients with BAIs due to SH.
most frequent symptom (57.1%). All patients underwent surgical treatment.
DOI: 10.1530/endoabs.49.EP80
Multiorgan resection was performed in 5 cases (22.6%). The surgery was R0 in
72.7%. After histological examination,
72.7% presented Weiss scoreO
2.
Adjuvant therapy was performed in 5 patients (22.6%). Considering the revision
of the Weiss score, TNM staging and margins status, 50% of the patients would
had indication for adjuvant treatments. In this series, the relapse rate (local or
distance) was 38.1% (8 cases) and the overall survival at 5 years was 62%; which
compares favorably with that described in the literature.
Conclusions
The rarity of this pathology makes diagnosis and therapeutic orientation difficult.
EP81
A rigorous and standardized histological evaluation is imperative to ensure the
most appropriate adjuvant treatment. The referral of this patients to centers of
Long term follow up of patients with adrenal incidentaloma and
expertise is essential, with the hope that new target therapies will lead to better
‘autonomous cortisol secretion’
results.
Ivana Kraljevic1, Mirsala Solak1, Tina Dusek1,2, Tanja Skoric Polovina1,
Annemarie Balasko1 & Darko Kastelan1,2
DOI: 10.1530/endoabs.49.EP82
1University Hospital Center Zagreb, Zagreb, Croatia;2ZAgreb University
School of Medicine, Zagreb, Croatia.
The aim of this study was to compare the long-term co-morbidities and
biochemical data between patients with adrenal incidentaloma and ‘autonomous
cortisol secretion’ who were treated surgically and conservatively.
Methods
The research of the database of the patients with adrenal incidentaloma diagnosed
between
2007
and
2014
was performed. Among them,
43
patients with
‘autonomous cortisol secretion’ were identified and invited for a follow-up
EP83
visit. Diagnostic criteria for
‘autonomous cortisol secretion’ were: cortisol-
A near miss on blaming the heart: a rare case of Adrenocortical
O83 nmol/l after 1 mg dexamethasone suppression test plus one additional
carcinoma with thrombus extension into right atrium and
criteria (suppressed ACTH secretion or elevated urinary free cortisol). At follow-
Cushing syndrome
up visit the anthropometric as well as biochemical data were collected (blood
Hadeil Morsi1, Mohamed Eisa3, Lynsey Goodwin2, Peter Flegg2 &
glucose, lipid panel test, HOMA index, cortisol after 1 mg dexamethasone,
Myint Aye2
urinary free cortisol, and ACTH). All patients were evaluated for hypertension,
1North West Health Education England, Manchester, UK;2Blackpool
dyslipidemia, osteoporosis and diabetes mellitus/impaired glucose tolerance.
Victoria Hospital Foundation Trust, Blackpool, UK;3Wellstar Atlanta
Results
Medical Center, Atlanta, GA, USA.
Of the 43 invited patients, 26 patients performed follow up visit (4 males). Among
them, 17 patients were treated surgically and 9 were treated conservatively.
Median follow-up was 6 years (range 2-16), median age at follow-up was 62
A 39 year old female patient presented with one week history of Shortness of
years (range 41-76). There was no difference in BMI at baseline and at follow up
breathing. Over the last four months she noted bilateral leg swelling, which failed
in both groups. In the group of surgically treated patients, during follow-up period
to improve on diuretic. Examination revealed no other evidence of fluid overload
one patient was diagnosed with arterial hypertension, 4 with hyperlipidemia, and
or heart failure. An element of right heart strain rather than failure was raised on
one with diabetes mellitus. Nevertheless, nine out of
12
patients with
cardiologists review. Subsequently, an echo showed a friable mass extending
hypertension in the surgical group reported improvement/disappearance of
form inferior vena cava to right atrium into proximal left ventricle. The nature of
arterial hypertension at the follow-up visit. Among conservatively treated
which was revealed to be a tumor thombus extending from the upper pole of right
patients, six out of nine patients had no difference in co-morbidities, one was
kidney with resultant pulmonary emboli. To this end, an impression of invasive
newly diagnosed with osteoporosis, one with arterial hypertension and one with
renal carcinoma was made. Until endocrinology review for erratic hyperglycemia,
renal insufficiency. Conclusion: Patient who underwent surgery for ‘autonomous
when the patient reported irritability, 6 weeks amenorrhea, change in weight
cortisol secretion’ experienced improvement in the regulation of hypertension
distribution and facial hirsutism in addition to abdominal striae on examination.
after medium follow-up of 6 years. No other significant differences were found in
Hence,the diagnosis shifted to Adrenocortical carcinoma with Cushing. Tertiary
the prevalence of comorbidities between conservatively versus surgically treated
center was consulted. In the meantime, Mitotane was started gradually, alongside
patients.
Hydrocortison. It was a difficult time for the patient who preferred palliative
DOI: 10.1530/endoabs.49.EP81
support at home. Unfortunately, few days after discharge she was readmitted with
hypoglycemiia, metabolic acidosis and liver impairment. She was treated as
Addison crises, though cortisol levels came normal later. Liver involvement was
not confirmed to be Mitotane related toxicity or ischemic injury with progression
of malignancy.
Unfortunately, she did not survive his well-known aggressive tumor. ACC are
tumors are rare tumors and presentation with such vascular invasion is an
additional rarity. As clinician on medical take, there is tendency to overclaim
heart failure. Having high index of suspicion for patients with Cushing syndrome
EP82
is central, although not all tumors are functional. The definitive management of
ACC is surgical which is not always feasible, particularly with such vascular
Adrenocortical carcinoma - casuistic analysis
extension. Wider scale clinical studies pave the management of ACC and
Catia Ribeiro, Joao Lobo, Ana Mesquita, Pedro C Martins,
optimize Mitotatne therapy.
Mariana Peyroteo, Maria Joao Matos, Pedro Antunes, Cristina Sanches,
Augusto Moreira & Joaquim Abreu de Sousa
DOI: 10.1530/endoabs.49.EP83
IPO, Porto, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP84
EP86
Congenital Adrenal Hyperplasia due to 11b-Hydroxilase Deficiency:
24 hour ambulatory blood pressure levels according to adrenal
clinical and molecular studies of two novel families with variable
adenoma size
phenotypes
Alp Atasoy1, Evrim Cakir2, Suleyman Ahbab1, Derya Kayas1,
Alessandra Pfeilsticker, Luciana Valadares, Selma Sousa, Sarah Cardoso,
Esra Ataoglu1 & Mustafa Yenigun1
Olivia Morais, Renata Santarem & Adriana Lofrano-Porto
1Internal Medicine Department, Haseki Training and Research Hospital,
University of Brasilia, Molecular Pharmacology Lab, Brasilia DF, Brazil.
Istanbul, Turkey;2Endocrinology and Metabolic Diseases Department,
Haseki Training and Research Hospital, Istanbul, Turkey.
11b-hydroxylase deficiency is the second most frequent cause of congenital
adrenal hyperplasia (CAH), corresponding to approximately 5% of cases., and
Aim
caused by inactivating mutations in the CYP11B1 gene. We aimed to describe
The etiology and underlying pathology of non-functional adrenal adenoma has
four new cases from two different families with a clinical diagnosis of 11b-
not been clearly defined, yet. Blood pressure levels according to adrenal adenoma
hydroxylase deficiency. Family
1: Two siblings born from consanguineous
size has not been evaluated, yet. Therefore, we evaluated 24 hour ambulatory
parents. A 31-year-old (yo) woman presented at 5 yo with genital ambiguity
blood pressure levels in patients with non functional adrenal adenoma.
(Prader II), high blood pressure (HBP) and precocious pubarche (PP). She lost
Materials & Methods
follow and returned after 3 full term normal pregnancies while using prednisone.
We studied thirty newly diagnosed adrenal adenoma patients in a tertiary health-
4 years after last gestation, she remained normotensive without any treatment.
care center. They grouped in two categories according to adenoma size. Cut-off
Her 24 yo brother presented at age 7 yo with PP, hypokalemia and HBP, when
size was taken 23 mm. 24 hour ambulatory blood pressures were evaluated in all
glucocorticoids and anti-hypertensives were started. He had low treatment
participants. Delta blood pressure was found by calculating the difference
adherence and evolved with persistent hypertension and left ventricular
between maximum and minimum blood pressure values.
hypertrophy. Family 2: A 2.9 yo boy presented with PP and high BP, managed
Results
with hydrocortisone and anti-hypertensives. His sister presented at 21 days of life
There were 17 patients with lower adenomas size, which was smaller than 23 mm,
with genital ambiguity and salt wasting, managed with hydrocortisone and oral
the remaining 13 patient’s adenomas size was equal or higher than 23 mm.
sodium. A detailed steroid profile was performed in all subjects, which confirmed
Patients with higher adenomas size had statistically higher systolic delta levels
the diagnosis. The CYP11B1 coding region of the patients’ and their parents’ was
compared to lower size group
(70.84G34.9
to
51.29G18.0, PZ0.004).
automatically sequenced. In the two siblings from Family 1, a homozygous splice
Additionally; the maximume systolic
(165.6G28.7
to
152.0G23.1) and
site point mutation, IVS4 ds-1 GOA, was identified in exon 4 (g.3132GO A). In
maximum diastolic blood pressure (115.1G37.8 to 100.2G14.9) were higher
Family 2, both siblings harbored a nonsense mutation in exon 6 (c.1066 CO T),
and also minimum systolic (94.76G11.05 to 100.70G18.60) and minimum
which generates a truncated protein (p.Q356X). The mutations presented herein
diastolic blood pressure (60.69G9.01 to 62.41G12.62) were lower in this group.
were associated with a highly variable phenotype, from a mildly virilizing
However; the differences did not reach statistically significance.
phenotype to a high degree of virilization with hypertension and with salt wasting,
Conclusion
which is unexpected. Further studies of variants in other genes associated with
Delta systolic blood pressure has been found toe higher in higher adenomas size
hypertension, in compensatory pathways of steroid synthesis and metabolism, or
group. Further studies are necessary to better clarify the association between
the verification of chimeric CYP11B genes are needed to clarify the phenotypic
blood pressure and non functional adrenal adenoma.
heterogeneity.
DOI: 10.1530/endoabs.49.EP86
DOI: 10.1530/endoabs.49.EP84
EP85
Adrenal Medulla
‘Record-breaking hyponatraemia’ with Addison’s disease
EP87
Irfan Khan & Elizabeth Cheyne
Coexisting Graves’s disease and pheochromocytoma
Southmead Hospital, Bristol, UK.
Rim Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari &
Néjib Ben Abdallah
Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.
Addisons disease is a rare but potentially life threatening endocrine disorder. It is
well-known for disguising as a variety of presentations before diagnosis. Here
we present a case report of Addison’s disease presenting with very severe
Introduction
hyponatraemia. A 35 year old lady was admitted with lethargy, low mood, weight
Although Graves’ disease is often accompanied by other autoimmune diseases,
loss and feeling generally unwell for the last 3 months. Six weeks prior to her
only a few cases of Graves’ disease accompanied by pheochromocytoma have
admission, her GP arranged some routine investigations including U&E which
been described.
were normal with a Na of 137. He later prescribed her Mirtazapine for her low
Herein we report a rare case of coexisting Graves’ disease and pheochromocytoma.
mood and anxiety which she took for 4 days. This made her feel more unwell and
Observation
triggered the hospital admission. She looked tanned but there was no buccal or
A 50-year-old male patient was referred to our department for the evaluation of right
palmar pigmentation. She was alert with normal cognition.
adrenal incidentaloma of 80*66 mm. He had a history of coronary disease and he
Admission blood results showed a plasma Sodium of 94 mmol/l, K 5.7 and
presented with heat intolerance, diaphoresis, palpitations, intense headaches,
normal urea/creatinine. Further investigations showed: Serum Osmolality 252,
excessive nervousness, mood disturbances as well as a rapid weight loss of 30 kg
Urine osmolality 192, Urine Na 27, TSH 3.2 and random cortisol 290. She was
during the last one year.
monitored on ITU and was given normal saline and IV Hydrocortisone for a
On physical examination, he had a body weight of 53 kg, a body mass index of
presumed diagnosis of Addison’s disease. Her Sodium level slowly came up to
16.5 kg/m2 and a blood pressure (BP) of 120/75 mm Hg in supine position and
114 and then to 118 over the next few days. The short synacthen test showed a flat
95/60 in standing position.
response with the following Cortisol values: 0 min 240, 30 min 242 and 60 min
However his blood profile showed paroxysmal hypertension with peaks of
260. She denied taking exogenous steroids in any form. Later her ACTH came
160/110 mm Hg. The pulse rate was 132 beats per minute (bpm). He had neither
back very high (O2000) with positive anti-adrenal antibodies confirming primary
goiter nor exophthalmos. Electrocardiogram
(ECG) showed a regular sinus
adrenal insufficiency. The Renin/Aldosterone results are still awaited. She
tachycardia at 138 bpm with signs of left ventricular hypertrophy.
transiently developed behavioral disturbance with strange affect raising the
Laboratory tests indicated diabetes mellitus with a fasting blood sugar of 2.86 g/l
suspicion of osmotic demyelination. Fortunately this resolved with reducing the
and a glycated hemoglobin of
7.9%, hyperthyroidism with a low TSH of
dose of Hydrocortisone suggesting ’steroid psychosis’ as cause of the behavioral
0.05 mIU/ml, an elevated free T4 of 1.96 ng/dl and urinary metanephrines and
symptoms. The sodium level stabilized in the low 120’s but increased further
normetanephrines were greater than
20 time normal values. TSH receptors
slowly with addition of Fludrocortisone.
antibodies were positive.
This case demonstrates the unusual presentation of Addisons disease with very
Thyroid scintigraphy showed homogeneous increased uptake involving the whole
severe hyponatraemia with surprisingly few neurological signs or symptoms. It
thyroid gland.
also highlights theproblem of antidepressants potentially exacerbating hypona-
The diagnosis of coexisting Graves’ disease and pheochromocytoma was
traemia in these patients.
established. Treatment with prazosin, benzylthiouracil and insulin was then
DOI: 10.1530/endoabs.49.EP85
initiated. Propranolol was added progressively. The patient was planned for right
adrenalectomy after achieving euthyroid state.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
Undiagnosed PHEO will put patients at unnecessary risk from having an
Pheochromocytoma and Graves’ disease are known by their similar clinical features
adrenergic crisis and even death. These cases highlight the importance of
making their differential diagnosis difficult. In our case, adrenal incidentaloma
considering routine biochemical screening for a catecholamine secreting tumour
evaluation had revealed the pheochromocytoma. Otherwise, a meticulous physical
in all patients with NF-1 to prevent the development of catastrophic events in the
examination and detailed laboratory investigations are needed in order to make a
future.
precise diagnosis.
DOI: 10.1530/endoabs.49.EP89
DOI: 10.1530/endoabs.49.EP87
EP90
EP88
Pheochromocytoma in pregnancy
Pheochromocytoma in neurofibromatosis type 1
Belgin Efe1,2, Goknur Yorulmaz1,2, Sevil Alaguney1,2, Funda Canaz1,3 &
Agustina Pia Marengo1, Paula García-Sancho1, Fernando Guerrero1,
Bartu Badak1,4
Inmaculada Peiró2, Elisa Santacruz3, Andrés Ortiz3, Juan José Diez3,
1Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey;
Pedro Iglesias3 & Carles Villabona1
2Division of Endocrinology, Eskisehir Osmangazi University School of
1Hospital Universitari Bellvitge, L’Hospitalet de Llobregat, Barcelona,
Medicine, Eskisehir, Turkey;3Pathology Department, Eskisehir Osmangazi
Spain;2Institut Català D’Oncologia, L’Hospitalet de Llobregat, Barcelona,
University School of Medicine, Eskisehir, Turkey;4Depertmant of General
Spain;3Hospital Ramón y Cajal, Madrid, Spain.
Surgery, Eskisehir Osmangazi University School of Medicine, Eskisehir,
Turkey.
Background
Individuals with neurofibromatosis type-1
(NF1) carry an increased risk of
Introductıon
pheochromocytoma (PHEO). Detection strategy is unknown but most experts
Pheochromocytoma is a tumor originating from the chromaffin cells. These
recommend screening if hypertension develops.
tumors secrete catecholamines which act on target organs and cause hypertensive
Objective
crises. They are rare during pregnancy, and a differential diagnosis must be
Report the characteristics of PHEO in patients with NF1 (NF1 group) and
carried out mainly with pregnancy-induced hypertension.
compare them with non-NF1-associated PHEO (non-NF1 group).
Case
Methods
A 27-year-old patient in week 17 of pregnancy admitted to our clinic with
Retrospective cohort study of patients undergoing PHEO resection in two Spanish
hypertension and 45!55 mm heterogeneous nodular lesion in left surrenal. The
tertiary hospitals, from 1980-2016.
hospitalized patient had tachycardia and hypertensive episodes despite the
Results
treatment. Urinary catecholamine and metanephrine collections revealed elevated
Of 78 patients undergoing PHEO resection, 5 (6.4%) had NF1. NF1 patients were
norepinephrine and normetanephrine. Magnetic resonance imaging identified a
younger than those with non-NF1 (mean age 41.8 vs 52.5 yr, PZ0.068). Males
adrenal adenoma. After subsequent pharmacological treatment with alpha and
comprised 60% versus 40% of the NF-1 group and non-NF1 group, respectively.
beta blockers, a left adrenalectomy was performed laparoscopically. The
PHEO was incidentally diagnosed in 3 of 5 (60%) from NF1 group and only in 29
histopathological report indicates pheochromocytoma (Pheochromocytoma of
of 73 (39.7%) from non-NF1 group (PZ0.395). Remaining NF1 cases were
the Adrenal gland Scaled Score: 6) and tumor weighing 70 g and measuring 6.5!
diagnosed by screening (hypertension, nZ1) and compatible adrenergic clinic
5.5!3.5 cm. After the surgery urinary catecholamine and metanephrine
(nZ1). Hypertension was present in 2 (40%) NF1 patients and in 33 (45%) non-
collections was normal. Postoperatively the patient with 24 weeks gestation
NF1 patients. Urinary and/or plasma catecholamines were elevated in all NF1
had no antihypertensive need.
patients and in 55 (88%) of non-NF-1 group. There was no significantly difference
Conclusion
(PZ0.207) in tumor size between both groups of patients (median 4.6 cm vs
Pheochromocytoma in pregnancy can cause the death of both the fetus and the
5.6 cm in NF1 and non-NF1 patients, respectively).
mother. This issue should be remembered in hypertensive pregnancies. The
Conclusion
approach to the biochemical diagnosis is the same as for the nonpregnant patient.
In our series, age at diagnosis and gender were similar in NF1 and non-NF1
MRI (without gadolinium enhancement) is the preferred imaging modality, and
PHEO patients. NF1-associated PHEO is diagnosed incidentally in more than half
123I-MIBG is contraindicated. Adrenal pheochromocytomas should be removed
of the patients. Although all NF1-PHEO tumors were functioning, only two of five
promptly if diagnosed during the first or second trimester of pregnancy. In our
patients had hypertension. It is necessary to keep in mind the possibility of
case, its recognized with new onset hypertention and adrenal tumor was removed
developing PHEO in NF1 patients even in those non-hypertensive patients. On the
in the 2nd trimester.
contrary, in all patients with PHEO is advisable to search clinical criteria used to
DOI: 10.1530/endoabs.49.EP90
diagnose NF1, and thus confirming an often-delayed diagnosis.
DOI: 10.1530/endoabs.49.EP88
EP91
EP89
The role of p27 in pheochromocytoma development
Should all patients with Neurofibromatosis type 1 undergo biochemical
Andrea Kugler1, Enzo Lalli2, Juan Higareda Almaraz1, Steffen Sass3 &
screening for Pheocromocytoma?
Natalia Pellegata1
Ahmed Al-Sharefi, Suhel Ashraff, Ramesh Vanka & Satyajit Nag
1Helmholtzzentrum Munchen, Institute of Diabetes and Cancer, Munich,
Department of Diabetes and Endocrinology, The James Cook Univeristy
Germany;2University Nice, Institute of Molecular and Cellular
Hospital, Middelsbrough, UK.
Pharmacology, Valbonne, France;3Helmholtzzentrum Munchen,
Institute of Computational Biology, Munich, Germany.
Pheocromocytomas (PHEO) are catecholamine secreting tumours which can
occur sporadically or as part of other hereditary/familial syndromes including
Defective p27 function predisposes mice and rats to pheochromocytomas (PCC),
Neurofibromotosis 1 (NF-1). Unlike the case with other genetic syndromes, the
and reduction of p27 repression is a feature of human PCCs. These findings
current neurofibromatosis guidelines do not recommend a routine hormonal
suggest that p27 plays a role in PCC tumorigenesis. Recently, it was reported that
screening strategy for PHEO in the absence of hypertension or other symptoms. In
p27 indirectly regulates gene transcription by associating with transcription
this paper we describe 2 asymptomatic and normotensive patients with NF-1
factors (TF) and inhibiting gene transcription at specific promoters.
where secretory PHEO were incidentally diagnosed. The first patient is 61- year
We hypothesized that defective p27 promotes tumor formation in adrenomedul-
old female with a history of NF-1 who received a diagnosis of takotsubo
lary cells because of aberrant gene expression. To address this hypothesis, we
cardiomyopathy and was found to have an incidental adrenal mass of 2.4 cm
used normal adrenomedullary tissue from wild-type rats or human individuals and
where subsequent investigations confirmed a diagnosis of secretory PHEO.The
performed chromatin immunoprecipitation-sequencing
(ChIP-Seq). DNA
second patient is a 44 - year old female with also a background of NF-1 who was
sequences bound by p27-contaning protein complexes were immunoprecipitated
found to have a 7.8 ! 7.0 ! 5.8 cm adrenal adenoma where further work up
from rat and human tissue extracts using an anti-p27 antibody coupled with
confirmed PHEO. Both patients underwent adrenalectomy and the histology
magnetic beads. DNA sequences were identified by quantitative next generation
confirmed the diagnosis and their catecholamines level normalised eventually.
sequencing (NGS).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
We successfully pulled down DNA sequences with the anti-p27 antibody,
Paragangliomas are rare neuroendocrine tumors derived from neural crest cells: if
indicating that p27, together with unknown transcription factors or co-factors
localized in the adrenal medulla they are called Pheocromocytomas (Pheo).The
binds the chromatin in adrenomedullary cells. DNA sequences bound by the p27-
30-40% of Pheo are mutated in one of the susceptibility genes among which there
containing complexes were mapped on the rat/human genome and analyzed using
are genes encoding for the four subunits of the succinate dehydrogenase (SDH).
both Genomatix and MEME suite software to identify the most enriched TFs and
Germ line mutations of SDHB are metastatic in about 80% of the cases. Surgery is
TF binding sites (Tcf19, Tcf4, Znf423, Runx1, Ascl2, Lhx4). The binding
the current therapy, but in presence of metastasis there is no effective treatment.
between p27 and these selected TFs is being verified by immunoprecipitation.
Using shRNA, we stably silenced for SDHB a Pheo murine cell line (MTT). The
The association of p27-containing complexes to specific promoters of these
proliferative growth of non-silenced cells (CN) was higher than that of the
identified genes is currently being validated. The p27-dependent regulation of the
silenced ones (B-). However, in co-culture with fibroblasts, the proliferation of
expression of selected target genes will be verified by modulating p27 levels in
B-was higher than that of the CN cultivated in the same conditions.
PCC cell lines. The significance of the p27-dependent gene expression will also
When cultured in fetal-bovine-serum (FBS), B- cells tended to aggregate more
be obtained by analyzing the expression of these target genes in normal adrenal
than the CN. When FBS was not present, both the cells lines lost this
medulla and PCC of MENX-affected rats (with loss of functional p27).
characteristic. When cultured in conditioned medium from activated murine
In conclusion, the observation that p27 may regulate gene transcription will give
fibroblasts (CAF), the aggregating effect disappeared, the cells assumed a longer
insight into the pathomechanisms associated with reduced p27
function
shape and started migrating.
specifically in adrenomedullary cells.
To understand whether this change corresponds to an epithelial to mesenchimal
DOI: 10.1530/endoabs.49.EP91
transition (EMT), we are evaluating the EMT markers and the expression of
metalloproteases either secreted in the medium or expressed on membranes. To
understand if the cross talk between fibroblasts and tumor cells was due to a signal
mediated by receptors, we evaluated the phosphorylation of mTOR, Akt and ERK
in B- and CN cells without detecting any difference.
These preliminary data suggest that the microenvironment, here represented by
EP92
fibroblasts, affects the behaviour of cancer cells and studies on this interaction are
Role of microenvironment on metabolic control of murine
needed to identify new therapeutic targets in SDHB mutated tumors.
pheochromocytoma SDHB silenced cells
Vanessa D’Antongiovanni1, Susan Richter3,4, Serena Martinelli1,
DOI: 10.1530/endoabs.49.EP93
Letizia Canu1, Tonino Ercolino1, Graeme Eisenhofer3,4, Karel Pacak5,
Elena Rapizzi2 & Massimo Mannelli1
1Department of Experimental and Clinical Biomedical Sciences, University
of Florence, Florence, Italy;2Department of Experimental and Clinical
Medicine, University of Florence, Florence, Italy;3Institute of Clinical
EP94
Chemistry & Laboratory Medicine, Dresden, Germany;4Department of
Pheochromocytoma: a clinical and pathological study
Medicine III, Technische Universitat Dresden, Dresden, Germany;5Eunice
Elisa Santacruz1, Agustina Pía Marengo3, Andrés Ortiz1, Inma Peiró3,
Kennedy Shriver National Institute of Child Health and Human
Héctor Pián2, Juan José Díez1, Paula García-Sancho3, Carles Villabona3 &
Development, National Institutes of Health, Bethesda, MD, USA.
Pedro Iglesias1
1Department of Endocrinology, Hospital Universitario Ramón y Cajal,
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendo-
Madrid, Spain;2Department of Pathology, Hospital Universitario Ramón y
crine tumors. About 30-40% of Pheo/PGLs are due to a germ-line mutation in one
Cajal, Madrid, Spain;3Department of Endocrinology, Hospital de Bellvitge,
of the 13 main susceptibility genes which include the genes encoding the four
L’ Hospitalet de Llobregat, Barcelona, Spain.
subunits of the succinate dehydrogenase (SDH - mitochondrial complex II). In
PHEO/PGL due to SDHB mutations up to 80% of affected patients develop
Objective
metastatic disease and no successful cure is at present available. Tumor
To assess clinical features, diagnosis, treatment and outcome in patients with
microenvironment plays a pivotal role in modifying the metabolism and the
pheochromocytoma surgically treated in the past 3 decades in two tertiary referral
functional characteristics of tumor cells, becoming a potential therapeutic target.
hospitals.
To obtain an experimental model resembling the in vivo conditions of the SDHB-
Methods
mutated PHEO, we evaluated the effects of SDHB silencing and microenviron-
A retrospective study on clinical and pathological characteristics, treatment, and
ment on metabolism in the mouse tumor tissue-derived cell line (MTT), cultured
outcome in patients with pheochromocytoma followed up in specialized
alone or in association with mouse primary fibroblasts (here representing the
neuroendocrinology units who underwent surgery in the period 1981-2016 was
tumor microenvironment). SDHB silenced cells showed a significant increase of
performed.
both glucose and lactate uptake, and an increase of intracellular lactate compared
Results
with control. This increase was even more evident when SDHB silenced cells was
81 patients (45 women (56%); age 51G15 year (range, 13-76)) were studied. The
co-cultured with mouse primary fibroblasts. The expression levels of
tumor was sporadic in 68 patients (84%) and familial in 13 patients, more
monocarboxilase transporter 4 (MCT4), responsible for the transport of lactate
frequently in the context of a MEN type 2 (nZ6).10% of the pheochromocytoma
from the intracellular to the extracellular space, was found upregulated in
were bilateral. Most of the patients (66%) were symptomatic. The main complains
fibroblasts in co-culture with tumor cells. Consequently, in co-cultures, primary
were the classic triad
(27%), and hypertensive crisis
(27%).
40% of the
fibroblasts showed an increase of extracellular lactate. Surprisingly, SDHB
pheochromocytoma were incidentally discovered on imaging investigations. 47%
silenced cells in co-culture showed a reduction of ATP levels compared to SDHB
of patients were hypertense at diagnosis. 24-h urinary catecholamines excretion
cultured alone and control cells in co-cultures. Our data demonstrate that
was determined in 80% of patients, being elevated in 75% of cases. Fractionated
SDHB silencing strongly affects tumor metabolism, and these changes are more
urinary metanephrines were only determined in 23% of patients, and were
evident in co-cultures. The comprehension of the mechanisms driving these
elevated in 84%. Abdominal CT was the most used imaging technique (87%,
changes in tumor metabolism may suggest new therapeutic targets.
nZ68), followed by123I-MIBG scintigraphy (54%, nZ42) which detected 88%
DOI: 10.1530/endoabs.49.EP92
of those tumors (nZ37). MRI was performed in 50% of the patients, 87% of those
tumors were hyperintense in T2. 89% (nZ65) patients had a preoperative alpha-
adrenergic blockage. 17 patients (22%) had a complication during surgery, being
hypertensive crisis the most common complication (12.5%, nZ10). Median
tumor diameter was 5.9G2.8 cm (range, 1.5-13). 15% of pheochromocytomas
EP93
had vascular invasion, 15% had capsular invasion and 23% presented necrosis.
Only 6% presented ganglionar or distant metastasis. 68 patients were followed in
Role of microenvironment on proliferation and migration of an SDHB
our two centers, 55 patients (81%) were cured, 4 of them (6%) had persistent
silenced murine Pheochromocytoma cell line
disease and 9 (13%) had recurrence after surgery.
Serena Martinelli1, Vanessa D’Antongiovanni1, Susan Richter3,4,
Conclusion
Letizia Canu1, Tonino Ercolino1, Graeme Eisenhofer3,4, Karel Pacak5,
Pheochromocytoma in our series is generally a large, symptomatic and sporadic
Elena Rapizzi2 & Massimo Mannelli1
tumor. Incidentally discovered pheochromocytoma is common. Abdominal CT
1Department of Experimental and Clinical Biomedical Sciences, University
is the preferred imaging technique for localization. Surgical complications are
of Florence, Florence, Italy;2Department of Experimental and Clinical
common. Despite the high rate of vascular invasion in the histopathological study,
Medicine, University of Florence, Florence, Italy;3Institute of Clinical
ganglionar and distant metastasis are rare. The presence of cases with persistent
Chemistry & Laboratory Medicine, Dresden, Germany;4Department of
and recurrent disease after surgery requires a long term follow-up. these tumors.
Medicine III, Technische Universitat Dresden, Dresden, Germany;5Eunice
Kennedy Shriver National Institute of Child Health and Human
DOI: 10.1530/endoabs.49.EP94
Development, National Institutes of Health, Bethesda, MD, USA.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP95
Conclusion
We report a challenging situation, life-threatening without surgical treatment, but
Biochemical testing for pheochromocytoma
with a high surgical risk due to the severe comorbidities. A positive outcome was
Carolina Faria, David Barbosa, Ana Sofia Osório, Ema Nobre,
strongly dependent on the multidisciplinary collaboration of different
Joaquim Sampaio & Maria João Bugalho
departments.
Hospital de Santa Maria, Lisboa, Portugal.
DOI: 10.1530/endoabs.49.EP96
Introduction
Biochemical testing for Paraganglioma/Pheochromocytoma
(PGL/PHEO) is
recommended in patients with classical symptoms, in those harbouring an
adrenal incidentaloma and in patients who have a hereditary risk for developing
a PGL/PHEO. Measurements of plasma free metanephrines and/or urinary
EP97
fractionated metanephrines provide a highly sensitive test for diagnosis but false-
positive results remain a problem.
Retrospective audit at a UK teaching hospital of phaeochromocytomas
Aim
and paragangliomas against the 2016 guidelines
Nawal Ibraheem & David Hughes
Comparative analysis of plasma and urinary metanephrines results in a group of
Derby Teaching Hospitals NHS Trust, Derby, UK.
individuals suspected of having PGL/PHEO.
Subjects and methods
Retrospective analysis of tests performed at a tertiary hospital during the year
Introduction
2015
(January 1st-December 31th) and correlation with imaging studies and
In this audit we explored the treatment and follow up of pre-2016 cases against the
clinical data.
2016 European Society of Endocrinology (ESE) guidelines on PPGL follow-up.
Results
Results
686
measurements of urinary and/or plasma metanephrines, ordered by
Demographics of the patients revealed 50% were male with median age (45G5),
physicians of different medical specialties, were performed. From the analysis
82% of patients underwent surgery of which 73% were diagnosed with adrenal
of these results, we identified 124 patients with both measurements; they were 77
phaeochromocytomas & 27% with paragangliomas. Only 64% of surgical cases
women and 47 men with a mean age of 47.3 years (range 6-82). The main reason
were followed up in clinic in the last year. Of all surgical cases only 73% had
for testing was therapy-resistant or paroxismal hypertension (nZ68; 54.8%)
evidence of undergoing genetic testing. In the first year post surgery the following
followed by the presence of an adrenal incidentaloma (nZ13,10.4%). Abnormal
appropriate biochemistry screening was performed: Chromogranin AZ36.5%,
high values were observed in 56 patients: in 44 (45.2%) only abnormal urine
(27% unknown), Urinary MN or catecholaminesZ64%
(27% unknown),
values, in 6 (4.8%) both urine and plasma abnormal values and in 6 (4.8%) only
CalciumZ64% (27% unknown), PTHZ56%, (unknown in 27%), Calcito-
abnormal plasma values. 3/6 patients who presented elevation of urinary and
ninZ46% (27% unknown), CEAZ0% (27% unknown). In the first year post
plasma metanephrines had histologically proven disease (2 PHEO, 1 abdominal
surgery between 9% and 27% of patients underwent USS/CT/MRI/MIBG/PET
PGL). Among the patients with normal plasma metanephrines and high urinary
scan of neck or abdomen appropriately.
metanephrines only one (2.3%) had a bilateral pheochromocytoma in the context
Discussion
of a MEN2A syndrome. None of the
6
patients with normal urinary
The recommendations made in these guidelines have been implemented locally
metanephrines and increased plasma metanephrines had disease.
and a local registry of cases is in development to improve follow up of cases (see
Conclusion
poster for further details).
In the present series, all patients with a histologic diagnosis of PGL/PHEO had
DOI: 10.1530/endoabs.49.EP97
elevated urinary metanephrines regardless, in one case, normal plasma
metanephrines. On the other hand, the frequency of increased urinary
metanephrines without a positive imaging was very frequent.
DOI: 10.1530/endoabs.49.EP95
EP98
Pheochromocytoma - surgical outcomes
Pedro Carvalho Martins, Cátia Ribeiro, Mariana Peyroteo, Helena Pereira &
EP96
Abreu de Sousa
Paraganglioma and Fallot Tetralogy: case report
IPO-Porto, Porto, Portugal.
Ana Filipa Martins1, João Martin Martins1,2 & Sónia do Vale1,2
1Hospital de Santa Maria - CHLN, Lisboa, Portugal;2Faculdade de
Medicina de Lisboa, Lisboa, Portugal.
Objective
To retrospectively evaluate the results of the pheochromocytoma surgery in our
institution assessing the surgical complications, perioperative hemodynamic
Introduction
instability and oncologic outcomes.
Catecholamine secreting tumors are rare neoplasias. About
15% are para-
Methods
gangliomas. If untreated, they are almost invariably lethal. Surgery is the only
The medical records of patients admitted for pathologically confirmed
curative therapy.
pheochromocytoma between 2000
and
2015 were reviewed. Patients with
Case report
paragangliomas were excluded.
A female caucasian patient aged 32 was evaluated in the endocrine department.
Results
She had a dramatic medical history: Fallot’s Tetralogy was diagnosed soon after
We identified 40 patients with 43 resected pheochromocytomas. The mean age
birth but was not corrected. Only a Blalock-Taussing shunt was performed after
was 47 years with an equal distribution between genders. Twelve cases (30%) had
three isquemic strokes due to endocarditis, when patient was 22. She suffered
a syndrome known to have an increased incidence of pheochromocytoma. The
from sequelar right-side hemiparesis and epilepsy. She had also glucose-6-
mean tumor size was 7 cm (range of 1.5-17.2 cm). Most of the lesions were
phosphate desidrogenase deficiency. At 32 she was assisted at the emergency
functional (95%) and preoperative alpha-blockade has been instituted in 93% of
department because of recent vomiting, headache and arterial hypertension. She
the patients, with 48% having a beta blocker simultaneously. Fourteen cases
had a recent weight loss with a BMI of 16 kg/m2. Examination revealed depressed
(30%) underwent a minimal invasive approach. The mean operative time was
mood, orthostatic hypotension, holosystolic aortic bruit and chronic hypoxia
150 min and the median of intraoperative blood loss was 150 ml. More than a half
signs. Several hypertensive paroxysms (maximum value: 240/140 mmHg) with
of the patients (54%) had a hypertensive crisis at some point during surgery,
diaphoresis were documented. Urinary normetanephrine and metanephrine were
almost always associated with manipulation of the lesion. Ten patients (25%)
very high (227 and 58 times higher than the upper limit of the reference range)
required vasopressor support after adrenal gland removal. Two patients (4.6%)
with a paradoxal increase in clonidine test. The CT scan revealed a solid
had CTCAE 3/4 complications. There were no cases of mortality and the median
hypervascular right paramedian retroperitoneal tumor with 49 mm of diameter at
length of stay was seven days. Two (5%) cases were defined as malignant: one
the level of the superior mesenteric artery with strong uptake in I123-MIBG
secondary to metastatic disease to distant organs (recurrence at 30 months of
scintigraphy. Surgery was uneventful after careful pre-operatory preparation with
follow-up in the form of multiple lung metastasis) and other to lymph nodes who
a- and b-blockers and volume expansion. Five months later the patient recovered
is alive and disease-free. Three patients were diagnosed with contralateral
weight and was normotensive without antihypertensive drugs. Succinate
pheochromocytoma during the follow-up, admitted as a new primary lesion, in
dehydrogenase mutations (SDHA, SDHB and SDHC) were not found.
context of a known genetic syndrome.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
gene mutations in PC/PGL and are associated with younger ages at presentation,
The results of our retrospective study show that adrenalectomy is a safe, effective
higher rates of metastases and poorer prognosis. Although familial PGL
and a low morbidity procedure. However, the organization of surgical, anesthetic
syndromes were initially thought to predispose only for PCC and PGL, other
and medical teams experienced in this type of pathology is fundamental for
tumor types such as gastrointestinal stromal tumors
(GISTs), renal cell
perioperative management.
carcinomas (RCCs), and pituitary adenomas (PAs) have expanded the SDHx-
DOI: 10.1530/endoabs.49.EP98
associated tumor spectrum.
Case Report
A 34-year-old female patient, with a history of mild asthma, non-smoker, was
referred to the Endocrinology Department as an asymptomatic carrier of a
pathogenic heterozygous germline SDHB mutation
(c.1-?_72C?del). Her
paternal-uncle died from metastatic bladder paraganglioma by the age of .She
had also family history of breast cancer (paternal-aunt) and prostate cancer
(paternal-grandparent). Twenty-four-hour urinary excretion of fractionated
catecholamines and metanephrines were in the normal range. Screening
EP99
computed tomography (CT) scan showed a 3 cm mass in the lower lobe of the
Role of urinary fractionated metanephrines and catecholaminas in the
right lung. CT guided transthoracic lung biopsy revealed adenocarcinoma of
diagnosis of pheochromocytoma/paraganglioma
probable primary lung origin. Staging positron emission tomography with
Ma Luisa Martinez-Triguero, Ma Isabel del Olmo, Rosa Cámara del Olmo,
2-deoxy-2-[fluorine-18]fluoro-D-glucose
(18F-FDG PET/CT) showed, besides
Amparo Alba, Francis Fernández, Juan Francisco Merino & Begon˜a Laiz
malignant right lung involvement, moderate left paratracheal FDG uptake. She
Servicio de Análisis Clínicos, Servicio de Endocrinología, Hospital
underwent inferior right lobectomy with mediastinal lymph node ressection and
Universitario y Politécnico La Fe, Valencia, Spain.
histologic examine confirmed lung adenocarcinoma pT2a N0 M0 R0, stage I B.
The patient is under surveillance.
Discussion
Introduction
Questions still remain unresolved concerning non PCC/PGL tumors in patients
Paragangliomas/pheochromocytomas present frequently with vague symptoma-
with germline pathogenic SDHx mutations with regard to their pathogenesis,
tology which makes its diagnosis difficult and challenging. Cuantification of
clinicopathological phenotype, and possible causal relation to the aforementioned
fractionated metanephrines and fractionated catecholamines in 24 h urine sample
mutations.
are used for diagnosis. There are situationes that can produce false positive results
such as stress, drugs or smoking that must be taken into account.
DOI: 10.1530/endoabs.49.EP100
Patients and methods
Retrospective study on the requests made for the diagnosis of pheochromocy-
toma/paraganglioma to the laboratory with the determinations of fractionated
catecholamines and metanephrines during
10 months. Determinations were
analysed by HPLC with electrochemical detector (Teknochromaw).
Results
During this period 260 determinatios (of 218 patients) were analysed. 10 of these
patients were diagnosed of pheochromocytoma, nine of extraadrenal para-
ganglioma and 199 patients did not present either of the pathologies. Patients with
paraganglioma were excluded (Table 1).
Table 1 Sensitivity and specificity of fractionated catecholamines and
EP101
metanephrines.
Pheochromositoma in childhood
Olcay Evliyaoglu, Oya Ercan, Aydilek
¸ akır, Duhan Hopurcuog˘ lu &
Sensitivity CI 95%
Specificity
CI 95%
Betul C¸ ınar
Catecholamines
0.9
0.71-1.09
0.88
0.83-0.92
Istanbul University Cerrahpa¸a Medical School Pediatric Endocrinology
Metanephrines
0.9
0.71-1.09
0.89
0.85-0.93
Department, Istanbul, Turkey.
Of the patients who did not present pheochromocytoma (199), 35 had elevated
Introduction
catecholamines and/or fractionated metanephrines (18% false positive), 17 were
Feochromositoma is a rare neuroendocrine tumor derived from chrommaffin cells
due to antihypertensive or antidepressant drugs, 11 had other adrenal pathologies
of adrenal medulla. The most characteristic clinical symptoms are headache,
and seven others.
perspiration, palpitation, and paroxysismal hypertension. Childhood feochromo-
Conclusions
sitoma is generally genetic while it is mostly sporadic in adults. Here we report
1. Urinary fractionated metanephrines have a higher specificity than catechol-
three feochromositoma cases in whom two had von Hippel Lindau syndrome
amines. Both of them present the same sensitivity in our patients.
(VHLs).
2. The rate of false positive results surpasses those of true positive, especially
Case 1
those produced by drugs, as published in literature.
10 years old girl with admitted with fever. Her physical examination revealed
hyperthermia and hypertension. Urine VMA level was increased and ultrasound
DOI: 10.1530/endoabs.49.EP99
examination showed left adrenal mass, diagnosis of pheochromositoma was
confirmed after resection. In the second year of her follow-up GA-68 Octreotide
scintigraphy determined accumulations in right adrenal and pancreas, patho-
logical diagnosis were feochromositoma and neuroendocrine carcinom respect-
ively after resection. Two disoreders together suggested VHLs and heterozygous
p.L129P mutation in VHL gene was detected.
Case 2
11-years-old boy admitted with perspiration and palpitation in whom
hypertension was determined. Urine VMA level was increased, and bilateral
EP100
adrenal mass was determined in ultrasonography. Diagnosis of pheochromosi-
toma was confirmed after resection. In his 5 years of follow-up he admitted with
Lung adenocarcinoma in a 34-year-old female SDHB asynptomatic
headache. Cranial MRI showed frontal, adrenal ultrasound showed right adrenal
mutation carrier - case report
masses, after resection hemangioblastoma and pheochromositoma were diag-
Maria João Matos, Claudia Costa, Ana Paula Santos, Manuel Teixeira,
nosed respectively. Associaton of two disorders suggested VHLs and
Carlos Franco, Joa˜o Bento, Isabel Azevedo, Susana Dias, Inês
heterozygous p.R161Q mutation in VHL gene was determined.
Lucena Sampaio, Ana Luísa Cunha & Isabel Torres
Case 3
Portuguese Oncology Institute of Porto, Porto, Portugal.
9-years-old boy admitted with perspiratation and palpitation in whom
hypertension was determined. His family history was significant with
Introduction
pheochromositoma in his father and grandmother. His urine VMA levels were
Patients with germline mutations in one of the succinate dehydrogenase (SDH)
high and adrenal ultrasound revealed bilateral adrenal masses. Diagnosis of
genes are at substantially increased risk of developing paragangliomas (PGL) and
pheochromositoma was confirmed after resection of both masses. No mutation in
pheochromocytomas (PCC). Mutations in SDHB are the most commonly found
VHL gene was detected.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
He had elevated 24-h urinary normetanephrines 6360 nmol/24 h and metane-
Although rare pheochromositoma should be thought in children with hyperten-
phrines 2530 nmol/24 h (normal !2129 and !1622 respectively), in keeping
sion. In children pheochromositoma is mostly genetic in which VHLs is most
with phaeochromocytoma. Subsequent meta-iodobenzylguanidine (MIBG) scan
frequent. Genetic tests should be performed in all children after diagnosis.
showed prominent activity in the region of the right adrenal gland. The patient
DOI: 10.1530/endoabs.49.EP101
was initially commenced on an alpha blocker doxazosin, and the dose was
incremented to the maximum of 16 mg BD. He was subsequently commenced on
beta blocker bisoprolol, and his blood pressure dropped from average of
150/100 mmHg (no history of hypertension) to around 110/70 mmHg.
This patient had a right adrenalectomy, made an uneventful recovery and was
discharged with no medication. His BP remained at around 130/85 mmHg at his
post-operative consultations. Phaeochromocytoma presents with various forms of
signs and symptoms. In our case, the history of episodes of intermittent
perspiration, back pain and severe aggression were uncommon symptoms
emphasising the importance of comprehensive history taking.
Since surgery the patient has no longer experienced any of the above, and he
EP102
describes himself to be calmer than ever.
A case of silent pheochromocytoma presenting with clinical and
DOI: 10.1530/endoabs.49.EP103
radiological findings suggesting metastatic adrenal lesion
Soner Cander1, Ozen Oz Gul1, Pinar Sisman2 & Canan Ersoy1
1Uludag University Medical School, Bursa, Turkey;2Kars State Hospital,
Kars, Turkey.
Case
A 75-year-old male patient was treated for lung adenocarcinoma 12 years ago.
During the routine imaging studies of the patient who was followed without
treatment after curing, a suspicious, non-adenomatous lesion in the right adrenal
gland, 16!9 mm in size was detected by thoracic computed tomography. Serum
aldosterone/renin ratio and urine catecholamine tests were normal with no
EP104
complaints of suspicion for pheochromocytoma. F18FDG PET-CT showed an
Improvement of insulin secretion and oral glucose tolerance after
increase in metabolic activity
(SUVmax:4,8) in the right hilar region. The
pheochromocytoma removal: a case report
cytological examination was benign with bronchoscopy. Laparoscopic right
Zoran Erlic, Kathrin Roost, Oliver Tschopp & Christoph Schmid
adrenalectomy was performed because no other lesions were detected.
Division of Endocrinology and Diabetology, University Hospital Zurich,
Histopathologic examination revealed non-invasive pheochromocytoma showing
Zurich, Switzerland.
positive staining with synaptophysin and chromogranin.
Discussion
Introduction/case report
Pheochromocytoma is very rare in adrenal incidentalomas, however, can be
Diabetes mellitus is an important clinical manifestation of catecholamine excess
asymptomatic at rates up to 10%, as they can manifest with attack symptoms or
in patients with pheochromocytoma, and glucose control is usually better after
less with persistent hypertension. It is suggested that catecholamine synthesis is
tumour removal. Both impaired insulin secretion and increased insulin resistance
defective in these tumors. In some reports it is specified that, this phenomenon
have been implicated as underlying causes. We describe the case of a 38-year-old
may be seen in some mutations in the succinate dehydrogenase gene. In some
male patient diagnosed with left adrenal pheochromocytoma and personal history
reports, however, about 10-20% of silent pheochromocytomas were reported to
of diabetes mellitus diagnosed at age
36, under treatment with metformin,
be due to laboratory error. On the other hand, non-adenomatous lesions in the
saxagliptin and gliclazide, with a preoperative HbA1c of 7.2%. BMI of the patient
adrenal glands in a patient known as primer malignancy are generally considered
was 23 kg/m2. After successful pheochromocytoma removal, the anti-diabetic
as metastases. In our case, the patient was referred to a similar presentation and it
medication was immediately stopped with remission of diabetes mellitus (HbA1c
was initially thought that the lesion may be a metastatic lesion. However, the fact
3-months-postoperative 5.7%).
that the primary malignancy has been in control for more than 10 years has been
Methods
questioned about metastasis. One of the methods that can be applied in such a case
is biopsy but pheochromocytoma should be firstly excluded. In this case report,
We performed oral glucose (75 g) tolerance tests and measured venous plasma
glucose and serum insulin levels at the time of diagnosis and three months after
we have demonstrated that; in non-adenomatous adrenal lesions, the absence of
successful surgery, to derive the insulinogenic index
(IGI) as proposed by
clinical signs and normal catecholamine levels do not exclude
Wareham, and whole body insulin sensitivity index (ISI) as proposed by Matsuda
pheochromocytoma.
and DeFronzo.
DOI: 10.1530/endoabs.49.EP102
Results
Plasma glucose and serum insulin levels are shown in the table 1.
Table 1
Time (min)
K15
0
30
60
90
120
Preop glucose (mmol/l)
9.8
9.5
10.9
12.7
15.8
16.1
Postop glucose (mmol/l)
5.3
5.3
8.0
10.7
10.9
7.0
Preop insulin (pmol/l)
28
42
104
161
248
181
EP103
Postop insulin (pmol/l)
74
47
316
461
613
354
The storm before the calm: a phaeochromocytoma
Yasmin Nikookam, Caoimhe Bonner, Edward Bettany,
Anthony Pittathankal, Ranjan Gunasekara, Edel Casey & Khash Nikookam
King George Hospital, London, UK.
Improved glucose levels were associated with increased insulin levels and an
increase in IGI, from a preoperative value of 5.7-33.6 pM/mM, while the ISI
remained unchanged.
We report a case of a male patient aged 45 years who presented with a history of
Conclusion/discussion
intermittent back discomfort over a year, but more persistent over the previous 2-
Remission of diabetes mellitus in our patient was associated with marked
3 months. His general practitioner (GP) referred him for an ultrasound of the spine
improvement of insulin secretion and oral glucose tolerance after removal of
for a possible encapsulated lipoma but the findings were unremarkable. He was
pheochromocytoma. Adrenergic alpha2A receptors on pancreatic beta cells play
then referred to a consultant gastroenterologist for further assessment. He had
an important role in mediating inhibitory effects of catecholamines on insulin
normal endoscopic examinations, however the MRI had shown a right adrenal
release, according to recent genetic association and pharmacological intervention
lesion which led to a referral to the endocrine team.
studies. In our case, impaired insulin secretion could be corrected by surgery.
On further history he reported episodes of perspiration and bursts of aggression,
for the past few years. Investigations revealed a normal cortisol response
DOI: 10.1530/endoabs.49.EP104
following overnight dexamethasone suppression and a normal renin aldosterone
ratio.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP105
palpitations, diaphoresis or tremors.123I-MIBG scintigraphy revealed focus of
hyperactivity located on projection of the right adrenal gland suggesting the
Ephedrine/caffeine toxicity masquerading as phaeochromocytoma in a
presence of pheochromocytoma. We sent this patient to multidisciplinary expert
vigorexic male with paroxysmal hypertension and headache
team. Plasma-free metanephrines were measured with elevated results: 125 pg/ml
Manuel Nivelo-Rivadeneira1, Agnieszka Kuzior1, Sara Quintana-Arroyo1,
(!65) and he will undergo unilateral adrenalectomy soon.
Carmen Acosta-Calero1, Claudia Arnas-Leon1, Ana Delia Santana-Suarez1,
Discussion
Alba Lucia Tocino-Hernandez3 & Francisco Javier Martinez-Martin2
This case illustrates the possibility of false negative results in hormonal
1Endocrinology Dpartment, Hospital Universitario de Gran Canaria Dr
evaluation of adrenal masses. These misleading results can happen, for example,
Negrin, Las Palmas de Gran Canaria, Spain;2Outpatient Hypertension
by an inadequate urine sampling. If we had not repeated the measurement of
Clinic, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de
metanephrines, the diagnosis of pheochromocytoma had not be done at this time.
Gran Canaria, Spain;3Primary Care Center, Arucas, Las Palmas de Gran
Canaria, Spain.
DOI: 10.1530/endoabs.49.EP106
Clinical case
A 19-year-old male came to the Emergency Department complaining about
a holocraneal nonpulsatile headache growing in intensity for the last
3 h,
unresponsive to common analgesics. He had been suffering anxiety sleep
deprivation, nervousness, tremor and heart palpitations for the last week. Family
EP107
history was irrelevant, and the patient had no history of hypertension,
Unexplained resistant hypertension in a young male with recurrent
dyslipidaemia, diabetes or smoking or medication use; he reported moderate
transient ischemic attacks, resembling endocrine hypertension
alcohol, coffee and energy drink consumption but no cocaine nor amphetamines.
Ana Delia Santana Suárez1, Manuel Nivelo-Rivadeneira1,
He was on a high-protein diet with casein-based supplements, maintained a very
Agnieszka Kuzior1, Sara Quintana Arroyo1, Carmen Acosta Calero1,
high level of physical exercise and lately had been consuming a ‘fat-burner’
Claudia Arnás León1, Esperanza Perdomo Herrera2 & Francisco Javier
obtained from a local gym, but ignored its composition. The patient was fully
Martínez Martín3
conscious and did not have chest pain, fever or dyspnoea. His BP was
1Endocrinology Department, University Hospital Dr Negrin, Las Palmas,
219/126 mmHg and HR 129 bpm, with sinus tachycardia in the EKG. He was
Spain;2Primary Care Center of Escaleritas, Las Palmas, Spain;3Outpatient
treated with diazepam and diltiazem, discharged with BP 154/87 and HR 98 and
Hypertension Clinic, University Hospital Dr Negrin, Las Palmas, Spain.
referred to our Endocrinology Clinic for phaeochromocytoma screening. He
brought the ‘fat-burner’ pills containing ephedrine 50, ASA 100 and caffeine
150 mg; he had been taking 1-2 daily during the week before the hypertensive
A 27-year-old male without relevant familial or personal history had three TIAs in
episode. He was asymptomatic, with athletic constitution, weight 87 kg, height
the last year, lasting for about 20 min with partial right palsy and aphasia. By the
173 cm, BMI 29 kg/m2, waist 88 cm, impedanciometry 19% fat mass, BP 119/76,
time he was cared for in the Emergency Department. he had already recovered;
HR 75. Physical exam was otherwise unremarkable. Lab tests including
his lab tests, chest X-ray and EKG were normal but his BP was high (PAS 170-
metanephrines, aldosterone, PRA, TSH and microalbuminuria; chest X-ray and
190 mmHg, PAD 105-120 mmHg). He had no chest pain, headache or
24 h. ABPM were normal.
neurovegetative symptoms. On discharge the patient was treated with manidipine
Diagnosis
and ASA and referred to the Neurology Clinic and to our Hypertension Clinic for
Paroxysmal hypertensive episode caused by ephedrine/caffeine toxicity, with
phaeochromocitoma/paraganglioma screening and diagnostic workup.
no target-organ damage. Vigorexia. Phaeochromocytoma/paraganglioma were
DOI: 10.1530/endoabs.49.EP107
ruled out.
Commentary
Ephedrine is a sympathomimetic amine with no legitimate medical indications at
present, but widely used as doping or to trim subcutaneous fat. Its use has been
linked with major cardiovascular and renal events, including ictus and sudden
death, and must be discouraged.
DOI: 10.1530/endoabs.49.EP105
Cardiovascular Endocrinology and Lipid Metabolism
EP108
Stress cardiomyopathy in pheochromocytoma
Cristina Alexandra Gheorghiu, Simona Jercalau & Corin Badiu
EP106
National Institute of Endocrinology ‘C.I. Parhon’, Bucharest, Romania.
Loss diagnosis of pheochromocytoma in the initial evaluation
Teresa Azevedo, Márcia Alves, Joana Guimara˜es, Rosa Dantas,
Introduction
Ana Margarida Balsa & Isabel Inácio
Rare cases of pheochromocytoma are associated with stress induced Takotsubo
Centro Hospitalar Baixo Vouga, Aveiro, Portugal.
cardiomyopathy explained by high catecholamine exposure causing micro-
vascular spasm and direct myocardial impact.
Case report
Introduction
A 49-year-old female with a history of poorly controlled hypertension, with
In most cases, adrenal masses are non-functioning adrenocortical adenomas. On
paroxysmal elevations in blood pressure and rare supraventricular extrasystoles,
‘Management of adrenal incidentalomas: European Society of Endocrinology
lipothymic events, was firstly assessed in the cardiologic department. She
Clinical Practice Guideline’ published in 2016, the experts ‘suggest against
presented with resistant hypertension, associated with acute pulmonary oedema
repeated hormonal work-up in patients with a normal hormonal work-up at initial
and cardiogenic shock. Echocardiography revealed new mid LV segment motion
evaluation unless new clinical signs of endocrine activity appear or there is
abnormality with apical ballooning, ECG - acute ST-segment elevation in the
worsening of comorbidities’.
anterior leads and a rise of cardiac biomarkers. The coronary angiography
Case report
excluded any coronary artery lesion. Thoraco-abdominal CT imaging revealed an
A 59-year-old male patient was referred to endocrinology with a right adrenal
86/85/68 mm left adrenal mass, suggestive for pheochromocytoma. Laboratory
mass of 17 mm compatible with adenoma, discovered in difficult-to-control
evaluation for
24-h urine and plasma catecholamine metabolites disclosed
hypertension study. The patient had no symptoms apart from hypertension, that
intermediary-low elevated values
(plasmatic MNZ10/11 pg/ml; plasmatic
was controlled with three classes of antihypertensive drugs. Initial hormonal
NMNZ59/41 pg/ml,
urinary
MNZ114/881 mg/24 h;
urinary
evaluation revealed normal urinary fractionated metanephrines, normal aldoster-
NMNZ632/1121 mg/24 h), despite high cardiac impact of the spells. She was
one/renin ratio (with interfering drugs suspension), intermediate hyperglycaemia
submitted to 12 days of alpha adrenergic blockade followed by beta blockers,
and subclinical hypercortisolism (1 mg overnight dexamethasone 2.1 mg/dl). One
during which control of blood pressure and spells was achieved. Improvement of
year later, adrenal mass was stable and hormonal study highlighted elevation of
systolic function (EKG and echocardiography) could be noticed. Laparoscopic
total and fractionated urinary metanephrines (total metanephrines 1921 mg/24 h
adrenalectomy was safely performed without hemodynamic events during
(329-1263), fractionated metanephrine 956 mg/24 h (64-302) and normetanephr-
surgery or immediately afterwards. Metanephrines and normetanephrines levels
ine 636 mg/24 h (162-527) with normal 3-methoxytyramine. The repetition of
normalised with good residual adrenal function. Long term systolic function as
metanephrines, with adequate preparation, confirmed these results: urinary total
well as high blood pressure returned to normal.
metanephrines
2005 mg/24 h
(329-1263), urinary fractionated metanephrine
Conclusions
1094 mg/24 h (64-302) and normetanephrine 545 mg/24 h (162-527) with normal
Takotsubo cardiomyopathy is associated with reversible LV-ballooning. In this
3-methoxytyramine. The patient kept lack of symptoms such as headache,
observation, we report a case of stress cardiomyopathy caused by
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
pheochromocytoma; a rare medical condition which is easily confused with acute
was applied and adrenal ganglioneuroma (mature type) was reported in the
coronary syndrome due to clinical and biochemical resemblance, especially in our
pathology examination.
case where plasma and urinary catecholamines were only slightly elevated.
Conclusion
DOI: 10.1530/endoabs.49.EP108
Ganglioneuroma is rarely seen in adults and diagnosis is difficult as it is
asymptomatic. As the masses are asymptomatic, they are not usually determined
before reaching large dimensions. With increased availability of high-resolution
tomography and MRI, an increase has been seen in the frequency of these types of
masses. In recent years, ganglioneuroma have been separated into two sub-types
as mature or maturing ganglioneuroma. In mature ganglioneuroma, the tumour is
Clinical Case Reports - Pituitary/Adrenal
completely formed of a ganglioneuromatous component. Diagnosis is made
EP109
histopathologically and it should be kept in mind as a rare tumour in adrenal
masses.
Prolonged zona glomerulosa insuffiency with hyperkalemia in primary
hyperaldosteronism after adrenalectomy
DOI: 10.1530/endoabs.49.EP110
Feyza Yener Ozturk, Esra Cil Sen, Rumeysa Selvinaz Erol, Emre
Sedar Saygili, Seda Erem Basmaz, Sezin Dogan Cakir, Adnan Batman &
Yuksel Altuntas
Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.
Introduction
EP111
Hyperkalemia due to zona glomerulosa (ZG) insufficiency is generally transient
Primary adrenal insufficiency and pregnancy - a case report
and mild for patients with aldosterone-producing adenoma
(APA) after
Slavica Savic1, Mirjana Stojkovic1,2, Biljana Nedeljkovic-Beleslin1,2,
adrenalectomy. We report here a case with prolonged ZG insuffiency requiring
Tanja Nisic1, Milos Stojanovic1,2, Marija Miletic1, Jasmina Ciric1,2,
long-term mineralocorticoid replacement (MR) therapy.
Svetlana Spremovic-Radjenovic2,3 & Milos Zarkovic1,2
Case report
1Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre
A 45-years-old female with hypertension and hypokalemia admitted to outpatient
of Serbia, Belgrade, Serbia;2School of Medicine, University of Belgrade,
clinic with incidentally detected right adrenal adenoma (3 cm) showing signal
Belgrade, Serbia;3Clinic for Gynecology and Obstetrics, Clinical Centre of
loss on opposed-phase images of MRI. Laboratory tests revealed high plasma
Serbia, Belgrade, Serbia.
aldosterone concentration (PAC) (72 ng/dl, N: 7-30 ng/dl), supressed plasma
direct renin concentrations
(DRC) (5.25 ng/l, N:
5.41-34.53 ng/l) and high
PAC/DRC ratio (13.71). PAC after saline infusion test was 30.7 ng/dl. After
Primary adrenal insufficiency (PAI) is uncommon in pregnancy. Women with
confirmation with adrenal venous sampling (AVS), right adrenalectomy was
PAI have reduced fertility and parity. If unrecognized or untreated during
performed laporoscopically. Serum urea, creatinine, sodium, PAC (19.6 ng/dl)
pregnancy PAI increases risk for maternal and foetal morbiditiy and mortality.
and DRC (13.6 ng/l) were in normal limits on postoperative 20th day; but serum
Majority of women diagnosed before conception and appropriately treated, have
potassium was markedly increased (5.9 mmol/l). The causes of pseudohyperka-
uneventful pregnancies, with increased risk of cesarean section (CS) and preterm
lemia and hyperkalemia were excluded. Because of low suppression index in the
delivery.
contralateral adrenal during AVS, hypoaldosteronism was thought to be the
We report a 38-year-old woman with PAI during first spontaneus pregnancy.
etiology as PAC did not increase while serum potassium level was higher than
The patient was diagnosed with Addison’s disease at the age of
17, and
5 mmol/l. Patient was followed-up with high-sodium, low-potassium diet on
hyperthyroidism 14 years later. Her family history revealed hyperthyroidism in
polystyrene sulfonate therapy. On the second month postoperatively, serum
mother. She had regular menstrual pattern and no pregnancy during 5 years of
potassium was still high
(5.6 mmol/l). MR therapy with fludrocortisone
marriage. Gynecological investigation was unremarkable, but she had addisonian
0.1 mg/day was started for persistent hyperkalemia. Treatment continued for
crisis during hysterosalpingography 6 months before conception. At that time she
eight months until PAC and DRC raised up to 23.27 and 20.8 ng/l, respectively.
was taking 30 mg hydrocortisone, 0.1 mg fludrocortisone and 50 mcg levothyr-
After then, serum potassium concentration remained at the upper limit of normal
oxine/daily. At 8 weeks of pregnancy she started to complain of fatigue, dizziness
range (5 mmol/l) with normal renal function tests, PAC (10.8 ng/dl) and DRC
and palpitations, with no nausea or vomiting. Physical examination was
(8.1 ng/l) without replacement.
unremarkable, BP
100/70 mmHg, with no orthostasis or discolouration of
Conclusion
skin/mucous membranes. Oral progesterone was started because of spotty vaginal
Suppression of contralateral ZG function by supressed plasma renin level in APA
bleeding and in 2 weeks she developed mild hyponatraemia. We recommended to
can lead to ZG insufficiency and hypoaldosteronism after adrenalectomy.
split hydrocortisone in four doses, and increased fludrocortisone to 0.125 mg.
Hypoaldosteronism cause impairment of renal potassium clearance and
During second trimester she was stable, plasma electrolytes and thyroid function
hyperkalemia. MR therapy may be essential in case of prolonged hyperkalemia.
test were normal, with no foetal or placental abnormalities on ultrasonography. In
DOI: 10.1530/endoabs.49.EP109
the middle of the third trimester hydrocortisone and fludrocortisone doses were
further ajusted to 35 mg and 0.15 mcg respectively. She underwent CS at the 39th
gestational week and a healthy baby girl weighing 3250 g was delivered. During
the 15-month follow-up period mother and baby were in good condition.
We presented a case of women with autoimmune polyglandular syndrome
(APS 2) and succesful pregnancy outcome. Women with PAI should be
EP110
monitored by a multidisciplinary team throughout pregnancy to ensure maternal
Mature ganglioneuroma of the adrenal gland
and foetal health.
Betul Aydin Buyruk1, Medine Nur Kebapci1, Goknur Yorulmaz1,
DOI: 10.1530/endoabs.49.EP111
Evrim Yilmaz2 & Enver Ihtiyar3
1Department of Endocrinology, Eskisehir Osmangazi University Medical
Faculty, Eskisehir, Turkey;2Department of Pathology, Eskisehir Osmangazi
University Medical Faculty, Eskisehir, Turkey;3Department of General
Surgery, Eskisehir Osmangazi University Medical Faculty, Eskisehir,
Turkey.
EP112
Paraganglioma (PG) and cyanotic congenital heart disease (CCHD): the
Introduction
role of tisular hypoxia
Ganglioneuroma is an extremely rarely seen tumour in the adrenal gland, which
Amelia Oleaga, Fernando Gon˜i, Miguel Paja, Estibaliz Ugarte,
originates from neural crest cells. Clinically, they generally have a silent course
Cristina Moreno, Natalia Iglesias, Eider Etxeberria, Laura Calles,
and in laboratory tests, the hormone levels expressed from the adrenal gland are
Maddalen Dublang & Alba Zabalegui
within the normal range.
Basurto University Hospital, Bilbao, Vizcaya, Spain.
Case
A 46-year old male patient, for whom a mass in the adrenal gland was diagnosed
incidentally on abdominal ultrasonography and MRI. The physical examination,
Introduction
laboratory tests and hormonal tests were within normal limits. As the appearance
CCHD comprises a number of different congenital heart defects associated with
on dynamic adrenal CT was compatible with an adenomatous lesion, a biopsy was
elevated pulmonary artery pressure and pulmonary vascular resistance, resulting
applied to the left adrenal gland. In the histopathological examination, findings
in a reversed or bidirectional shunt (Eisenmenger syndrome). These entities
were determined of neuroblastic tumour and ganglioneuroma, so adrenalectomy
develop systemic hypoxia. Pheochromocytoma and paraganglioma (PHEO/PG)
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
are neuroendocrine tumours. Several inheritance genetic alterations have been
EP114
reported in PHEO/PG syndromes. A pathogenic association between these
Large adrenal adenoma presenting as a clinically inapparent Cushing
entities is proposed.
syndrome, a trap diagnosis
Case report
Denisa Petrescu1, Cristina Alina Silaghi2, Doina Crisan3, Daniel
A 41-year-old female diagnosed of a CCHD in the new-born period, on stable
Tudor Cosma4, Ionela Lungu1, Carmen Emanuela Georgescu2,
medical treatment, as surgery was rejected. She presented with symptoms
Romeo Ioan Chira5 & Horatiu Silaghi6
suggesting exacerbation of heart failure. Catecholamine hypersecretion was
1County of Emergency Hospital, Cluj-Napoca, Romania;2Department of
suspected; 24 hour urine metanephrine: 215 mg/24 h (NV!341) and normeta-
Endocrinology, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy,
nephrine
(NM): 2491 mg/24 h (NV!444). Abdominal CT showed a retro-
Cluj-Napoca, Romania;3Discipline of Pathology, Department of Morpho-
peritoneal lesion consistent with a PG. Functional imaging with Iodine123MIBG
logical Sciences, ‘Iuliu Hatieganu’ University of Medicine and Pharmacy,
showed a pathological uptake area at the same localization. No other pathological
Cluj-Napoca, Romania;4Diabetes, Nutrition and Metabolic Diseases
images were observed. Genetic testing was performed and no mutations in
Clinical Center, Cluj-Napoca, Romania;5Ist Internal Medicine Department,
SDHD, SDHC, SDHB, VHL, SDHAF2, MAX and TMEM127 genes were found.
‘Iuliu Hatieganu’ University of Medicine and Pharmacy, Cluj-Napoca,
She underwent surgery after alpha blockade. Pathological examination confirmed
Romania;65th Department of Surgery, ‘Iuliu Hatieganu’ University of
the diagnosis of a PG. NM became normal after surgery and patient symptoms
Medicine and Pharmacy, Cluj-Napoca, Romania.
improved.
Discussion
Several hypoxemic phenomenon have been related to be implicated in the
Adrenal incidentalomas (prevalence between 0.4 and 7%) have become a very
pathogenesis of PHEO/PG, as it is known that some of the genetic alterations
common clinical problem, the major concern being the risk of malignancy and
(SDHx, VHL, HIF2) lead to enhanced production of hypoxia inducible factors,
hormone overproduction.
which induce an increase in angiogenic factors leading to the development of
A 57-year-old woman was admitted for asthenia and uncontrolled hypertension.
tumours. The patient had an evolved heart disease with significant cyanosis.
The only relevant clinical signs were abdominal obesity (BMIZ31.1 kg/m2) and
Chronic exposure to hypoxia in patients with CCHD could increase the risk for
hypertension. Abdominal ultrasonography showed a voluminous left adrenal
developing PHEO/PG. In addition, the noradrenergic biochemical phenotype
solid mass of 10/9 cm, with well-defined sharp borders, hypoechoic with necrotic
found agrees with that observed in some of the PHEO/PG syndromes. In patients
areas and hyperechogenic foci of scars and calcifications. The differential
with CCHD the diagnosis of PHEO/PG can be difficult to suspect because
diagnosis of an atypical adenoma and pheochromocytoma or adrenocarcinoma
symptoms may be confounding, nevertheless catecholamine excess may be
was difficult.
dangerous. Therefore we consider that the existence of a PHEO/PG should be
Laboratory assays revealed hypercortisolism, indicated by the loss of the
ruled out in patients with CCHD and aggravation of the previous heart function.
circadian rhythm of cortisol secretion: cortisol value at 8 a.m. of 7.84 mg/dl and at
DOI: 10.1530/endoabs.49.EP112
midnight of 11.2 mg/dl, elevated free 24 h urinary cortisol of 731.4 mg/24 h
(normal range: 50-190 mg/24 h), no suppression at overnight dexamethasone
suppression test (cortisol of 5.46 mg/dl), low ACTH level of ! 1 pg/ml and
decreased cortisol level !50% at the high dose dexamethasone test. Plasmatic
metanephrines, normetanephrines, renine and aldosterone were normal. Abdomi-
nal CT scan indicated a tumoral left adrenal mass of 10/8.5/8.5 cm, well defined,
inhomogeneous, with microcalcifications, !10 HU, induced caudal displacement
of the left kidney, no lymphadenopathy or other visceral involvement. She
underwent left laparoscopic adrenalectomy. The histopathological evaluation
EP113
indicated Ki67!1% and chromogranin, synaptophysin, calretin, protein S100,
inhibin were isolated low positive; PanCK, EMA were negative; CD31 showed
Von Hippel Lindau disease in two Turkish families with different
the capillary network, without emboli; vimentin was positive; suggesting an
mutations
atypical adenoma and excluding an adrenocarcinoma, a kidney and liver tumor,
Mine Ada¸, İlkim Deniz Toprak & Recep Yılmaz Bayraktarli
but also a pheochromocytoma. Two weeks after surgery, a large ischemic
Istanbul Okmeydani Education and Research Hospital, Istanbul, S¸ i¸li,
vascular attack occurred, with poor prognosis. We should keep in mind that
Turkey.
voluminous cortisol-producing adrenal adenomas could have clinically inappar-
ent features, but with hidden vascular damages and increased cardiovascular risk.
Von Hippel-Lindau (VHL) disease is an inherited, autosomal dominant syndrome
DOI: 10.1530/endoabs.49.EP114
manifested by a variety of benign and malignant tumors. Herein we describe, two
families who had VHL. A 21-year-old man (index case 1) presented with bilateral
adrenal mass, serendipitously discovered by radiologic examination. He had
newly diagnosed arterial hypertension. His family history was significant for his
mother who had operated for pheochromocytoma, his two uncles who had
experienced cerebral tumors and his mother’s cousin who had bilateral
pheochromocytoma. After the diagnosis of bilateral pheochromocytoma, bilateral
EP115
adrenalectomy was performed. Histopathological data correlated with pheochro-
NK/T lymphoma adrenal presenting as adrenal insufficiency and
mocytoma. A genetic test was carried out. A germline mutation p.R167Q
cranial nerves neuropathies-a case report
(c.500GOA) was detected in the patient confirming VHL. A further genetic test
Shalini Sree Dharan, Norazizah Aziz, Shueh Lin Lim &
was prescribed in other family members. His mother had a history of cystic
Pavitratha Puspanathan
astrocytoma, meningioma, hemangioblastoma and right adrenalectomy for
Penang General Hospital, Penang, Malaysia.
pheochromocytoma. A germline mutation p.R167Q (c.500GOA) was detected,
too. Index case 1’s brother had a history of arterial hypertension and the germline
mutation p.R167Q (c.500GOA) was detected, too. Index case 1’s mother’s
Adrenal Lymphoma is extremely rare with fewer than 200 cases reported. The
cousin had a
24-year history of hypertension. He had experienced right
most common subtype is the diffuse large B cell lymphoma. Malignant lymphoma
adrenalectomy
24 years ago and left adrenalectomy
4 years ago with the
arising in the endocrine glands represents only 3% of extranodal malignant
diagnosis of pheochromocytoma. The germline mutation p.R167Q (c.500GOA)
lymphomas and is usually confined to the thyroid gland. NK/T-cell lymphoma
was detected, too. A 43-year-old woman (index case 2) was referred from the
presents primarily in the nasopharynx and sinuses. Although involvement of the
cardiology department to our outpatient clinic to examine the etiology of
adrenal glands can be seen in disseminated disease, primary presentation with
endocrine-induced arterial hypertension (150/90 mmhg). After the diagnosis of
adrenal masses and adrenal insufficiency is extremely rare. We report a case of 34
pheochromocytoma, the right adrenalectomy was performed. 5 years after the
years old gentleman presenting with prolonged fever, constitutional symptoms
operation she had operated for the pancreatic neuroendocrine tumor and 15 years
and symptoms and signs of adrenal insufficiency. He was treated as adrenal crisis
after the operation she was diagnosed as hemangioblastoma. A genetic test was
in the district hospital with hypotension, hyponatremia, and hyperkalemia. He
carried out. A germline mutation p.L118R was detected in the patient. A genetic
appeared cachexic, with no hyperpigmentation or palpable lymph nodes. His
test was prescribed to the other members of the family. Her two boy’s genetic tests
lactate dehydrogenase enzymes (LDH) was elevated. Cortisol taken during this
were detected the same mutation. All patients with pheochromocytomas should
stressful period was deemed too low. This was confirmed by an inadequate
be screened for the genetic syndromes for example MEN 2 and VHL. It is
response to the Synacthen test. CT Adrenal was performed and reported as
important for averting the further morbidity and mortality in the patients and their
bilateral enlarged adrenal, likely hyperplasia. He developed multiple cranial
families. Family screening is crucial in patients who are diagnosed with the
nerves neuropathies that progressively worsened. CT Brain was normal. Lumbar
disease.
puncture revealed high opening pressure and CSF biochemistry revealed no cells
DOI: 10.1530/endoabs.49.EP113
and negative for tuberculosis. With the possibility of disseminated tuberculosis,
empirical anti-tuberculosis medications were started but failed to abate his
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
symptoms. Laparoscopic left adrenal excision biopsy was performed and
Results
histology features are in keeping with high grade NK/T cell lymphoma. His
A 61-year woman was admitted for a right adrenal and a thyroid incidentaloma
condition deteriorated fast and he succumbed to his illness. This case illustrates
after left UN for renal cancer with clear cells, Fuhrman Nuclear Grade of 2
the need to include Primary Adrenal Lymphoma in the differential diagnosis of
(pT3N0Mx). Post-operatory endocrine panel of investigations were consistent for
adrenal masses especially when adrenal contour is preserved on imaging,
non-secretor low risk lesion. A fine needle aspiration biopsy at thyroid excluded a
hypoadrenalism and high LDH.
second malignancy. A 56-year old female had left UN 14 years ago for a benign
DOI: 10.1530/endoabs.49.EP115
condition. One year after surgery a right adrenal tumour of 1.2 cm was discovered
at CT
(computer tomography) scan. After
13
years, the subject became
hypertensive and experienced hot flushes in association with secondary
amenorrhea so an endocrine evaluation was considered. Non-secretor adrenal
profile and high Follicle Stimulant Hormone consistent for physiological
menopause was associated with stationary CT aspects for right adrenal tumor
EP116
but also a left adrenal tumor of 1.3 cm was identified. Nevertheless, abdominal
Primary hyperparathyroidism and primary hyperaldosteronism -
CT scan performed 1 year later showed similar aspects. Further serial imaging
cause or coincidence in arterial hypertension - case report
was recommended.
Tijana Icin1,2, Ivana Bajkin1,2, Dusan Tomic1, Jovanka Novakovic-Paro1,2,
Discussion
Bojan Vukovic1,2, Jovana Prodanovic1 & Milica Medic-Stojanoska1,2
Adrenal incidentaloma discovered in menopausal patients with UN requires a
1Clinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical
complex differential diagnosis including the fact that they need to be
Center of Vojvodina, Novi Sad, Serbia;2Department of Internal Medicine,
differentiated from metastases arising from kidney cancer. Also, serial imaging
Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
assessments after kidney removal may lead to the discovery of different solid
masses as thyroid incidentaloma or nodules.
Introduction
DOI: 10.1530/endoabs.49.EP117
30% of the adult population has high blood pressure. About
6% of the
hypertension may be caused by primary aldosteronism and very rare by primary
hyperparathyroidism. The combination of these two causes is very rare.
Case report
Our patient is women (age 50) with a 21 year long history of uncontrolled
hypertension. Treatment of hypertension consist of a beta-blocker, calcium
EP118
channel blockers, angiotensin converting enzyme inhibitor, loop diuretics and
Case with metastatic lung cancer who developed adrenal insufficiency
thiazide diuretics. Laboratory tests confirmed the presence of hypercalcemia
Buket Yilmaz Bulbul1, Ece Celik2, Mehmet Celik1, Semra Ayturk1,
(ionized calcium 1.42 mmol/l), and hypokalemia (3.4 mmol/l). After correction
Funda Ustun3 & Sibel Guldiken1
of medical therapy results shows elevated levels of parathyroid hormone
1Department of Endocrinology and Metabolism, Medical Faculty, Trakya
(221.7 pg/ml) and aldosterone/renin ratio (A/RO30), normal value of metane-
University, Edirne, Turkey;2Department of Chest Diseases, Edirne Sultan 1.
phrines and normetanefrine, normal ACTH and cortisol levels and diurnal rithm
Murat State Hospital, Edirne, Turkey;3Department of Nuclear Medicine,
of secretion. CT of the abdomen showed adenoma like enlargement of left adrenal
Medical Faculty, Trakya University, Edirne, Turkey.
gland of
2 cm. Scintigraphy and ultrasound confirmed the presence of
hyperplasia/adenoma of the lower left parathyroid gland. Bone mineral density
indicates osteoporosis and ultrasound of abdomen described nephrolithiasis in the
Adrenal metastasis is common (35%) among the patients with lung cancer, while
left kidney. Due to hypercalcemia, first we have decided to operate the
less than
3% of the patients develop bilateral adrenal metastasis. Adrenal
parathyroid glands. Surgery leads to normalization of calcium. The pressure is
metastases are generally small and clinically asymptomatic. Adrenal insufficiency
regulated without both the diuretics at a reduced dose of a calcium channel
is rare despite the presence of adrenal metastasis. Lam et al. reported this ratio as
blockers. After recovering from surgery, in a hospital setting we discontinued
0.7%. We aimed to present a case with lung cancer and bilateral adrenal
therapy and dynamic testing was conducted (volume loading test and postural
metastasis who developed adrenal insufficiency.
stimulation test) that indicate adrenal hyperplasia as a cause of primary
A 63-year old male patient was presented with cough. Chest X-ray revealed a mass
hyperaldosteronism. Patient started with spironolactone therapy that even in
lesion in the upper zone of left lung. PET/CT examination was performed and
small doses leads to normalization of potassium and reduce the need for other
demonstrated increased FDG uptake in upper lobe mass lesion of left lung,
antihypertensive agents.
mediastinal lymph nodes, bilateral surrenal glands (9 mm at the right and 5.5!
Conclusion
2 cm at the left),liver and bones. Following bronchoscopy, the patient was
More endocrine disorders can simultaneously affect arterial hypertension.
diagnosed with non-small cell lung cancer. Pathologic examination of surrenal
Treatment of hyperparathyroidism may lead to better control of hypertension.
biopsy material revealed surrenal metastasis. The patient had no signs of adrenal
Despite the existence of left adrenal enlargement that looks like an adenoma,
insufficiency and electrolyte imbalance at the time of diagnosis. He was scheduled
adrenal hyperplasia is a possible cause of primary hyperaldosteronism.
for cisplatinCgemcitabine chemotherapy. Although lung and adrenal gland
DOI: 10.1530/endoabs.49.EP116
lesions were stable within
6 months after treatment, the patient developed
hypoglycemia, hypovolemia, hyponatremia and hyperkalemia. Laboratory
examination revelaed ACTH:1250 pg/ml (normal: 0-46), and cortisol 4.43 mg/dl
(n:5-29). The patient was given prednisolone and fludrocortisone treatment with
the diagnosis of adrenal insufficiency. Symptoms of the patient were subsided after
treatment. Post-treatment laboratory examination revealed Na:138 mEq/l
EP117
(normal:135-145), K: 4 mEq/L/normal:3.5-5.5) and ACTH:37 pg/ml.
Endocrine masses displayed as incidentalomas in patients with
It should be considered that patients with lung cancer and adrenal metastasis may
unilateral nephrectomy
later develop adrenal insufficiency despite the absence of adrenal insufficiency at
Adina Ghemigian1, Eugenia Petrova2, Nicoleta Dumitru2, Andra Buruiana2,
the time of diagnosis. Although fatigue, nausea, hypotension and hyponatremia
Mara Carsote1 & Ana Valea3
may also be seen in the patients with cancer, these may also be the signs of adrenal
1C.Davila UMPh & I.Parhon National Institute of Endocrinology,
insufficiency.
Bucharest, Romania;2Parhon National Institute of Endocrinology,
DOI: 10.1530/endoabs.49.EP118
Bucharest, Romania;3I.Hatieganu UMPh & Clinical County Hospital,
Cluj-Napoca, Romania.
Introduction
Menopausal adrenal tumours may be elements of a complex panel of
co-morbidities. Some of these are represented by the presence of a second
EP119
pathology requiring surgery at the kidney level.
Adrenal haemorrhage: from Urology to Endocrinology
Aim
Catarina Silvestre, Ana Gomes, Raquel Carvalho & Maria João Bugalho
We aim to introduce a series of two cases involving menopausal women who were
Santa Maria Hospital, Lisbon, Portugal.
referred for specific endocrine assays after they had a unilateral nephrectomy
(UN).
Method
Background
This is a cases series observational study. The patients gave their consent. They
Bilateral adrenal haemorrhage (Waterhouse-Friderichsen syndrome) is a rare
were followed in different medical and surgical centres from Romania.
consequence of sepsis (usually a result of meningococcal infection), with an
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
estimated 15% mortality. Despite the predominant association with meningo-
EP121
coccal infection, there are other recognised aetiologies: sepsis resulting from
A rare case: adrenal lymphangioma
other organisms, and non-infectious causes, such as anticoagulant treatment,
Yusuf Durmus1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
trauma and postoperative adrenal haemorrhage.
Nuray Can3, Ebru Tastekin3 & Sibel Guldiken2
Case report
1Department of Internal Medicine, Medical Faculty, Trakya University,
A 53-year-old man was admitted in the Urology department, to undergo a
Edirne, Turkey;2Department of Endocrinology and Metabolism, Medical
retropubic radical prostatectomy
(prostatic adenocarcinoma). Other medical
Faculty, Trakya University, Edirne, Turkey;3Department of Pathology,
history: thromboangiitis obliterans, managed with warfarin and acetylsalicylic
Medical Faculty, Trakya University, Edirne, Turkey.
acid. No complications on the postoperative period; prophylactic antibiotherapy
was started with ceftriaxone. On the 7th postoperative-day, the patient had a
lipothymia episode, with a decrease of consciousness level
(Glasgow
9),
Adrenal lymphangioma is a rare benign tumors of the adrenal gland. Because of
hypotensive and subfebrile condition. Blood evaluation consistent with sepsis:
the increased use of imaging methods in recent times, the diagnosis is usually
leukopenia, thrombocytopenia, raised transaminases, C-protein reactive and
made incidentally. It is usually due to malformation between the lymphatic and
troponin, and severe hyposmolar hyponatremia
(113 mEq/l). No anomalies
the venous system. Those with small indiameters are generally asymptomatic
detected on neurologic evaluation or cranial computerized-tomography (CT).
and can be evacuated by needlea spiration. However, surgery is recommended
Antibiotherapy was changed to Piperacillin-Tazobactam. A random ACTH,
for cysts over 6 cm in diameter due to risk of infection, bleeding, compression of
cortisol and TSH were performed as workup for hyponatremia: ACTH 141 pg/ml
neighboring organs, and perforation. A 45-year-old male patient was admitted
(0-46), cortisol 2.5 ug/dl (4.3-23), normal TSH. Abdominal CT scanning was
due to left abdominal pain and swelling for 2 months. There was no chronic
performed: grossly abnormal adrenal glands bilaterally, with masses compatible
disease or drug use in hisstory. Blood pressure: 130/80 mm/hg, pulse rate was
with hematomas. On the 8th day he began intravenous hydrocortisone in high
94/min. Ultrasonography revealed a grade II hepatosteatosis in the liver and a
doses, with recovery of natremia and consciousness level. Blood and urine
70 mm multilocular cystic lesion in the left suprarenal region. A mass lesion
cultures results were negative (probably “decapitated”). When discharged, the
with multilocule cystic components was observed in the abdominal MRI was T1
patient was asymptomatic, with normal blood evaluation, and taking long-term
hypointense, T2 hyperintense in the left adrenal gland and 75 mm in diameter.
hydrocortisone and fludrocortisone. So far, the patient has been asymptomatic and
There were no blood pressure attacks, flushing and palpitations. In laboratory
is being monitored by the Endocrinology department.
tests: sodium 138 mmol/l (n:135-145), potassium 4.3 mmol/l (n:3.5-5.5), ACTH
Conclusions
27.4 pg/ml (n:0-46), basal cortisol 15.83 mg/dl (n:5-29), 1 mg dexamethasone
This case highlights the importance of awareness for symptoms/signs and
supression test
0.83 mg/dl (!1.8) was detected. Plasma aldosterone-to-renin
electrolyte variation when assessing surgical patients post-operatively. The early
ratio was!10, metanephrine and normetanephrine were normal in 24 hour
recognition of this disease allowed immediate treatment, avoiding a worse
urine.
outcome and leading to a quick recovery. There are risk factors, as antic-
Laparoscopic left surrenalectomy was performed for the hormone inactive mass.
oagulation therapy, predisposing the development of this rare, but serious,
Pathologic examination revealed D2.40 positive, CD34 positive, MelanA on
disease.
cystwall as local positive lymphangioma. The patient was asymptomatic for
DOI: 10.1530/endoabs.49.EP119
8 months. We aimed to present the rare case of adrenal lymphangioma in
ourcase.
DOI: 10.1530/endoabs.49.EP121
EP120
EP122
Hemangioma a rare adrenal tumors: report of two cases
A rare case of a patient with MEN 4 phenotype and associated
Aribi Yamina, Bensaleh Meriem, Brakni Lila, Iabassen Malek &
pheochromocytoma
Ould Kablia Samia
Alexandra Mirica1, Rodica Petris1, Radu Mirica3, Sorin Paun2,4 &
Central Hospital of the Army, Algiers, Algeria.
Diana Loreta Paun1,2
1C.I.Parhon National Institute of Endocrinology, Bucharest, Romania;
Introduction
2Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
Dramatically with increased use of computed tomography (CT) and magnetic
3Saint John Emergency Hospital, Bucharest, Romania;4Floreasca
resonance imaging (MRI), more and more uncommon adrenal masses have been
Emergency Hospital, Bucharest, Romania.
detected at abdominal examinations. Adrenal cavernous hemangiomas (ACH) are
rare vascular tumor. The first case report was published in 195 by Johnson and
Introduction
Jeppesen. Approximately less than 70 cases were reported in the literature to date.
MEN4 syndrome is a recently described form of MEN in patients with parathyroid
ACH are nonfunctioning benign tumors that is often discovered incidentally.
and anterior pituitary tumors, which may also develop bronchial, gastric and
They are more frequent in women in the 5th or 7th decade. Their differential
pancreatic neuroendocrine tumors. In general, the patients present with clinical
diagnosis preoperatively is rather challenging.
signs of primary hyperparathyroidism and simptoms caused by pituitary hormones
These tumors are unilateral lesions in general large and most usually cavernous.
hypersecretion or due to the tumor mass. However, clinical cases with the
All cases reported were treated with surgery.
coexistence of pituitary tumors and pheochromocytoma are very rare described.
Case report
Case presentation
We describe two cases of ACH in a 66 years old woman and a 36 years old men.
We present a young male patient of 44 years old, who presented in our department
In the first case ACH was discovered as incidentaloma and in the second it was
for endocrinological pre-operative assessment of a pituitary macroadenoma. The
revealed by flank pain.
brain MRI indicated a macroadenoma (31/30/21 mm) with supra- and para-sellar
The diagnostic was performed on ultrasonography. Because of the impossibility
extension, compressing the optic chiasm, optic tract and the 3rd cranial nerve on the
of ruling out the presence of malignancy (CT, MRI), surgical adrenalectomy was
right side. The patient accused acute right blindness starting 2 weeks ago, denying
performed. The patients did well postoperatively. Pathological examination
other simptoms. On clinical examination, the patient was obese (BMIZ36 kg/m2)
revealed that the adrenal masse corresponded to an ACH.
and hypertensive (BP Z170/100 mmHg). In addition, personal and family medical
Discussion
history were not significant, excepting personal arterial hypertension debut at 36
ACH is an uncommon benign vascular tumor. These rare tumors usually localized
years old. Endocrinological evaluations showed normal levels of pituitary, thyroid,
in the liver and the skin. Adrenal site is extremely rare occurring only in 0.01% of
mineralocorticoid and glucocorticoid hormones. However, there were detected
cases and accounts for 63 reported cases in the literature.
elevated values of parathyroid hormone
(110 pg/ml), plasmatic and urinary
ACH are often discovered as incidentalomas either by imaging studies or
normetanephrines (250 pg/ml and 900 ug/24 h) and plasmatic chromogranin A
histologic examination.
(230 ng/ml). Furthermore, abdominal computed tomography have identified a left
The indications for resection of this neoplasm particularly in tumours more than
adrenal nodule of 1.02/1.14 cm with no other lesions. Thus, in the first instance, the
3 cm in diameter are to relieve the mass-effect-type symptoms, to exclude
patient underwent laparoscopic left adrenalectomy and afterwards transsphenoidal
malignancy, and to treat complications such as haemorrhage, necrosis and
pituitary surgery, after which he regained visual acuity of the right eye and also it
thrombosis.
was obtained normalized blood pressure values. Adrenal histopathology confirmed
DOI: 10.1530/endoabs.49.EP120
the presence of pheochromocytoma. Blood samples were collected for genetic
testing.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
EP125
We present the case of a young patient with pituitary non-functioning
Incidentaloma as a first manifestation of lymphoma
macroadenoma and hyperparathyroidism (MEN4syndrome), also associating
Pamela R. Chávez Díaz, Cristina Álvarez Escola, Miriam Zapatero Larrauri,
left pheochromocytoma.
José Tomás Castell Gómez, Alfredo Aguilera Bazán & Lucrecia Herranz de
Keywords: MEN 4 phenotype; pheochromocytoma.
la Morena
DOI: 10.1530/endoabs.49.EP122
Hospital U. La Paz, Madrid, Spain.
Introduction
Incidentally discovered adrenal masses (incidentalomas) are common and in
some cases differential diagnosis could be a challenge.
EP123
Case report
The difficulty in predicting aggressive tumour behaviour of
A 55-years old woman presented with an incidental left adrenal mass of 36mm
phaeochromocytomas
discovered on an abdominal ultrasound. As sole background she underwent
Edouard Mills, Ali Naqvi, Roberto Dina, Fausto Palazzo & Florian Wernig
resective surgery of an ovarian serous cyst. She denied symptoms like flushing,
Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust,
headache, diaphoresis or palpitations. Physical examination was irrelevant. BP:
London, UK.
130/76 mmHg; CF:78 bpm.
Fractionated metanephrines and catecholamines in a 24-hour urine specimen,
sodium and potassium levels, 24-hour urinary free cortisol, adrenocorticotropic
Phaeochromocytoma and paragangliomas
(PH/PG) are rare neuroendocrine
hormone, aldosterone/plasma renin plasma ratio and dehydroepiandrosterone
tumours. Prediction of aggressive tumour behaviour remains a major challenge.
sulfate were normal.
The Phaeochromocytoma of the Adrenal gland Scaled Score (PASS) is used to
Abdominal computed tomography showed an heterogeneous left adrenal gland
separate benign from malignant lesions with a score O 4 showing potential for
and multiple nodes in locations such as subdiaphragmatic region, celiac trunk,
biologically aggressive behaviour. Pre-operatively, MIBG together with CT/MRI
gastrohepatic ligament, splenic hilum and retroperitoneal area, most of them with
remain the diagnostic radiological gold standard.
the presence of central necrosis.
We report a 68-year-old female who was found to have a locally arising colonic
Additionally axillary and paratracheal nodes were found, and also lungs nodules
adenocarcinoma on biopsies. Staging also identified a 10.7 cm right adrenal lesion
less than 5mm in diameter were described. PET F-18 FDG scan identified an
and work-up revealed markedly raised urinary metanephrines and positive MIBG
hypodense centrum area suggestive of necrosis into the left adrenal. A
imaging. The MDT decision was to first remove the colonic cancer with
tomography guided biopsy only detected necrotic cells. Finally a left
appropriate alpha blockade. It was felt that a combined laparoscopic approach
adrenalectomy was performed and histopathological study revealed a diffuse
would not be appropriate given the adrenal lesion size, which might require an
large B-Cell non-Hodgkin’s lymphoma. The patient was started on chemotherapy
open procedure. Histology confirmed a stage III Duke’s C tumour and adjuvant
with a successful response.
chemotherapy commenced. Although adrenal surgery had been planned once she
Conclusion
completed chemotherapy, she did not tolerate chemotherapy and it had to be
Biopsy could be necessary in the differential diagnosis of necrotic adrenal masses
discontinued. An open adrenalectomy was undertaken. Histology was consistent
even when lymph nodes are present.
with a phaeochromocytoma with a PASS score of eight. 2 months after adrenal
DOI: 10.1530/endoabs.49.EP125
surgery, she reported intermittent tingling and numbness in the left arm with
thoracic back pain. An MRI confirmed a soft tissue mass at T2 extending into the
spinal cord. Urinary metanephrines confirmed persistently elevated normeta-
drenaline levels. She underwent bilateral laminectomy under alpha-blockade.
Histology confirmed a metastatic phaeochromocytoma. She is currently awaiting
Ga68-DOTATATE PET-CT imaging to guide further management.
Ga68-DOTATATE PET-CT has been shown to be the most sensitive imaging
modality for detection of metastatic PH/PG and would potentially have identified
metastatic lesion(s) not seen on MIBG scanning. We therefore propose that Ga68-
EP126
DOTATATE PET-CT - where available - should be used for initial staging and
Clinical case of aldosterone-producing adrenocortical carcinoma
MIBG should be reserved for those patients only for whom MIBG therapy is
Alexey Krivosheev1, Iya Voronkova1,2, A Platonova1 & Timur Britvin1
being considered.
1Moscow Regional Research and Clinical Institute, Moscow, Russia;
DOI: 10.1530/endoabs.49.EP123
2Endocrinology Research Centre, Moscow, Russia.
Aldosterone-secreting adrenocortical carcinoma (ACC) is rare neoplasm, which
detected in 2.5% of active ACCs.
EP124
Clinical case
A 58 years old female, was admitted to our clinic with complaints of high blood
An unusual cause of unilateral adrenal haemorrhage
pressure, back pain, weakness, convulsions. Biochemical evaluation confirmed
Jayamalee Jayaweera1, Emily Symington2 & John Clark1
primary hyperaldosteronism
(serum aldosterone
1012 pg\ml, serum renin
1West Suffolk Hospital, Suffolk, UK;2Addenbrookes Hospital-Cambridge
concentration
0.5 mkME\ml, aldosterone-renin ratio
202.4, hypokalemia
University Hospitals, Cambridge, UK.
1.2 mmol\l). There was no evidence of cortisol co-secretion on standart low-
dose dexamethasone test. The level of metanephrine and normetanephrine in
A 24 year old man was admitted by the Surgeons with left sided abdominal pain. He
urine were in normal range. A CT scan with contrast-enhanced identified right
was febrile and tachycardic and found to have raised inflammatory markers.
adrenal tumor 8*6*9 cm with heterogeneous structure. Native density of tumor
Abdominal CT scan revealed a 6 cm left adrenal haemorrhage with no evidence of
was 38 Hounsfield units (HU). In arterial and venous phase tumor density was 70
an underlying lesion. Initial endocrine investigations were unremarkable for
HU, delayed - 55 HU. Dynamics of growth was C5 cm in 6 months. Surgical
Cushings, Conn’s and adrenal insufficiency. Norepinephrine levels were high but
treatment was performed: in the right retroperitoneal there was tumor about 15 cm
settled subsequently. He had a coagulopathy and evidence of reactivation of EB virus.
in diameter, comressed the inferior vena cava, right renal artery, and renal veins.
He had a past history of Multiple sclerosis treated eighteen months previously with
Adrenalectomy with a tumor and lymph node dissection was performed.
Alemtuzumab.
Histological examination revealed adrenocortical cancer. Ki-67
expression
He remained febrile and developed acute kidney injury. His symptoms and signs
was up to 75% in ‘hot spots’. Number of Weiss score - 6. A 1.5 month follow-
fitted the criteria for haemophagocytic lymphohistiocytosis (HLH), confirmed on
up CT-scan was no evidence of local reccurence. Serum aldosterone level was in
bone marrow biopsy. His coagulopathy was due to antibodies to factor VIII (acquired
normal range.
haemophilia) and he developed autoimmune thyroiditis requiring Thyroxine
Although rare, this case demonstrates the ability of this pathology, and therefore
replacement. His HLH was successfully treated with steroids and Rituximab.
requires caution against the ACC at the small size of the tumor. As a method of
We think Alemtuzumab treatment had induced the autoimmune disorders (his
follow-up screening can be a controlling level of aldosterone and potassium in the
coagulopathy and thyroid disease), as well as reactivating EB virus. The combination
blood and monitoring blood pressure. To improve the results of treatment these
of coagulopathy and EB viral infection may have caused his adrenal haemorrhage.
patients it is necessary to conduct studies with larger numbers of patients, as well
Endocrinologists should be aware of the wide spectrum of autoimmune disorders that
as development of new diagnostic and prognostic criteria allowing to improving
can be precipitated by monoclonal antibody treatment.
diagnosis ACC before and after surgery.
DOI: 10.1530/endoabs.49.EP124
DOI: 10.1530/endoabs.49.EP126
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP127
tumours with supressed renin but inappropriate low aldosterone, not suggesting
PA. Early diagnosis can be very important because malignancy is the rule in this
The case of adrenal incidentaloma due to unrecognized nonclassic
peculiar pathology.
congenital adrenal hyperplasia
Milina Tancic-Gajic, Miomira Ivovic, Ljiljana Marina, Zorana Arizanovic,
DOI: 10.1530/endoabs.49.EP128
Zorana Stojanovic, Aleksandra Kendereski & Svetlana Vujovic
Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic
Diseases, Clinical Center of Serbia, University of Belgrade, Belgrade,
Serbia.
EP129
Introduction
Aldosterone-producing adrenocortical carcinoma and alteration of
A rare cause of adrenal incidentaloma is congenital adrenal hyperplasia (CAH).
secretion pattern on recurrence: a case report
Nonclassic CAH is one of the most frequent autosomal recessive disorders. Most
Joana Lima Ferreira, Ana Paula Marques, Carlos Sottomayor &
cases of nonclassic CAH are never diagnosed due to very mild symptoms.
Vitor Valente
Case report
Hospital Pedro Hispano, ULS Matosinhos, Portugal.
A 62-year-old woman admitted at our Department for right adrenal incidentaloma
sized 39!34!38 mm confirmed by MRI. She was asymptomatic. Her past
Introduction
medical history included stabile hypertension, euthyroid Hashimoto thyroiditis,
Adrenocortical carcinoma (ACC) is a rare neoplasm with a variable but overall
uterine leiomyoma, varicose vein surgery and pulmonary embolism. Menarche
poor prognosis. The presentation is heterogeneous usually with mass effect and
occured at the age of 18, and the monthly menstrual cycle continued until the
less often with evidence of hormonal secretion. About half of cases the tumors are
menopause at the age of 51. She had a miscarriage and three failed in vitro
hormonally active most commonly with cortisol secretion followed by sexual
fertilisation attempts. Upon physical examination clitoromegaly was present.
hormones production, being rare the aldosterone secretion.
Endocrine assessment for excess of cortisol, catecholamine and aldosterone
Case report
concluded that the adrenal mass was hormonally non-functioning. ACTH level
A 41-year-old male presented with hypertensive crisis and marked hypokalemia.
was normal. 17- hydroxyprogesterone, total testosterone, androstenedione and
A primary hyperaldosteronism was diagnosed and Computed Tomography (CT)
progesterone were elevated:
26 nmol/l,
3.4 nmol/l,
8.5 ng/ml,
16.2 nmol/l,
showed a 9 cm suspicious adrenal mass. The patient started on spironolactone and
respectively. A
0.25-mg intravenous ACTH-stimulation level of cortisol
underwent open adrenalectomy. A total resection was done (R0) and it was a
(341/347/402) and
17- hydroxyprogesterone
(29/51) showed partial cortisol
10 cm adrenal carcinoma, Weiss score 5, Ki67 30% and stage II ENSAT. There
insufficiency and nonclasssic CAH. After informed consent molecular genetic
was clinical and biochemical normalization and at 9 months CT didn’t show any
study for CAH was conducted. Our patient was found to be a heterozygote with
recurrence. Due to high risk carcinoma therapy with mitotane was proposed,
two mutations in the CYP21A2 gene: p.P30L i I2G, that verified the diagnosis of
however the patient refused and left follow-up. 30 months after surgery, he was
CAH. In order to prevent adrenal insufficiency Hydrocortisone was advised in a
admitted to the Emergency Department for adrenal carcinoma relapse and
case of surgical procedures or illness. During the 2 year follow-ups there were
disseminated metastatic disease with simultaneous secretion of aldosterone and
changes in either clinical and biochemical presentations or in repeated abdominal
cortisol. He started on chemotherapy with EDP-M (etoposide, doxorubicin,
MRI examinations.
cisplatin and mitotane). Despite initial favorable course, the patient got worse
Conclusion
with disease progression, culminating in death 44 months after the diagnosis.
Undiagnosed nonclassic CAH is the cause of miscarriage, infertility and adrenal
Discussion
incidentaloma in our patient. 17- hydroxyprogesterone would be determined in all
The management of ACC is challenging. Surgery is crucial for treatment and
patients with infertility or adrenal incidentaloma.
mitotane is important as an adjuvant therapy, as a chemotherapeutic agent and
DOI: 10.1530/endoabs.49.EP127
also to control the hormonal secretion. We report a case of an aldosterone-
producing ACC, an extremely rare cause of primary hyperaldosteronism. Even
rarer was the change on secretion profile throughout disease evolution with
multiple steroid production. The hormonal profile should be carefully
investigated in an ACC and the possibility of multiple combined hormonal
secretion or the shift of the profile secretion should be considered.
DOI: 10.1530/endoabs.49.EP129
EP128
DOC secreting adrenal adenoma, a rare cause of hypertension
Miguel Paja, Maddalen Dublang, Alba Zabalegui, Cristina Arrizabalaga,
Amaia Expósito & Javier Espiga
Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain.
EP130
Congenital adrenal hyperplasia: hazards of non-compliance with
treatment!
Secondary endocrine hypertension affects around
10% of all hypertensive
Mazhar Dalvi1 & Faisal Dalvi2
population, most frequently primary aldosteronism (PA). Less frequent forms
1Al Noor Hospital, Abu Dhabi, United Arab Emirates;2Aster Medical
of adrenal hypertension include pheochromocytomas and other causes of
Centre, Dubai, United Arab Emirates.
mineralocorticoid excess than PA, featuring suppressed renin without excess of
aldosterone. Featuring. We present a 29-year-old woman with difficult to control
hypertension diagnosed two years before and poor response to ACEI and ARA II
treatment. She was referred for study and treatment. She had a normal appearance,
A 30-year-old male presented to emergency with history of palpitations for
without Cushing’s stigmata, overweight nor clinical suspect of pheochromocy-
6 months. At birth he was diagnosed with salt-losing congenital adrenal
tomas. She had not noticed hirsutism and maintained regular menstrual cycles.
hyperplasia
(female pseudohermaphrodite) and commenced on steroid
Biochemical study was normal except for slightly lower potassium (3.48 mmol/l).
therapy. He also underwent corrective surgery. He needed both fludrocorti-
Hormonal study showed suppressed renin activity (!0.2 ng/ml per h), with
sone and hydrocortisone. At age 17, he visited urology because of bilateral
normal to low aldosterone (7.3 ng/dl), normal urinary metanephrines and normal
testicular enlargement. On examination he had normal secondary sexual
plasma ACTH (34.5 pg/ml). Abdominal CT revealed a well-defined hetero-
features, but his testicles felt hard and four times the normal size. His serum
geneous and much vascularized right adrenal mass of
6 cm in diameter.
testosterone level was
50.4 nmol/l
(10-38 nmol/l),
17-OH-progesterone
Deoxycorticosterone
(DOC) measured in previous stored sample was
142 nmol/l (!13 nmol/l) and ACTH (corticotrophin) of 139 ng/l (0-50 ng/l),
237.9 ng/dl (normal ! 15 ng/dl) with normal deoxycortisol (4.5 ng/ml; NV ! 7.2),
clearly indicating non-compliance. He had bilateral orchidectomy. Upon
testosterone, DHEAs and plasmatic and urinary cortisol. Open right adrena-
pathologic review, these lesions were most consistent with testicular tumors
lectomy was performed due to the size and suspicion of malignancy. On light
of the adrenogenital syndrome. Patient continued to default at clinic
microscopic examination, the tumour was an adenoma of
6.5 cm not
appointments. At age 26, he presented to the surgeon with increasing
encapsulated, composed of cells with clear and eosinophilic cytoplasm and
abdominal girth and abdominal pain. CT of the abdomen demonstrated very
large nuclei without mitosis nor necrosis. Weiss’s criteria classified it as
low-density adrenal masses (18!11 cm on the left side and 8!4.5 cm on
adrenocortical adenoma. Postoperatively, DOC level fell to 7.1 ng/dl and blood
the right side). Blood work up showed high 17-OH- progesterone indicating
pressure and potassium normalized.
inadequate suppression with glucorticoids partly due to non-compliance. As
Conclusion
these adenomas was new onset and there was a possibility of adrenocortical
DOCA-producing adrenal neoplasm are exceptionally reported, and they are
cancer the patient underwent laparoscopic bilateral adrenelectomy. The final
usually malignant tumours. They should be suspected in the presence of adrenal
histology to be consistent with adrenal myelolipomas. Hydrocortisone dose
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
was doubled and fludrocortisone 100 mcg/day was started. Now at age 30,
134/92 mmHg (sleep).
24-hour urinary levels of catecholamine and
he presented with history of palpitations and dizziness. He had sinus
metabolites were significantly higher than normal ranges; noradrenaline
tachycardia In ECG
(HR120/min). Blood work up: Na
130 mmol/l
was 787.99 mg/24 h, dopamine 3635.43 mg/24 h, normetanephrine 1605.31
(135-145 mmol/l) K
5.33 mmol/l
(3.5-5.1 mmol/l) Plasma renin
mg/24 h. MR imaging revelaed a heterogeneous lesion (49!37 mm) in the
100 mIU/ml (!40 mIU/ml). This indicated under replacement. He was clearly
left adrenal gland. Because of the early stage of pregnancy laparoscopic
tachycardic because of volume depletion. His compliance was enforced.
surrenalectomy was performed. Histopathologic examination revealed a
Within 6 weeks his heart rate normalised with normalisation of renin levels.
tumor consistent with pheochromocytoma. In the follow-up, there was no
Persons with CAH are at increased risk of developing adrenal myelolipomas,
maternal problem except hypotensive state but unfortunately, because of
testicular adrenal rest tumours particularly if their CAH is poorly controlled.
anhydramnios and intrauterine growth retardation, medical abortion was
DOI: 10.1530/endoabs.49.EP130
applied at the 27th gestational-week. Pheochromocytoma is a very rare
cause of hypertension in pregnancy however, early detection are crucial
because of the increased risk of maternal-fetal mortality. Therefore, in cases
of high blood pressure which can not be explained by gestational
hypertension, it is necessary to carefully evaluate other secondary causes
such as pheochromocytoma. The most suitable period for the operation is the
second-trimester. Surgical approach was used and no complication related to
the operation occurred in our case. However, it was thought that the outcome
EP131
of fetal loss due to developmental delay was related to the adverse effects of
Adrenal insufficiency due to both hemorrhage and thrombosis related
circulatory factors due to long-term illness in the patient. The fact that the
with primary antiphospholipid syndrome
patient could not be examined in the pre-pregnancy period and probably the
Buket Bicer1, Pinar Sisman2, Soner Cander3, Ozen Oz Gul3 & Canan Ersoy3
prolongation of the duration of the illness resulted in a negative result.
1Uludag University Medical School, Department of Internal Medicine,
Especially in women of childbearing age, the importance of hypertension in
Bursa, Turkey;2Harakani State Hospital, Endocrinology and Metabolism
terms of maternal and fetal outcomes is emphasized by this case report.
Clinic, Kars, Turkey;3Uludag University Medical School, Department of
DOI: 10.1530/endoabs.49.EP132
Endocrinology and Metabolism, Bursa, Turkey.
Background
Antiphospholipid syndrome
(APS) is characterized by venous or arterial
thrombosis and/or an adverse pregnancy outcome in the presence of persistent
laboratory evidence of antiphospholipid antibodies. Loss of adrenal function due
to bilateral adrenal vein thrombosis, resulting in hemorrhagic infarction, may
occur in association with APS.
EP133
Case presentation
POEMS: a rare cause of adrenal insufficiency in a young male
We present the case of a 45-year-old woman with APS diagnosis since she was
Joanna Prokop1, João Estorninho1, Sara Marote2, Teresa Sabino1,
37, with history of multiple thrombotic events (deep vein thrombosis, sigmoid
Aida Botelho de Sousa3, Eduardo Silva2 & Ana Agapito1
sinus thrombosis, spontaneous abortion, adrenal hematoma and pulmonary
1Endocrinology Department, Centro Hospitalar de Lisboa Central, Lisbon,
embolism). She was hospitalized for adrenal hematoma under anticoagulant
Portugal;2Internal Medicine Department, Centro Hospitalar Lisboa Central,
therapy with warfarin. The basal adrenal function tests revealed morning serum
Lisbon, Portugal;3Hemato-Oncology Department, Centro Hospitalar Lisboa
cortisol
0.7 mg/dl
(reference range
3.7-19.4) and ACTH 345 pg/ml (5-46).
Central, Lisbon, Portugal.
Abdominal CT showed nodular lesion with
55
HU density (29!27 mm)
suggestive of adrenal hematoma in the left adrenal gland; right gland is
thickenned. Adrenal insufficiency was associated with both hematoma in the left
adrenal gland and thrombosis in the right gland. The patient was discharged under
POEMS syndrome characterized by polyneuropathy, organomegaly,
corticosteroid treatment and low molecule weight heparin (LMWH). After being
endocrinopathy, monoclonal gammopathy and skin changes is a rare disease
discharged, warfarin was started again and she was admitted in the emergency
that usually presents in the 6th decade. We report a case of a young male in
department with dyspnea and pleuritic chest pain. Initial analytical study revealed
whom the presenting manifestations were mandibular mass, adrenal
INR (2.26), hypoxemia (PO2:64 mm/Hg) and hypocapnia (32 mm/Hg). She was
insufficiency and peripheral polyneuropathy. Clinical case: A thirty-three
restarted on therapy with LMWH. Further study showed deep vein thrombosis in
year old man from Guinea-Bissau was admitted to our hospital with
right lower extremity. The patient was discharged after vena cava filter
asthenia, weight loss, decreased tactile sensibility with pain and muscle
replacement.
weakness in upper and lower limbs. Bedridden for 2 years, after surgery of
Discussion
mandibular mass with nondiagnostic histological examination. Physical
The recurrence rate of thrombotic events among patients with APS is highly
examination revealed mandibular deformity, unilateral gynecomastia,
variable among studies, with an annual recurrent thrombosis risk ranging from
bilateral axillary lymphadenopathy, sensorial motor peripherial polyneuro-
5 to 12%. However adrenal involvement has been reported in 13% of cases of
pathy, edema of lower limbs. Lab. evaluation: normochromic, normocytic
catastrophic APS. In patients with antiphospholipid antibody syndrome, adrenal
anemia, thrombocytosis, hyperkalemia, normal renal/liver function and
insufficiency is often seen with bilateral adrenal thrombosis, although rarely in
protein electrophoresis, immunofixation: monoclonal protein negative,
some patients an adrenal gland hemorrhage may occur with other adrenal gland
urine: increased kappa/lambda chains, Bence Jones protein neg., morning
hematomas.
cortisol 8.3 ug/dl, ACTH 129 pg/ml. Laboratory workup confirmed adrenal
DOI: 10.1530/endoabs.49.EP131
insufficiency, subclinical primary hypothyroidism and primary hypogonad-
ism. Thoracic-abdominal CT: hepatosplenomegaly, multiple sclerotic
lesions in thoracic vertebras and ribs. Gluco- mineralocorticoid substitution
and levothyroxine therapy were started with clinical improvement. Bone
marrow biopsy revealed plasma cell dyscrasia and confirmed POEMS
syndrome. Axillary lymphadenopathy biopsy: Castleman disease. The
patient had several community-acquired, nosocomial pneumonias and an
EP132
episode of pulmonary edema. Autologous hematopoietic cell transplantation
(HCT) was planned, cyclophosphamide induction started. Meanwhile he
In spite of long-term symptoms, a pheochromocytoma diagnosed in
suffered two ischemic strokes which resulted in motor aphasia and
pregnancy results in fetal loss despite proper approach
hemiparesis. Cerebral angiography revealed vascular lesions compatible
Soner Cander, Ozen Oz Gul, Erdinc Erturk & Canan Ersoy
with vasculitis and stenosis of two cerebral arteries. Comments: In this case,
Uludag University Medical School, Bursa, Turkey.
although serum immunofixation was negative for monoclonal protein, bone
marrow biopsy confirmed POEMS syndrome. There is no standard therapy,
however patients with disseminated bone marrow involvement are treated
A 27-year-old woman with had sweating flushing attacks for three years
with chemotherapy with or without HCT. In this patient despite the young
prior to pregnancy, but did not follow with any medical examination. At
age, the disease was already advanced and resulted in severe complications,
12th gestational week, hypertension was detected and alpha-methyldopa
which led to resignation from chemotherapy and HCT complications, which
was started, no abnormal findings were found in the routine examinations,
led to resignation from chemotherapy and HCT.
in the 24-h holter study, blood pressure values (using alpha-methyldopa)
DOI: 10.1530/endoabs.49.EP133
were found to be higher than 144/99 (general),
147/101 (awake) and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP134
1Endocrinologist, Sparti, Greece;2Endocrinologist, Athens, Greece;
Recurrent phaeochromocytoma - Iatrogenic
3Department of Rheumatology, St. Paul’s Hospital, Thessaloniki, Greece;
Samantha Anandappa, Jeya Navaratnam, David Fish, Brendon Conry,
4Department of Endocrinology, Red Cross Hospital, Athens, Greece.
Sithara Perera & Jesse Kumar
Maidstone and Tunbridge Wells NHS Trust, Kent, UK.
Adrenocortical tumorigenesis has been observed in mice. It is speculated to
be gonadotropin dependent. In particular LH receptors appear to be found
Phaeochromocytoma is a common endocrinological diagnosis with an
within such adrenal tumors in high density and elevated LH levels may be
incidence of 1-2 per 10 000 people. Prompt evaluation and treatment leads
related to adrenal tumorigenesis. The aim was to describe the case of a
patient who after ovariectomy developed a large malignant adrenal tumor.
to an excellent prognosis. Recurrence has been documented rarely (with
A patient, female, aged 42 presented with uterine leiomyomas. She was
literature reporting possibility of up to
8 years delay) and causes are
treated by surgical excision of the uterus along with ovariectomy.
generally attributed to inherited mutations, seeding during surgery or
Subsequently, she refused to be treated with estrogens, developing however
malignancy. Malignancy rates have been variable from 10% depending on
severe postmenopausal symptoms. At the age of 50 she presented with
site and mutations. In addition, the definition of malignant pheochromocy-
musculoskeletal symptoms affecting the spine, both knees and the left
toma/paraganglioma is not always clear as there is no combination of
shoulder. A CT scan of the abdomen was performed showing a large mass
clinical, histopathologic, or biochemical features to reliably predict biologic
originating from the left adrenal gland. An MRI was performed and the
behaviour. In general; pathologic evaluations provide little prognostic
patient was treated by left adrenalectomy. The adrenal tumor was malignant,
insight to predict risk of recurrences or metastases reliably. We present a
measuring
6!6!5 cm, androgen receptor positive and progesterone
case that demonstrates relapse as a result of possible seeding from original
receptor positive in some areas. The patient recovered. On follow up 6
laparoscopic adrenalectomy as one of the factors. Thus, pre-operative
months later she was free of any malignant disease. She developed
features that potentially make the tumour a high risk for recurrence should
Hashimoto’s thyroiditis, antithyroglobulin antibodies being
425 IU/ml
be identified and aid in creating an individualised management plan. Aspects
(normal values
!115 IU/ml) and antimicrosomal antibodies being
that have been recognised to be directly related to outcome such as the size
213 IU/ml (normal values !34 IU/ml), while TSH was 3.9 IU/L (0.3-
of tumour, underlying conditions such as MEN 2A/B and neurofibromatosis,
4.2 IU/L). In conclusion, the case of a patient is presented who developed a
the site of the tumour and anatomical ease of surgical intervention. This case
large adrenal tumor following ovariectomy. Adrenal tumorigenesis has been
highlights the importance of the recognition of such factors & multi-
observed in mice following ovariectomy. It is believed to be related to LH
disciplinary team input, to prevent recurrences which have a significant
stimulation by elevated LH levels, LH receptors having been observed
effect on long-term cure and prognosis.
within the adrenal tumors. In mice tumorigenesis may be prevented by the
DOI: 10.1530/endoabs.49.EP134
administration of agents lowering gonadotropin levels
(Rahman et al,
Reprod Biol 2001). It may be that in such cases of premature ovarian failure
following surgical ovariectomy, thought should be given to possible
treatment aiming at low gonadotropin levels.
DOI: 10.1530/endoabs.49.EP136
EP135
An association of adrenal ganglioneuroma, Addison’s disease and
Mediterranean fever: a case report
EP137
Nabila Rkik, Houcem Mrabet, Mouna Elleuch, Mouna Ammar,
Faten Haj Kacem & Mohammed Abid
ACTH-independent Cushing syndrome with concomitant parathyroid
Department of Endocrinology, Hedi Cheker University Hospital, Sfax,
carcinoma
Tunisia.
Georgiana Alexandra Smarandoiu1, Raluca Trifanescu1,2,
Andra Caragheorgheopol1, Anda Dumitrascu1, Sorina Schipor1 &
1,2
Catalina Poiana
Introduction
1C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;
Ganglioneuroma is a rare benign tumour arising from neural crest sympathogonia.
2Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
It is usually asymptomatic and non functional. An association between
ganglioeneuroma and genetic or autoimmune diseases such as Addison’s disease
or Mediterranean fever has never been described.
Introduction
Case description
The incidence of parathyroid carcinoma in primary hyperparathyroidism is less
We report the case of a
24-year-old woman presenting with paroxysmal
than 1% and the association with ACTH-independent Cushing syndrome is very
abdominal pain with loss of weight and no fever. Physical examination along with
rare.
biological and hormonal explorations were normal. CT scan showed a solid
Case report
tumour of the right adrenal gland, measuring 50!31 mm, with no sign of
A 40-year-old female was admitted for weight gain and reddish-purple striae. One
malignancy and a moderate ascites, so the patient underwent adrenalectomy.
month earlier she had a34 parathyroidectomy for primary hyperparathyroidism
Anatomopathological examination of the adrenal gland confirmed the presence of
with histopathological examination showing a parathyroid carcinoma and two
a ganglioneuroma, and the patient presented an adrenal insufficiency 4 days after
parathyroid adenomas. She also had a history of deep vein thrombosis. She had no
the surgery. Addison’s disease was confirmed with positive anti- adrenal
family history of endocrinopathies. The physical exam revealed a positive
antibodies, with anti-21-hydroxylase at 2866.9 U/ml and she received corticos-
Chvostek sign, facio-troncular obesity, reddish-purple striae and grade I
teroid replacement therapy. The patient continued to have recurrent abdominal
hypertension. Biochemical assessment revealed hypocalcaemia
(5.75 mg/dl)
pain, fever and ascites. A Mediterranean fever was suspected, and she was put on
and diabetes mellitus. Hormonal assessment revealed hypoparathyroidism
colchicine 1 mg per day, with improvement of paroxysmal abdominal pain.
(PTHZ12.45 pg/ml), no catecholamine excess, normal prolactin level. High
Genetic confirmation is underway.
levels of urine free cortisol
(415.91 mg/dl) and positive long low dose
Conclusion
DST(2mg/day!2 days) (12.29 mg/dl) confirmed the clinical suspicion of Cushing
We report for the first time an association between ganglioneuroma, Addison’s
syndrome. ACTH levels were suppressed. Chromogranin A levels were normal.
disease and Mediterranean fever whose clinical features can be confused.
We performed a pituitary MRI and a CT of the neck, thorax and abdomen that
A possible underlying genetic mechanism can be suspected rather than just a
showed bilateral adrenal macronodular hyperplasia with no other suspicious
random association.
masses including pituitary adenomas. DXA evaluation showed osteoporosis for
which she later received bisphosphonate therapy. A bilateral adrenalectomy was
DOI: 10.1530/endoabs.49.EP135
performed and subsequent mineralocorticoid and glucocorticoid replacement
therapy was initiated. Genetic test for MEN1
syndrome is pending. The
hyperparathyroidism relapsed 18 months after the parathyroidectomy. Calcium
levels remained in the high normal range during monitoring with normal renal
function and the last scintigraphy and CT scan showed an adenoma of the
EP136
remaining parathyroid with no sign of local recurrence of the parathyroid
Adrenal carcinoma after ovariectomy. Report of a case
carcinoma. Periodic follow-up also revealed a pituitary microadenoma with
Eleni Xanthakou1, Panagiotis Spyropoulos2, Panagiotis Athanassiou3
minimally raised prolactin and a thymic lesion that were stationary over the last
& Ifigenia Kostoglou-Athanassiou4
7 years of monitoring.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
carcinoma, the images were suggestive of malignancy. Although there
In patients with primary hyperparathyroidism special attention should be given
were no signs of metastasis in toraco-abdomino-pelvic-CT, a PET-scan
to signs of other endocrinopathies as hyperparathyroidism could be the first
is arranged to exclude some other lesions. Gynecomastia in adult males is
manifestation of a MEN syndrome.
usually related with drugs and systemic or endocrine diseases. However, it is
DOI: 10.1530/endoabs.49.EP137
less often related with rare conditions, such as the testicular tumor of Leydig
cells and the rarest adrenal feminizing tumor. Surgery is the main option for
EPAGT, nevertheless the prognosis is very poor.
DOI: 10.1530/endoabs.49.EP139
EP138
Incidental adrenal cyst: a case report
Aribi Yamina, Bensaleh Meriem, Brakni Lila, Khaldi Hassiba, Sellal Zoubir
& Ould Kablia Samia
EP140
Central Hospital of the Army, Algiers, Algeria.
Virilization - a non-negligible manifestation of an adrenal tumor
Daniela Magalhães1,2, Eduardo Vinha1, João Sérgio Neves1,2,
Pedro Souteiro1,2, Celestino Neves1,2, Paula Freitas1,2, José Costa Maia3,
Introduction
Elisabete Rios4, Ana Catarina Fernandes5, Elisabete Rodrigues1,6 &
Cystic adrenal lesions (CAL) are a rare diseases representing 5.4-6.0% of all
Davide Carvalho1,2
pathological changes affecting adrenal glands. In about one-third of the cases,
1Department of Endocrinology, Diabetes and Metabolism of Centro
lesions are detected incidentally; in the remaining two-thirds cysts lesions are
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,
symptomatic, which is typically related to their large size or rapid growth.
Portugal;3Department of General Surgery of Centro Hospitalar de São João,
Although CAL are usually benign, since malignancy is reported in up to 7% of all
Porto, Portugal;4Department of Pathological Anatomy of Centro Hospitalar
CAL. Management algorithms for CAL vary and are controversial because of the
de São Joa˜o, Porto, Portugal;5Department of Oncology of Centro Hospitalar
overall rarity of such lesions.
de Sa˜o João, Porto, Portugal;6Endocrine and Cervical Pathology Multi-
Case report
disciplinary Group of Centro Hospitalar de São João, Porto, Portugal.
We describe a case of a 29-year-old man who presented with abdominal pain. The
computed tomography of the upper abdomen revealing the presence of a 4-cm
simple cyst originating from the left adrenal. All serological and hormonal
Introduction
secretion tests were negative. So the final diagnosis was a simple left adrenal cyst;
Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy
8 months later, abdominal ultrasound follow-up revealed adequate cyst shrinkage
with a poor prognosis. Hormone-secreting ACC appear with manifestations of
down to 2.8!6.9 cm. The patient remains symptom free to date.
virilization, feminization or Cushing syndrome.
Discussion
Case Report
Surgical excision of adrenal cysts is indicated by the presence of symptoms,
A 63-year-old woman with no pathological history of relief was referred to
suspicion of malignancy, or the detection of a functioning adrenal cyst. Cysts
Endocrinology evaluation with an history of deepening of the voice since 1-year
may coexist with primary and metastatic adrenal tumours. Malignancy of the cyst
ago, as well as hair loss and facial and abdominal hirsutism with 6-month
is found in
7% of all affected patients. Adrenocortical and adrenomedullar
evolution. The analytical study revealed the following results: total testosterone
hyperfunction is accompanied by adrenal cysts in ca. 15% of cases. What is more,
6.03
(Normal Range (NR) 0.06-0.82) ng/ml, delta-4 androstenedione O10.00
adrenal cysts accompany approximately 7% of primary and metastatic cancerous
(NR 0.30-2.99) ng/ml, DHEA-S 545.8 (NR 18.9-205) mg/dl, 17-OH-Proges-
processes, and in 0.5% of cases they are of parasitic origin and their clinical
terone 6.32 ng/ml, SHBG 71.4 (NR 14.1-68.9) nmol/l, FSH 7.96 ng/ml, LH
management remains controversial. However, surgical intervention is not
5.96 ng/ml Estradiol 123.8 pg/ml; normal urinary catecholamines and metane-
recommended for asymptomatic patients with incidental cysts, for the fact that
phrines; normal renin and aldosterone values; ACTH 2.1 ng/l (NR !63.3),
the pathological data of our series revealed no malignant cases. Patients after
urinary free cortisol 353.6 (NR 36-137) mg/day, late-night salivary cortisol 0.499
surgical resection should be followed up closely especially in functional cysts and
(NR !0.32) mg/dl and plasma cortisol after 1-mg overnight dexamethasone
when histopathology showed cystic tumor.
suppression test 13.3 mg/dl (NR!1.8). She performed an abdominal MRI with
DOI: 10.1530/endoabs.49.EP138
documentation of a massive solid tumor lesion with heterogeneous contrast
uptake, well delimited and measuring about 13.4 cm in diameter, which was
admitted to be dependent on the left adrenal gland. Were identified several hepatic
and lung nodularities suggestive of secondary lesions. In a multidisciplinary
evaluation, it was decided to perform left adrenalectomy by laparotomy. No
ascites or signs of peritoneal carcinomatosis were present. The anatomopatho-
logical examination revealed an ACC ENSAT stage IV, pT2NxMx, with a
modified Weiss score of five and a classic Weiss score of seven. The patient is
EP139
now proposed for adjuvant chemotherapy with mitotane.
Gynecomastia in men: A rare case of adrenal feminizing tumors
Conclusions
Vitória Duarte, David Veríssimo, Dolores Passos, Filipa Serra, João Silva,
We report a case of an ACC combining hyperandrogenism with Cushing’s
Luís Lopes, J.J. Castro & Mafalda Marcelino
syndrome. Hormonal hypersecretion, particularly hypercortisolism, is associated
Hospital das Forc¸as Armadas, Lisbon, Portugal.
with a worst outcome. Complete tumor removal remains the only potentially
curative treatment.
DOI: 10.1530/endoabs.49.EP140
Estrogen-producing adrenal gland tumors (EPAGT) are extremely rare,
accounting for only 1-2% of all adrenal tumors. They are most commonly
observed in men or in children, and are unusual in women. They are almost
always malignant even if they seem benign at presentation, and most of them
have a poor prognosis. We present a case of a 71-year-old man with painful
bilateral gynecomastia, without galactorrhea, over
4 months. Markedly
elevated plasma estradiol levels were found (161.7 ng/l; normal 15.5-63.3)
with low LH and FSH values. All other parameters were within normal
Clinical Case Reports - Thyroid/Others
range (b-HCG, PRL, TSH, FT4, total testosterone, SHBG, cortisol, ACTH,
EP141
DHEA SO4, delta-4-androstenedione,
17OHPRG, fractionated metane-
The ovarian origin of hiperandrogenism in the postmenopausal woman
phrines, cromogranine-A). Echographic images and mammography showed
with the adrenal adenoma - a case report
bilateral mammary gland hypertrophy excluding any nodules. CT abdo-
Marta Kialka1, Tomasz Milewicz1, Katarzyna Doroszewska1,
minal scan indicated a large retroperitoneal mass measuring 14!8 cm with
Sandra Mrozinska2 & Robert Jach1
posterior and inferior deviation of the left kidney, with heterogeneus
1Department of Gynecological Endocrinology, Jagiellonian University,
contrast uptake. It appeared to be a retroperitoneal tumor independent of any
Medical College, Cracow, Poland;2Department of Metabolic Diseases,
other retroperitoneal organ. To clarify its etiology, a biopsy was performed.
Jagiellonian University, Medical College, Cracow, Poland.
The histology suggested an adrenal cortex tumor. It displayed cell
proliferation with abnormal nuclei. Immunohystochemistry was positive
for melan A, HMB45, INHA and focal AE1/AE3. The Ki-67 was around
Hyperandrogenism is a clinical condition characterized by excessive secretion of
15%. While it was impossible to distinguish between adenoma and
male sex hormones. An excess amount of androgens in women is manifested by
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
symptoms of defeminization and masculinization. Hormonally active adrenal and
microprolactinoma, primary hyperparathyroidism). He was first referred to our
ovarian tumors and non-tumor causes must be considered in the differential
Clinic in
2007 after being incidendally diagnosed with well differentiated
diagnosis. The authors describe the case of a 77-year-old patient who had
pancreatic neuroendocrine tumor (CT-scan performed for nephrolithiasis and
hirsutism and reduction of the timbre of the voice. At the beginning she was
repeated renal colic revealed a pancreatic mass that was surgically removed).
suspected to have adrenal hyperandrogenism because of the tumor in the adrenal
In
2009 the patient was diagnosed with primary hyperparathyroidism and
gland. Then adrenalectomy was conducted but it did not lead to alleviate
multinodular goiter for which subtotal parathyroidectomy and total thyroid-
symptoms. A MRI of the pelvis revealed a change of appendages projection and
ectomy were performed. He also presented MEN1 associated tumors such as non-
the patient underwent the total hysterectomy. The normalization of testosterone
functioning left adrenal adenoma, bilateral asymmetric lipomastia and multiple
levels as well as reduction of the symptoms was observed after the operation.
subcutaneous lipomas and conditions associated with calcium disorders:
Finally, the ovary etiology of hyperandrogenism was confirmed. This case report
nephrolithiasis, nephrocalcinosis, secondary osteoporosis. Regarding these
is an example of difficulties in recognition the etiology of hyperandrogenism.
findings, the patient was diagnosed with MEN1 syndrome and started undergoing
DOI: 10.1530/endoabs.49.EP141
periodical follow-up. Between 2009 and 2016, at the anual reevaluation, no
clinical or paraclinical evidence of tumor recurrence was found. In October 2016
he presented a mild elevation of calcium and PTH levels and the sestamibi
parathyroid scan revealed the presence of parathyroid adenoma. The CT-scan
showed two pancreatic masses, immunohistochemistry tests from the biopsy
supported the diagnosis of neuroendocrine tumor NET G1 and the patient started
treatment with somatostatin analogues. Further assessment of the possibility of
tumor resection and parathyroidectomy is considered.
Conclusion
Considering the high risk of tumor recurrence in MEN1 patients, regular follow-
EP142
up is crucial in detecting and treating the relapses. Our patient developed both
Secondary autonomic neuropathy in patient with polyglandular
recurrence of neuroendocrine tumor and hyperparathyroidism.
autoimmune syndrome III and type 1 gastric neuroendocrine tumor:
DOI: 10.1530/endoabs.49.EP143
a case report
Jekaterina Nagaiceva1, Natalija Fokina2, Karina Levina1, Janis Mednieks2,
Kristine Bernarde2 & Valdis Pirags1,2
1Latvian University, Riga, Latvia;2Paul Stradins Clinical University
Hospital, Riga, Latvia.
The polyglandular autoimmune syndromes (PAS) are rare disorders characterized
as multiple autoimmune-mediated organ failure. PAS III includes chronic
autoimmune thyroiditis with type 1 diabetes mellitus or pernicious anemia and/or
EP144
vitiligo or alopecia and many other organ-specific autoimmune diseases, but
Insulinoma- from diagnosis to full recovery. Case study
never involves adrenal cortex. Several patients with PAS III and associated type 1
Marcin Lewicki1,2, Magdalena Urbanczuk2,3, Agnieszka Zwolak2,4,
gastric neuroendocrine tumor (NET) have already been reported. We report
Marta Dudzinska2,4, Monika Lenart-Lipinska2,5 & Jerzy S. Tarach2
probably the first case of PAS III, type 1 gastric NET and concomitant secondary
1Chair and Department of Epidemiology and Clinical Research Method-
autonomic failure as the main clinical manifestation. A 65-years-old woman with
ology of Medical University of Lublin, Lublin, Poland;2Department and
severe postural and postprandial orthostatic hypotension admitted to the hospital.
Clinic of Endocrinology of Medical University of Lublin, Lublin, Poland;
The orthostasis has been debilitating and gradually has worsened in the past year.
3Chair and Department of Clinical Pathomorphology of Medical University
She has lost about 25 kg due to postprandial sickness and consequent dietary
of Lublin, Lublin, Poland;4Department of Internal Medicine and Internal
restrictions. The patient has a history of mild type 2 diabetes mellitus. She has
Medicine in Nursing, Medical University of Lublin, Lublin, Poland;
been treated with metformin and her HbA1c has been ! 6% during the last
5Department of Laboratory Diagnostics of Medical University of Lublin,
8 years. Diabetes has resolved due to weight loss and the patient has had a good
Lublin, Poland.
glycemic control without any treatment for the past year. The patient has a history
of primary hypothyroidism due to chronic autoimmune thyroiditis. Besides that
she has suffered from hair loss with global alopecia over the last decades of life.
Introduction
Initial B12
vitamin deficiency without anemia has been detected. Upper
Insulinoma is a rare form of a functional neuroendocrine tumor with an estimated
endoscopy was performed, showing multiple gastric polyps. Histological
incidence at
1-2 new cases per million persons per year. This infrequent
examination revealed chronic atrophic gastritis, hyperplasia of endocrine cells
endocrinopathy, frequently escaping standard disease course, constitutes a
and gastric NET G1, Ki-67Z1%. Numerous gastric polyps have been removed
diagnostic challenge for every endocrinologist. Successful surgical resection of
during endoscopy. The patient has been treated with intramuscular B12 vitamin
the lesion is the only available method that ensures patient’s full recovery.
injections with a gradual positive effect on the autonomic dysfunction. Annual
Case study
endoscopic follow-up and lanreotide injections are recommended to prevent
53 years old patient with complaints about recurring episodes of hypoglycemia,
progression and dissemination of the gastric NET.
without accompanying adrenergic symptoms though, was admitted to Department
DOI: 10.1530/endoabs.49.EP142
and Clinic of Endocrinology, Medical University of Lublin. During diagnostic
procedures: low glucose levels
(ranging from
1.94-3.56 mmol/l) with
corresponding inadequately high insulin levels were observed in a prolonged
glucose tolerance test, where glucose and insulin concentrations measurements
had been carried out every hour. Afterwards supervised 72-h fast was introduced,
only to be terminated after just
24 h, due to symptomatic hypoglycemia
(2.28 mmol/l). Insulin levels at the end of fasting remained disproportionately
elevated (10.7 mU/l). Based on follow up diagnostic tests we were able to exclude
EP143
other potential causes of hypoglycemia in the form of adrenal insufficiency and
hypothyroidism. Abdomen CT scan didn’t reveal any lesions in pancreas whereas
MEN 1 Syndrome- a case with recurrence of neuroendocrine tumor and
abdomen MRI unveiled presence of the tumor, 2 cm in diameter, located in the
hyperparathyroidism after 9 years of follow up
tail of pancreas. On the
1st of September 2016 patient underwent surgical
Bianca Maria Leca1, Iustina Gherasim1, Elisabeta Sava2, Sorina Martin1,2,
resection of the pancreas mass. Histologic evaluation confirmed the diagnosis of
Suzana Florea1 & Simona Fica1,2
insulinoma
(pNET: G2 insulinoma). Octreoscan and abdomen MRI didn’t
1Elias University Clinical Hospital, Bucharest, Romania;2Carol Davila
indicate a diffuse process. Currently all of the symptoms subsided, the patient
University of Medicine and Pharmacy, Bucharest, Romania.
doesn’t require any additional treatment.
Conclusions
Introduction
Insulinomas are neuroendocrine tumors of rare occurrence. The readily available
Life expectancy is decreased in MEN1 patients due to multiple tumors that may
imaging methods rarely allow for a location confirmed diagnosis because of
be larger, more aggressive, resistant to treatment and with a higher risk of
borderline small size of lesions. Persistent hypoglycemia being the most
recurrence.
characteristic symptom facilitates the diagnosis and introduction of proper
Case report
treatment.
We report a 59-year-old male patient with family history of endocrine tumors
DOI: 10.1530/endoabs.49.EP144
(father- pituitary adenoma, son- primary hyperparathyroidism, daughter-
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP145
study designed to evaluate the MetS prevalence in the general population, pair-
matched by age, gender and place of birth. Hyperinsulinemia and IR were defined
Insulinoma masquerading as neurologic disease
according to Mattews’s classification. WD DNETs were classified according to
Catarina Machado, Patrícia Tavares, Sara Monteiro, Gustavo Rocha
primary tumour localization, hormonal secretion, TNM stage and WHO grading.
& Maria João Oliveira
Results
Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,
MetS was present in 45.8% of WD DNETs. According to grading, 66.7% were G1
Portugal.
and 27.1% were G2 tumours. The disease was localized in 31.3%, locoregional in
16.7% and disseminated in 43.8%. Both patients and controls had high mean body
Introduction
weight (26.9 vs 27.2 kg/m2, PZ0.645). No significant differences were found
Insulinomas are the most frequent cause of hypoglycemia and the most common
between the two groups for waist circumference, Fasting Plasma Insulin (FPI) and
functional endocrine pancreatic tumors. Whipple triad is often present and should
HOMA-IR (PZ0.236; PZ0.372 and PZ0.274, respectively). Median Fasting
alert to the diagnosis.
Plasma Glucose (FPG) and Impaired Fasting Glucose (IFG) frequency were
Case report
higher in WD DNETs (P!0.001 and PZ0.013, respectively). FPGR100 mg/dl
A 36-year-old male was admitted in the emergency room with loss of
and HOMA-RIR5 were associated with a higher risk for WD DNETs (OR 4.3
consciousness, diaphoresis and blurred vision, and hypoglycemia (50 mg/dl).
(95%CI 2.3-8.2, P!0.001); OR 4.1 (95%CI 1.2-13.5, PZ0.014), respectively).
The patient recalled recurrent symptoms of diaphoresis, tremors and palpitations,
When anthropometric and metabolic parameters are compared, there was no
sometimes with loss of consciousness and incontinence of urinary sphincters, for
difference between somatostatin analogues users and no-users.
the past 4 months, having been diagnosed with epilepsy and medicated with
Conclusion
anticonvulsive drugs. This symptoms were associated with weight gain, occurred
Association of glucose metabolism abnormalities and IR with WD DNETs
before meals and were relieved with eating carbon hydrates. He had no family
confirmation can open new perspectives for prevention and treatment, through
history of endocrine disease. Prolonged supervised fasting test was applied and
modifying lifestyle and insulin sensitizers use.
led to symptomatic hypoglycemia with hyperinsulinemia
(blood glucose
DOI: 10.1530/endoabs.49.EP146
40 mg/dl, plasma insulin 68.7 mIU/ml and C-peptide 7.07 ng/ml). Other hormonal
studies were normal, rejecting the diagnosis of multiple endocrine neoplasia. He
maintained severe hypoglycemia despite glucose fluid administration and
nutritional adequate plan, and medical treatment was necessary with octreotide
300 mg/day and diaxozide
900 mg/day. Abdominal magnetic resonance
demonstrated a well-defined enhanced lesion in the tail of the pancreas measuring
14 mm. Nodule enucleation was performed by laparoscopy and pathological
examination revealed an encapsulated pancreatic mass measuring 17!14!
15 mm. Mitotic index was !2 per 10 CGA and proliferation index ki-67 was
estimated !2%. Immunohistochemically, tumor cells showed a positive staining
for insulin, synaptophysin and cromogranine. Shortly after surgical treatment,
EP147
glucose level increased to normal range. The patient was discharged without any
Clinical and hormonal characteristics of adrenal incidentalomas
hypoglycemic symptoms after 7 days.
Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari,
Conclusion
Nadia Mchirgui & Néjib Ben Abdallah
The diagnosis of insulinoma may be challenging due to its rarity and variable
Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.
presentation. Other diseases, such as neurologic, may be considered first, but it’s
important to contemplate the diagnosis since chronic and severe hypoglycemia
can be fatal and the surgery is usually curative.
Introduction
DOI: 10.1530/endoabs.49.EP145
Widespread use of abdominal imaging has led to the identification of an
increasing number of adrenal incidentalomas (AI) in the last decades. Causes of
these adrenal masses are multiple.
Aim
The aim of this study was to investigate the clinical and hormonal characteristics
of AI.
Materials and methods
The study was a retrospective monocentric analysis of 44 patients with AI who
underwent radiographic and endocrine evaluations.
Results
The mean age was 59.25G10.3 years and the sex ratio (F/M) was 1.3. Arterial
hypertension was diagnosed in 27 patients (61.4%), obesity or overweight in 84%,
Endocrine Tumours and Neoplasia
diabetes in 18 patients (40.9%), dyslipidemia in 7 patients (15.9%). Five patients
EP146
had an extra-adrenal tumor (11.4%). First diagnostic procedure was computed
Glucose metabolism abnormalities and insulin resistance are frequent
tomography (CT) in 63.6%, abdominal ultrasonography in 31.8% and magnetic
in well diferentiated digestive NETs
resonance imaging in 4.5%. Regarding the location of the masses: 36.4% were in
Ana P Santos1,6, Ana C Santos2,5, Clara Castro1,2, Luís Raposo2,
right side,
34.1% were in left side and 29.5% were bilateral. The Cause of
Isabel Torres1, Rui Henrique6,7, Mariana P Monteiro3 &
radiologic imaging was kidney problems in 50%, liver disorders in 20.4%,
M Helena Cardoso3,4
epigastralgia in 13.6%, thorax pathology in 6.8%, rheumatologic causes in 6.8%
1IPO Porto, Porto, Portugal;2ISPUP/EPI Unit - UP, Porto, Portugal;
and an inflammatory syndrome in 2.3% of cases. The average diameter of tumors
3UMIB/ICBAS - UP, Porto, Portugal;4CHP, Porto, Portugal;5FMUP - UP,
was 26.6G15.9 mm. The mass was single in 65.9%, well limited in 95.5% and
Porto, Portugal;6IPO Porto, Research Unit, Porto, Portugal;7EPOP, Porto,
homogeneous in 81.8%. Patients with functioning tumors had larger tumor
Portugal.
diameters than those with non-functioning tumors (P!0.05). Final diagnosis
was: non-functioning adenomas in
68.2%, pheochromocytoma in
6.8%,
Cushing’s syndrome in
6.8%, primary aldosteronism in
4.5%, subclinical
Introduction
Cushing’s syndrome associated to phéochromocytoma in 2.3%, hematoma in
Incidence of Digestive NETs (DNETs) has increased in the last 40 years. Visceral
2.3%, tuberculosis in 2.3% and metastasis in 6.8%. Patients with functioning
obesity, metabolic syndrome
(MetS) and insulin resistance
(IR) have been
tumors had larger tumor diameters than those with non-functioning tumors
associated with several types of cancer.
(P!0.05). Two patients were diagnosed with adrenal insufficiency.
Aim
Conclusion
To evaluate possible associations of obesity, hyperinsulinemia and IR with well-
Our study showed that AI occurred more frequently in overweight or obese
differentiated (WD) DNETs through a case control study.
women with diabetes and hypertension. Its most common diagnostic procedure
Materials and methods
was CT and etiologies were dominated by nonfunctioning adenomas.
Ninety-six patients with gastrointestinal (75.0%) and pNET (22.9%) WD DNETs
were recruited from Endocrine Tumours Clinic of IPO Porto and cross-matched
DOI: 10.1530/endoabs.49.EP147
with a control group (nZ96) from PORMETS, a nationwide epidemiological
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP148
Conclusion
The hypersecretion of Gh induces an organomegaly, and the development of
Pituitary insufficiency, the beginning of a diagnostic journey
multinodular goiter is very frequent but discovery of thyroid carcinoma is rare, the
Amalia Ioana Arhire1, Lumnita Cima1,2, Simona Petrescu1,2,
prevalence of this association remains to be determined.
Miron Adrian1,2, Florin Andrei1 & Carmen Gabriela Barbu1,2
1Elias Hospital, Bucharest, Romania;2“Carol Davila” University of
DOI: 10.1530/endoabs.49.EP149
Medicine and Pharmacy, Bucharest, Romania.
Introduction
We report a case of a pituitary insufficiency apparently resistant to treatment.
Case report
A 74 year old patient was admitted through the ER in our department for a
EP150
recently discovered pituitary macroadenoma. His general condition was poor in
spite of the initiation of corticotherapy. Evaluation: Smoker, with no significant
Small pancreatic neuroendocrine incidentalomas: an observational
medical history, the BP: 100/60 mmHg, no orthostatic hypotension, disoriented,
prospective study
C Villabona1, J Busquets2, L San Martín1, A Planas1, N Peláez2, J Fabregat2,
confused, with moderately altered general state and no visual deficit.
A Teulé3 & I Peiró4
Biologically: normal ionogram, TSH: 0.076 mcIU/ml, fT4: 0.767 ng/dl, total
1Department of Endocrinology, Hospital Universitari de Bellvitge (HUB),
T3 !40 ng/dl, prolactin: 21.5 ng/dl, IGF1: 84.8 ng/ (low). He had leukocytosis,
l’Hospitalet de Llobregat, Spain;2Department of Surgery, HUB,
high neutrophils, but normal markers of inflammation. No causes of infection
l’Hospitalet de Llobregat, Spain;3Department of Oncology, Institut Català
were found, but the clinical condition worsened in the next 2 days despite an i.v.
d’Oncologia (ICO), l’Hospitalet de Llobregat, Spain;4Clinical Nutrition
with Hydrocortisone and oral Levothyroxine. Additional imaging studies showed
Unit, ICO, l’Hospitalet de Llobregat, Spain.
an adenoma of 3.4/2.8/3.8 cm, with a mass effect on the optic chiasm, multiple
secondary lesions in the upper and infratentorial regions at the cerebral MRI.
During the neck ultrasound we found a multinodular goiter with a large nodule
Background
of 1.53/1.33 cm with multiple large pathological laterocervical adenopathies.
Diagnosis of small pancreatic neuroendocrine incidentalomas
(PNETs-I) is
The thoraco-abdomino-pelvic CT found a large pulmonary mass of 45/49 mm in
increasing during last years and often their management remains unclear.
the left lung, some osteholytic lesions in the right ribs and body of L5, a large
Objective
cephalic pancreatic lesion of 35/24 mm and bilateral adrenal metastatic lesions.
To describe our experience with patients with PNETs-I in our institution.
At that moment we thought that the pituitary macroadenoma was highly probable
Methods
to be a metastatic lesion with multiple options regarding the origin of the primary
Since March 2000, patients with non functioning PNETs-I %30 mm were
neoplasia. The biopsy of an excised cervical adenopathy showed an aggressive
evaluated in our center, prospectively. A descriptive analysis of all patients and
neuroendocrine tumour as the probable cause, diagnosis which was unfortunately
a comparative study between observational group (OG) vs resection group (RG)
sustained by the lethal outcome of the patient.
was made.
Conclusion
Results
The pituitary insufficiency in normally a benign condition which responds to
Forty-six patients were evaluated: 36 in OG and 10 in RG. Median follow up
treatment and has a favourable outcome; if this is not the case we must search for
(months) was 35.9 in OG and 76.6 in RG. Most of patients (69.9%) were
additional causes of poor responders.
diagnosed in the last 6 years. Mean age (years): 69.5 in OG and 57 in RG
DOI: 10.1530/endoabs.49.EP148
(P!0.003). Gender: 56.5% women. Mean tumor size (mm) was 12.5 (11 in OG
vs 18.7in RG P!0.005). PNETs-I were multiple in 17.4% cases. At diagnosis, all
PNETs-I’s size were%20 mm in OG, without metastases. In RG, 8 patients (80%)
had surgery complications, mostly mild to moderate without deaths. Diagnosis
was made by imaging procedures in 91.6% of OG. In our series, 82% had a CgA
assessment at diagnosis. Median CgA value was 179 mg/l (72-304). At the end of
follow up, 88% in OG of patients had no change in tumor size, the rest had tumor
growth !20%; In OG no PNETs-I resection were needed, and none of the
patients metastasized or died because of PNETs-I in this group.
Conclusions
EP149
Non functioning PNETs-I is increasing in incidence in our center. After almost
Thyroid carcinoma in multiple endocrine neoplasia type 1
36 months of follow up, no patients had significant growth, developed metastases
Khelil Nour El Houda1,2, Loudjedi Lotfi2, Meghelli Sidi Med1,2
and neither of them died from PNETs-I. In OG, active surveillance is safe in
& Berber Necib1,2
selected PNETs-I patients. We need prospective multicentric studies to confirm
1Abou Bekr Belkaid University, Tlemcen, Algeria;2University Hospital of
our results.
Tlemcen, Tlemcen, Algeria.
DOI: 10.1530/endoabs.49.EP150
Introduction
Multiple endocrine neoplasia type 1 (MEN1) is a cancer syndrome characterized
by the development of neuroendocrine tumors of the pituitary gland, parathyroid
and pancreas, and other neoplasms such as adrenocortical tumors and carcinoid.
Observation
We report the case of a 70-year-old women with acromegaly that diagnosed 15
EP151
years ago, in relation with pituitary macroadenoma (30!25 mm) invading the
Potential inhibitory effect of progesterone on breast cancer metastasis
left cavernous sinus and in contact with the third ventricle without endocrine or
via the regulation on protein expression of apoptosis- and EMT-related
ophthalmological repercussions. The impact of acromegaly is diabetes mellitus
genes
treated with insulin complicated by retinopathy. The visceral assessment revealed
Gyu-Sik Kim, So-Ye Jeon & Kyung-Chul Choi
a hypertension with cardiomegaly and a multinodular goiter diagnosed 2 years
Laboratory of Biochemistry and Immunology, Veterinary Medical Center
after the discovery of the acromegaly. Refusing pituitary surgery and radio-
and College of Veterinary Medicine, Chungbuk National University,
therapy, the patient remains uncontrolled with maximal dose of somatostatin
Cheongju, Chungbuk, Republic of Korea.
analogues and dopaminergic agonists, the Gh level is 70 and IGF1 is 638 ng/ml.
Exploration of the goiter finds 3 nodules (20 to 30 mm of diameter) benign in fine
needle aspiration biopsy, operated 10 years later and the pathological examination
Breast cancers that are estrogen receptor
(ER)/progesterone receptor
(PR)-
finds papillary carcinoma of the thyroid, patient is treated by iodine 131 under
positive are more likely to respond to hormone-related treatments than tumors
recombinant TSH, It is currently in remission, her thyroglobulin level is under
that are ER/PR-negative. The present study investigated the effect of progesterone
0.20 ng/ml. During evolution, the patient presents bilateral renal lithiasis
(P4) on
17b-estradiol
(E2)-induced cell proliferation, apoptosis, EMT, and
repeatedly, the balance allowed the discovery of a primary hyperparathyroidism
migratory and invasive features of MCF-7 clonal varient (CV) breast cancer cells
with high serum calcium and PTH around 150 pg/ml due to a right inferior
that are ER/PR-positive. Preferentially, E2 was verified to induce breast cancer
parathyroid adenoma, complicated with osteoporosis for which the patient
progression by stimulating cell proliferation, EMT, and migration of MCF-7 CV
refused surgery. In this clinical context, the genetic studies to search presence of
breast cancer cells. On the other hand, P4 reduced E2-induced MCF-7 CV cell
mutation in MEN1 gene encoding the menin protein was performed and confirm
proliferation by down-regulating the protein expression of cyclin D1 and E1 and
multiple endocrine neoplasia type1.
induced apoptosis of MCF-7 CV cells by up-regulating Bax and p53 and by
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
down-regulating Bcl-2. Also, P4 appeared to inhibit E2-induced EMT process by
decades. Primary hepatic neuroendocrine tumors (PHNETs) are rare neoplasms.
increasing mRNA and protein expression of E-cadherin, a crucial epithelial
Despite increased incidence of PHNETs over time, these tumors remain a rarity.
marker, as well as by reducing the expression of mesenchymal markers such as
According to the previously reported cases, primary neuroendocrine carcinoma of
N-cadherin and vimentin and EMT-associated transcription factors such as snail
the liver is usually multicentric, often mimicking liver metastases. The
and slug. Eventually, E2-induced migration and invasion ability of MCF-7 CV
demonstration of the hepatic origin of a neuroendocrine carcinoma is often
cells and the protein expression of proteolytic enzymes such as MMP-9 and
arduous.
cathepsin B were reduced by P4 treatment. Co-treatment of RU486, a PR
Case presentation
inhibitor, restored the inhibited cellular migration and invasion and the reduced
A 59-year-old woman underwent ultrasound examination 3 years ago, that
expression of proteases by P4 to the control levels, suggesting the involvement of
revealed two liver nodular tumors (the largest having approximately 4 cm), with a
PR in P4-induced inhibition on migration and invasion of MCF-7 CV cells. Taken
complex structure. Abdominal IRM images confirmed multiple liver nodular
together, P4 treatment may be suggested as an effective tool for suppression of
tumors with intense vascularization, suggesting liver metastases. The patient was
human breast cancer progression and metastasis. (This work was supported by a
asymptomatic. In order to determinate the primary site of the tumor, the patient
grant from the Next-Generation BioGreen 21 Program (no. PJ011355-2015),
underwent multiple imagistic investigations and endoscopies. Among the blood
Rural Development Administration, Republic of Korea.)
tests (5-hydroxy indole acetic acid, carcinoembryonic antigen, chromogranin A,
Keywords: Progesterone; breast cancer cells; epithelial-mesenchymal transition;
serotonin), only chromogranin A presented significantly high values. Further, a
metastasis; migration.
liver aspiration biopsy was performed. The histopathological examination result
DOI: 10.1530/endoabs.49.EP151
completed with the immunohistochemistry techniques suggested a well
differentiated neuroendocrine carcinoma of an intermediary stage, with a
proliferation marker ki67 of 4%, most likely a metastasis. For a full diagnosis,
Octreoscan (11In-pantreotide scintigraphy) was performed. The whole body
scintigraphy at 10 minutes completed with the SPECT/CT at 4 hours established a
primary liver site with secondary spleen metastases, along with liver and renal
adenopathies. Treatment with somatostatin analogues (SANDOSTATIN LAR
30 mg/month), was commenced, with favourable outcome. After 18 months of
EP152
treatment, serum chromogranin values are still normal, while the volume of the
Incidental paraganglioma, diagnosis and follow-up - case report
tumors decreased significantly (by repeated MRI).
Alice Violante1, Roberto Lemme1, Sarah Galva˜o1 & Erika Naliato2
Conclusion
1Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;2Ricardo A T
Despite that the liver represents the common site for metastases from other
Catilho Center of Studies Teresopolis Medical Association, Teresopolis,
gastrointestinal neuroendocrine carcinomas or other tumors, primary hepatic
Brazil.
neuroendocrine tumors are rare, but can occur. The diagnosis of primary
neuroendocrine tumors of the liver is difficult, as radiological appearances on
ultrasound, CT scan and MRI can mimic other pathologies.
Paragangliomas and Pheochromocytomas are tumors originated from chromaffin
Keywords: Neuroendocrine tumors; liver metastases.
cells
(Pheochromocytomas (PHEO): adrenal glands; Paragangliomas (PGL):
paravertebral thoracic, abdominal, and/or pelvic sympathetic ganglia, and
DOI: 10.1530/endoabs.49.EP153
glossopharyngeal and vagal neck and skull base parasympathetic ganglia).
Catecholamine hypersecretion predominates in PHEO, while PGL are
oligosymptomatic with compression-related symptoms. The authors report the
case of a 33-year-old male with an incidental retroperitoneal PGL, detected
during an investigation for urinary lithiasis
(abdominal pain that shifted to
different location, varying in intensity), without clinical evidence of catechol-
amine hypersecretion. The abdominal ultrasound identified a well-defined
5.0!4.5 cm hypoechoic nodular area at the right retroperitoneal region, above
the renal pelvis, dislocating the renal vein anteriorly. The image was confirmed by
CT (a 5.6!4.5!4.1 cm nodular area anterior to the right adrenal gland without a
EP154
cleavage line with the inferior cava vein), MRA (a 5.4!3.5!4.6 cm nodular area
anterior to the right adrenal gland), and PET/TC with FDG (a right retroperitoneal
Development of an everolimus-resistant BON1 cell line with altered cell
5.2!3.8 cm mass that dislocated the inferior cava vein at the confluence of the
cycle and c-Met activity
renal veins; SUVmax Z29.7).123I-MIBG scintigraphy showed a discrete tumoral
Elke Tatjana Aristizabal Prada, Julian Maurer, Gerald Spottl,
uptake. Ultrasound-guided biopsy: the patient presented a hypertensive peak
Christoph Auernhammer & Svenja Nolting
during this procedure and was successfully medicated. He did not present arterial
Klinikum der Universitat Munchen, Munich, Germany.
hypertension during the follow-up. Histopathology: suggestive of paraganglioma
and neuroendocrine tumor.chemical investigation for catecholamines and
Introduction
plasmatic metanephrines hypersecretion: negative. Surgery: anterior laparotomy
Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis.
(without pharmacological preparation, since the tumor was non-secreting)
The mTORC1 inhibitor everolimus is approved for the treatment of advanced
without complications. Histopathology: paraganglioma/neuroendocrine tumor.
NETs. Unfortunately, the development of resistance against everolimus limits its
Post-op follow-up: normal levels of metanephrines/catecholamines. I123 MIBG
clinical efficacy.
scintigraphy without evidence of the previously described lesion in the right
Aim
lumbar region. No recurrence or clinical evidence of disease after a 5-year period.
Our aim was to establish an everolimus-resistant panNET cell line to find
Conclusion
common mechanisms of resistance.
Despite the tumour dimensions, there were no symptomatology previously to the
Methods
diagnosis and no recurrence at a 5-year follow-up.
Pancreatic neuroendocrine tumor cells (BON1) were treated for 24 weeks with
DOI: 10.1530/endoabs.49.EP152
10 nM everolimus (Novartis). Medium supplemented with 10 nM everolimus was
changed every 3 days. Two independent everolimus resistant BON1 cell lines
were established (RR1 and RR2). Resistance was defined with an at least 2-fold
higher IC50, compared to the parental/control cell line.
Results
After 24 weeks of permanent exposure to everolimus both cell lines (RR1 and
EP153
RR2) showed morphologic changes when compared to the control cell line. The
Primary hepatic neuroendocrine tumor with multiple liver metastases
control cell line showed sensitivity to everolimus with cellular survival declining
treated with somatostatin analogues: case report
to 54.70% (IC50Z34 nM) at 144 h treatment, whereas RR1 and RR2 showed
Ioana Golu1, Melania Balas1, Daniela Amzar1, Marioara Cornianu2 &
resistance with cellular survival rates of 96.70% (IC50Z5200 nM) and 92.30%
Mihaela Vlad1
(IC50Z2500 nM), respectively. Western blot analysis showed different adaptive
1Department of Endocrinology, University of Medicine and Pharmacy
changes of the protein expression level in RR1 and RR2, but two prominent
“Victor Babes”, Timisoara, Romania;2Department of Morphopatology,
mutual features: The cell cycle component CDK1 (cdc2), which orchestrates the
University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania.
G1-S and G2-M progression was remarkably downregulated and the tyrosine
kinase c-Met responsible for tumor cell motility, invasion and metastasis
Introduction
formation was upregulated. Consequently, flow cytometric analysis showed a
Somatostatin analogues (SSA) have been used as first line treatment to control the
significant cell cycle shift to G1 phase in RR1 and RR2 cells as well as a higher
symtoms in hormonally active neuroendocrine tumors (NET), for over three
migration potential than control cells after everolimus treatment.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
Methods
Everolimus resistance might be acquired by permanently altering the cell cycle
Cases coded as D35.0; D44.1; C74.1; C74.9; E26.0; E27,8; E24,8 according to
and the migration potential. Combinatory treatment approaches to overcome
ICD-10 classification were retrieved from database. Electronic data capture
resistance will be subject of further studies.
system was used to extract CT scans and biochemical testing data retrospectively.
DOI: 10.1530/endoabs.49.EP154
Results
There were 714 subjects assessed for adrenal masses from 2010 to 2016 at
VUHSK. At least one FU and non-functioning adrenal masses with obvious
benign features on CT scan had 216 subjects and thus were included into further
analysis. They were 61.6G11.2 years of age (184 female) with tumour size at
baseline of 22.8G12.8 mm. Average FU time was 4.1G1.4 years (from 2 to 7),
during which tumour size increased in 84 (39%), decreased in 48 (22%), did not
change in 84 (39%) cases. Significant increase (by O 20% in addition to at least
EP155
5 mm increase in maximum diameter) was observed in 19 (8.8%) cases. Average
False positive findings on 6-[18F]fluor-L-3,4-dihydroxyphenylalanine
size of
19 significantly enlarged tumours changed from 19.37G7.60 mm to
Positron Emission Tomography (18F-FDOPA-PET) performed for
30.58G13.68 mm in 2.7G1.4 years. All these tumours were associated with
imaging of neuroendocrine tumors
female gender. Despite tumour size enlargement, none of them became
MA Berends1, JW Bolt1, MN Kerstens1, TP Links1, E Korpershoek2,
functioning during observation time.
RR de Krijger2,3, AME Walenkamp1, W Noordzij1, B van Etten1,
Conclusions
G Kats-Urgurlu1, AH Brouwers1 & ANA van der Horst-Schrivers1
Our study showed, that the significant enlargement of non-secreting initially
1University Medical Center Groningen, Groningen, The Netherlands;
benign adrenal masses during follow up of about 2.7 years occurred in 8.8% of
2Erasmus University Medical Center, Rotterdam, The Netherlands;3Reinier
cases and was associated with female gender. Further larger studies with longer
de Graaf Hospital, Delft, The Netherlands.
follow up are needed to suggest time-frame for imaging follow up in order not to
miss the enlargement of the adrenal masses that could require surgery and also to
Background/Aim
estimate possible enlargement prediction factors.
Neuroendocrine tumors (NETs) are rare tumors arising from neuroendocrine cells
DOI: 10.1530/endoabs.49.EP156
throughout the body. Positron Emission Tomography (PET) scanning with 6-
[18F]fluor-L-3,4-dihydroxyphenylalanine (18F-FDOPA) has been shown to be a
valuable technique for the imaging of NETs. While the sensitivity has been
assessed numerously, studies systematically describing false positive results,
other than physiological variants, are lacking. Our aim was to systematically
examine, in a large series of18F-FDOPA PET scans, false-positive results and
determine which other tumor types have the potential of18F-FDOPA uptake.
Patients and methods
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A single-center study was conducted among patients, aged 18 years or older, who
Medullary thyroid carcinoma and pheochromocytoma in multiple
underwent a18F-FDOPA-PET scan for the clinical suspicion or follow-up of a
endocrine neoplasia type 2A - a reversed order diagnosis
NET between January 2004 and December 2014. Clinical data were retrieved
Ana Coelho Gomes, Catarina Silvestre, José Marçalo,
from medical charts. We compared the original18F-FDOPA PET scan report
Maria Raquel Carvalho & Maria João Bugalho
with the pathology report of the18F-FDOPA PET-positive lesion. In case this
Endocrinology, Diabetes and Metabolism Department, Santa Maria
was inconsistent with the diagnosis of a NET, both the scan and the pathology
Hospital, Lisbon, Portugal.
slides were reassessed. Non- NET tissues were immunohistochemically stained
for aromatic-L-aminoacid decarboxylase
(AADC), Chromogranin A and
Synaptophysin.
Introduction
Results
RET germline mutation in codon 634 of exon 11 is one of the most frequent
107018F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple
mutations of classical multiple endocrine neoplasia type 2A (MEN2A). Virtually
18F-FDOPA avid lesions were described in 70918F-FDOPA PET scans (66%).
all patients with classical MEN2A develop medullary thyroid carcinoma (MTC),
Histology of these18F-FDOPA PET positive lesions was present for 508 (72%)
which is often the first manifestation of the disease and usually occurs early in
scans. In eight cases the original pathology report and revision was not compatible
life. Pheochromocytomas (PHEOs) tend to be diagnosed several years later or
with a NET but showed a squamous cell carcinoma of the cervix and larynx, a
simultaneously with the MTC.
multiple myeloma (in two cases), a hepatocellular carcinoma, a schwannoma, an
Case report
adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive
The patient, a 45 year-old man, was referred to the Endocrinology outpatient
immunohistochemical staining for AADC in four out of the seven stained tumor
department following a bilateral adrenalectomy, performed 2 months before,
tissues.
(Pheochromocytoma of the Adrenal gland Scaled Score: left Z0, right Z4) and
Conclusions
the finding of a thyroid micro nodule in a neck ultrasonography. There was no
Pathological uptake of18F-FDOPA does not always indicate the presence of a
familiar history of MEN2 neither of its components. The physical examination
NET. The possibilty of18F-FDOPA uptake by tumor types other than NETs
did not disclose particular signs namely skin alterations in the interscapular
should be considered.
region. Laboratory tests revealed elevated calcitonin (63.47 pg/ml, n !2). CEA,
DOI: 10.1530/endoabs.49.EP155
calcium, phosphorus, parathyroid hormone and plasmatic metanephrines were
within the normal range. Thyroid, ultrasound guided, fine needle aspiration
cytology of a 7 mm nodule in the left lobe was negative. Genetic testing of the
RET proto-oncogene identified the heterozigous pathogenic variant c.1901GOA
(p.Cys634Tyr) in the exon 11. The patient was submitted to total thyroidectomy
with bilateral central neck dissection. The histology revealed multifocal and
bilateral MTC (biggest diameter - 10 mm).
EP156
Discussion
Although less common the PHEO can be the first manifestation of MEN2A.
Imaging follow-up of non-functioning adrenal masses at Vilnius
Moreover, MTC is not always the most aggressive component of the syndrome.
University Hospital Santariskiu Klinikos: 2010-2016
Kristina Svaikeviciene1,2, Milda Girdziute3 & Zydrune Visockiene1,2
DOI: 10.1530/endoabs.49.EP157
1Vilnius University Faculty of Medicine, Vilnius, Lithuania;2Vilnius
University Hospital Santariskiu Klinikos, Vilnius, Lithuania;3Antakalnis
Clinic, Vilnius, Lithuania.
Background
EP158
Current guidelines suggest against further imaging follow-up (FU) of patients
Bilateral pheochromocytomas, asyptomatic medullary thyroid
with non-functioning adrenal masses with clear benign features on imaging
carcinoma associated with left side thyroid hemiagenesis in a patient
studies.
with MEN2A: diagnostic correlations
Aim
Ionela Lungu1, Carmen Emanuela Georgescu1,2, Anca Ciurea3,
To analyse the data of patients with non-functioning adrenal masses who had FU
Carmen Georgiu4, Denisa Petrescu1, Daniel Tudor Cosma5, Horatiu Silaghi6
at Vilnius University Hospital Santariskiu Klinikos (VUHSK) from 2010 to 2016.
& Cristina Alina Silaghi1,2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Endocrinology Clinic, County Emergency Hospital, Cluj-Napoca,
with unilateral AI there was a significant growth (28.85G15.63 mm), so they
Romania;2Department of Endocrinology, Iuliu Hatieganu University of
underwent surgery to remove them. None of them were malignant.
Medicine and Pharmacy, Cluj-Napoca, Romania;3Department of
Conclusions
Radiology, Iuliu Hatieganu University of Medicine and Pharmacy,
There wasn’t any patient with new cathecolamine production in the follow-up. In
Cluj-Napoca, Romania;4Department of Pathology, Iuliu Hatieganu
10.20% of patients we discovered a subclinical Cushing. Our findings agree with
University of Medicine and Pharmacy, Cluj-Napoca, Romania;5Diabet,
previously published studies. There was a significant AI growth in 5% of the
Nutrition and Metabolic Diseases Clinical Center, Cluj-Napoca, Romania;
patients so they were operated upon. Pathological diagnosis didn’t show
65th Department of Surgery, Iuliu Hatieganu University of Medicine and
malignancy in any case, which is consistent with the available scientific evidence.
Pharmacy, Cluj-Napoca, Romania.
DOI: 10.1530/endoabs.49.EP159
Multiple endocrine neoplasia 2A (MEN2A), an autosomal dominant genetic
syndrome caused by germline mutation in RET proto-oncogene, associates
medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and primary
hyperparathyroidism (HPT). Thyroid hemiagenesis (TH), the absence of one lobe,
is a rare congenital abnormality (300 cases are reported in literature). Most cases
of TH are diagnosed when patients present a lesion in the functioning lobe. TH
was observed among members of the same family and genetic causes have been
evoked. The present case is a 35 year-old-female patient with family history of
MEN2A (the pedigree was studied). Genetic testing of the patient’s cousin and
EP160
nephew indicated heterozygosity for the same mutation at codon 634. Plasma
A case of silent pancreatic neuroendocrine tumour of carcinoid variety
metanephrines, normethanephrines, parathormone (PTH) and calcitonin (CT)
masquerading as an insulinoma
levels were increased. Serum ionized calcium was normal. Abdominal computed
Tarik Elhadd1, Noor Suleiman1, Mohamed Bashir1, Emad Naem1,
tomography provided the bilateral heterogeneous adrenal masses measuring 30!
Khalid Mohamed2, Ahmed Elaffandi2 & Abdul Badie Abou Samra1
21 mm on the right and 20!16 mm on the left with an intense enhancement after
1Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;
contrast infusion. Neck ultrasound examination described
2
hypo-echoic,
2Section of Hepato-biliary Surgery, Hamad Medical Corporation, Doha,
heterogeneous thyroid micro-nodules in the right thyroid lobe, with micro-
Qatar.
calcifications inside, which measure 78!58, respectively 45!47 mm. In the left
side, hemiagenesis of the thyroid lobe was observed. No parathyroid adenoma or
lymphadenopathy were found. The patient had underwent a bilateral laparoscopic
Objective
adrenalectomy for PHEO followed by total right thyroidectomy. Microscopic
To highlight an unusual cause of hyperinsulinaemic hypoglycemia
examinations established the diagnosis of multicentric PHEO and synchronicity
Methods: Case Report
of C-cell hyperplasia with medullary thyroid microcarcinoma. Although the
Results or Case Presentation
identified RET mutation has hight risk, suggesting a possible aggressive
A previously healthy and fit 52 year old gentleman of Asian descent presented
evolution, in this case the CMT development was gentle, with a good prognosis
with recurrent severe neuroglycopenic hyperinsulinemic hypoglycemic symp-
(lesion
! 1 cm diameter, without distant metastases, preoperative basal
toms, suggestive of insulinoma. On several occasions he was confirmed to have
calcitonin ! 150 pg/ml). In conclusion our patient is a rare case of association
severe hypoglcaemia with venous blood glucose values ranging between 1.5 and
of an anatomic thyroid abnormality and MTC in the context of a complex genetic
2.7 mmol/l with inappropriate high level of insulin and C-peptide of 32 mc/unit
disease.
per ml (N. 2-23) & 4.5 ng/ml (N. 0.78-5.19) respectively. Other hormonal
assessment including pituitary hormones, chromogranin A, urinary 5-HIAA, and
DOI: 10.1530/endoabs.49.EP158
cortisol were all normal. CT imaging picked up a 4!4 cm well circumscribed
lesion in the tail of the pancreas, with no lesion elsewhere. Endoscopic
ultrasonography confirmed the mass to be avascular and within the pancreas. He
underwent laparoscopic distal pancreatectomy uneventfully in February 2016.
Histology of the tumour showed a well differentiated neuroendocrine tumour of a
carcinoid variety, grade
2, with positive staining for chromogranin A, and
Synaptophysin CK. Following surgery, the patient had no further hypoglycemia
and remained symptom free up to 9 month of follow up. Postoperative PET scan
and CT scanning of chest, abdomen and pelvis showed no recurrence of the
tumour, and no lesion elsewhere.
Discussion
EP159
Non-islet cell tumours induced hypoglycemia is generally caused by big IGF-II
Follow-up of adrenal incidentalomas after the initial approach
molecules secretion. Rarely carcinoid tumours were reported to secrete insulin but
Ángel Rebollo-Román, Paloma Moreno-Moreno,
this is usually in the context of carcinoid syndrome and has been reported to arise
Inmaculada Prior-Sánchez, Aura-Dulcinea Herrera-Martínez,
from tumours in the lungs, appendix and the liver. For a silent pancreatic
Ana Barrera-Martín & María-Ángeles Gálvez-Moreno
carcinoid tumour to cause hyperinsulinaemic hypoglycemia is rather unusual.
Endocrinology Service, Hospital Universitario Reina Sofía, Córdoba, Spain.
Plausible mechanisms include processing and secretion of insulin from tumour
cells. Alternatively secretion of insulin from adjacent islet cells may have been
Aim
caused by paracrine effects. The exact mechanism in our case, however, only
To describe the follow-up of adrenal incidentalomas (AI) classified as non-
remains speculative.
functioning and no suspicious for malignancy in the first approach.
Conclusion
Patients and methods
Tumours of the pancreas causing hypoglcemia may not necessarily be
Observational retrospective study of a cohort of patients who consulted in the
insulinoma. Silent neuroendocrine tumour of the carcinoid
(Argantafinoma)
Endocrinology service between 2005 and 2015 because of an AI. Statistical
variety may be the culprit.
analysis performed with SPSS 19th version.
DOI: 10.1530/endoabs.49.EP160
Results
Two hundred and one patients with IA were firstly evaluated. Thirty two of them
(15.92%) underwent surgery after the initial evaluation. One hundred and twenty
four patients out of the 169 who didn’t undergo surgery (73.37%) were followed:
97 unilateral AI and 27 bilateral AI. Age: 58.48G11.84 years. Size: 26.36G
14.14 mm. 57.3% Women. Repeated measurement of plasma metanephrines in
26 patients (20.97%): 21 unilateral AI (21.65%) and five bilateral AI (18.52%).
No catecholamine production in any AI. Median follow-up: 4.12G3.44 years.
Ninety eight patients (79.03%) underwent a 1 mg dexamethasone suppression test
to screen the cortisol autonomous production: 76 unilateral AI (78.35%) and 22
EP161
(81.48%) bilateral AI. Follow-up:
2.83G2.67 years.
10 patients
(10.20%)
CYP2W1*6 polymorphism as a potential predictive marker of
diagnosed with subclinical Cushing not present in the first evaluation. The rest of
sensitivity to mitotane treatment in adrenocortical carcinoma.
them showed no autonomous cortisol production. A follow-up imaging study was
Barbara Altieri1,2, Sabine Herterich3, Silviu Sbiera1, Marco Volante4,
performed in 103 patients (83.06%): 80 with unilateral AI (82.47%) and 23 with
Matthias Kroiss1, Silvia Della Casa2, Alfredo Pontecorvi2,
bilateral AI (85.19%). Median follow-up: 2.77G2.70 years. In four patients (5%)
Massimo Terzolo5, Martin Fassnacht1 & Cristina L. Ronchi1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Division of Endocrinology and Diabetes, Department of Internal Medicine
Results
I, University Hospital of Wuerzburg, Wuerzburg, Germany;2Division of
Of the 31 patients, 65% (20/31) were women and 35% (11/31) men. Median
Endocrinology and Metabolic Diseases, Catholic University of the Sacred
follow-up was 23 months (0-217). Median age at diagnosis was 62 years (21-78),
Heart, Rome, Italy;3Central Laboratory, University Hospital of Wuerzburg,
with peak incidences in age groups 30-39 and 60-69 years. Most patients
Wuerzburg, Germany;4Department of Oncology, San Luigi Hospital,
presented with hypokalemia (87%), muscle weakness (77%), ankle edema (74%),
University of Turin, Turin, Italy;5Division of Internal Medicine I, San Luigi
hypertension
(71%), psychiatric manifestations
(58%), changes in body fat
Hospital, University of Turin, Turin, Italy.
distribution (58%), and bruises (51%). Median (range) cortisol, ACTH and 24 h
urinary free cortisol were
1467 nmol/l
(121-4380),
155 ng/l
(16-4700),
8221 nmol/l
(568-69038), and median
(range) cortisol after
1 mg DST
Mitotane is the only approved drug for the treatment of advanced adrenocortical
1103 nmol/l (74-3390), respectively. Thirteen (42%) underwent CRH-testing,
carcinoma (ACC) and we recently demonstrated that a high expression of
which was accurate (! 50% increase in ACTH and ! 20% in cortisol) in 9/13
cytochrome P450 2W1 (CYP2W1) correlated with response to mitotane. The
(69%) patients. Underlying tumours: pancreatic NET (nZ6), pulmonary NET
association between CYP2W1 alleles and a generally increased cancer risk is
(nZ6), pulmonary small cell carcinoma (nZ6), unknown primary (nZ4; no
under debate. Aim of the study was to evaluate the frequency of CYP2W1
tumour detected nZ2, disseminated disease nZ2), medullary thyroid carcinoma
polymorphisms and its correlation with the response to mitotane treatment in
(nZ3), thymic NET (nZ2), and, ileum NET, prostate carcinoma, poorly
ACC patients.
differentiated pulmonary NEC, poorly differentiated pulmonary LCC (nZ1 for
Methods
each). Median overall survival was 23 month (0-217). At the end of follow-up,
DNA was isolated from whole blood of 108 Caucasian ACC patients (F/MZ
12/31 (39%) patients were alive. Four patients initially cured recurred at 2, 6, 6
68/40) treated with mitotane monotherapy in adjuvant (nsZ66) or palliative
and 10, and 12 years, respectively. Surgery of the primary tumour was possible in
(nZ42) setting. Three CYP2W1 polymorphisms were genotyped by PCR and
10/31 (32%) patients, nine (90%) of whom were alive at the end of follow-up.
sequenced: CYP2W1*2 (p.A181T), CYP2W1*5 (p.Q482H) and CYP2W1*6
Bilateral adrenalectomy was performed in 10/31 (32%) patients, three (30%) of
(p.P448L). The response to therapy was evaluated by time to progression (TTP).
whom were alive at the end of follow-up. Outcome was best in thymic and
Results
pulmonary NETs.
The allele frequencies for CYP2W1*2 and CYP2W1*6 were 8 and 18%,
Conclusion
respectively, and are comparable to those found in the European population (1000
EAS affects women in 65% of cases. Incidence peaks in age groups 30-39 and
Genomes Project Phase 3 allele frequencies, ENSEMBLE, 5% for CYP2W1*2
60-69 years. Recurrences are possible O 10 years later. Overall survival is poor.
and
17% for CYP2W1*6). For CYP2W1*6
there were slightly more
DOI: 10.1530/endoabs.49.EP163
homozygotes than expected (PZ0.1). Both variant alleles were in the Hardy-
Weinberg equilibrium. CYP2W1*5, which is only reported in non-Causasian
population, was not found. We did not find any correlation between CYP2W1*2
allele and clinical outcomes. Whereas, we observed that patients with advanced
disease who have CYP2W1*6 allele have a worse response to therapy (median
TTP 3.0 vs 5.5 months, PZ0.03, HR 1.83). Among these patients, 86% who have
CYP2W1*6 allele did not reach the therapeutic range of mitotane plasma level
(14-20 mg/l) in comparison to 61% of those without CYP2W1*6 allele (PZ0.09,
chi-squaredZ2.7). No relevant impact of CYP2W1*6 was observed in patients
treated with adjuvant mitotane.
EP164
Conclusion
Ectopic Cushing’s syndrome caused by a pulmonary
This study further suggests that CYP2W1
might be involved on mitotane
adrenocorticotropic hormone secreting tumour: a case report
metabolism and that CYP2W1*6 allele might correlate with a worse sensitivity
Renata Pauliukiene1, Edita Prakapiene1,2, Rasa Koreiviene1,2,
to mitotane palliative treatment.
Raimonda Klimaite1,2, Lina Barsiene1 & Valdas Sarauskas3
DOI: 10.1530/endoabs.49.EP161
1Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,
Endocrinology Department, Kaunas, Lithuania;2Lithuanian University of
Health Sciences, Kaunas, Lithuania;3Hospital of Lithuanian University of
Health Sciences, Kauno Klinikos, Pathological Anatomy Department,
Kaunas, Lithuania.
Introduction
Ectopic adrenocorticotropic hormone (ACTH) production by the pulmonary
EP162
neuroendocrine tumour (p-NET) is rare, and is considered an aggressive variant
of carcinoid tumours with poor prognosis.
Case presentation
Abstract unavailable.
59-year-old male with fast progressing generalized fatigue, abdominal
discomfort, and diarrhea was hospitalized in gastroenterology unit of Hospital
of Lithuanian University of Health Sciences, Kauno klinikos (HLUHS KK).
Digestive tract diseases were ruled out. Persistent hypokalaemia
(up to
2.2 mmol/l) was observed and endocrine pathology changes were considered.
Examinations revealed markedly elevated plasma ACTH
(44.4 pmol/l) and
cortisol (O1665 nmol/l) levels, diabetes, osteoporosis. No suppression of serum
cortisol level with high-dose dexamethasone test was found, confirming ACTH
dependent Cushing syndrome. The treatment with Metirapone was started.
Pituitary and abdominal magnetic resonance imaging
(MRI), abdominal
computer tomography (CT) scans were normal. Thoracic CT scan showed
nodules in the S2, S3, S6 of the left lung. No cytologic changes were found in
repetitive bronchial leachates through endoscopic bronchoscopy. There were two
episodes of pneumonia (Pseudomonas aeruginosa) and two episodes of sepsis
EP163
(Staphylococcus aureus and Enterococcus faecium). Suspected fungal infection,
Ectopic ACTH-syndrome - 31 consecutive patients from the Helsinki
intended antifungal treatment. Single nodule in S3 of the left lung with no changes
University Hospital
in size was found in repeated chest CT.99MTc-tectrotyd SPECT-CT showed left
Sanna Toivanen1, Helena Leijon2, Timo Sane1 & Camilla Schalin-Jantti1
lung S3 neuroendocrine tumour. The radical surgery (bilobectomia superior
1Endocrinology, Abdominal Center, University of Helsinki and Helsinki
sinistri) was performed. Histological result was well-differentiated p-NET (pT1a
University Hospital, Helsinki, Finland;2Department of Pathology,
N0 R0 G1). No radiochemotherapy was suggested. On the follow up visit after
University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
three months normal glycaemia, potassium and cortisol were found.
Conclusion
Background
We present ectopic ACTH secreting neuroendocrine lung carcinoma with likely
Ectopic ACTH syndrome (EAS) is rare and published series are scarce.
good prognosis. No clearly defined guidelines of follow up exist.
Aim
DOI: 10.1530/endoabs.49.EP164
To increase the understanding of EAS we describe 31 consecutive cases in years
1997-2016.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP165
mostly distributed in abdomen (60%), head and neck (26.2%), rarely in spine
(9.2%) and chest (4.6%). Hereditary form of disease was present in 22.5% of
Could alcohol ablation become the standard of care for benign
patients. The most common mutation was in SDHB gene (10/16), hereafter in
insulinomas?
VHL gene (3/16); two patients had mutation in SDHD gene and one in SDHC.
Isabel Mazarico1, David Subías1, Fèlix Junquera2, Carme Vilardell3,
Multiple PGLs were identified in six patients. Hormonally secreting tumors were
Ignasi Saigí4, Albert Cano1, Laia Casamitjana1, Olga Giménez-Palop1,
present in 28%; 16/30 patients had positive finding on I-123 MIBG scintigraphy.
Lara Albert1, Ismael Capel1, Assumpta Caixàs1 & Mercedes Rigla1
Surgical resection was performed in 79% of patients, tumor embolization in 11%.
1Endocrinology and Nutrition Department, Parc Taulí Hospital Universitari,
At 22 patients the median proliferation index Ki67 was 1.8% (0.1-18%) and
Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma
median PASS score 3(1-6). Metastatic disease was present in 18.8% of patient at
de Barcelona, Sabadell, Spain;2Department of Gastroenterology, Parc Taulí
the time of diagnosis and five patients had acquired metastasis. These patients
Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT,
were treated with PRRT (6/14), chemotherapy (3/14) and sutent (3/14). Median
Universitat Autònoma de Barcelona, Sabadell, Spain;3Endocrinology and
overall survival (OS) was 284 months (95%CI 251-318) with 10-year OS 88%.
Nutrition Department, Althaia Fundation, Manresa, Spain;4Internal
Mean disease free survival was estimated 20 months (95%CI 8-31). We presented
Medicine Department, Consorci Hospitalari de Vic, Vic, Spain.
clinical characteristics, genetic profile, treatment options and survival of our
patients with PGLs, our experience as single tertiary center.
Introduction
DOI: 10.1530/endoabs.49.EP166
Surgical resection is currently considered the standard treatment for symptomatic
insulinomas; however, its morbidity is high (O10%) and it is restricted to suitable
candidates. In recent years, alternative minimally invasive therapies, such as
endoscopic ultrasound (EUS)-guided ethanol ablation (EA), have emerged as new
therapeutic options, especially for small lesions or poor surgical candidates. We
report two cases of insulinoma ablated with EA.
Cases report
We report two cases of recurrent hypoglycaemia due to benign insulinoma: a
75-year- old man, with a 9 mm hypoechoic lesion in the neck of the pancreas,
unfit for surgery because of comorbidities (case 1); and a 71-year- old man with
a 19!14 mm hypoechoic lesion in the pancreas head, who refused surgery
treatment
(case
2). EUS fine needle aspiration
(EUS-FNA) confirmed
EP167
neuroendocrine tumor with a Ki67 !5% in both of them. They were admitted
Corticotroph deficiency in patients with insulinoma
to our department for EA. Insulinomas were punctured under EUS guidance with
Faten Hadj Kacem1, Mouna Ammar1, Mouna Elleuch1, Dorra ghorbel1,
a 22 G needle. A total volume of 0.8 ml (case 1) and 13 ml (case 2) ethanol 98%
Rihab Ben Abdallah2, Nadia Charfi1, Wajdi Sefi1, Mouna Mnif1 &
was injected. After each injection a whitish halo was observed inside the lesion,
Mohamed Abid1
and no extravasation of alcohol was detected. There were no perioperative or
postoperative complications. In case 1, hypoglycaemia was not reported along the
1Department of Endocrinology and Diabetes Hedi Chaker, Sfax, Tunisia;
two years follow-up period. Case 2 presented occasional mild hypoglycaemia
2Faculty of sciences, Sfax, Tunisia.
1 year after treatment, so we considered repeating EA, but the patient refused it.
Conclusion
Introduction
EUS-guided ethanol ablation of a single small insulinoma is an effective,
The metabolic stressor, hypoglycemia, elicits integrated counterregulatory
minimally invasive, and safe therapeutic modality. Currently, it is considered
responses, including activation of the hypothalamic-pituitary-adrenal axis.
when surgery cannot be an option. However, this new technique should be applied
However, it is suggested that recurring insulin-induced hypoglycemia can impair
to a wider range of potential candidates. A multicentric study seems necessary to
this counter-regulation. Here we report three cases of patients with isulinoma and
establish the indications of EA in insulinomas.
corticotroph deficiency.
DOI: 10.1530/endoabs.49.EP165
Case reports
The first case, 38-year-old man was referred because of recurrent episodes of
hypoglycemia. Hormonal investigations were in favour of dissociated anterior
pituitary failure, with growth hormone and corticotroph deficiency. The
hypothalamic-pituitary MRI was normal. The fasting test argued in favour of a
hyperinsulinemic hypoglycemia. The abdominal scan and the endoscopic
ultrasound showed a mass within the tail of the pancreas. Distal pancreatectomy
was performed. Histology disclosed an insulinoma. On follow up, no
hypoglycemic episodes recurred and cortisol and GH response to induced
hypoglycemia was normal. The second case, 68 years old man referred for
investigation of hypoglycemic episodes. He was diagnosed with corticotroph
EP166
deficiency and hypergonadotropic hypogonadism with negative investigations.
Clinical characteristics and survival of patients with paraganglioma:
The hypothalamic-pituitary MRI was normal. After treatment with glucocorti-
a single center experience
coids, hypoglycemic episodes were significantly improved. After 6 years, he
Valentina Elezovic, Djuro Macut, Sanja Ognjanovic, Tatjana Isailovic,
presented severe hypoglycemia and investigations revealed a 1.5 cm tumor in the
Bojana Popovic, Ivana Bozic-Antic, Tamara Bogavac, Dusan Ilic,
head of the pancreas with hepatic and pulmonary metastases. The third case,
Jovana Bankovic & Svetozar Damjanovic
38 years old woman with a history of primary hypothyroidism for 6 years,
Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center
presented with symptomatic hypoglycemia and a history of weight gain.
of Serbia, Belgrade, Serbia.
Laboratory investigations argued in favour of a hyperinsulinemic hypoglycemia
and the abdominal scan showed a mass within the tail of the pancreas.
Furthermore, she was diagnosed with corticotroph deficiency. The hypothalamic-
Paragangliomas (PGLs) and pheochromocytomas (PCCs) are rare neuroendocrine
pituitary MRI was normal.
tumors that derived from pluripotent neural crest stem cells. PCCs are derived
Conclusions
from the adrenal medulla, while PGLs are histologically identical tumors derived
Our clinical cases show that hyperinsulinemia and hypoglycemia in patients with
from ganglia outside the adrenal gland. Even though the majority of tumors are
insulinoma can give rise to functional corticotrophin deficiency. The pathophy-
benign, they are associated with high morbidity rates caused by excessive
siological mechanism of this defective counter-regulation remains to be clarified;
catecholamine secretion. We retrospectively analyzed 71 patients (36 female and
some studies suggest it could be related to hyperinsulinemia-induced decreased in
35 males) with PGLs between January 2002 and December 2016. Twenty three
CRF secretion.
patients were lost to follow up. Kaplan-Meier curve was used as the univariate
DOI: 10.1530/endoabs.49.EP167
version of survival analysis. The median age at diagnosis was 47.0 years (11-75)
and the mean tumor size was 53 mm (26-170 mm). PGLs in our group were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP168
EP170
Hyperinsulinemic hypoglycemia in a 71-year-old patient with a
A rare cause of secondary endocrine hypertension in a young woman
suspected case of b-cells hyperplasia of pancreatic body and
with hypokaliemia and recurrent transient ischemic attacks
tail- case report
Francisco Javier Martinez-Martin3, Sara Quintana-Arroyo1,
Jelena Malinovic Pancic1,2, Bojana Caric1,2 & Bojana Popovic3
Carmen Acosta-Calero1, Claudia Arnas-Leon1, Ana Delia Santana-Suarez1,
1University Clinical Center of Republic of Srpska, Banja Luka, Bosnia and
Manuel Nivelo-Rivadeneira1, Agnieszka Kuzior1 & Elisa Gonzalez-
Herzegovina;2Medical Faculty Banja Luka, Banja Luka, Bosnia and
Rodriguez2
Herzegovina;3Clinical Center of Serbia, Belgrade, Serbia.
1Endocrinology Department, Hospital Universitario de Gran Canaria Dr.
Negrin, Las Palmas de Gran Ganaria, Spain;2Endocrinology Department,
Hospital Vithas Santa Catalina, Las Palmas de Gran Ganaria, Spain;
B-pancreatic cells are programmed to react to plasma glucose level with insulin
3Outpatient Hypertension Clinic, Hospital Universitario de Gran Canaria
secretion. Insulin secretion is precisely regulated and in the physiological
Dr. Negrin, Las Palmas de Gran Ganaria, Spain.
conditions fasting glucose levels are maintained in the range 3.5-5.5 mmol/l. In
hyperinsulinemic hypoglycemia, a disorder of the regulation of insulin secretion,
insulin secretion continues at low concentrations of plasma glucose. In adults
Clinical Case
hyperinsulinemic hypoglycemia is the cause of 0.5 to 5.0% of hypoglicaemias and
A 39-year-old woman was referred to our Hypertension Clinic for workup after
are result of eather b-cell tumor
(insulinoma), or b-cell hyperplasia. Rapid
three episodes of TIA with SBP O180 mmHg in the last 6 months. Diagnosed and
diagnosis and treatment is essential in the prevention of acute and chronic
treated of hypertension and hypokaliemia since she was
15 years old, no
complications of hypoglycaemia, especially in central nervous system.
secondary cause had been searched. She was treated with Telmisartan/Amlodi-
We are presenting the 71-year-old patient who had been previously diagnostic
pine/Hydrochlorothiazide
80/10/25 mg plus Carvedilol
12.5 mg BID and
evaluated at the primary health care level due to frequent episodes of
potassium supplements. She had no history of diabetes or dyslipidemia and did
unconsciousness and weakness periodically in period of
3 years prior to
not smoke. Height was 168 cm, weight 63 kg, IMC 22.3 kg/m2, office BP
admission. After established refractory hypoglycemia patient was sent to our
142/88 mmHg, HR 72 bpm. The physical exam was otherwise normal.
department where endogenous hyperinsulinism after 72-hour test of hunger was
Treatment was changed to Diltiazem/Doxazosin for 3 weeks. Lab: normal
found. After endoscopic ultrasound showed probable b-cells hyperplasia of the
including TSH and metanephrines, except venous pH 7.51, Cr 1.23 mg/dl, CKD-
body and tail of the pancreas. I-131
ocreotid scintigraphy of somatostatin
EPI eGFR 57 ml/min/1.73 m2, albuminuria 139 mg/g Cr, aldosterone 792 ng/ml,
receptors was negative. Calcium artery stimulation of the pancreas with insulin
PRA 58 ng/ml per h, normal ratio (13.7).
sampling from vein lienalis showed a clear gradient of insulin and distal
Funduscopy: stage 2 hypertensive retinopathy, brain RMN: scattered white matter
pancreatectomy was suggested which patient refused. inhibitor of potassium
microinfarctions, heart US: normal function, mild LVH (LVMI 92 g/m2). Chest
channels-diazoxide was introduced in the therapy which led to reduction in
X-ray and abdominal US: normal.
subjective symptoms and no registered hypoglycaemas.
AngioCT excluded renal artery sclerosis, but showed a 12 mm subcapsular mass
DOI: 10.1530/endoabs.49.EP168
in the right kidney. The adrenals were normal.
Renal venous sampling for renin: Peripheral 628 U/l (normal ! 42), Left renal
vein 645 right renal vein 3120 U/l; right/left ratio 4.8. Laparoscopic nodulectomy
was performed; a encapsulated 14 mm adenoma with clean margins was obtained.
It tested positive for renin.
EP169
Diagnosis
Respiratory symtoms lead to a diagnosis of pheochromocytoma:
Secondary aldosteronism due to reninoma, resistant hypertension and target-
An unusual presentation
organ damage (retinopathy, brain microinfarctions and TIAs, stage IIA CKD with
Luís Teles1,2, João Sérgio Neves2, Pedro Souteiro2, Sofia Castro Oliveira2,
microalbuminuria, LVH). Two months after surgery the patient is normotensive
Celestino Neves2, Paula Freitas2 & Davide Carvalho2
with manidipine 10mg/day: aldosterone, ARP, KC, venous pH and albuminuria
1Internal Medicine Department Centro Hospitalar Entre Douro e Vouga,
are normal.
Santa Maria da Feira, Portugal;2Endrocrinology Department Centro
Commentary
Hospitalar São João, Porto, Portugal.
Reninoma is rare but probably infradiagnosed, and a long diagnostic delay is not
unusual. Even with well-controlled BP, it may cause severe organ damage due to
hyperaldosteronism. Thus, it should be included in the workup of secondary
Introduction
hypertension.
Pheochromocytoma is one of the major secondary causes of hypertension. The
DOI: 10.1530/endoabs.49.EP170
classic triad of pheochromocytoma symptoms of headache, sweating and
tachycardia is not present in a high percentage of patients and is sometimes
diagnosed as incidentaloma or atypical presentations.
Case report
The authors present a 56-year-old man, with no known diseases, referred to
Endocrinology evaluation by incidentaloma of the right adrenal gland, from the
Pneumology appoitment, where he was followed by persistent cough, after an
episode of bronchospasm. From the complementary study, a 32 mm nodule in the
right adrenal gland was observed on thoracic computed tomography and
EP171
confirmed by MRI. Bronchofibroscopy with bronchoalveolar lavage and
Atypical symptoms of hypoglycemia, hiding a diagnosis of insulinoma:
functional respiratory tests were also performed, which were normal. Patient
a case report
didn’t refer any symtoms, however, he maintained a sustained hypertension in the
Agne Petrenaite1,2, Greta Jagucianskaite1,2, Rasa Juskiene2, Rasa Ziukaite2
ambulatory monitorization. Analytically, there was a significant increase in the
& Zydrune Visockiene1,2
urinary normetanephrines (2585 ug/24 h for a reference value !390) and urinary
1Faculty of Medicine, Vilnius University, Vilnius, Lithuania;2Vilnius
metanephrines (1551 ug/24 h, for a reference value !320), as well as plasma
University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
noradrenaline (1107 pg/ml for a reference value !750) and plasma adrenaline
(137 pg/ml, for a reference value
!110). Remaining study was without
alterations, namely renin-angiotensin-aldosterone axis, thyroid function and
Introduction
urinary free cortisol. Patient started alpha-adrenergic blockade with phenox-
Insulinoma is a rare pancreatic tumor, typically sporadic, solitary and benign.
ybenzamine and laparoscopic adrenalectomy was performed 3 weeks later.
However, nonspecific symptoms of hypoglycemia, negative laboratory investi-
Pathological anatomy confirmed diagnosis of pheochromocytoma.
gations and small size of these tumors can retard the diagnosis, and symptoms
Conclusion
may be misattributed to psychiatric, cardiac, neurological disorders.
Authors present a case of atypical presentation of pheochromocytoma. The
Case presentation
respiratory airways are sensitive to the effects of catecholamines. Although they
A 35-year-old male had history of night time seizures with hallucinations,
have mainly beta-adrenergic receptors, there are also alpha receptors that may
delirium and spasms, lasting from 10 minutes to 1.5 hours for about 2 years. These
explain the patient’s clinical condition (bronchospasm).
seizures were always resolving spontaneously. Due to recurrent seizures he was
Given the existence of multiple presentations, detection of a pheochromocytoma
consulted by phychiatrist and diagnosed with depression and conversion disorder
might be difficult but is mandatory, not only for the potential cure of the
and treated with psychotropic medications. As the spasms remained, he was
hypertension but also to avoid the potentially lethal effects of the unrecognized
referred to neurologists. During examination early in the morning while
tumor.
performing electroencephalography typical dyscognitive seizures occured.
DOI: 10.1530/endoabs.49.EP169
Plasma glucose analysis was performed for the first time and hypoglycemia of
1.4 mmol/l was found. Symptoms disappeared after intravenous glucose infusion.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Management and outcome
Relation of dehydroepiandrosterone sulphate
(DHEAS) concentration and
The patient was hospitalized due to suspected insulinoma and supervised 72-hour
adrenal tumors (AT) has never been investigated systematically. After promising
fast test was performed. Plasma glucose was
3.5 mmol/l, plasma insulin
-
Terzolo group (1995, 1996, 2000) investigations, there was made a recommen-
49.3 pmol/l (43-210 pmol/l) and C-peptide - 780 pmol/l (260-1730 pmol/l) at the
dation in the last clinical guidelines for adrenal incidentaloma (2016) to assess
baseline. The test was ended after 16 hours with plasma glucose of 1.7 mmol/l,
concentration of DHEAS in special clinical situations. Here we present the first
plasma insulin - 29.7 pmol/l, C-peptide - 521 pmol/l. These results confirmed the
systemic study of DHEAS in adrenal tumors.
diagnosis of insulinoma. Abdominal computed tomography scan with contrast
The aim was to analyse the clinical and laboratory characteristics (including
demonstrated a well-defined hypervascular lesion involving the head of pancreas
DHEAS) of 109 males and 54 females with AT.
measuring 10!15 mm in diameter, typical of neuroendocrine tumor. The patient
Methods
underwent laparoscopic extirpation of the pancreatic mass. Histopathological
During 2014-2016 years concentration of DHEAS was determined in 5133
evaluation revealed a pancreatic well-differentiated (G1) neuroendocrine tumor -
patients. Out of those case records of 590 females and 450 males were randomly
benign insulinoma. The patient gradually discontinued all psychotropic
selected for a detailed retrospective analysis. The relation between presence or
medications following the operation. Currently he is feeling well, without any
absence of AT and DHEAS was established. Age and gender adjusted maximal
seizures and normal plasma glucose for about 1.5 years.
values (R max) and minimal values (R min) of DHEAS concentration were used
Conclusion
to express the results.
We recommend to check plasma glucose for all patients with seizures of unknown
Results
origin, although they are not typical to hypoglycemia.
AT were detected in 109 males and in 54 females. R max %0.4 was found in
DOI: 10.1530/endoabs.49.EP171
64.81% of females starting from 45 years-old and in 67% of males starting from
60 years-old. R max value O1 was found in 11 cases of females (20.4%) and only
in one case of males (0.92%). R min !1 value was detected in 13 cases of males
(11.92%) and in two cases (3.7%) of females.
Conclusions
Out of all 163 cases of adrenal tumors, high level of DHEAS was found more
frequently in females (7.36%), otherwise, low level of DHEAS was found more
EP172
frequently in males (7.97%).
A nomogram consisted of routine biochemical tests may increase the
DOI: 10.1530/endoabs.49.EP173
diagnostic accuracy of chromogranin A in detecting patients with
neuroendocrine tumors
Ivan Vurnek1, Ivan Kruljac2, Miroslav
´ a
´i
´2, Bo
ˇidar Peri
´2,
Maja Filipovi
´-Grči
´2, Gorana Miroševic´2, Davor Kust2 & Milan Vrkljan1,2
1School of Medicine, University of Zagreb, Zagreb, Croatia;2University
Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.
EP174
Introduction
Falsely elevated serum chromogranin A (CgA) is associated with the use of
Jejunum/ ileum Neuroendocrine Tumours: results of a multicentric
proton pump inhibitors, the presence of renal impairment and systemic
retrospective study
inflammation. We aimed to investigate which laboratory parameters are
Ana Paula Marques1, Ana Paula Santos2, Isabel Claro3, Ana
independently associated with increased CgA and to develop a nomogram, in
Cristina Sanches2, Isabel Fernandes5, José Manuel Lopes6, John Preto6,
order to improve the diagnostic accuracy of CgA in detecting patients with
Fernando Rodrigues7, Ana Luisa Catarino8, Juan Mellidez9,
neuroendocrine tumors (NET).
Bernardo Pereira10, Gustavo Rocha11, Maria Joa˜o Bugalho5 & Grupo
Methods
Estudos Tumores Neuroendócrinos12
Our retrospective study included 155 subjects (controls) and 55 treatment naïve
1Hospital Pedro Hispano, Matosinhos, Portugal;2Instituto Português
patients with NET, with available data on CgA, other laboratory tests, medical
Oncologia, Porto, Portugal;3Instituto Português Oncologia, Lisboa,
history and antropomethric parameters. Nomogram was developed in a form of
Portugal;4Instituto Português Oncologia, Porto, Portugal;5CHLN, Lisboa,
scoring system, based on z-score obtained from receiver operating curve analysis
Portugal;6CHSJ/IPATIMUP, Porto, Portugal;7Instituto Português Onco-
for each parameter that was independently associated with CgA.
logia, Coimbra, Portugal;8HBA, Loures, Portugal;9HSP, Aveiro, Portugal;
Results
10HGO, Almada, Portugal;11CHVNG, Vila Nova de Gaia, Portugal;
CgA was positively associated with erythrocyte sedimentation rate, red cell
12Portugal, Portugal, Portugal.
distribution width, serum creatinin, glucose, urine leukocyte casts and the use of
proton pump inhibitors. The combination of all these parameters was associated
Introduction
with increased CgA with an area under the curve of 0.771 (P!0.001). Overall,
The Neuroendocrine Tumors Study Group of the Portuguese Endocrine Society
CgA level of 189 had a sensitivity of 56.4% (42.3-69.7) and a specificity of 76.8%
(SPEDM) performed the first observational study between November 2012 and
(69.3-83.2) in detecting patients with NET
(area under the curve
0.656,
July
2014 too assess the profile of Gastroenteropancreatic Neuroendocrine
P!0.001). In subjects with a score of !6, CgA level of 150 ng/ml had a
Tumours (GEP-NET) patients (pts) followed at the main Portuguese hospitals.
sensitivity of 68.2% (45.1-86.1) and specificity of 89.4% (80.8-95.0), (AUC
Several demographic and clinical data were collected
0.767, P!0.001). In subjects with a scoreR6, AUC decreased to
0.534
Objective
(PZ0.538).
Characterize the clinicopathological features and treatment of patients with NET
Conclusion
originating in the jejunum and ileum.
CgA should not be used as a biomarker for NET in patients with laboratory signs
Material and methods
of inflammation and renal impairment. Our study suggests the possibility to adjust
Included 71 pts with R18 years and a confirmed diagnosis of jejunum /ileum
CgA in these patients in order to increase its diagnostic accuracy.
NET based on histopathology/cytology findings.
DOI: 10.1530/endoabs.49.EP172
Results
Mean age was 57.2 (32-83) years, 61% (nZ43) males. Most tumors 89% (nZ63)
were located at the ileum; two were multifocal. Ki67 was available in 86% of pts,
64% G1. At diagnosis 91% (51/56) had lymph node metastases and 70% (43/61)
distant metastases.
The most common symptom, available in 59 pts, was abdominal pain in 49%
(29/59). Serum Chromogranin A (Crg A) was available in 65% (46/71) and was
EP173
2!R upper limit of normal in 61%(28/46). Urinary 5HIAA checked in 61%
Concentration of dehydroepiandrosterone sulphate in 109 males and
(43/71) was elevated in 56%(24/43), 86% of these with distant metastases. CT
54 females with adrenal tumors
scan was the preferred radiologic procedure in 87% of pts. Nuclear medicine
Ilona Banisauskaite1, Paulina Simaityte1, Milda Sarkinaite1,
imaging, either octreotide scan or68 Ga-DOTA-NOC Pet Scan was used in
Viktorija Bakstyte1, Juste Baksanskaite1, Rasa Steponaviciute2,
75%(53/71) of pts Tumor size known in 58 pts was 24G14.7 mm. Primary tumor
Astra Vitkauskiene2, Vaidotas Urbanavicius3 & Valentinas Matulevicius1
surgery was performed in 90 and 32% did surgery of hepatic metastases. 62% of
1Institute of Endocrinology, Lithuanian University of Health Sciences,
the pts received somatostatin analogues(SA), two were treated with SA and
Kaunas, Lithuania;2Department of Clinical Laboratory, Hospital of
interferon and two with systemic chemotherapy. 11 cases were submitted to
Lithuanian University of Health Sciences, Kaunas, Lithuania;3Faculty of
hepatic transarterial embolization. Peptide Receptor Radionuclide Therapy with
Medicine, Vilnius University, Kaunas, Lithuania.
177Lu was done in 9%.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
Methods
This paper reveals important information regarding clinical practice. Most of our
Fifty-nine (45 females) patients with GNEN1 were retrospectively studied. All
pts presented with well differentiated tumors but in an advanced stage. Regarding
patients included in the study had positive parietal-cell antibodies. All patients
therapy there was an extensive use of surgery and systemic treatment mainly
underwent a gastroscopy with multiple biopsies. Chromogranin A, gastrin,
with SA.
vitamin B12, folate and ferritin levels were also assessed.
DOI: 10.1530/endoabs.49.EP174
Results
The mean age and follow up were 54.14G13.62 years and 67.66G48.9 months,
respectively. At diagnosis, chromogranin A, gastrin, vitamin B12, folate and
ferritin levels were:
277.54G173.54 ng/ml
(!98),
896.18G818.98 pg/ml
(!110),
395.43G488.18 pg/ml
(300-960),
12G11.36 ng/ml
(2-20) and
58.02G75.08 ng/ml (20-350), respectively. Intestinal metaplasia appeared in
48 patients (81.35%) with GNEN1; 41 (85.5%) had large IM, 1 (2%) had small
and 6 (12.5%) had both small and large IM. In univariate regression analysis, only
EP175
mean follow-up from the parameters studied
(age at diagnosis, gender,
Follow-up in neuroendocrine tumors: is chromogranin A the
biochemical markers) predicted the presence of intestinal metaplasia
(OR:
confounder?
0.979; 95%CI: 0.961-0.997, PZ0.021).
Diana Martins1, Carla Baptista1, Ana Velez2, Fernando Macário3 &
Conclusion
Francisco Carrilho1
Our study showed a high prevalence of large IM in GNEN1. Mean follow up
1Endocrinology, Diabetes and Metabolism Department of Coimbra Hospital
predicted IM presence. Further clinical studies are required to determine which
and Universitary Centre, Coimbra, Portugal;2General Surgery Department
parameters predict the presence of IM in patients with GNEN1.
of Coimbra Hospital and Universitary Centre, Coimbra, Portugal;
DOI: 10.1530/endoabs.49.EP176
3Nephrology Department of Coimbra Hospital and University Centre,
Coimbra, Portugal.
Introduction
Chromogranin A continues to be one of the most valuable markers for
neuroendocrine tumors (NETs) however, it has several limitations, including
its reduced specificity.
EP177
Methods
Pancreatic neuroendocrine tumors (PNETs) in patients with MEN1
The authors present the case of a patient diagnosed with a midgut NET, during
syndrome
follow-up.
Tatjana Isailovic1, Djuro Macut1, Sanja Ognjanovic1, Milan Petakov1,
Results
Valentina Elezovic1, Ivana Milicevic2, Bojana Popovic1, Ivana
Male patient, 61 years old, with chronic renal disease (CRD), underwent right
Bozic Antic1, Tamara Bogavac1, Dusan Ilic1 & Svetozar Damjanovic1
hemicolectomy owing to ileo-cecal valve lesion; histological result consistent
1Clinic for Endocrinology, Department for Endocrine Tumors and Heritable
with NET. Pre-operatory staging: without metastatic disease on thoracic-
Cancer Syndromes, Belgrade, Serbia;2Clinic for Endocrinology, Genetic
abdominal CT; octreoscan with elevated expression of somatostatin receptors
Laboratory, Belgrade, Serbia.
on ileo-cecal valve topography; CgA 32 nmol/l (!6.0), NSE 14 ng/ml (!15.0).
Anatomopathological examination of surgical specimen: well-differentiated G1
NET; mesenteric infiltration and metastization in 1 of 20 lymph nodes (T3N1Mx;
PNETs represent the leading cause of mortality in MEN1 patients. Yet, their
AJCC-IIB; R0). After 3 years of stable disease, the patient presented CgA of
characteristics, behaviour, and therefore management, are still uncertain.
1173.8 ng/ml (!85), with impaired CRD (Cr 4.42 mg/dl), on dyalisis. 3 months
The aim of this study was to describe the main clinical characteristics of NETs in
later: CgA
1619.0 pg/ml and Calcitonin
26 pg/ml
(!10). In additional
MEN1, and to compare them with sporadic NETs.
investigation, cervical-thoracic-abdominal CT and 68 Ga-PET rated negative
We investigated 164 patients with PNETs retrospectively, treated in one centre
for relapse. Total colonoscopy, including evaluation of ileocolonic anastomosis,
from 2004-2016. We identified 15 (9.1%) patients with MEN1. All patients had
didn’t demonstrate alterations. The patient maintained follow-up with clinical
germline mutations in MEN1 gene, except one who had sporadic MEN1. There
stability, showing in the last evaluation CgA 272.3 ng/ml, Calcitonin 38 pg/ml,
was no gender difference among the groups. No difference in age at onset between
NSE 12 ng/ml (!15) and Cr 6.88 mg/dl.
the groups was noted (48G16.1 in MEN1 vs 53.8G13.5 years in sporadic,
Conclusions
PO0.05). According to WHO classification, well-differentiated tumors were the
Evaluation of CgA in end stage renal disease is not reliable. Although it’s
most frequent in MEN1, in contrast to sporadic PNETs where well-differentiated
postulated that higher the degree of renal failure, higher the CgA concentration, it
carcinomas prevailed (P!0,01). Functioning PNETs were more frequent in
wasn’t verified such correlation. In NET patients, renal function should be
MEN1 group (60 vs 30%, P!0.05). Among functioning tumors, insulinoma and
carefully evaluated and ruled out the potential impact on the concentration of
gastrinoma were the most frequent in both groups (PO0.05). MEN1 patients had
CgA.
multiple tumors more frequently (33.3 vs 5%, P!0.05). Metastatic disease as
DOI: 10.1530/endoabs.49.EP175
initial presentation had 17% of MEN1, and 26% of sporadic patients (PO0.05).
Surgery was performed in 70% of MEN1, and 92% of sporadic patients. Tumor
size did not correlate with the presence of metastases at surgery in any of the
groups. Median OS was 149 months (95%CI 71-226) with no difference between
the groups (X2Z2.049, PO0.05). Mean time to tumor progression (TTP) was
estimated to 41 months (95%CI 10-75). However, no difference was found
regarding the MEN1 status (X2Z0.22, PO0.05). TTP negatively correlated to
Ki-67, local invasiveness and stage of the disease in all patients, but not to size or
functionality. These data suggest that MEN1
PNETs share similar clinical
EP176
behaviour as sporadic PNETs. Therefore, close tumor surveillance and early
Large intestinal metaplasia is a precancerous lesion present in patients
surgery are advocated, irrespective of the tumor size or functionality.
with gastric neuroendocrine neoplasms type 1
DOI: 10.1530/endoabs.49.EP177
Georgios Boutzios1, Krystallenia Alexandraki1, Vassiliki Mavroeidi1,
Eleni Koukoulioti2, Ioannis Papanikolaou2 & Gregory Kaltsas1
1Endocrine Unit, Department of Pathophysiology, Medical School, National
and Kapodistrian University, Laikon University General Hospital, Athens,
Greece;2Hepatogastroenterology Unit, Second Department of Internal
Medicine - Propaedeutic, Research Institute and Diabetes Center, Medical
School, National and Kapodistrian University, Attikon University Gen,
EP178
Athens, Greece.
Dysregulation of the components of the splicing machinery in
neuroendocrine tumors and its association with malignancy and
Background
aggressiveness
Intestinal metaplasia
(IM) of the gastric mucosa is a relatively frequent
Sergio Pedraza-Arévalo1, Emilia Alors-Pérez1, Aura D. Herrera-Martínez2,
precancerous lesion. The aim of the study was to assess the prevalence and the
Mercedes del Río-Moreno1, Rafael Sánchez-Sánchez3, Rosa Ortega-Salas3,
kind of IM and also to find parameters that could predict the presence of IM in
Raquel Serrano-Blanch4, María A. Gálvez-Moreno2, Manuel D. Gahete1,
gastric neuroendocrine neoplasms type 1 (GNEN1).
Raúl M. Luque1 & Justo P. Casta
˜o1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Department of Cell Biology, Physiology and Immunology, Maimonides
mutated vs WT patients. Quantification of serum succinate levels after treatment
Institute of Biomedical Research of Cordoba (IMIBIC), Reina Sofia
is in progress and aims to evaluate succinate as a biomarker of response in SDH-x
University Hospital (HURS), University of Cordoba (UCO), CIBER Physi,
MPP patients.
Cordoba, Spain;2Service of Endocrinology and Nutrition, HURS/IMIBIC,
DOI: 10.1530/endoabs.49.EP179
Cordoba, Spain;3Service of Anatomical Pathology, HURS/IMIBIC,
Cordoba, Spain;4Service of Medical Oncology, HURS/IMIBIC, Cordoba,
Spain.
Dysregulation of the splicing machinery is emerging as a novel cancer hallmark
due to its association with multiple dysfunctions in tumor cells. An inappropriate
function of the components of this machinery (spliceosome) could be primarily
EP180
linked with the generation of tumor-associated aberrant splicing variants. In line
Survival analysis of patients with gastroenteropancreatic
with this, we have previously reported that overexpression of aberrantly spliced
neuroendocrine tumors
variants of somatostatin receptor 5 (sst5TMD4) and ghrelin (In1-ghrelin) is
Miguel Sampedro-Nún˜ ez1,2, Angeles Maillo-Nieto1,
directly associated to malignancy features in gastroenteropancreatic neuroendo-
Ana María Ramos-Leví1,2, Isabel Huguet1,2, Sandra Campos1,2,
crine tumors (GEP-NETs). Therefore, in this study we aimed to characterize, for
Elena Fernandez1, Nerea Aguirre1, Jose Luis Mun˜oz de Nova3,
the first time, the pattern of expression of a selected set of components of the
Elena Martín3 & Mónica Marazuela1,2
splicing machinery in GEP-NETs samples, compared to adjacent non-tumoral
1Department of Endocrinology, Hospital Universitario de La Princesa,
control-tissues, and to determine its relationship with the aggressiveness of these
Madrid, Spain;2Instituto de Investigación Princesa, Madrid, Spain;
tumors. Accordingly, we designed a PCR-based array to determine the expression
3Department of Surgery, Hospital Universitario de La Princesa, Madrid,
levels of components of the major (nZ13) and minor spliceosome (nZ4) and
Spain.
associated splicing factors
(nZ28) using a microfluidic technology in
20
pancreatic NET-samples (47% G1, 47% G2 and 6% G3) and control-tissues. The
Introduction
results showed that the expression of several splicing factors and spliceosome
One of the main difficulties in the study of gastroenteropancreatic neuroendocrine
components was altered in tumor tissues compared to non-tumoral adjacent
tumors (GEP-NETs) is their wide heterogeneity and variable outcome. Several
tissues. Remarkably, important splicing factors (e.g. CELF4, NOVA1, SNW1,
potential influencing factors on patient survival have been recently identified.
and RAVER1) and components of spliceosome
(e.g. PRP8) were clearly
These factors could help predict patients’ prognosis.
overexpressed in NET-samples, wherein they were correlated with some
Objectives
malignancy features. Furthermore, in vitro assays using NETs cellular models
Analysis of long-term survival of our GEP-NETs cohort according to the presence
(i.e. BON-I/QGP-I-cells) demonstrated that CELF4 and NOVA1 overexpression
of metastatic disease, tumor grade, age, sex, tumor functionality and tumor origin.
induced an increase on cell-proliferation, while their silencing (using specific
Materials and methods
siRNAs) caused a marked decrease on cell-proliferation, suggesting a role in the
Ambispective study of patients with GEP-NETs in Hospital Universitario La
aggressiveness of these tumors and their putative suitability as therapeutic targets
Princesa (Madrid, Spain) from 1995 to the present. Survival analysis and factors
in pancreatic NETs. Hence, our results demonstrate an alteration of splicing
involved were assessed by Kaplan-Meier method and Cox regression analysis
machinery in pancreatic NETs and unveil its putative relevance in NETs
using STATA v12.0.
development/progression, where it could provide novel diagnostic biomarkers
Results
and therapeutic tools for this pathology.
One hundred and four patients were evaluated (55 women, age 61G16 years).
DOI: 10.1530/endoabs.49.EP178
Primary origin was pancreatic in 39, intestinal in 69 and unknown in 6 cases.
Histological tumor grade was G1 in 51%, G2 in 39% and G3 in 10% of cases. 68%
patients had metastatic disease and 33 died during follow-up. Median survival
time was 5261 days (CI 3247 to not reached). Grade G3 multiplied the risk of
mortality by 26 (CI 6 - 112); metastatic disease doubled the risk (CI 1.3 - 5.1);
every 10-year increase in age multiplied the risk by 1.6 (CI 1.2 - 2.2); and if the
tumor had unknown primary origin, the risk was multiplied by 2.5 (IC 0.9 - 7.4).
Sex and tumor functionality did not significantly affect survival.
Conclusions
EP179
Several factors influence the heterogeneity and clinical outcome of patients with
NETs. Median survival is reduced in patients with G3, metastasis, and primary
Serum succinate: investigation of its putative role as a new biomarker in
tumors of unknown origin. Knowing these factors guides the therapeutic approach
malignant SDH-x mutated pheochromocytoma-paraganglioma
of this rare disease.
patients?
DOI: 10.1530/endoabs.49.EP180
Constance Lamy1, Julien Hadoux1, Lionel Mercier1, Dorian Bailleux1,
Ségolène Hescot1, Angelo Paci1,2, Eric Baudin1 & Sophie Broutin1
1Gustave Roussy, Villejuif, France;2Université Paris-Sud,
Châtenay-Malabry, France.
Introduction
Malignant paraganglioma/pheochromocytoma (MPP) are very rare neuroendo-
EP181
crine tumors with heterogeneous prognostic and no gold-standard treatment. MPP
Insulinoma - clinical features and outcome of patients diagnosed at a
can be associated with germline mutations at SDH-x genes which encode for the
central hospital
succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate.
Joanna Prokop, Ana Cláudia Martins, Carolina Neves, Teresa Sabino,
SDH-x mutations lead to inactivation of the enzyme and thus accumulation of
Paula Bogalho, José Silva Nunes, Fernando Fonseca & Ana Agapito
succinate.
Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,
Aim
Portugal.
This project aims to evaluate succinate as a potential early serum biomarker in
SDH-x MPP patients.
Material & Methods
A fully validated LC-MS/MS method has been developed to quantify succinate
Insulinoma, a rare neuroendocrine tumor (NET), is benign in more than 90%
serum levels. A prospective collection of MPP patients ‘serum has been initiated.
of cases. We present a review of patients diagnosed with insulinoma at our
Results
Department.
Succinate has been quantified in 108 serum samples collected from 47 MPP
Methods
patients. Among them 25 presented a SDH-B mutation, 4 a SDH-D mutation and
Retrospective review of clinical records of patients diagnosed with insulinoma
15 were SDH wild-type (WT). Succinate levels were statistically higher in the
between 2011 and 2016.
SDH-B group (mean Z25 mM, min-max: w3-106 mM) compared to the WT
Results
group (mean Z7 mM, min-max: 4-11 mM) (PZ0.01).
Six female patients were diagnosed with insulinoma (age at presentation 30-66,
Conclusion
follow-up:
0.25-3.25
years). Episodes of sweating, palpitations, tremor,
These results suggest a role of succinate as serum biomarker in SDH-x patients.
confusion, visual disturbances and weight gain were present in five patients
TNM adjustment is ongoing to determine cut-off value that may differentiate
from 2 months to 5 years before diagnosis. There was no familial history or
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
clinical findings of hereditary tumor syndromes. The 72-h fast test confirmed
EP183
endogenous hyperinsulinism at 4-12 h of fast. Abdominal CT: pancreatic lesion
Treatment with (177Lu)-DOTATATE in patients with advanced
in four patients
(14-25 mm). Endoscopic ultrasound done in four patients
metastatic somatostatin receptor-positive tumors
revealed pancreatic nodule; three performed cytology/biopsy compatible with
Antonio Ballesteros Martín-Portugués, María Isabel Del Olmo García, Pilar
pancreatic neuroendocrine tumor (pNET). Five patients underwent surgery: two
Bello Arqués, Ángel Segura Huerta, Rosa Cámara Gómez & Juan Francisco
tumor enucleation, three central and distal pancreatectomy with left hepatectomy
Merino Torres
and splenectomy in 1 of these. Histopathology: well differentiated pNET G1(two
Hospital la Fe, Valencia, Comunidad Valenciana, Spain.
patients) and G2 (three patients). Two patients had lymph node involvement and
one of them liver metastases. Among five surgically treated patients: four did not
have recurrence of hypoglycemia and the one with liver metastases was treated
Introduction
with octreotide and deceased 2 years after diagnosis. The sixth patient had
The NETTER 1 trial resulted in markedly longer progression-free survival (PFS),
undergone central and distal pancreatectomy with splenectomy 5 years earlier due
with preliminary evidence of an overall survival benefit. We report the results of
to pNET without diagnosis of insulinoma at that time and presented us with large
PFS and safety of (177Lu)-DOTATATE in patients treated in our hospital
hepatic metastases and hypoglycemia. Octreotide and peptide receptor radio-
between 2014 and 2016.
nucleide therapy (DOTA-TATE) were started due to hepatic hyperfixation in
Methods
PET-68Ga-DOTANOC.
Transversal and descriptive study of seven patients with advanced, progressive,
Discussion
somatostatin receptor-positive tumors who had received previous treatments. All
In this group there was a high prevalence of malignancy, which is unusual. Time
of them were treated in progressive disease with (177Lu)-DOTATATE. Results
elapsed from onset of symptoms to diagnosis was highly variable. The natural
are expressed in average (S.D.) or percentage(%). SPSS version 2.2 was used for
history of malignant insulinoma is difficult to predict, however uncontrolled
statistical analysis.
hypoglycemia, liver tumor burden exceeding 30% of liver volume, morphologic
Results
progression and Ki67 O10-20% are factors of poor prognosis.
71.4% (5) were women, with an average age of 46.4 (16.2). Histological
DOI: 10.1530/endoabs.49.EP181
classification was: 4 (57%) well-moderate differentiated neuroendocrine tumors
(three pancreatic, one ileal), 2 (28.6%) paragangliomas and 1 (14.3%) follicular
thyroid carcinoma. At the time of administration of (177Lu)-DOTATATE, all
tumors were in metastatic stage. The localization of the metastasis was: bone
85.7% (6), liver 57.1% (4), lymph nodes 42.8% (3) and lungs 14.3% (1). All
patients had received previous treatments: two underwent surgery exclusively,
five of them several systemic therapies: one with somatostatin analogues (SA) and
surgery, two only SA, one surgery, SA, temsirolimus and sunitinib, and one
patient with diagnosis of metastatic follicular thyroid carcinoma, received:
surgery, radioiodine, sorafenib, sunitinib, everolimus, adryamicine, and SA.
EP182
177Lu-DOTATE was infused every eight weeks in four doses, except in two
Effects of ketoconazole on ACTH-producing and non ACTH-producing
patients who have received only three. At the data-cutoff date PFS was of 20.29
neuroendocrine tumor cells
(7.13) months. Two patients had adverse events related to the treatment: one
Aura D Herrera-Martínez2,3, Richard Feelders1, Justo Castan˜o2,4,
hematologic events (mild-moderate thrombocytopenia and anemia), and one self-
Fadime Dogan1, Peter van Koetsveld1 & Leo Hofland1
limited nausea and vomiting. Death occurred in one patient after 15 months of
1Department of Internal Medicine, Division of Endocrinology Erasmus
stable disease.
University Medical Center, Rotterdam, The Netherlands;2Maimonides
Conclusions
Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain;
In real world practice treatment with (177Lu)-DOTATATE not only shows
3Endocrinology and Nutrition Service, Reina Sofia University Hospital,
benefit in advanced intestinal NETS but also in other patients with metastatic
Córdoba, Spain;4Department of Cell Biology, Physiology, and Immu-
disease, previous treatments, and positive somatostatin-receptor expression it
nology, University of Córdoba, Córdoba, Spain.
seems to have favorable results attending to PFS and safety.
DOI: 10.1530/endoabs.49.EP183
Prolonged spontaneous remission of hypercortisolemia in ectopic ACTH
syndrome after long-term treatment with steroidogenesis inhibitors has been
described. Direct drug effect on the adrenal glands, effects on tumoral
ACTH secretion and/or POMC gene expression have been suggested.
Medical treatment could be used for symptoms, but also for disease control.
Materials and methods
In human BON-1 and DMS-79 cells, we have evaluated the effects of
ketoconazole on cell growth, apoptosis, cell cycle, LDH production, POMC/-
EP184
chromogranin-A mRNA expression and ACTH/serotonin secretion.
Results
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) followed
In the BON-1 cells, ketoconazole significantly suppressed cell growth in a dose
in the endocrinology and nutrition service’s monographic outpatient
and time-dependent manner. Maximal inhibitory effects by 10 mM ketoconazole
clinics of neuroendocrine tumors in hospital clínico san carlos (HCSC).
were 41 and 95% after 3 and 7 days (P!0.0001); the ratio LDH/DNA after 3 days
Description of its characteristics and evolution
was increased. The IC50 value of growth inhibition was 7.8 mM after 7 days of
Ines Jimenez-Varas1, Angela Amengual1, Rona Penso1, Anna Ortolá2,
treatment. Ketoconazole also induced a significant G1-phase arrest accompanied
Ane Azkutia1, Lorea Herraiz1, Paz de Miguel1 & Jose Angel Díaz1
by a decrease in S-phase and G2-phase, as well as a significant increase in early
1Hospital Clinico San Carlos, Madrid, Spain;2Hospital Clinico Universi-
and late apoptosis (P!0,01), confirmed using an ELISA method. Ketoconazole
tario, Valladolid, Spain.
(up to 10 mM) did not significantly affect the chromogranin-A expression or
serotonin secretion (corrected for cell number). DMS-79 cells are less sensitive to
Introduction
ketoconazole, with maximally inhibitory effects by 50 mM ketoconazole of 44 and
The multidisciplinary approach of the patients with GEP-NETs is very important,
94% after 3 and 7 days of treatment (P!0.0001). The IC50 value of the growth
having a fundamental role the participation of the endocrinologist.
inhibitory effect was 15 mM after 7 days of treatment. The highest ketoconazole
Methods
concentration (50 mM) tested induced a significant G1-phase arrest (P!0.001),
Description of cases of GEP-NETs followed in the Service of Endocrinology of
increased number of dead cells (P!0,001) without significant effect on early/late
the SCCH from 1990 to 2016.
apoptosis, increased total apoptosis
(ELISA; P!0.0001), as well as the
Results
LDH/DNA (P!0.001). Ketoconazole up to 10 mM suppressed ACTH secretion
95 patients were included, 53.7% were males, age 61.2 years (IR: 50.5-73.5). The
(P!0.01). POMC expression did not show significant changes.
diagnosis was incidental in 53.8%. 27.6% presented clinical secretion, from them
Conclusions
the most frequent was carcinoid (13.8%). The median primary tumor size was
These results suggest a potential direct effect of ketoconazole on cell
3 cm (IR: 2-4). The most frequent location was pancreas (43.2%) followed by
proliferation, apoptosis and cell cycle in ACTH- and non-ACTH producing
small intestine (20%). The initial stage was 49.5% I and 39.6% IV (72% hepatic
NET cells. Additional studies are required to confirm and extend these results.
metastases). Clinic as a cause of diagnosis was significantly associated with
DOI: 10.1530/endoabs.49.EP182
staging (Cramer’s V (V) 0.72, P!0.05). Chromogranin A (CrA) was high in 30%
and 5-Hydroxyindolacetic in 18.7% (only 73.7 and 58.4%, respectively) were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
studied.
9.4% of the patients had history of familiar syndrome. Degree of
Introduction
differentiation (DD) 1 and 2 (63 and 30.3%) predominated. The follow-up was
In recent years, it is thought that cardiovascular risk is increased in patients with
6.63 years (IR: 4.6-9.3). During that period, 30.2% of the cases were lost, with
nonfunctional adrenal insidentaloma (NFAI). There are not enough studies in the
mortality rate of 17.9% of the remaining group, due to progression in 83.3% of the
literature that evaluating this condition in patients with NFAI who don’t have
patients. The most frequently used treatment was surgery (39.1%). From stage IV
traditional cardiovascular risk factors. The aim of our study is to determine
patients 20.8% received only somatostatin analogues and 45% received more than
peripheral and central blood pressures and arterial stiffness in patients with NFAI
one treatment
(surgery, chemotherapy, antiangiogenic drugs, somatostatin
who don’t have traditional risk factors and autonomous cortisol release with pulse
analogues or everolimus) There was significant association between mortality
wave analysis (PWA) measurement.
and stage (V 0.42, P 0.04), CrA (V 0.38, P 0.012), presence of symptoms at
Material and methods
diagnosis (V 0.32, P 0.017) and DD (V 0.41, P 0.02).
In our cross-sectional study, we evaluated 70 participants (35 patients with NFAI
Conclusion
and 35 healthy volunteers) without traditional cardiovascular risk factors. All
Patients followed in the endocrinology outpatients clinic are more frequently
participants were similar in terms of gender, age and body mass index.
stages I and DD1 and DD2 that have been incidentally diagnosed. More than 50%
Measurements of peripheral and central blood pressures and PWA were made
of the cases were treated only with surgery or somatostatin analogues. One third
with Mobil-O-Graph PWA/ABPM device (I.E.M. GmBH, Stolberg, Germany).
of the patients had secretion.
Radiological and biochemical data were obtained retrospectively in the NFAI
DOI: 10.1530/endoabs.49.EP184
group.
Results
In the NFAI group, systolic blood pressure (SBP), diastolic blood pressure (DBP),
mean arterial pressure (MAP), central SBP, central DBP, peripheral vascular
resistance, augmentation pressure (AP), augmentation index that corrected based
on pulse rate of
75 bpm (Aix@75) and pulse wave velocity (PWV) were
significantly higher than control group. We also found that PWA measurements
are affected by age and the time from diagnosis to PWA measurement. There was
no significant correlations between biochemical parameters and central blood
pressures and arterial stiffness parameters in NFAI group.
EP185
Conclusion
Descriptive and survival study of 142 cases of gastroenteropancreatic
In patients without traditional cardiovascular risk factors who have NFAI that
neuroendocrine tumor (GEP-NETs) diagnosed at the Hospital Clínico
known as cardiometabolically innocent, both peripheral and central blood
San Carlos (HCSC)
pressures and arterial stiffness parameters are affected negatively. These patients
Rona Penso1, Inés Jiménez-Varas1, Angela Amengual1, Lorea Herraiz1,
are at risk for cardiovascular diseases.
Ane Azkutia1, Anna Ortolá2, Paz de Miguel1 & José Angel Díaz1
DOI: 10.1530/endoabs.49.EP186
1Hospital Clinico San Carlos, Madrid, Spain;2Hospital Clinico
Universitario, Valladolid, Spain.
Introduction
Neuroendocrine tumors (NETs) constitute a very heterogeneous group of rare
neoplasms, although their incidence has increased in recent years. We describe its
evolution and survival.
Methods
Retrospective study. All patients with histopathological diagnosis of GEP-NETs
performed at the HCSC between 2000 and 2016 were selected, data from the
EP187
medical history were included. Statistical analysis were done with SPSS.
Landscape of sporadic adrenal tumours from surgical unit -
Results
histopathological audit of 101 cases from a single centre in Poland
One hundred and forty-two patients, 54.9% male, mean age 60.2 years (S.D. 19.7).
Anna Jodkowska1, Maciej Sroczynski2, Monika Sepek2,
The median follow-up time was 3.3 years (IR: 0.78-6.33). The most frequent
Krzysztof Tupikowski3 & Grzegorz Mazur1
locations were pancreatic (28.2%) and rectal (16.2%). The tumor stage was: I
1Department and Clinic of Internal and Occupational Diseases, Hyperten-
47.2%, II 4.9%, III 13.4%, IV 34.5%. The initial stage (IS) presented positive
sion and Clinical Oncology, Wroclaw Medical University, Wroclaw,
correlation with the degree of differentiation (DD) (Cramer’s V 0.46, P !0.05)
Poland;2Department of Minimally Invasive Surgery and Proctology,
and with levels of Chromogranin A (Cramer’s V 0.37, P !0.05). 12% had
Wroclaw Medical University, Wroclaw, Poland;3Department of Urologic
progression and 64% died during follow-up (72% due to tumor). Overall survival
Oncology, Lowersilesan Oncology Centre, Wroclaw, Poland.
at 5 years was 69 and 53% at 10 years. There were significant differences in
survival according to location, with gallbladder and colon being the lowest (0 and
38% at 5 years, respectively). DD, IS and sex were also associated with survival
(at 10 years: G1 95% vs G3 14.3% P!0.01, stage I 91% vs IV 28% P!0.01,
Laparoscopic surgery of adrenal tumours is widely used because of its high
median males 7.5 years vs 16.9 in females P 0.018). These differences were
effectiveness, patients safety and relatively low cost. Current indications to
maintained after multivariate analysis in the case of DD and IS.
adrenalectomy of oncological and endocrinological origin are highly
In stage IV survival was modified according to surgical treatment (operated
accepted. However there is still lack of perfect clinical tool identifying
median 5.9 years vs non-operated 0.64 years, P!0.01).
malignant lesions. In everyday practice clinicians rely on low specific
Conclusion
features, especially considering larger nonsecretory lesions to surgery.
In our sample the overall mortality was high, despite having a low rate of
To show the landscape of sporadic adrenal tumours we analysed
progression. DD and IS were determinants of survival. In advanced stages
retrospectively histopathological findings from 101 consecutive adrenalec-
surgical treatment improves survival significantly.
tomies performed in our centre in 71 women and 30 men of average age 57.7
DOI: 10.1530/endoabs.49.EP185
years (S.D. 13.5), between 2009 and 2016 years.
There were 53 (52.47%) adenomas found; 7 (6.93%) of them secreting: 4
(3.96%)-cortisol,
3
(2.97%)-aldosterone. Pheochromocytoma occurrence
was notably often-14 cases (13,86%). Adrenal cancer was found in two
cases (1.98%), metastatic lesions from lung, kidney and urinary bladder in
three cases (2.97%); and 1(0.99%) malignant peripherial nerve seath tumor
(MPNST) derived from ganglioneuroma of adrenal gland was found.
Thirteen cases (12.87%) of adrenal hyperplasia were found. In 16 cases
(15.84%) the histopathological findings were classified as “various” in detail
EP186
consisting of: 3 myelolipomas, 1 angiomyolipoma, 2 cysts, 6 pseudocysts or
Nonfunctional adrenal incidentaloma affects central blood pressures
secondary posthaemorrhagic/inflammatory lesions, 1 normal adrenal tissue,
and arterial stiffness parameters
1 fatty tissue, 1 mesenteric cyst and 1 teratoma. In two cases benign adrenal
Tolga Akkan1, Mustafa Altay2, Yasemin Aydogan Unsal1,
lesions coincided with unilateral kidney cancer. Seventeen patients
Murat Dagdeviren2 & Esin Beyan1
(16,83%) had previous oncological anamnesis positive, while patients
1Internal Medicine, Kecioren Education and Research Hospital, Ankara,
with adrenal cancer had negative previous oncological anamnesis.
Turkey;2Endocrinology and Metabolism, Kecioren Education and Research
We observe that adrenalectomy of oncological indications is prevalent:
Hospital, Ankara, Turkey.
adrenal lesions with positive previous cancer history; lesions suspected of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
malignancy because of the CT morphological features. In the audit almost
Introduction
half of them occur benign incydentalomas. Are we overtreating, then?
Neuroendocrine tumors may develop in almost any organ. These types of tumors
We conclude there is a great need of new specific clinical tools to identify
may present with giant and asymptomatic mass. We describe a case of a large non
malignancy in adrenal glands in everyday practice.
functional neuroendocrine tumor reported in the department of endocrinology and
diabetology of Hedi Chaker hospital in Sfax-Tunisia in 2016.
DOI: 10.1530/endoabs.49.EP187
Presentation of case
A 28 years old male presented with asthenia, gastric heaviness and epigastric
pain. Further computerized tomography, a large mass (20 cm) near the stomach in
the coeliomesenteric region has been demonstrated. Magnetic Resonance
Imaging has showed the presence of a voluminous encapsulated mass with
abundant vascularization and central necroses, measuring
18.5 cm!14.5 cm
compressing the vascular structures. The dosage of methoxylated plasma
derivatives was negative. The dosage of NSE was returned positive at
30.5 ng/l. The biopsy of the mass showed a histological and immunohistochem-
EP188
ical aspect of a neuroendocrine tumor. The therapeutic decision was to start with
An elevated chromogranin A: is it always a tumor progression?-case
exploratory laparotomy and tumor excision if possible. Because of the
report
vascularized character and significant bleeding during the intervention, a surgical
Anamaria Bursuc1, Alina Daniela Belceanu1, Ioana Armasu1,
abstention was decided. The patient had two chemoembolization sessions with
Mirela Tirnovan1, Adina Manolachie1, Felicia Crumpei2, Delia Ciobanu3,
good tumor response. It is being evaluated for possible re-intervention.
Letitia Leustean1 & Carmen Vulpoi1
Conclusion
1Department of Endocrinology, ‘Gr. T. Popa’ University of Medicine and
The incidence of neuroendocrine tumors has been increasing during the last
Pharmacy, Iasi, Romania;2Department of Radiology, ‘Gr. T. Popa’
decade, underscoring the need to improve our understanding of their biology and
University of Medicine and Pharmacy, Iasi, Romania;3Department of
behavior especially.
Pathology, ‘Gr. T. Popa’ University of Medicine and Pharmacy, Iasi,
DOI: 10.1530/endoabs.49.EP189
Romania.
Introduction
Pancreatic neuroendocrine tumors
(PNET) are rare, with an incidence of
1/100,000/year. Chromogranin A (CgA) is the most valuable marker in the
diagnosis and monitoring of PNET. One of the disadvantages is its low specificity
and the existence of a number of processes leading to an increase in its
concentration, which often results in confusion and diagnostic difficulties.
Case report
EP190
We present a 44-years-old female patient with a history of PNET-pT3NxMx-G3
A challenging case of metastatic paraganglioma and metastatic
surgically excised in 2007, chemotreated with 6 cycles of Gemcitabine and
melanoma and prolactinoma
Capecitabine. In 2009, a left thoracotomy for lung metastasis was performed,
Rehmat Karim1, Kamrudeen Mohammed1, Najeeb Zaheer Shah1 &
followed by 10 cycles of chemotherapy and in 2015 the patient was diagnosed
Muhammad Fahad Arshad2
with a recurrence of PNET which required atypical pancreatectomy. Immuno-
1Hull Royal Infirmary, Kingston Upon Hull, East Yorkshire, UK;
histochemistry revealed intense positive markers: NSE, chromogranin, synapto-
2Doncaster Royal Infirmary, Doncaster, South Yorkshire, UK.
physin CD56
and ki67Z3%. The subsequent evaluations showed normal
biological
(CgA, serotonin,
5HIAA) and morphological (thoraco-abdominal
CT) parameters until 2016, when CgA level was 7-fold higher that the upper
Background
normal value (545 ng/ml vs 76 ng/ml) but with normal thorax and abdomino-
Paragangliomas are extremely rare endocrine tumours and can cause diagnostic
pelvic CT. As the patient took moderate doses (40 mg/day) of Omeprazole 6
difficulty, especially with a coexistent metastatic malignancy.
months for gastroesophageal reflux disease, iatrogenic elevation of CgA was
Case
suspected. After cessation of proton pump inhibitors (PPIs) therapy for 1 week,
A 78-year-old man with diagnosed metastatic melanoma underwent a PET scan for
serum CgA level rapidly decreased to 66 mg/l (N!100 mg/l).
staging of the malignancy. It showed a left upper quadrant mass with multiple
Conclusions
skeletal deposits and a lesion in the pituitary all with intense focal uptake. The mass
In this case, the elevated CgA raised the suspicion of a new recurrence which
was unusual for a metastatic lesion from melanoma although other lesions,
required further investigations. PPIs may cause serious differential diagnostic
including pituitary could be explained by metastatic melanoma. A biopsy of the
problems with elevation of serum CgA especially in suspected neuroendocrine
abdominal mass showed histological features of a paraganglioma; 24-h urinary
tumors. An interesting phenomenon highlighted by this case is the report of rapid
catecholamines showed raised noradrenaline 1474 nmol/24 h (70-550 nmol/24 h),
normalization of CgA after withdrawal of PPI. Giving particular attention to the
dopamine 6277 nmol/24 h (400-3000 nmol/24 h) and a normal adrenaline
use of PPIs as a possible cause for elevated CgA levels might help to prevent the
!21 nmol/24 h (0-190 nmol/24 h) confirming a functional paraganglioma. The
need for further diagnostic procedures.
diagnosis of the skeletal lesions was unclear, and a 123-MIBG scan showed
increased activity at the skeletal lesions but no avidity at pituitary confirming
DOI: 10.1530/endoabs.49.EP188
skeletal metastases from the paraganglioma with no definite explanation for the
pituitary lesion. An MRI pituitary showed diffuse enlargement of pituitary gland
with fossa expansion indicating chronicity and suggestive of prolactinoma rather
than metastasis as his prolactin was 9400 mU/l and rest of his pituitary function was
normal. He had no symptoms of diabetes insipidus. Resection of the paraganglioma
was performed after preoperative alpha and beta blockade. His post-operative
catecholamines normalised and post operative PET scan has shown stable
appearance of skeletal lesions. He was started on Cabergoline for his prolactinoma
and referred for chemotherapy for the metastatic skeletal lesions.
EP189
Conclusion
An unknown giant neuroendocrine tumor
Metastatic paragangliomas in patients with a separate existing metastatic
Nabila Rekik, Dorra Ghorbel, Fatma Mnif, Mahdi Kalthoum,
malignancy provides a diagnostic and management challenge. With a structured
Houcem Mrabet, Nadia Charfi, Hamza Elfekih, Mouna Mnif &
approach to investigation and management the clinical picture can be clarified,
Mohamed Abid
which then facilitates appropriate intervention.
The Department of Endocrinology and Diabetology of Hedi Chaker
DOI: 10.1530/endoabs.49.EP190
Hospital in Sfax, Sfax, Tunisia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP191
Accurate identification of disease site, cell type and associated hormone
Biology and differential diagnosis of calcitonin secreting
secretion is paramount in delivering optimal clinical care - evidence based
neuroendocrine tumors
guidelines are available for most neuro/endocrine tumours - but consideration
Bojana Popovic, Djuro Macut, Valentina Elezovic Kovacevic,
should also be given to meeting the psychosocial and informational needs of
Tatjana Isailovic, Ivana Bozic Antic, Tamara Bogavac, Dusan Ilic,
the individual diagnosed with one of these rare cancers.
Sanja Ognjanovic, Gordana Rodic, Milan Petakov & Svetozar Damjanovic
Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center
of Serbia, Belgrade, Serbia.
DOI: 10.1530/endoabs.49.EP192
Introduction
Calcitonin secreting neuroendocrine tumors
(NET) are rare and not well
recognized. Due to many similarities, it is sometimes difficult to differentiate
them from medullary thyroid carcinoma (MTC), which can hamper choice of
proper therapy. We investigated our group of patients with this type of NET in
terms of diagnosis and biology.
EP193
Patients and Methods
We analyzed 38 patients with calcitonin secreting NET (5% of all our patients
Short-term contralateral recurrence of a Litynski-Conn adenoma
with NET). In addition to standard work up, calcium-stimulation test for
Agnieszka Kuzior1, Manuel Nivelo-Rivadeneira1, Ana Delia Santana-
calcitonin was performed in 15 of them, and results compared to 34 patients with
Suarez1, Claudia Arnas-Leon1, Carmen Acosta-Calero1, Sara Quintana-
MTC, and 21 control subjects with elevated calcitonin level and thyroid
Arroyo1, Marta Martin-Perez2 & Francisco Javier Martinez-Martin1
pathology other than MTC. Statistical analysis was done with SPSS software.
1Division of Endocrinology and Nutrition, Doctor Negrin University
Results
Hospital of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria,
Primary localization of NET was lung (16), pancreas (12), unknown primary (8)
Spain;2Primary Care Center of Guia, Doctor Negrin University Hospital of
and intestine (2), with majority (54.1%) being grade G3, and high majority being
Gran Canaria, Las Palmas de Gran Canaria, Spain.
metastatic (94.7%). Majority (55.6%) had goiter and 26.3% concomitant TPOAb,
while 28.9% co-secreted another hormone (ADH, insulin, serotonin, PTHrP).
Clinical Case
Patients with NET had significantly higher basal calcitonin levels compared to
A hypertensive 60-year-old woman with nephroangiosclerotic stage IV chronic
controls (P(0.01), but with no significant difference compared to patients with
renal failure (eGFR 23.44 ml/min/1.73 m2) was referred to our hypertension clinic
MTC (PZ0.427). Unlike this, patients with NET achieved significantly lower
after the CT finding of a 26-mm left adrenal mass with adenoma density during
calcitonin levels after calcium stimulation compared to patients with MTC
hypertension workup, with normal right adrenal. Physical exam was unremark-
(P(0.01), but no different compared to controls
(PZ0.102). There was no
able except for BP 167/98 mmHg. Plasma aldosterone was 353 ng/ml, PRA
significant correlation between basal calcitonin level and presence of TPOAb
1.3 ng/ml/h, ratio 90.2, KC3.1 mEq/l, and metanephrines were normal. Primary
(PZ0.816) or goiter (PZ0.670) in these patients. Their median overall survival
aldosteronism was confirmed by standard captopril test. Adrenal vein sampling
was 24.0 months (95% CI 10.9-37.1).
showed full left lateralization of aldosterone secretion. The patient underwent
Conclusion
laparoscopic adrenectomy, and a 21-g left adrenal -including a 4-cm adenoma
Patients with calcitonin secreting NET can secrete very high calcitonin levels, but
with clean margins- was removed. One month after surgery, KC, aldosterone and
can be differentiated from patients with MTC by absence of significant response
ARP were normal, and BP was controlled with manidipine 20 mg.
to stimulation with calcium. Survival of these patients is poor, but influence of
One year later, BP and plasma KC were still controlled but the patient showed
calcitonin on survival is yet to be determined.
again a pattern of primary aldosteronism with aldosterone
747 ng/ml, PRA
DOI: 10.1530/endoabs.49.EP191
0.9 ng/ml/h, ratio 83.0. A new CT showed absent left adrenal, and a 17!11 mm
mass in the right adrenal, with adenoma density. Low-dose
(12.5 mg)
spironolactone was added to the treatment, but surgery was deferred.
Diagnosis
Primary aldosteronism caused by aldosterone-producing adenoma (Litynski-
Conn syndrome), with contralateral recurrence after one year. Secondary
hypertension with nephroangiosclerotic stage IV chronic renal failure.
EP192
Commentary
Cancerous neuroendocrine vs endocrine tumours: broad commonalities
Contralateral recurrence of an aldosterone-producing adenoma in a previously
and differences
normal adrenal after a complete surgical removal is exceedingly rare, particularly
Nicola Jervis & Catherine Bouvier
after such a short follow-up. The differential diagnosis would include familial
NET Patient Foundation, Leamington Spa, UK.
type II aldosteronism (as types I and III usually cause severe hypertension in the
pediatric age and associate normal or bilaterally hyperplastic adrenals but not
adenomas, while type II may associate adenomas in adult patients) but as there is
no known genetic marker for this condition, confirmation is not possible at this
Endocrine cancers are defined, by European Taskforce on Endocrine Cancer,
point.
as malignant tumours arising from endocrine organs including thyroid,
adrenal, parathyroid, pituitary, as well as neuroendocrine tumours in general.
DOI: 10.1530/endoabs.49.EP193
Cancerous neuroendocrine tumours arise from neuroendocrine cells which
can be found within the endocrine system: in the pituitary, pineal, parathyroid
and (medulla of the) adrenal gland, or more scantily within the thyroid,
pancreas, ovaries and testicles, or more diffusely throughout the body, being
present in respiratory, urinary and digestive tracts, as well as breast, skin,
prostate and gynaecological structures.
Neuroendocrine and most endocrine cancers are considered both rare and
EP194
complex.
Acinic cell adenocarcinoma of the parotid gland associated with
Commonalities exist in terms of gross classification, that is, designation by
paraneoplastic Cushing’s syndrome - a rare clinical case
site, cell type and whether they are associated with excess hormone/peptide
Sofia Castro Oliveira1,2, Joa˜o Sérgio Neves1,2, Pedro Souteiro1,2,
secretion - differences are revealed as this broad definition narrows.
Sandra Belo1,2, Ana Isabel Oliveira1,2, Celestino Neves1,2, Paula Freitas1,2 &
For example: within the adrenal gland:
Davide Carvalho1,3
Endocrine - adrenocorticol carcinoma (ACC) arises within the cortex, and
1Department of Endocrinology, Diabetes and Metabolism of Sa˜o João
may be associated with excess secretion of steroidal hormones. TNM staging.
Hospital Center, Porto, Portugal;2Faculty of Medicine, University of Porto,
Neuroendocrine - pheochromocytoma arises within the medulla, and may be
Porto, Portugal;3Instituto de Investigação e Inovação em Saúde, University
associated with the overproduction of catecholamines. No standardised
of Porto, Porto, Portugal.
staging and malignancy designation may be withheld in the absence of
metastatic disease, though presentation, family history and proliferation rate
will influence treatment planning and follow-up.
Introduction
Both may be associated with inherited disorders such as multiple endocrine
Primary acinic cell carcinoma (ACC) is an uncommon salivary gland (SG) tumor,
neoplasia, therefore careful history taking and consideration of genetic
making up 1-3% of all SG neoplasms, more frequent in women, at 40-60 year
counselling (Table & diagram of sites, cell type and associated hormone).
old. The cause is still unknown and the only well-established risk factor is
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
ionizing radiation. ACC metastasize in 10-15% of the cases, 35% tends to recur
Conclusion
and the rate of disease-associated death is about 16%. Surgical resection is the
Malignant pheochromocytomas present clinicians with three major challenges:
mainstay treatment, but radiation therapy may be used in some cases and, more
scarcity, complexity of characterization, and heterogeneous behavior and
rarely, chemotherapy in advanced ACC.
prognosis.
Case Report
DOI: 10.1530/endoabs.49.EP195
We describe a case of a 46-year-old man referred by paresthesias, general malaise
and hypokalemia of 2.5 mEq/l. The patient had a history of pericentimetric nodule
in the left submandibular gland diagnosed 1 year before, hypertension and
dyslipidemia diagnosed 4 months before and also new-onset diabetes mellitus
(DM) diagnosed in the previous month. Ambulatory analysis showed endogenous
hypercortisolism, and he was admitted to the endocrinology department for
further investigation. Hormonal study revealed: ACTH 206.8 (!63.3) ng/l,
Neuroendocrinology
cortisol 30.1(6.2-19.4) mg/dl; cortisoluria, 24-hour salivary cortisol and low-dose
EP196
dexamethasone suppression test confirmed Cushing’s syndrome(CS); high-dose
Identification of molecular targets of Sunitinib in pancreatic
dexamethasone suppression test was compatible with ectopic CS. Initial imaging
neuroendocrine tumours
study found several hepatic nodular lesions, suggestive of secondary lesions by
Giulia Bresciani1, Teresa Gagliano1, Leo J Hofland2, Erica Gentilin1,
neoplastic process. Investigation was continued, with imaging and cytological
Simona Falletta1, Eleonora Riva1 & Maria Chiara Zatelli1,3
documentation of probable primary parotid malignancy with hepatic metastasis.
1Section of Endocrinology, Department of Medical Sciences, University of
Octreoscan revealed increased uptake in the parotid gland and mild expression
Ferrara, 44121 Ferrara, Italy;2Department of Internal Medicine, Erasmus
in hepatic metastasis. No uptake was observed in PET-Gallium. The patient
Medical Center, Rotterdam, The Netherlands;3Laboratorio in Rete del
underwent right parotidectomy, with the histological diagnosis of ACC,
Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of
pT3NxR1, with no neuroendocrine differentiation, Ki67
70%. Imaging
Ferrara, 44121 Ferrara, Italy.
reevaluation revealed disease progression, with pulmonary and bone metastasis,
and the patient started chemotherapy. Meanwhile, hypercortisolism was
controlled with metyrapone (3 g/day), ketoconazole (400 mg/day) and lanreotide
(120 mg/month).
Pancreatic neuroendocrine tumours (pNETs) are rare neoplasms arising from the
Conclusion
endocrine pancreas. The fist line treatment is surgery that is often not curative in
The authors present a very rare case of ACC, with paraneoplastic CS and
the presence of metastatic disease. Therefore, there is an increasing need for
aggressive behavior, presenting significant diagnostic and management
medical therapy. Sunitinib is a multi-target receptor tyrosine-kinase
(RTK)
challenges.
inhibitor, described as having as main target VEGF receptor, with antitumor and
DOI: 10.1530/endoabs.49.EP194
antiangiogenic effects, approved for pNETs medical treatment. This study is
aimed at evaluating Sunitinib effects in the human pNET cell line, BON1, in order
to identify tissue-specific molecular targets that might predict the efficacy of the
treatment. We tested BON1
cell viability and proliferation by means of
Proliferation Assay and Luminescent Cell Viability Assay after treatment with
Sunitinib
(0.25-7.5 mM) and found an IC50Z5 mM. Western blot analysis
confirmed that BON1 cells express VEGF, IGF1 and EGF receptors, therefore we
tested the effects of VEGF 50 ng/ml, IGF1 100 nM and EGF 15 nM alone or each
in combination with Sunitinib 5 mM. We found that BON1 cell viability is not
affected by VEGF and EGF, while it is significantly enhanced by IGF1 (C20%;
EP195
P!0.05), that was capable of blocking the antiproliferative action of Sunitinib,
Malignant pheochromocytoma - a challenging diagnosis with
suggesting that the main target of this drug is IGF1 receptor. Therefore, we tested
nonconsensual management
Linsitinib, a specific IGF1 receptor inhibitor, and found that it significantly
Sofia Castro Oliveira1,2, João Sérgio Neves1,2, Pedro Souteiro1,2, Eva Lau1,2,
reduces BON1 cell viability (K25%; P!0.05) and blocks the proliferative effects
Ana Isabel Oliveira1,2, Celestino Neves1,2, Paula Freitas1,2 &
of IGF-1. These data indicate that IGF1 receptor represents the main molecular
Davide Carvalho1,3
target of Sunitinib in BON1 cells and that it may play a crucial role in pNET cell
1Department of Endocrinology, Diabetes and Metabolism of São Jo
˜o
proliferation control, suggesting that Linsitinib might be an effective medical
Hospital Center, Porto, Portugal;2Faculty of Medicine, University of Porto,
treatment.
Porto, Portugal;3Instituto de Investiga
¸
˜o e Inova
¸a˜o em Saúde,
DOI: 10.1530/endoabs.49.EP196
University of Porto, Porto, Portugal.
Introduction
Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine
tumors, with a peak incidence between the 3rd-5th decades of life and about 10%
are malignant. Although they have the same radiographic and histologic
EP197
characteristics of their benign counterpart, malignant pheochromocytomas are
Study of different in vitro systems for the evalutation of Sunitinib effects
diagnosed by the presence of local invasion or metastatic tumor in the non-
in pancreatic neuroendocrine tumour cells
chromaffin tissues, and offer a poorer prognosis. Treatment is typically extirpative
Giulia Bresciani1, Teresa Gagliano1, Leo J Hofland2, Erica Gentilin1,
surgery, although MIBG-radiotherapy and chemotherapy have been offered in
Simona Falletta1, Eleonora Riva1 & Maria Chiara Zatelli1,3
nonsurgical cases.
1Section of Endocrinology, Department of Medical Sciences, University of
Case Report
Ferrara, 44121 Ferrara, Italy;2Department of Internal Medicine, Erasmus
An 83-year-old man with history of diabetes mellitus and hypertension presented
Medical Center, Rotterdam, The Netherlands;3Laboratorio in Rete del
abdominal pain, anorexia and weight loss. An abdominal CT revealed a large,
Tecnopolo Tecnologie delle Terapie Avanzate (LTTA), University of
hypocaptant and heterogenous neoformative lesion of left adrenal gland, 48!
Ferrara, 44121 Ferrara, Italy.
58 mm, and adjacent metastatic adenomegaly with 18 mm. He was then referred
to our Endocrine Department. Imaging study was repeated and revealed an
additionally left renal mass, on the posterior face, exophytic, with 40!13!
38 mm, suspected for metastasis. Biochemical diagnosis of pheochromocytoma
Finding new preclinical models to study the effects of anticancer drugs is
was established by a marked increase of urinary catecholamines and fractionated
one of the aims of biomedical research. Indeed, testing different in vitro
metanephrines: norepinephrine 1222 (!97) mg/24 h, epinephrine 106 (!27)
systems can lead to a better understanding of the molecular pathways
mg/24 h and dopamine 1166 (!500) mg/24 h; normetanephrines 3711 (!390)
regulating tumor development and growth, and help to find new therapeutic
mg/24 h and metanephrines 1226 (!320) mg/24 h; vanillylmandelic acid (VMA)
approaches. This is crucial especially in the settings of pancreatic
was
29.3
(1.4-6.5) mg/24 h.
123I-MIBG scintigraphy was performed and
neuroendocrine tumours (pNET), where one of the main drugs approved
evidenced left adrenal gland lesion compatible with pheochromocytoma, without
for medical treatment is Sunitinib, a multi-targeted receptor kinase inhibitor.
uptake on left renal mass. The patient started alpha-adrenergic blockade with
Clarifying the effects of this drug may be important to develop more
phenoxybenzamine (10C10 mg/day) and 6 weeks later underwent exploratory
effective medical treatment, therefore we tested Sunitinib on the human
laparotomy surgery, with left adrenalectomy and nefrectomy. Histological
pNET cell line, BON1, grown in two different in vitro systems, monolayer
examination confirmed malignant pheochromocytoma diagnosis and the patient
and spheroid, in order to understand the different effects of the drug in 2D
maintains close surveillance.
and 3D settings.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
BON1 cells were grown in monolayer and treated with Sunitinib at increasing
1Department of Endocrinology, Asaf Harofe Medical Center, Zeriffin,
concentrations
(0.25-5 mM). Cell Proliferation Assay and Luminescent
Israel;2Department of Oncology, Asaf Harofe Medical Center, Zeriffin,
Cell Viability Assay were employed to test Sunitinib antiproliferative effects.
Israel;3Department of Gastroenterology, Asaf Harofe Medical Center,
We found that Sunitinib 5 mM significantly reduced BON1 cell viability by
Zeriffin, Israel;4Department of Surgery, Asaf Harofe Medical Center,
30% (P!0.01 vs control) after
3
days. Similarly, Sunitinib
5 mM
Zeriffin, Israel;5Department of Pathology, Asaf Harofe Medical Center,
significantly reduced BON1 cell proliferation by 50% (P!0.05 vs control)
Zeriffin, Israel;6Sackler School of Medicine, Tel Aviv University,
after 3 days and by 90% (P!0.05 vs control) after 7 days.
Tel Aviv, Israel.
Then, BON1 cells were grown in spheroids with Sunitinib at increasing
concentrations
(0.25-5 mM). Spheroids size was analyzed with ImageJ
Introduction
software after 3 and 7 days. We found that Sunitinib does not affect spheroid
GEP-NETs incidence increased markedly over the past decades probably due to
size, but induces spheroid disgregation after 7 days of treatment at 5 mM.
increased imaging. GEP-NETs are generally indolent but often have unpredict-
These results indicate that measuring spheroid diameter in a 3D system is not
able biological behavior and aggressive clinical course.
the optimal system to assess the antiproliferative effects of Sunitinib on
Aims
BON1 cells. On the other hand, the differences observed between the
To collect information regarding demographics, presentation, pathology
employed models could reflect the variations in drug response depending on
characteristics, treatment and outcome of GEP-NETs.
cell aggregation state.
Methods
DOI: 10.1530/endoabs.49.EP197
Following approval of our institutional ethical board, pathology and clinical
records of all GEP-NETs patients diagnosed and treated at our institution during
2005-2015 were reviewed.
Results
We identified 110 patients with GEP-NETs distributed by site as pancreatic 32
EP198
(FZ45.1%, age 61.2G6.8), gastric 19 (FZ50%, age 66.2G11), duodenum 9
(FZ33.3%, age 66.3G12), small bowel 13 (FZ25%, age 60G12), appendix 34
Von Hippel-Lindau syndrome: in vivo portrait with 68Ga-DOTANOC
(FZ55.8%, age 36G19) and colorectal 3. The pNETs presented with abdominal
PET-CT
pain
(45.1%) incidentally
(25.8%) or syndromatic
(21.8%); including two
Ana Paula Moreira1,2, Gracinda Costa1,3 & João Pedroso de Lima1,2
insulinomas, one gastrinoma and four MEN1 patients. Mean size was 31G23 mm
1Centro Hospitalar e Universitário de Coimbra (Nuclear Medicine
Department), Coimbra, Portugal;2Instituto de Ciências Nucleares Aplicadas
and grading was G1 39.2, G2 42.8, G3 17.8%. Distant metastases (DM) were seen
à Saúde - Universidade de Coimbra (ICNAS-UC), Coimbra, Portugal;
in five patients (M1Z3). Surgery was performed in 61.3%, additional treatment
3Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
given to 32.2% (re-op, somatostatin analogue, TKI, chemotherapy). The gNETs
presented mostly during work-up for anemia or GI bleeding (70.6%). Mean size
was 15 mm and the majority (82.3%) were GCT1 and there were no DM. The
Introduction
dNETs presented with anemia (43%), abdominal pain (43%) or incidentally.
Von Hippel-Lindau syndrome (VHL) is an autosomal dominantly inherited
None was syndromatic. Mean size was 11.2 mm, 50% were G1, and 2 had DM at
neoplastic disorder with marked phenotypic variability, characterized by a broad
presentation. Surgery was performed in 33.3% patients. The sbNETs presented
spectrum of clinical manifestations in central nervous system (CNS) and viscera.
with bowel obstruction (27%), abdominal pain (36%) or incidentally. None were
Specific gene mutation can be demonstrated; however imaging plays an important
syndromatic. Only 15% were G1, 6 had DM (M1Z5), and 77% had surgery.
role in diagnosis. 68Ga-labelled somatostatin analog (68Ga-DOTANOC) PET-
Excluding aNETs, the overall mortality at last visit was 23.7% (7.9% disease
CT is routinely employed for somatostatin receptor (SSTR) imaging, mainly for
related) at mean follow-up of 34.5 months.
neuroendocrine tumors evaluation, but could be an optimal whole body imaging
Conclusion
method for screening and follow-up VHL patients.
GEP-NETs are associated with significant morbidity and mortality. The primary
Purpose
site of the tumor has clinical implication for disease management.
To present 68Ga-DOTANOC-PET-CT findings in three VHL female patients (58,
DOI: 10.1530/endoabs.49.EP199
58 and 65 years old), demonstrating both CNS and visceral tumors.
Material and Methods
68Ga-DOTANOC-PET/CT scan was acquired 45 min after intravenous admin-
istration of 100-200MBq 68Ga-DOTANOC in three patients with VHL referred
for pancreatic neuroendocrine tumor (PNET) evaluation. Abnormal findings were
correlated with histopathology or other imaging modalities
(CT, MR,
ophthalmoscopy).
Results
68Ga-DOTANOC-PET/CT showed, in all patients, other lesions than PNET,
EP200
which proved to be related to VHL. Retinal and spinal cord hemangioblastomas
Insulinoma: diagnostic features and treatment management
were detected in two patients. Endolymphatic sac tumor was demonstrated in one.
Liana Khacimova1, Tatiana Karonova1,2, Uliana Tsoy1, Liubov Ianevskaia1
Lung hemangioblastoma was suspected in one. Liver and lymph node metastasis
& Elena Grineva1,2
were present in one patient. Two patients had a pheocromocytoma previously
1Federal Almazov North-West Medical Research Centre, Saint-Petersburg,
removed by surgery.
Russia;2Pavlov First Saint Petersburg State Medical University,
Discussion
Saint-Petersburg, Russia.
In VHL diagnosis a multidisciplinary approach is mandatory. Although genetic
testing is available, imaging plays a key role in the identification of abnormalities,
Backgraund
their follow-up and in the screening of asymptomatic gene carriers. Several
Insulinoma is the most common functional pancreatic neuroendocrine tumor
analytic and imaging modalities are needed for diagnosis and follow-up.
originating from b-cells, with unregulated insulin production and rarely
Screening is essential because the lesions in VHL disease are treatable. Early
associated with MEN-I syndrome. Diagnosis and treatment of insulinoma are a
detection enables more conservative therapy and may enhance the patient’s length
challenge in the practice of endocrinologist.
and quality of life. In these three VHL patients, 68Ga-DOTANOC-PET-CT has
Aim
demonstrated to be a promising whole-body screening high-resolution imaging
To determine on the basis of retrospective analysis the optimal approaches to the
method for evaluation of the entire picture of this disease.
management of patients with organic hyperinsulinism.
DOI: 10.1530/endoabs.49.EP198
Materials and methods
Medical records of 72 patients admitted with suspected organic hyperinsulinism
had been screened and medical histories of patients with a confirmed diagnosis of
organic hyperinsulinism were included into the analysis. Anamnesis, results of
objective, laboratory and instrumental examinations, methods and results of the
EP199
treatment were analyzed.
Results
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs):
The diagnosis of insulinoma was confirmed in thirty two cases. Hypoglycemia
clinico-pathological characteristics and disease outcome of 110 patients
treated at single referral medical center
was achieved within the first 48 h after the start of the 72-h fasting test in 100% of
Shlomit Koren1, Karen Or1, Miri Steinschneider1, Esther Kummer1,
cases. Study results showed that in 50% of cases the size of the pancreatic
Nirit Yarom2,6, Haim Shirin3,6, Ron Lavy4, Gratiana Gratiana5,6 &
neoplasm was more than 1.4 cm. Inverse correlation between tumor size and
Carlos Benbassat1,6
plasma glucose concentration at the time of hypoglycemia was found (rZK0.45,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
PZ0.02). Surgical treatment was carried out in thirty out of 32 patients. Surgical
Case report
enucleation of insulinoma was performed in 12 (40%) cases, distal pancrea-
A 59-year-old woman presented with a 3-month history of episodic hypotension,
tectomy - in 18(60%). Insulinoma was confirmed in 27 cases, while in three
tachycardia and face and upper trunk flushes. She had a history of cecum tumor
patients diagnosis of non-insulinoma pancreatogenous hypoglycemia (‘nesidio-
resection 18 years ago. It was a poorly differentiated mixed adenoneuroendocrine
blastosis’) was established according to histological findings. Positive clinical
carcinoma. The tumor extended in the pericolic adipose tissue with perineural and
result was achieved after all surgeries. In postoperative period patients were
lymphonodular invasion. It was TNM stage IIIB (T3N1M0). Postoperatively, she
discharged within 11-30 days. Patients without post-operative complications
received interferon and 5-fluoracil chemotherapy for 6 months.
were discharged 13.0G1.4 days after surgery. Twelve (40%) patients developed
The patient was asymptomatic for 18 years until symptoms of carcinoid syndrome
post-operative complications. The duration of hospital stay in these cases was
(CS) appeared. Serum chromogranin A and 24-h urine 5-hydroxy-indole-acetic-
significantly longer 20.1G1.9 (P!0.01).
acid (5-HIAA) were abnormally high. An abdominal magnetic resonance imaging
Conclusions
revealed multiple metastatic liver lesions confirmed by biopsy. In111-
Obtained data confirmed that comprehensive approach including 72-h fasting test,
pentetreotide scintigraphy detected the lesions in the liver and others in the left
use of modern imaging techniques and application of high-tech treatment
shoulder and the right sternum-clavicle joint. Bone lesions were also
methods, is crucial for successful diagnosis and treatment of insulinoma.
demonstrated by Tc-99m DTP scan. Octreotide LAR 30 mg per month was
DOI: 10.1530/endoabs.49.EP200
initiated and resulted in amelioration of symptoms. Chromogranin A and 5-HIAA
decreased but remained above normal range. The symptoms of CS reappeared
after 2 years and the patient received 9 cycles of targeted radiotherapy (177Lu-
Dotatate), which finally resulted in clinical and imaging improvement.
Conclusion
We report a rare case of a patient with a mixed adenoneuroendocrine carcinoma
of the cecum who presented with metastatic disease and carcinoid syndrome 18
years postoperatively. Due to the rarity of these tumours and the unknown natural
EP201
history, lifelong follow up is required.
A rare case: non-islet cell tumor hypoglycemia with adrenal
DOI: 10.1530/endoabs.49.EP202
insufficiency
Veysi Asoglu1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
Funda Ustun3 & Sibel Guldiken2
1Department of Internal Medicine, Medical Faculty, Trakya University,
Edirne, Turkey;2Department of Endocrinology and Metabolism, Medical
Faculty, Trakya University, Edirne, Turkey;3Department of Nuclear
Medicine, Medical Faculty, Trakya University, Edirne, Turkey.
Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome
and is the second most common cause of tumor-related hypoglycemia following
EP203
insulinoma. Its prevalence is not known and is likely that many cases would go
undiagnosed. In here, we describe a patient with PNET who presented with severe
Quality of life in patients with neuroendocrine tumors treated with
hypoglycemia.
177Lu-[DOTA0,Tyr3]-octreotate: a Single Tertiary Care Portuguese
A 37-year-old male with known metastatic Pancreatic neuroendocrine tumors
Center Experience
(PNET) presented with weight loss, sweating, and tremor, episodic altered
Adriana Lages, Helder Moreira, Gracinda Costa, Patrícia Oliveira,
sensorium. He had documented blood glucose values below 35 mg/dl during
Diana Oliveira, Diana Martins, Mara Ventura, Nelson Cunha &
those episodes. He received two cycles of lutetium therapy and was referred to our
Francisco Carrilho
institute. At blood glucose of 33 mg/dl, he had undetectable plasma insulin
Coimbra Hospital and University Center, Coimbra, Portugal.
(%0.19 mU/l), low C-peptide 0.159 ng/ml (normal: 0.8-4), cortisol: 5.6 mg/dl
(n:5-29), GH: !0.05 ng/ml and low IGF1 !25 ng/ml (normal: 109-284 ng/ml).
Introduction and purpose
ACTH: 60 pg/ml (normal:
0-46), Na:
136 mmol/l
(normal:
132-146), K:
177Lu-[DOTA0,Tyr3]octreotate (177Lu-DOTA-TATE) is a radiopharmaceutical
4.2 mmol/l (normal:3.5-5.5), TSH 1.274 uIU/ml (n: 0.35-4.94), FT4: 1.47 ng/dl
frequently used in peptide receptor radionuclide therapy (PRRT), which is a
(n:0.7-1.48), FT3: 2.6 pg/ml (n: 1.71-3.81), prolactin: 8.28 ng/ml (n:2.1-17.7),
promising treatment modality in patients with metastasized neuroendocrine
LH: 5.08 IU/l (1.5-9.3), FSH: 10.22 IU/l (n:1.4-18.1), testosterone: 405.78 ng/dl
tumors (NETs). We purpose to evaluate the quality of life (QoL) in patients with
(n:241-2270). Magnetic resonance imaging of pituitary gland was normal. We
somatostatin receptor positive inoperable or metastatic NETs throughout the three
were started prednisolone 30 mg/day with which his symptoms abated. After
cycle’s (with three months intervals) protocol used in our hospital.
prednisolone treatment, there was no recurrence of hypoglycemia on follow-up.
Patients and methods
In NICTH patients, the serum levels of insulin, C-peptide, and IGF1 are usually
We included 24 patients, 16 men and 8 women (age: meanZ67 years; rangeZ
decreased or undetectable; however, the circulating level of total IGF2
as
29-81). The majority (13/24 cases; 54.2%) were gastroenteropancreatic NETs.
determined by conventional immunometric or receptor assays may be increased,
Patients were treated with a mean cumulative 177Lu-DOTA-TATE activity of
decreased, or normal. In the absence of IGF2 assays, low serum insulin in
614 mCi (range: 303-1177 mCi).
combination with low IGF1 levels at the time of hypoglycemia is a strong
Patients were invited to self-report QoL during PRRT cycles. We analyzed the
biochemical evidence of NICTH. High-dose glucocorticoid therapy has
overall QoL and specific domains of QoL according to the Organization for the
immediate beneficial effect on symptomatic hypoglycemia.
Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC
DOI: 10.1530/endoabs.49.EP201
QLQ-C30) scoring manual.
Results
From 24 patients, 15 completed at least 2 copies of the EORTC QLQ-C30 at
different time-points (during the 1st or 2nd cycle and during the 3rd). Twelve
patients had progressive disease, eleven had stable disease and one had notable
lesions regression during PRRT.
Regardless the treatment outcome, Global Health Status/QoL (GHS/QoL) and all
EP202
the functional scales (except social status) improved significantly in all group
Late manifestation of a mixed adenoneuroendocrine carcinoma of the
(P!0.05). On GHS/QoL, we found an improvement on scores superior to 10
cecum
points before vs after therapy (DC10.56; PZ0.003).
Paraskevi Kazakou, Xakousti Tzamali, Alexis Travlos, Evangelia Vogiatzi,
Besides GHS and functional scales, we observed also a favorable impact on
Georgia Ntali, Vasiliki Sarantopoulou & Antonis Polymeris
disease-related symptoms as fatigue
(PZ0.00003), insomnia
(PZ0.0003),
Department of Endocrinology, Alexandra General Hospital, Athens, Greece.
appetite loss (PZ0.0003), constipation (PZ0.033) and diarrhea (PZ0.014).
Conclusions
Introduction
A better health-related QoL in cancer patients with incurable disease is an
Mixed adenoneuroendocrine carcinoma
(MANEC) is a rare tumor of the
important outcome of cancer therapy, especially when survival is prolonged.
gastrointestinal tract that consists of a dual adenocarcinomatous and neuroendo-
Therapy with 177Lu-DOTA-TATE significantly improved QoL regarding to
crine differentiation. The clinical behavior seems to be influenced by the
several functions and had favorable impact on global health status even on those
neuroendocrine component. We report a patient with mixed adenoneuroendocrine
with progressive disease.
carcinoma of cecum who presented 18 years after her initial diagnosis and
DOI: 10.1530/endoabs.49.EP202
treatment.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP204
whereas the frequency of heterozygous (DN) was 0 in patients and 0.15 in
controls. The frequency of allele D was 0 in patients and 0.075 in controls. The
Triple tumors in a patient with insulinoma
frequency of allele N was 1 and 0.925 in patients and controls respectively.
Urska Ksela & Mitja Krajnc
UKC Maribor, Maribor, Slovenia.
DOI: 10.1530/endoabs.49.EP205
Introduction
Hypoglycemia is a rare clinical problem in patients not being treated for diabetes
mellitus and requires further evaluation and management if Whipple’s triad is
present. Insulinoma commonly presents with fasting hypoglycemia. Insulinoma is
rarely associated with type 1 multiple endocrine neoplasia, when tumors are
usually multiple and more frequently malignant. The diagnosis of insulinoma is
established by demonstrating inappropriately high serum insulin concentrations
during a spontaneous or induced episode of hypoglycemia, e.g. 72-h fast.
EP206
Patient
Congenital adrenal hyperplasia: impact of therapy on growth and
46-years old female was referred to our department for evaluation of spontaneous
sexual maturation - a 5-year retrospective study of a Tertiary Pediatric
fasting hypoglycemia. She had multiple episodes of temporary probably
Endocrinology Center
neurohypoglycemic symptoms (confusion, unusual behaviour) and gained a lot
Camelia Procopiuc, Madalina Vintila, Iuliana Gherlan, Amel Cirla,
of weight in 2016 (C20 kg). Before the beginning of 72-h fast her serum glucose
Andreea Brehar, Andra Caragheorgheopol, Suzana Vladoiu Oana Popa &
was
1.8 mmol/l, insulin concentration
20.6 mcU/ml, C-peptide
1.2 nmol/l.
Cristina Dumitrescu
Testing was stopped after 6 h due to very low glucose levels (1.5 mmol/l) but
CI Parhon National Institute of Endocrinology, Bucharest, Romania.
without any obvious symptoms of hypoglycemia, insulin was high. After
glucagone 1 mg i.v. glucose increased for 1.5 mmol/l. Her serum calcium, iPTH,
prolactin and IGF-1 were normal. CT showed 1.8 cm lesion in the pancreatic neck
Objective
and also unusual lesion in proximal jejunum that appeared to be a neuroendocrine
To evaluate the comparative effects of different glucocorticoid treatments on
tumor. There was also typical teratoma in left ovary (maximal size 6.6 cm), also
growth and sexual maturation in patients with congenital adrenal hyperplasia.
seen on US. The patient underwent operation - partial pancreatectomy, proximal
Patients and methods
jejunal resection with anastomosis and left ovariectomy. Based on patohistology
We conducted a retrospective observational cohort study in 78 patients (60 girls,
and imaging results benign insulinoma was confirmed, in jejunum there was
18 boys) diagnosed with congenital adrenal hyperplasia (CAH), followed-up for a
ectopic pancreatic tissue, and there was mature teratoma of left ovary. We have
period of 5 years. The majority had 21-hydroxylase deficiency (75 patients), 2 had
not performed genetic testing for MEN1 since we thought it was unlikely. After
11-b hydroxylase deficiency and 1 patient had 3-b hydroxysteroid dehydrogenase
operation, the patient was asymptomatic and normoglycemic.
deficiency. Patients received either Prednisone (PDN), Hydrocortisone (HC) or
Conclusions
Hydrocortisone plus Dexamethasone (DEX). Data on growth, bone maturation,
We found three different tumors, including insulinoma, in a single patient. This
puberty onset, predicted adult height, and parental height were collected. Height
combination has not yet been described to coincide and is not due to multiple
gain was calculated as the difference between parentally determined target height
endocrine neoplasia.
and final or predicted height at the last evaluation.
Results
DOI: 10.1530/endoabs.49.EP204
Height gain with therapy was 0.42 S.D. over the initial estimated height deficit.
Height gain correlated with the clinical form of CAH, with better outcome in non-
classical vs classic forms (P!0.01). There were no significantly differences
between groups in regard to type of therapy (PZ0.164). There was no difference
in change of body mass index regarding the type of treatment (PZ0.99). Girls
Paediatric Endocrinology
over 12 years of age treated with HC had higher rates of spontaneous menarche
versus PDN treated girls (PZ0.006). Twelve children developed precocious
EP205
puberty, which correlated with older age at treatment initiation (PZ0.048).
An analysis of R356W and Q318X mutations and 8 bp deletion in
Conclusions
21-hydroxylase gene CYP21A2 in causing pseudo-precocious puberty in
The type of therapy did not influenced height gain. HC facilitated spontaneous
patients with congenital adrenal hyperplasia in Pakistani children
menarche onset in normal age range. Late diagnosis and therapy led to higher
Nadiaj Parveen1, Samar Minallah1, Muhammad Ismail2, Qaiser Mansoor2,
rates of precocious puberty in children with CAH.
Maleeha Akram1, Zubaria Iqbal1, Sarwat Jahan3, Kiran Afshan3,
DOI: 10.1530/endoabs.49.EP206
Gulbin Shahid4, Faheem Tahir5, Afzaal Ahmed Naseem1, Mazhar Qayyum1
& Syed Shakeel Raza Rizvi1
1Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University
Rawalpindi, Rawalpindi, Punjab, Pakistan;2Institute of Biomedical and
Genetic Engineering (IBGE), Islamabad, Pakistan;3Department of Animal
Sciences, Quaid-e-Azam University, Islamabad, Pakistan;4The Children’s
Hospital, Pakistan Institute of Medical Sciences (PIMS), Islamabad,
Pakistan;5Reproductive Physiology, Public Health Laboratories Division,
National Institute of Health, Islamabad, Pakistan.
Pituitary - Clinical
The first signs of puberty are visible around the age of 8 years in girls and 9 years
EP207
in boys. If signs of puberty appear before the designated ages in girls and boys,
The risk of hypotension, evaluated by ambulatory blood pressure
puberty is viewed as precocious. In peripheral precocious puberty, androgens
monitoring, during fasting and outside fasting in patients with adrenal
concentrations increase due to testicular tumours or congenital adrenal
insufficiency
hyperplasia (CAH). Two mutations, R356W and Q318X, and one 8 bp deletion
Melika Chihaoui1, Wafa Grira1, Meriem Yazidi1, Ons Rejeb1,
in CYP21A2 gene, causing CAH type of precocious puberty were examined.
Fatma Chaker1, Ibtissem Oueslati1, Jihane Bettaieb2 & Hedia Slimane1
Blood samples were obtained from 42 CAH patients (30 boys and 12 girls)
1Department of Endocrinology, Faculty of Medicine of Tunis, La Rabta
exhibiting higher 17-OH progesterone concentrations and 42 normal healthy
Hospital, University of Tunis El Manar, Tunis, Tunisia;2Department of
controls. DNA was extracted, primers of exons of CYP21A2 splice sites were
Medical Epidemiology, Faculty of Medicine of Tunis, Pasteur Institute of
designed and PCR-RFLP method was employed. The PCR product of CYP21A2
Tunis, University of Tunis El Manar, Tunis, Tunisia.
digested by enzyme Fnu4HI for R356W mutation gave bands of AA (w106, 110,
229 and 37 bp). The frequency of this genotype was 100% in both groups
indicating absence of R356W mutation in both groups. For Q318X, the restriction
The risk of hypotension during Ramadan fasting in patients with adrenal
enzyme, PstI gave bands of 3 different genotypes, GG (161 and 329 bp segments)
insufficiency is unknown. The aim of our study was to evaluate objectively this
in
18 patients, GC (490, 329 and 161 bp segments) in 21 patients and CC
risk.
(segment of 490 bp) in 3 patients (2 boys and 1 girl). For 8 bp deletion, PCR
Methods
amplification with allele specific primers yielded a segment of w710 bp; 8 bp
It is a prospective case-crossover study on 28 patients with known and treated AI.
deletion was not found in any patient but 3 control subjects were heterozygous for
Patients had no hypertension and were regular fasters. All patients underwent a
it. The frequency of homozygous wild type (NN) was 1 in patients and 0.85 in
clinical examination and a 24-hours blood pressure monitoring during Ramadan
controls; the frequency of homozygous mutants (DD) was 0 in both groups,
fasting then outside fasting.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
This clearly demonstrates the key role of
11b-hydroxylase being the most
There were 23 women. The mean age was 37G14 years. It was a central adrenal
influenced enzyme by the adrenocortical axis suppression.
insufficiency in 26 patients. The mean duration of the disease was 9G8 years. The
DOI: 10.1530/endoabs.49.EP208
mean daily dose of hydrocortisone was
19G3 mg. Systolic hypotension
(!90 mmHg) did not occur during fasting and occurred in two cases outside
fasting. Diastolic hypotension (!60 mmHg) occurred in 12 cases during fasting
and in 13 cases outside fasting without a significant difference. All cases of
hypotension were asymptomatic. The levels of systolic and diastolic blood
pressure during the 24 h and during the fasting period (from pre dawn to sunset)
did not significantly differ between the fasting day and the non-fasting day.
Thyroid Cancer
Conclusion
EP209
Blood pressure levels during fasting were comparable to those outside fasting and
there was not an increased risk of hypotension during fasting.
Clinical relevance of RET proto-oncogene variants L769L and S836S
(exon 11, 13, 14, and 15) in patients with sporadic medullary thyroid
DOI: 10.1530/endoabs.49.EP207
carcinoma
Darko Katalinic1, Miljenko Solter2 & Nora Nikolac2
1
Department of Internal Medicine, Faculty of Medicine, J.J. Strossmayer
University of Osijek, Osijek, Croatia;2Faculty of Medicine, UHC Sisters of
Charity, University of Zagreb, Zagreb, Croatia.
Steroid Metabolism C Action
Background
Medullary thyroid cancer (MTC) makes up to 5-10% of all cases of thyroid
EP208
malignancies. The clinical course of MTC varies from an extremely indolent
Steroid metabolome changes in the 1 mg dexamethasone
tumour to an aggressive variant that is associated with a high mortality rate. RET
suppression test
proto-oncogene germline mutations are crucial for the onset and the progression
Václav Hána jr1, Mikuláš Kosák1, Václav Hána1 & Martin Hill2
of MTC. The aim of this study was to evaluate the L769L (subgroup L) and S836S
13rd Department of Internal Medicine, 1st Faculty of Medicine, Charles
(subgroup S) allele frequencies in patients with sporadic MTC (group A, nZ89)
University and General Teaching Hospital, Prague, Czech Republic;
compared to healthy subjects
(group B, nZ83) and to determine if these
2Institute of Endocrinology, Prague, Czech Republic.
polymorphisms have influence the clinical presentation and the course of MTC.
Methods
A non-isotopic polymerase chain reaction based single strand confirmation
Introduction
polymorphism analysis and heteroduplex gel electrophoresis method was used
Dexamethasone induced negative feedback on CRH, ACTH and cortisol secretion
to screen tumour DNA extracted from 89 formaldehyde fixed and paraffin
is one of the key principles in the diagnostic workup of hypercortisolism. Cortisol
embedded MTC specimens. We also analysed relevant clinical data in the group
secretion has been studied extensively, but changes of other steroids remained
of patients with MTC. The study was conducted according to the Declaration of
apart. Our aim was to establish steroid profile changes in 1 mg dexamethasone
Helsinki, the protocol was reviewed and approved by the institutional
test.
independent ethics committee. All patients were provided with written informed
Methods
consent.
The Steroid profile consisting of 103 steroids and their metabolites from the
Results
serum of 9 male and 8 healthy female controls was measured before and in the
Mean age was 51.6G9.2 years for the patients with MTC (range, 42.4-60.8) vs
morning at 0800 hours after 1 mg dexamethasone administered at 1100 hours.
45.4G7.1 (range
38.3-52.5) for the group of healthy subjects. The allele
Samples were analyzed using GCMS/MS for the measurement of most of the
frequencies showed a similar level of the L769L and S836S variants in both
steroids. Only a few were measured by RIA.
subgroups of examinees (group L, 52.5% vs group S, 47.5%; PO0.001). Lymph
Results
node metastases were found in all patients with MTC (subgroup L, nZ42 vs
Dexamethasone administration suppressed the most the levels of corticosterone
subgroup S, nZ47; PO0.001), and distant metastases in nine patients (subgroup
(29!), cortisol (20!), 11-OH-androstenedione (12!), 11b-Hydroxy-androster-
L, nZ5 vs subgroup S, nZ4; PO0.001). Postoperatively, 52% of patients in
one (13!), 11b-Hydroxy-etiocholanolone (13!), 11b-Hydroxy-epiandrosterone
subgroup L vs 55% of patients in subgroup S were biochemically cure (PO0.001).
(6!),
17-Hydroxypregnenolone
(5!). Other steroids like DHEA
(3!),
In the subgroup L, pT-category was: T0, nZ23; T1, nZ14; and T2, nZ5. In the
Androstenedione (2!), Pregnenolone (2!) were suppressed at much lower
subgroup S, pT-category was: T0, nZ21; T1, nZ16; and T2, nZ10.
rate than their 11b-hydroxylated metabolites. As expected, none of the measured
Conclusion
steroids increased after dexamethasone.
We did not find any statistically significant difference in representation of the
Conclusions
L769L and S836S gene variants. The RET L769L and S836S (exon 11, 13, 14,
Inhibition of ACTH secretion leads to a strong suppression of the whole adrenal
and 15) gene variants are not contributing factor in the development of sporadic
steroidogenesis including androgen production.
MTC and are not promoting factor for development of metastatic MTC.
The most prominent changes were observed in corticosterone, cortisol, and
interestingly 11-OH-androstenedione and their 5-b/a-reduced metabolites, which
DOI: 10.1530/endoabs.49.EP209
all decrease more than 10 times in comparison with the basal levels.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations:
Calcium and Bone
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Bone & Osteoporosis
(Orx C CT; 100 IU/kg b.w.) every second day for 6 weeks. The rats from SO and
second Orx group received the same volume of vehicle alone by the same
EP210
schedule. The peroxidase-antiperoxidase method was applied for localization of
CT in C-cells. CT-immunopositive thyroid C-cells, thyroid follicular epithelium,
interstitium and colloid were evaluated morphometrically. An ImageJ public
Abstract withdrawn.
domain image processing program was used to measure bone histomorphometric
parameters of the proximal tibial specimens. Blood serum samples were analyzed
for CT, osteocalcin (OC) and thyroxine (T4), and urine samples fot calcium
(Ca2C) concentration. We found a significant decrease in the Vc and Vv of
thyroid C-cells after CT treatment compared to both SO and Orx. The Vv of the
colloid was higher, while VV of the follicular epithelium was lower after CT
treatment compared to Orx. Analysis of trabecular microarchitecture showed that
salmon CT administration significantly increases of cancellous bone area (B.Ar),
trabecular thickness (Tb.Th), and trabecular number (Tb.N) whereas trabecular
separation (Tb.Sp) was significantly decreased. CT treatment markedly elevated
serum CT, but serum OC, T4 and urinary Ca2C concentrations were lower than in
the Orx group. These findings indicate that administration of salmon CT inhibited
EP211
calcitonin-producing thyroid C-cells and changes the structure of the thyroid
gland indicating hypoactivity.
Bisphosphonate related osteonecrosis of the jaw: risk factors: a case
report
DOI: 10.1530/endoabs.49.EP212
Pablo Young, Natalia Elias, Noelia Rella, Marcela Moran & Marina Curria
British Hospital, Buenos Aires, Argentina.
Introduction
Bisphosphonates
(BP) have been employed for many years and have
demonstrated an excellent safety profile. Nevertheless, severe osteonecrosis of
the jaw (ONJ) have been described in patients with bone metastases that were
treated with BP for many years.
EP213
Case
Primary hyperparathyroidism: hormonal profile and risk of
A 72 year old female with breast cancer and bone metastases treated with
complications
quadrantectomy, axillary lymph node dissection, radiotherapy, tamoxifen and
Alina-Andreea Gatu1, Cristian Velicescu1,2, Cristina Preda1,2,
pamidronate 90 mg/month. Two years later, the patient suffered from pain in the
Voichita Mogos1,2, Carmen Vulpoi1,2, Simona Mogos1,2, Valentin Zaharia2,
right body of the jaw one month after the extraction of low dental pieces. She had
Adrian Aancute2 & Dumitru Branisteanu1,2
an extended intraoral ulcer, which leaved exposed part of the body of the jaw and
1Gr. T Popa University of Medicine and Pharmacy, Iasi, Romania;
loss of dental pieces. The patient had not received radiotherapy in the jaw. X ray
2St. Spiridon Emergency Hospital, Iasi, Romania.
revealed osteolysis and CT scan showed lesions in bone and soft parts of the jaw.
Biopsy confirmed necrosis. Irrigation with chlorhexidine gluconate 0,12% and
extraction of dental pieces were performed. In spite of the conservative treatment,
Background
she presented severe pain and suppuration. The right side of the jaw was removed.
Vitamin D deficiency is frequently associated with primary hyperparathyroidism,
Pamidronate treatment was discontinued. The patient had cancer progression and
but the impact of this association on disease evolution and complications is ill
died some months later.
defined. Aims: to assess the role of vitamin D status on the metabolic profile and
Conclusion
spectrum of complications at patients with primary hyperparathyroidism.
The aim of this presentation is to emphasize the importance of taking into account
Materials and methods
the risk factors of ONJ at the moment of performing an invasive procedure. The
Transversal study involving
42
patients with primary hyperparathyroidism
estimated incidence of ONJ in patients with malignancy who receive BP seems to
submitted to parathyroidectomy. We evaluated serum calcium, phosphate, serum
range between 1 and 10%. The risk factors of ONJ are related to BP, local,
PTH and 25OHD3, bone mineral density by DXA (Hologic) and anamnestic
systemic and demographic factors. The use of less traumatic techniques available
episodes of bone fractures and kidney lithiasis. Fifteen patients had episodes of
and adequate antibiotic treatment is mandatory in the presence of risk factors of
kidney lithiasis, whereas 27 patients did not develop this complication. Twenty
ONJ. BP treatment should be interrupted after surgery until the wound is fully
patients were diagnosed with osteoporosis whereas 22 patients had bone mass in
healed.
the range of normal or osteopenia. Data between groups were compared using the
DOI: 10.1530/endoabs.49.EP211
t test and were considered significant at P values ! 0.05.
Results
Twenty-nine of the 42 patients had 25OHD3 in the range of deficiency (lower
than 20 ng/ml) and 20 had severe 25OHD3 deficiency (lower than 10 ng/ml).
Serum calcium and phosphate were similar irrespective of the presence or absence
of complications. No differences were found between mean PTH and 25OHD3
levels of patients with or without osteoporosis. Patients with kidney lithiasis had,
however, higher PTH (390C/K 90 pg/ml vs 209C/K 64 pg/ml, P!0.001) and
lower 25OHD3 levels (12.8C/K 6 ng/ml vs 19.2C/K 7.8 ng/ml, P!0.05) than
patients without kidney lithiasis.
EP212
Conclusions
D hypovitaminosis accompanies frequently primary hyperparathyroidism.
Salmon calcitonin affects thyroid endocrine cells and trabecular bone in
Patients with higher risk of kidney lithiasis seem to have higher PTH and lower
a rat model of male osteoporosis
25OHD3 levels.
Branko Filipović1, Branka
ˇ oši
´-Jurjevi
´1, Jasmina
ˇivanović1,
Milica Manojlovi
´-Stojanoski1, Nataša Nestorovi
´1, Svetlana Trifunovi
´1,
DOI: 10.1530/endoabs.49.EP213
Ivana Jarić1, Gordana Ušćebrka2 & Verica Miloševi
´1
1Institute for Biological Research “Siniša Stankovic´”, University of
Belgrade, Belgrade, Serbia;2Faculty of Agriculture, University of Novi Sad,
Novi Sad, Serbia.
Calcitonin (CT) is a hypocalcemic hormone produced by thyroid C-cells that acts
as an bone antiresorptive agent. The other endocrine cell population in thyroid,
called follicular cells produce thyroid hormones (TH) which also affect bone
EP214
turnover. In this study, we evaluated the effects of salmon CT administration on
structure and function of both CT and TH producing thyroid cells as well as
Efficacy and safety of bisphosphonate discontinuation in
trabecular bone microarchitecture in orchidectomized (Orx) middle-aged rats.
postmenopausal osteoporosis: a systematic review
Fifteen-month-old male Wistar rats were either Orx or sham-operated (SO). One
Panagiotis Anagnostis1, Stavroula Paschou1, Gesthimani Mintziori1,
group of Orx animals were injected subcutaneously with synthetic salmon CT
Irene Lambrinoudaki2 & Dimitrios Goulis1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Unit of Reproductive Endocrinology, First Department of Obstetrics and
but not indicated in osteopetrosis. Our approach was to treat her with activ vit.D
Gynecology, Medical School, Aristotle University of Thessaloniki,
products since her actual fracture risk was not cinsidered increased.
Thessaloniki, Greece;2Second Department of Obstetrics and Gynecology,
DOI: 10.1530/endoabs.49.EP215
National and Kapodistrian University of Athens, Athens, Greece.
Introduction
The maximum period of bisphosphonate use has not been determined, as their
long-term appliance has been associated with adverse effects, such as
osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF).
The aim of this study was to systematically present existent data regarding the effect
of bisphosphonate discontinuation on fracture risk and bone mineral density (BMD).
Methods/design
MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to
December 2016) for randomized placebo-controlled trials.
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Results
Osteonecrosis of the jaw and bilateral atypical femoral fracture both
Regarding alendronate, five studies fulfilled eligibility criteria (“drug holiday”:
occurring during treatment of osteoporosis
two-five years). Extending alendronate
(5-10 mg/d) use to five years, after
Edelissa Payumo, Thelma Crisostomo & Ivan Cudal
continuous treatment for five years, reduced clinical vertebral fracture risk by 55%,
Makati Medical Center, Makati, The Philippines.
without difference in morphometric vertebral or non-vertebral fractures (one study).
Lumbar BMD remained higher than pre-treatment levels in the discontinuation
Background
group, although lower compared with the extension group. Hip BMD decreased or
Osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) are rare
remained unchanged.
potential adverse effects of bisphosphonates and RANK-L inhibitor, occurring in
Regarding zoledronic acid, two studies fulfilled eligibility criteria. After three
1 and 2 per 100,000 person-years, respectively. The pathogenic mechanisms of
annual infusions (5 mg/y), extending treatment to six years reduced risk of new
both conditions are known to be independent of each other. Here, we report both
morphometric vertebral fractures by 49%, without benefit in clinical vertebral or
conditions sequentially occurring in the same patient.
other types of fractures. Lumbar BMD remained above pre-treatment values in the
Clinical case
discontinuation group, but reduced in hip sites. Extending treatment to nine years
An 81-year old, obese, diabetic, female was admitted due to hypertensive urgency
provided no additional benefit.
and persistent jaw pain after tooth extraction. The patient has postmenopausal
Regarding risedronate, one study fulfilled eligibility criteria. Discontinuation for
osteoporosis for fourteen years and was on intermittent unsupervised treatment
one year (after 5 mg/d for three years) did not increase non-vertebral fracture risk,
with alendronate, denosumab and ibandronate. She had suffered sequential
but continued to confer a reduced risk in vertebral fractures (46%). Lumbar BMD
fracture of both femurs during the eighth and eleventh year of treatment. Both
remained higher, whereas femoral neck BMD decreased, compared with
fractures were transverse, non-comminuted, at the proximal femoral shaft, which
pretreatment levels. No increased risk of ONJ or AFF was shown in these studies.
occurred after a minor trauma, and were managed with open reduction and
Conclusions
internal fixation.
A “bisphosphonate holiday” may be considered after five years of treatment with
Upon presentation, the patient was noted with tenderness intraorally of tooth
alendronate, three with risedronate and three with zoledronic acid for up to five, one
number 35 periapical region, no pus, no mandibular swelling. There was
and three years, respectively. However, this decision should be individualized.
peripheral leukocytosis, elevated erythrocyte sedimentation rate, C-reactive
DOI: 10.1530/endoabs.49.EP214
protein. Panoramic with periapical view radiograph showed presence of bony
sclerosis which represent a sequestrum compatible to chronic osteomyelitis in the
molar area of the left hemi-mandible. Antibiotic infusion and excision and
debridement of left posterior mandible were done. Necrotic bone with
histopathologic finding of acute and chronic osteomyelitis with bacterial colonies
was removed consistent with a diagnosis of osteonecrosis of the jaw. The patient
was discharged on the fourth post-operative day and was placed on drug holiday.
Conclusion
ONJ and AFF can occur both in the same patient during prolonged treatment with
bisphosphonates and RANK-L inhibitor and may suggest a common pathogenic
mechanism. This case further emphasized that to avoid these grave consequences,
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bisphosphonates should be given in a limited period—five years, as recommended
Osteopetrosis vs Osteogenesis Imperfecta-is that so hard to distinquish?
by experts.
Case report
DOI: 10.1530/endoabs.49.EP216
Theodor-Eugen Oprea, Mirela Bonea, Suzana Florea & Carmen Barbu
Elias University Emergency Hospital, Endocrinology Clinic, Bucharest,
Romania.
Osteopetrosis and O.I. are both bone metabolic disorders with opposite features in
terms of the metabolic turnover: while osteopetrozis has a low turnover and
increased BMD due to the failure of osteoclasts to resorb bone, O.I. is well known
as a high turnover disease with low BMD caused bt mutations in the COL1A1 and
EP217
col COL1A2 genes that encode type 1 procollagen; yet, both condition, in spite of
Clinical manifestations and treatment approach in osteogenesis
different mechanism, end up with increased ftracure prevalence. We report the
imperfecta
case of a 46 year old women who presented for clinical and biological evaluation
Dimitra Tampouratzi1, Styliani Kalaitzidou1, Aggeliki Sapera1,
with a prior diagnisis of osteopetrosis. The anamnesis revealed that the diagnosis
Michalis Kotis1, Fotini Kanouta1, Eleni Triantafillou1, Taxiarchis Kyrimis1,
of osteopetrozis was set when the patient was 2 year old based on radiologycal
Georgios Papadakis2, Anna Drakopoulou1, Victoria Kaltzidou1 &
features and multiple nontraumatic fractures suffered in childwhood; last fracture
Athanasia Tertipi1
she recalls was at
20 year old and. Also she claims a familial history of
1Endocrinology Department, Metaxa Anticancer Hospital, Piraeus, Athens,
osteogenesis imperfecta
(maternal grandfather). The clinical examination
Greece;2STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland.
revealed: Hight-125 cm; Weight-50 kg; BMI-32 kg/sm; blue sclerae, left leg
orthosis, with unequal inferior limbs accompanied by difuze joint pain. Lab tests
highlighted mild hypercholesterolemia,
25OHVitD insufficiency, low beta-
Objectives
crosslaps level, normal PTH, normal TSH and fT4. Near normal BMD. Dorsal
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affects
and lombar spine X-ray:rarefaction of trabecular bone structure, suggesting a
the bones. The underlying mechanism is usually a disorder of connective tissue
medium grade of demineralization.
due to lack of type I collagen. Usually, the disease is due to mutations in the
Our O.I. final diagnosis proved to be quite difficult, taking into account the prior
COL1A1 or COL1A2 genes. The disease is inherited in an autosomal dominant
one of osteopetrosis, the history of pubertal fractures, familial history of O.I.,
manner or occurs via a de novo mutation. There are eight types of the disease.
growth impairment, lack of decreased BMD and increased bone turnover, mild
Type I is the most common and the least sever type and is due to mutation in
VitD insufficiency. However, the importance of establishing the diagnosis, in our
COL1A1 gene. We evaluated the clinical, laboratory and radiological profile of a
case, consists in choosing the optimal treatment; bisphosfonates are used in O.I.
woman with OI Type I who was treated over a 3-years period in our clinic.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
Introduction
A 61-year old female patient with family history of OI (son and sister) was treated
The improvement of the survival of diabetics is accompanied by the emergence of
in our clinic. She had history of multiple repeated fractures since 18 years old,
bone fragility which can directly affect, at various levels, the various components
short stature (138 cm), discoloration of the sclera, dental abnormalities, poor
of the bone tissue leading to quantitative and qualitative anomalies. The effects of
muscle tone in arms and legs, triangular face and skeletal deformities such as
type 2 diabetes on bone are complex because they are associated with the
osteoporosis, spinal canal stenosis and kyphoscoliosis. Bone densitometry found
sometimes associated disorders of nutrition, weight and age. Densitometric
severe osteoporosis. Treatment included zoledronic acid IV, vitamin D and
studies in this context are quite contradictory. We proposed to study the bone
calcium carbonate per os.
status of type 2 diabetics.
Results
Patients and methods
After treatment with zoledronic acid the patient reported reduced bone pain and
We carried out a cross-sectional study of 290 type 2 diabetics. These patients
had stable bone mass (0.547 g/cm2 before treatment and 0.535 g/cm2 (femoral
benefited from a measurement of bone mineral density (BMD) associated with
neck) after treatment) and increased T-score (femoral neck) (K3.3 SD before
PTH, vitamin D and calcemia.
treatment and K2.88 SD after treatment, 3 years later).
The results
Conclusion
The average age of our population was 62.5 years. 38% of our patients were
Osteogenesis imperfecta is a heterogeneous disease and may have an indolent
treated with insulin with a predominantly mixed regimen (basal insulin combined
course. The diagnosis may be brought forward late in adulthood. The
with oral treatments), with an average HBA1C of 7.05% for an average duration
management includes the replacement of a calcium and vitamin D deficit and
of diabetes of 8 years. Mean calcium in the general population was 2.33 mmol/l,
biphosphonates. Bisphosphonates remain effective and can increase bone mass,
with 2.36 mmol/l in males and 2.27 mmol/l in females, with no significant
reduce bone pain and fractures.
relationship between the two sexes (PZ0.1370).
DOI: 10.1530/endoabs.49.EP217
5 patients had secondary hyperparathyroidism (O 65 pg/ml), the mean PTH in the
study population was 46.82 ng/ml, higher in women than in men. 75.6% of
patients had normal BMD, 23.3% had osteopenia, 24.3% were women, and 21%
were men. The mean concentration of vitamin D is 13.93 ng/ml, with a maximum
of 35 ng/ml and a minimum of 3 ng/ml. The mean concentration in males was 15,
14 ng/ml, significantly higher than that of females in the order of 11.91 ng/ml
(P!0.1ZPZ0.0018). A negative and significant correlation was found between
the serum levels of 25OHD3 and those of PTH. This correlation persisted after
adjusting for age and BMI. Our study did not find any significant relationship
between PTH levels and BMD scores with (PZ0.6091).
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Conclusion
Special features of body composition and bone mineral metabolism in
According to data from the literature and despite normal BMD in patients with
children with primary nephrotic syndrome
type 2 diabetes, it should be borne in mind that BMD alone is insufficient to assess
Natalia Volkova1 & Angelika Soltsava2
bone status, management of other factors such as Diet rich in vitamin D and
12th City Children’s Hospital, Minsk, Belarus;2Belarusian State Medical
sufficient calcium intake is required.
University, Minsk, Belarus.
DOI: 10.1530/endoabs.49.EP219
Objective
To learn characteristics of biochemical markers of bone metabolism, parameters
of bone mineral density (BMD) and fat component of body composition for early
diagnosis of bone disorders in children with primary nephrotic syndrome (NS).
Material and methods
We compared data of laboratory investigations (phosphorus (P), total calcium
(Ca), parathyroid hormone (PTH), and alkaline phosphatase (ALP)), protocols of
dual-energy X-ray absorbtiometry of the axial skeleton and total body of 27
children with NS (group 1 - G1, age 9.71G4.23 yrs) and 13 children of control
group (G2, age 10.84G3.84 yrs, PZ0.48). Group 1 was divided in subgroups G1a
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(relapse of NS, nZ12) and G1b (remission of NS, nZ15). Results were processed
using SPSS17.
Effects of acromegaly on bone tissue mRNA levels relevant to bone
metabolism
Results
Tatiana Grebennikova1, Zhanna Belaya1, Galina Melnichenko1,
G1 showed significantly lower age-matched z-score of BMD of lumbal spine (L1-
Olga Brovkina2, Alexey Nikitin2, Ludmila Astaf’eva3, Andrej Grigoriev1 &
4)
(K0.71G0.96) compared with G2 (0.08G1.13, PZ0.036). One child of G1
Ivan Dedov1
had low bone density of lumbal spine with z-score K2.9. Total BMD was similar
1Federal State Institution “The National Research Center for Endo-
in the groups
(0.88C/K0.12 g/cm2
in G1
vs
0.91C/K0.19 g/cm2
in G2,
crinology”, Moscow, Russia;2Federal Research and Clinical Center FMBA,
PZ0.39). Fat component of body composition was increased in G1 (38.33G
Moscow, Russia;3N.N. Burdenko Neurosurgery Institute, Moscow, Russia.
11.30%) compared with G2 (27.52G6.59%, PZ0.0001). Android/gynoid fat
ratio was higher in G1 (0.90G0.18) than in G2 (0.70C/K0.20, PZ0.013).
Children of G1a showed lower level of Ca than control (2.24G0.18 mmol/l vs
Molecular basis of the bone disorders in patients with acromegaly are largely
2.37G0.07 mmol/l, PZ0.009). Concentration of Ca in G1b was similar to G2
unknown.
(2.37G0.07C/K 0.13
vs
2.44G0.15 mmol/l, PZ0.71) We didn’t reveal
Objective
significant difference in of PTH, P and ALP levels in the groups (PO0.05).
To investigate gene expression profiles that regulate bone metabolism in bone
Conclusions
tissue samples from patients with acromegaly.
Most children with NS showed normal BMD of lumbal spine, though it was lower
Materials and Methods
than in healthy controls. Patients with NS had higher fat component of body
Patients with clinically evident and biochemically proven active acromegaly and
composition with increased android type of its distribution.
patients with hormonally inactive pituitary adenoma matched by age, sex and
DOI: 10.1530/endoabs.49.EP218
BMI were invited to participate. Bone samples were taken during transsphenoidal
adenomectomy from the base of the sella-turcica, immediately placed in lysis
buffer (QIAzol) and subjected to homogenization. Insulin-like growth factor 1
(IGF-1) was measured by an electrochemiluminescence assay on a Liaison. Total
RNA isolation from bone tissue with on-cjlumn digestion of the genomic DNA
was carried out with miRNeasy Mini Kit on the automatic station ‘QIAcube’.
Reverse transcription was carried out using a High-Capacity RNA-to-cDNA Kit.
Gene expression analysis was performed by Real-Time PCR on StepOnePlus
instrument with Custom TaqMan Array 48 Plus plates, TaqMan Advanced
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miRNA Assays.
Results
Bone densitometry of type 2 diabetics (about 290 patients)
We enrolled 21 subjects (12 patients with acromegaly and 9 with hormonally
Samir Ait Abderrahmane, Zahra Kemali, Sihem Hatri, Elmahdi Haffaf,
inactive pituitary adenomas); 13 females and 8 males, the mean age was 38 years
Nacer Sobhi, Lila Brakni & Brahim Oudjit
(confident interval (CI) 95% 33-43) mean BMI - 28 (CI95% 25-31) kg/m2. There
HCA, Kouba, Algeria.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
were no significant difference within the groups. Mean IGF-1 in subjects with
drug treatment for osteoporosis have raised the hypothesis that osteoporosis may
acromegaly - 785 (CI95% 527-1042) ng/ml. The expression of SOST 5,7 (CI95%
be not only a treatable but moreover a curable disease.
1,01-10,44, PZ0.022), DKK1 7,97 (CI95% 4,4-11,54, P!0.001), BGLAP 1,51
The aim was to describe the case of a patient with osteoporosis who after
(CI95% 0.82-2,19, P!0.001) was increased in subjects with acromegaly as
treatment with alendronate for 6 years had osteopenia and remains in the state of
compared to inactive pituitary adenoma. miRNA 199a-5p 0,37 (CI95% 0.06-
osteopenia for a long period after drug cessation.
0,68, PZ0.023) was suppressed.
A patient, female, aged 65 years, postmenopausal, presented with osteoporosis, T
Conclusion
score in the spine being K3.2. Alendronate 70 mg once weekly was administered
In spite of increased expression of Wnt signaling antagonist, bone formation is not
along with calcium and vitamin D. The patient also had hypothyroidism on
suppressed in subjects with acromegaly. The suppression of miRNA might
treatment with L-thyroxine, TSH levels being within the normal range.
explain the predominant differentiation to the cartilage tissue.
Bone mineral density measurement was performed yearly while the patient was
Disclosures
on treatment with alendronate, calcium and vitamin D. Six years later bone
This study was supported by the Russian Science Foundation (grant # 15-1530032).
mineral density measurement in both the spine and the hip revealed osteopenia, T
DOI: 10.1530/endoabs.49.EP220
score being K1.3 and K1.1 in the spine and the hip, respectively. Alendronate
was discontinued, while calcium and vitamin D were administered to the patient.
The patient is being followed for her osteopenia yearly, T score in the hip being
K1.1 five years after treatment cessation.
In the case presented alendronate appears to have had a long lasting beneficial
effect on the bone in a patient with osteoporosis. The state of osteopenia appears
to be stable in the presented patient. This case of persistent improvement of
osteoporosis after long lasting treatment with alendronate raises the question of
whether osteoporosis may be a curable disease, not being merely a manifestation
of aging. This case raises the hopeful hypothesis that osteoporosis with the
emergence of novel effective forms of therapy may be cured.
DOI: 10.1530/endoabs.49.EP222
EP221
Osteoporosis and fractures in the real world setting
Eleni Pantazi1, Alexios Travlos1, Evaggelia Vogiatzi1 &
Ifigenia Kostoglou-Athanassiou2
1Department of Endocrinology, Alexandra Hospital, Athens, Greece;
2Department of Endocrinology, Red Cross Hospital, Athens, Greece.
Osteoporosis is a bone disease predisposing to bone fragility. Nowadays, the
population is screened for osteoporosis and measures are taken for fracture
prevention. Additionally, people are urged to have a diet rich in calcium, are
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given calcium supplements and are being treated for vitamin D deficiency.
Fractures at post-partum and lactation: common presentation of
Moreover, osteoporosis treatment is administered. Therefore, the relationship
different clinical entities
between osteoporosis and fractures in the real world setting is very interesting.
Zoe Efstathiadou, Albana Sykja, Athanasios Panagiotou & Marina Kita
The aim was to study the prevalence of fragility fractures in a cohort of patients
“Hippokration” General Hospital of Thessaloniki, Thessaloniki, Greece.
being followed up and treated for osteoporosis in a center of excellence for the
management of osteoporosis in Athens.
A cohort of 91 patients, 82 female and 9 male, aged 69.71G1.09 years, who were
Introduction
followed up and treated as needed for osteoporosis in a center of excellence was
Osteoporosis of pregnancy and postpartum is a rare clinical entity, which usually
studied. Bone mineral density was measured in the spine and the hip. The number
presents with back pain, due to spine fractures. We aimed to describe four
of fractures having occurred in the cohort studied was recorded.
different cases presenting with back pain and fractures post-partum, in who, with
Bone mineral density in the spine as assessed by T score was K1.9G0.11 (meanG
diverse underlying pathophysiology, recovery time and treatments used.
SEM) and in the left hip K2.6G0.11. In the cohort of patients studied 19 patients
Case 1
(20.88%), 15 female and 4 male, suffered a fracture. The fractures recorded were 8
A 32-year-old patient presented with intense back pain and difficulty in standing
vertebral, 7 distal radius, 2 tarsal joint, 2 rib fractures and 1 fracture of the calcaneus.
and walking, 2 weeks after delivery. She had hypercalcaemia, hyperphosphatemia
Within the cohort studied 2 patients had suffered two fractures, a distal radius and a
and multiple vertebral fractures. Breast examination and mammography were
vertebral and a rib and a vertebral fracture, respectively.
inconclusive due to lactation. The diagnosis of metastatic breast cancer was made
It appears that in the modern real world setting despite the measures taken for
after a bone lesion biopsy. The patient received zolendronic acid and was referred
osteoporosis prevention and management in a cohort of patients being followed up
to an oncologist.
within a center of excellence in Athens, fractures tend to occur especially in the
Case 2
female population. However, interestingly, within the cohort studied many patients
A 35 year-old patient, several weeks after a singleton pregnancy, presented with
with osteoporosis remained free of fracture at the point of time of the study.
acute back pain. Imaging studies revealed an L2
fracture and laboratory
assessment showed increased bone turnover markers and vitamin D deficiency.
DOI: 10.1530/endoabs.49.EP221
She received zolendronic acid and was started on vitamin D3 substitution. Her
clinical course was uneventful.
Case 3
A 41 year-old lady was diagnosed with T12 and L3 vertebral fractures, while still
breast-feeding. No secondary causes of osteoporosis were found. She received an
18-month course of teriparatide and Vitamin D3 supplementation. Six months
after teriparatide discontinuation she presented with urinary tract lithiasis
complicated by upper urinary tract infection.
Case 4
A 32-year-old patient presented with lumbar spine bone mineral density Z-score
of K2.8, but no fractures, after her first pregnancy. She was treated with
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intranasal calcitonin and VitD3
supplementation. An improved BMD
(Z-
Is osteoporosis a curable disease?
scoreZK2.1) was measured after 2 years. Her second pregnancy was uneventful.
Ifigenia Kostoglou-Athanassiou1, Eleni Pantazi2 & Panagiotis Athanassiou3
Conclusions
1Department of Endocrinology, Red Cross Hospital, Athens, Greece;
Post-partum osteoporosis is a rare cause of bone pain during the puerperium.
2Department of Endocrinology, Alexandra Hospital, Athens, Greece;
Fractures should be diagnosed early in order to avoid permanent incapacity. It is
3Department of Rheumatology, St. Paul’s Hospital, Thessaloniki, Greece.
mandatory to look for and exclude secondary causes of osteoporosis including
breast cancer and vitamin D deficiency.
DOI: 10.1530/endoabs.49.EP223
Osteoporosis may be a disease of unknown etiology, or a degenerative disorder in
the context of aging. Nowadays, the availability of multiple forms of effective
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP224
Spontaneous BMD increase (LS Z-score K2.4) was observed already 2 months
after surgery. Except for calcium and vitamin D supplementation, no bispho-
A multidisciplinary clinic for bone metabolism diseases; descriptive
sphonate therapy was prescribed, given this impressive increase of BMD and
analysis of our experience in quiron salud malaga hospital
because she was still premenopausal. X-Rays did not show any new vertebral
Araceli Mu
˜ oz-Garach1, Maria Carmen Ordo
˜ ez-Can˜ izares2,
fracture. BMD continued to increase. 24 months after surgery, densitometry
Ana Nieto-Gonzalez2, Pablo Manzano Fernández-Amigo2 &
showed 40% absolute increase in LS BMD and 16% in FN BMD, vs baseline. She
Jose Manuel García-Almeida1
reached normal BMD values at all sites 3 years following surgery.
1Endocrinology and Nutrition Department. Quiron Salud Hospital, Málaga,
After a 9-years follow-up (DXA and BTMs, yearly), complete spontaneous BMD
Spain;2Rheumatology Department. Quiron Salud Hospital, Málaga, Spain.
recovery was confirmed (LS T-score C1.2 and FN T-score K0.3) with normal
and stable BTMs.
Introduction
Our case suggests no need for any antiresorptive therapy in severe osteoporosis
A multidisciplinary clinic has been developed to optimize the diagnosis and
due to cortisol-secreting adrenal adenoma after successful surgery, at least in
treatment of bone metabolism diseases. Initiated in March 2013, it is carried out
premenopausal women.
simultaneously, once a week by an Endocrinologist and a Rheumatologist.
DOI: 10.1530/endoabs.49.EP225
Objective
To describe the experience of this unit in the last 12 months.
Material and methods
Cross-sectional observational study. 235 patients were attended from December
2015 to December 2016. In the first visit, we carried out a medical record using a
checklist form and impedancemetry. We requested a blood test with bone
remodeling markers (CTX-I and P1NP), vitamin D, PTH, sex hormones and
24-hour urine with calciuria and phosphaturia, densitometry and dorsum-lumbar
spine x-rays. In the following visit the results were evaluated and the team formed
by both specialists agreed the protocol of action. Subsequently we studied
treatment tolerance and analytical, radiographic and densitometric changes.
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Results
Cinacalcet for control of primary hyperparathyroidism: a single centre
97% were women with a mean age of 60G9.7 years. Weight 66.3G12.7 kg,
experience
height 158.2G5.8 cm, BMI 26.6G4.9 kg/m2. Impedancemetry showed mean
Tiago Nunes da Silva, Ana Gonc¸alves Ferreira, Maria Carlos Cordeiro,
lean mass was 43.0G5.9 kg and mean fat mass 23.3G10.1 kg. 36.2% and 20% of
Ana Catarina Matos & Jorge Portugal
the patients had a personal and family history of fracture, respectively. 15.2%
Endocrinology Department Hospital Garcia de Orta, Almada, Portugal.
patients had taken previous corticoid treatment; 9.5% had more than 2 falls in the
Although primary hyperparathyroidism (PHPT) is usually cured by surgery, some
last year. 5.7% were active smokers. 87.4% had menopause; early menopause in
individuals are unable to undergo parathyroidectomy and are refractory to
13.4% and surgical menopause in 10.7%. 60% practiced more than 3 days of
standard calcium lowering medical therapy. In such cases, targeted therapy with
physical activity per week, 78.8% sunbathed more than 10 minutes a day and
cinacalcet may be useful.
36.2% took adequate dairy milk consumption. Among the digestive antecedents,
The aim of this study was to access the short-term efficacy of cinacalcet in
39% had gastroesophageal reflux and 16.2% hiatus hernia. 17.5% have had a
lowering calcium
(Ca2C) levels in patients with PHPT unable to undergo
vertebral fracture. In the densitometric data according to T-score they had
parathyroidectomy and refractory to standard medical therapy.
osteoporosis 55.06%; Osteopenia 42.76% and normal 2.24%. The FRAX index
Methods
was 4.3% for major fracture and 0.9% for hip fracture. Among the treatments
Patients with PHPT refractory to standard medical treatment were treated with
received prior to the first consultation,
29.5% took bisphosphonates,
9.5%
cinacalcet. Statistical analysis was carried out using the Wilcoxon test.
denosumab, 2.9% PTH. 37.5% calcium plus vitamin D.
Results
Conclusions
Five patients (all female) with a median age of 76 years were included. The
A high percentage of patients received treatment before coming to the clinic. The
known duration of the PHPT was 60 months. The median follow-up of cinacalcet
most used was bisphosphonates. The aggregate management by two specialists in
treatment was 12 months. Hypercalcemia related comorbidities were mental
the multidisciplinary clinic is beneficial and improves the quality of care in our
changes in 4, osteoporosis in 3 and kidney stones in 2 patients. Before medical
patients.
treatment, baseline median (quartile 1 (Q1), Q3) serum PTH was 252 (159, 614)
DOI: 10.1530/endoabs.49.EP224
pg/ml (reference range 15-65) and serum Ca2C was 11.7 (11.6, 12.65) mg/dl
(reference range 8.1-10.2). After standard medical treatment, baseline median
(quartile 1 (Q1), Q3) serum PTH was 222 (149, 304) pg/ml and serum Ca2C was
11.9
(11.2, 12.6) mg/dl (PO0.05). After the last stable dose of cinacalcet, median
(quartile 1 (Q1), Q3) serum PTH was 190 (139, 361) pg/ml and serum Ca2C was
10.1
(9.7, 12) mg/dl (PZ0,005). Serum Ca2C normalized in 60% of patients. The
median decrease of Ca2C was 15.1% (PZ0,005) and of PTH was 14.4%
(PZ0,174). Only one patient developed side effects (muscle spasms) without the
need to stop cinacalcet.
Conclusions
EP225
These results demonstrate the efficacy and safety of cinacalcet in controlling
Spontaneous recovery of BMD after surgical cure of Cushing’s
hypercalcemia refractory to standard medical therapy.
syndrome due to an adrenocortical adenoma: a 9-years follow-up
DOI: 10.1530/endoabs.49.EP226
F. Baleanu, L. Iconaru, R. Karmali & J.J. Body
Centre Hospitalier Universitaire Brugmann, Université Libre de Bruxelles,
Brussels, Belgium.
A 33-year-old Belgian woman was referred in June 2006 to our Metabolic Bone
Diseases Clinic for recent vertebral fractures. X-Rays showed a 3-level severe
compression fractures with collapse of the superior endplates of D11, D12 and L1.
DXA showed significantly decreased lumbar spine (LS) and femoral neck (FN)
Z-scores, at K3.1 and K2.5, respectively.
She was complaining of severe back pain, muscle weakness, cognitive
dysfunction, anxiety and irritability. Physical examination revealed moon-shaped
face, ecchymosis, purple stretch marks on the breasts, arms, abdomen and thighs.
EP227
Morning cortisol was normal but ACTH level was suppressed. Urinary free
Bone remodeling markers predict bone loss in premenopausal women
cortisol was elevated. A late-night salivary cortisol also elevated. Standard 2-day
Gala Gutierrez Buey1, Sonsoles Botella1, Patricia Restituto2, Macarena
2-mg dexamethasone suppression test showed no cortisol suppression. A loss of
Rodriguez Fraile3, Amparo Calleja1, María Llavero1, Javier Gargallo1,
diurnal variation in ACTH and cortisol levels was also demonstrated. Cushing’s
Carolina Perdomo1, Patricia Andrada1, Nerea Varo2 & Juan C Galofré1
syndrome was confirmed. Abdominal MRI showed a 3 cm left adrenal mass.
1Department of Endocrinology, University of Navarra, Pamplona, Spain;
Osteoporosis was considered secondary to this endogenous hypercortisolism.
2Department of Clinical Chemistry, University of Navarra, Pamplona,
Bone turnover markers (BTMs) and 24h urinary calcium excretion were elevated.
Spain;3Department of Nuclear Medicine. University of Navarra, Pamplona,
Successful laparoscopic left adrenalectomy was performed in October 2006.
Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Aim
EP229
Bone turnover markers (BTMs) predict more rapid rates of bone loss. However,
Association between bone mineral density and muscle strength in
most of these studies have been carried out in postmenopausal women. Few
patients with Turner syndrome, after consideration of selected
prospective studies have examined the degradation marker C-terminal telopeptide
hormonal and metabolic parameters
of type I collagen
(CTX) and the bone formation marker N-aminoterminal
Elzbieta Sowinska-Przepiera, Monika Koziolek, Lilianna Osowicz-
propeptide of type I collagen (P1NP) measured during the menopausal transition
Korolonek, Jakub Poblocki, Martyna Patalong-Nowak & Anhelli Syrenicz
to predict the subsequent bone loss.
Pomeranian Medical University, Szczecin, Poland.
Methods
We performed a prospective cohort study including 72 healthy premenopausal
women from de Endocrinology service at the Clinica Universidad de Navarra. Six
Turner syndrome (TS), resulting from complete or partial loss of X chromosome,
women were lost in the follow-up and two were excluded because of treatment
occurs in 1 per 2000-2500 liveborn female neonates. Most patients with TS,
that affects bone. We measure demographic variables, CTX, P1NP and bone
especially those untreated with growth hormone, present with osteoporosis or
mineral density at baseline and five years later. SPSS 20.0 was used for statistical
osteopenia, and are at increased risk of bone fractures. Available evidence suggests
analysis. Differences between study groups were evaluated by Student’s t test for
that depletion of bone mass may be associated with inadequate level of physical
normally and Mann-Whitney-U test for non-normally distributed variables.
activity, and consequently, with too low muscle mass and strength. The aim of the
Results
study was to analyse an association between muscle strength and bone mineral
Mean age at baseline was 49.2G0.3. After 5 years, there were no significant
density in patients with TS, after consideration of selected hormonal and metabolic
changes in baseline demographic characteristics (percentage of smokers, coffee
factors. The study included 52 subjects (age 28-45 years), among them 32 women
intake, sun exposure and physical activity) although there was a significant
with TS (45,X karyotype; Group A) and 20 controls (Group K). The list of analysed
increase in BMI (PZ0.027).
variables included body height, body weight, BMI, bone mineral density (BMD
Five years later, 69% became menopausal, 48.4% (31) had normal bone, and
L1-4 and BMD Total), total body fat (BF) and visceral adipose tissue (VAT)
51.6% (33) had pathological bone (below the expected range for age and/or
volumes determined by means of DXA, hand grip strength measured with a manual
osteoporosis). There was a significant decrease in BMD at 5 years of follow-up
dynamometer, and laboratory parameters: TSH, FT4, FSH, oestradiol, testoster-
compared to baseline (femoral neck 0.92G0.1vs 0.87G0.1 (PZ0.000), lumbar
one, DHEA-SO4, ACTH, cortisol, PTH, vitamin D3 concentrations, lipidogram,
spine 1.17G0.19 vs 1.08G0.1 (PZ0.000) and a significant increase in BTMs
levels of glucose and insulin during OGTT. Patients from Group A presented with
P1NP (ng/ml) 37.22G10 vs 52.23G21 (PZ0.000) and CTX (ng/ml) 0.245G
significantly lower left (PZ0.001) and right handgrip strength (P!0.000), lower
0.125 vs 0.441G0.233 (PZ0.000). Increased levels of P1NP and s-CTX in the
BMD (P!0.000), lower concentrations of testosterone (P!0.000) and DHEA-
premenopausal group at baseline associated with pathological bone five years
SO4 (PZ0.006), larger VAT volumes (PZ0.005), higher BMI (PZ0.05), higher
later (P!0.001 and P!0.001, respectively).
levels of insulin (PZ0.026) and FSH (PZ0.000). The study groups did not differ in
Conclusion
terms of their TSH, fT4, ACTH and cortisol concentrations, and the only significant
Our data suggest that measurement of CTX and P1NP in premenopausal women
difference in lipidogram pertained to triglyceride level, higher in Group A
detects those patients who will suffer bone loss five years later.
(PZ0.032). Right handgrip strength in Group A correlated significantly with BMD
L1-4 (rZ0.1318, PZ0.0486), VAT volume (rZ0.1478, PZ0.0360) and BMD
DOI: 10.1530/endoabs.49.EP227
Total (rZ0.1921, PZ0.0154). These findings suggest that handgrip strength may
constitute a predictor of osteoporosis in patients with TS.
DOI: 10.1530/endoabs.49.EP229
EP228
Bone mineral density in hospital male physicians over the age of 65
Noa Sylvetsky, Chen Futeran, Meir Frankel & Gabriel Munter
Endocrine Unit-Shaare Zedek Medical Center affiliated with Faculty nof
Medicine-Hebrew University, Jerusalem, Israel.
EP230
Volumes of visceral adipose tissue, gynoid and android fat as predictors
Background
of reduced bone mineral density in women with menstrual disorders
Hospital physicians are indoor workers, with higher prevalence of vitamin D
Malgorzata Syrenicz, Elzbieta Sowinska-Przepiera, Elzbieta Andrysiak-
deficiency as compared to community-based physicians. The correlation between
Mamos & Anhelli Syrenicz
vitamin D deficiency and osteoporosis later in life has not been fully studied, and
Pomeranian Medical University, Szczecin, Poland.
bone mineral density
(BMD) in elderly hospital physicians has not been
systematically examined.
Disorders of bone mineralization observed in women with ovarian insufficiency
Methods
are unlikely a simple function of decreased concentration of oestrogens.
A cross-sectional study measuring BMD in hospital male physicians aged 65 and
Published evidence suggests that adipose tissue is a central component within
older was carried out. BMD was measured at the hip, spine and distal forearm.
the complex system of metabolic and hormonal interactions responsible for
FRAX analysis with BMD was performed, using the IOF recommended FRAX
adequate mineralization of the bone. However, to the best of our knowledge, the
cut-offs for treatment (10-year probability of hip fracture R3% and 10-year
composite effects of specific substances synthesized within adipose tissue from
probability of major osteoporotic fracture R20%).
various anatomical compartments, ovarian hormones and insulin on bone
Results
turnover, have not been a subject of a complex analysis in women with menstrual
51 male physicians, employees and pensioners, participated in our study. The
disorders. Therefore, the aim of this retrospective study was to verify if volume
mean age was 71 years (median 69 years; range 65-86), all of them naive to
and distribution of adipose tissue may predict bone loss in this group. The study
specific treatment for osteoporosis. 14/51(27%) had osteoporosis, 7 of them
included 293 Caucasian women (mean age 26.7G4.4 years) with at least 6-month
defined only by distal forearm examination. 29 (56%) had osteopenia, 4 of them
history of secondary amenorrhea. Based on T-score values for bone mineral
defined only by distal forearm examination. According to their FRAX score, 9 of
density (BMD) in lumbar spine, the study subjects were divided into two groups,
the osteopenic examinees had high risk of major osteoporotic fracture and/or hip
with T-scores below K0.5 and at least 0.5. Univariate logistic regression analysis
fracture.
showed that lower bone mineral density (as shown by T-score below K0.5) was
Conclusion
associated with larger volumes of gynoid (odds ratio, ORZ7.45), android (ORZ
In elderly hospital-based male physicians, the prevalence of osteoporosis is higher
3.03) and visceral adipose tissue (ORZ1.55), as well as with higher values of
than expected. After adding the FRAX score results, 45% of the physicians would
body mass index (BMI, ORZ1.17), fasting concentration of insulin (ORZ1.08)
require specific treatment for fracture prevention, according to customary
and body weight (ORZ1.06). However, none of these variables turned out to be
international clinical guidelines. Using only hip and spine BMD, 31% would
an independent predictor of BMD deficiency on multivariate analysis. These
require treatment. Based on our data we suggest screening elderly physicians for
findings imply that excessive volume of adipose tissue, irrespective of distribution
osteoporosis.
thereof, is a strong determinant of reduced BMD in women with ovarian
DOI: 10.1530/endoabs.49.EP228
insufficiency. The lack of region-specific effects of adipose tissue volume on
BMD is probably associated with the influence of ovarian insufficiency on
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
systemic metabolism and endocrine processes, in particular with the development
kg/m2). Metabolic bone remodelling parameters were analysed: LDL, HDL,
of insulin resistance.
total cholesterol, HOMAIR, insulin, glycaemia, alkaline phosphatase, osteocalcin
DOI: 10.1530/endoabs.49.EP230
and parathormone. It was determined the platelet and plasma serotonin
concentrations by ELISA.
5HTTVNTR was evaluated by PCR and the
5HT2A_T102C by PCR-RFLP. Statistical analysis by SPSS 21.0.
Results
In osteoporosis, we found increased osteocalcin (PZ0.030) and plasma 5HT
concentration (PZ0.012) and decreased insulin (PZ0.023) and total cholesterol
(PZ0.027). In women with normal BMD, we found an association between
genotype 10/10 of 5HTTVNTR and decreased osteocalcin (PZ0.035). and
between genotype CC of 5HT2A and decreased HDL (PZ0.029). Within this
group, we also found inverse correlations between HDL and alkaline phosphatase
(PZ0.030) and HOMAIR (PZ0.018). In women with osteoporosis, we found
direct correlations between glycaemia and osteocalcin (PZ0.017) and HDL
EP231
(PZ0.049).
Effect of chronic atrophic gastritis on bone mineral density of Korean
Conclusion
women
In normal BMD, 5HTTVNTR and 5HT2A_T102C polymorphisms appear to
CB Lee1, YC Jeon1 & KY Lee2
modulate directly or indirectly some metabolic parameters associated with bone
1Hanyang University Guri Hospital, Guri, Republic of Korea;2Incheon Gil
remodelling. These polymorphisms seem to have no effect in women with
Hospital, Incheon, Republic of Korea.
osteoporosis suggesting that they may play a relevant role in the susceptibility to
osteoporosis development by modulating metabolic bone remodelling
Hydrochloric acid has been demonstrated to be important for the absorption of
parameters.
calcium and the bone loss is often seen in human after total gastrectomy. The aim
DOI: 10.1530/endoabs.49.EP232
of our study was to document the change of calcium and bone metabolism in the
patients with decreased capacity of gastric acid secretion like chronic atrophic
gastritis.
The study sample consisted of chronic atrophic gastritis group and control group.
Chronic atrophic gastritis group was 20 post-menopausal females (age: 60.3G5.1
yr) who was confirmed by gastroscopic biopsy, demonstrating atrophic change of
gastric mucosal secretory tissue. Control group had 21 healthy females (age:
58.7G6.5 yr) with normal gastroscopic biopsy results. Gastric pH, serum levels
of calcium, phosphorus, total alkaline phosphatase, intact PTH, and bone mineral
density (Delphi, Hologic, USA) were monitored in all the patients in both group
before medication. There were no significant differences of gastric pH (3.9G0.6
EP233
vs
3.3G1.0, PO0.05), calcium
(8.9G0.9
vs
8.8G1.4 mg/dl, PO0.05),
phosphorus (3.2G1.5 vs 3.5G0.9 mg/dl, PO0.05), total alkaline phosphatase
The effect of mechanical assisted squat exercise on pulmonary function,
(72.5G24.5 vs 60.3G22.4 U/l, PO0.05) and intact PTH (29.3G5.1 vs 27.2G
muscle mass and function with or without sarcopenia
3.8 pg/ml, PO0.05) between chronic atrophic gastritis group and control group.
YunKyung Jeon, MyungJun Shin, InJoo Kim, BoHyun Kim &
Bone mineral density showed decreased average value in atrophic gastritis group
YongBeom Shin
comparing control group (0.78G0.27 vs 0.85G0.31 g/cm2, PZ0.09).
Pusan National University Hospital, Busan, Republic of Korea.
In conclusion, chronic atrophic gastritis which have lower capacity of gastric acid
secretion may cause decrease of bone mineral density. And this mechanism may
Introduction
be one of the pathogenesis of senile osteoporosis.
Sarcopenia is a geriatric syndrome that causes age-related changes to muscle mass
DOI: 10.1530/endoabs.49.EP231
and function. Lung function is reduced in elderly patients with sarcopenia. We
explored whether a mechanically assisted squat exercise improved muscle
function and mass and pulmonary function in community-dwelling elderly
women with or without sarcopenia.
Methods
Participants were recruited via posters or the websites of regional health centers.
In total,
76 community-dwelling elderly subjects
(aged O60 years) were
screened. We finally included 47 subjects in this prospective study. They were
randomly assigned to exercise or non-exercise group as a ratio of 2:1. We
measured lung function, knee extensor strength, hand grip strength, and the body
composition before and after 6 weeks of mechanically assisted squat exercises
(3 days a week, 30 min per day).
Results
EP232
Subjects with sarcopenia had poor hand grip strength and knee extensor strength.
May serotonin metabolism polymorphisms 5HTTVNTR and 5HT2A
Their lung function parameters
[including vital capacity, forced expiratory
have a clinical impact in osteoporosis development?
volume in 1 s (FEV1), and forced vital capacity (FVC)] were lower than those of
Raquel Simo˜ es1,2, Joana Freitas1,2, Ana Paula Barbosa3,4,
controls. After 6 weeks of squat exercises, the hand grip strength and knee
Rui Mascarenhas3,4 & Manuel Bicho1,2
extensor strength increased significantly in both the sarcopenia and control
1Institute for Scientific Research Bento Rocha Cabral, Lisbon, Portugal;
groups. Appendicular skeletal muscle mass was increased in exercise group only
2ISAMB, Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal;
in without sarcopenia group (PZ0.013). Leg fat mass was significantly decreased
3Clinic of Endocrinology, Diabetes and Metabolism, Lda., Lisbon, Portugal;
in both sarcopenia and non-sarcopenic group. However, leg lean mass was
4Department of Endocrinology, Diabetes and Metabolism, Santa Maria
significantly increased only in non-sarcopenic group after exercise. The FVC (L)
Hospital, Lisbon, Portugal.
and FVC (%) increased significantly only in the sarcopenia group (PZ0.019 and
PZ0.041, respectively), but not in the control group.
Objectives
Conclusion
To study the association of serotonin transporter gene (SLC6A4) polymorphism
Squat exercises improved not only lower extremity functionality, but also upper
5HTTVNTR and serotonin receptor 2A polymorphism 5HT2A_T102C with bone
extremity functionality, including hand grip strength. Muscle mass was
mineral density and metabolic parameters of bone remodelling.
significantly increased in without sarcopenia after exercise. The FVC increased
Materials and methods
in the sarcopenia group. Thus, squat exercises may improve lung function in
BMD (g/cm2) was measured by DEXA in 105 post-menopausal women: 35 with
patients with sarcopenia.
normal BMD (ageZ58.30G1.33 years; BMIZ28.18 [19.13-39.87] kg/m2) and
DOI: 10.1530/endoabs.49.EP233
70
with osteoporosis
(ageZ68.30G1.09 years; BMIZ28.90
[20.78-43.86]
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP234
EP236
Beta-2 adrenergic receptor (ADRB2) gene polymorphism Arg16Gly as
Differences in bone strength and metabolic parameters according to the
risk factor for osteoporosis
presence of hyperadiponectinemia and obesity in Korean adults: The
Raquel Simo˜ es1,2, Joana Freitas1,2, Ana Paula Barbosa3,4,
KoGES- ARIRANG study
Mário Mascarenhas3,4 & Manuel Bicho3,4
Jung Soo Lim1, Eunhee Choi2, Ji Hye Huh1, Mi Young Lee1, Jang Yel Shin1,
1Institute for Scientific Research Bento Rocha Cabral, Lisbon, Portugal;
Choon Hee Chung1, Sang Baek Koh3 & Song Vogue Ahn3
2ISAMB, Genetics Laboratory, Lisbon Medical School, Lisbon, Portugal;
1Department of Internal Medicine, Yonsei University Wonju College of
3Clinic of Endocrinology, Diabetes and Metabolism, Lda., Lisbon, Portugal;
Medicine, Wonju, Gangwon, Republic of Korea;2Smith Center for
4Department of Endocrinology, Diabetes and Metabolism, Santa Maria
Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center,
Hospital, Lisbon, Portugal.
Boston, MA, USA;3Department of Preventive Medicine, Yonsei University
Wonju College of Medicine, Wonju, Gangwon, Republic of Korea.
Objectives
To study the association of Beta-2
adrenergic receptor
(ADRB2) gene
Adiponectin has been thought to exert important influences in energy homeostasis
polymorphism Arg16Gly with bone mineral density and metabolic parameters
and insulin signalling pathway. Some obese individuals showed paradoxical
of bone remodelling.
hyperadiponectine-mia (HA), however, the effect of HA on bone metabolism has
Materials and methods
not been fully clarified.
BMD (g/cm2) was measured by DEXA in 105 post-menopausal women: 35 with
This study aimed to evaluate bone strength and metabolic parameters according to
normal BMD (ageZ58.30G1.33 years; BMIZ28.18 [19.13-39.87] kg/m2) and
the presence of HA and obesity in Korean adults. A total of 9,172 adults (59.4%
70
with osteoporosis
(ageZ68.30G1.09 years; BMIZ28.90
[20.78-43.86]
women) aged 40-70 years assessed in the Korean Genomic Rural Cohort Study
kg/m2). Metabolic bone remodelling parameters were analysed: LDL, HDL,
from 2005 to 2008 were examined. HA was defined as the levels of higher than or
total cholesterol, HOMAIR, insulin, glycaemia, alkaline phosphatase, osteocalcin
equal to the upper tertile among metabolically healthy subjects with a bone mass
and parathormone. Arg16Gly polymorphism was evaluated by PCR-RFLP.
index (BMI) less than 23 kg/m2.
Statistical analysis by SPSS 21.0. Statistical significance for P!0.05.
Moreover, obesity was defined as a BMI of more than or equal to 25 kg/m2. The
Results
serum con-centrations of adiponecti-n were measured by radioimmunoassay. In
We found association between Arg16Gly polymorphism and osteoporosis with an
addition, bone status was assessed using the calcaneal quantitative ultrasound
increase of homozygous Gly/Gly in women with osteoporosis (PZ0.009). They
method. Obese subjects and those who have HA accounted for 40.3% and 15.7%,
showed a higher risk for the development of osteoporosis (ORZ6.517; CI95%
respectively; about twenty percent of the non-obese and 9.5% of the obese had
[1.663-25.539]). In osteoporosis, we found increased osteocalcin (PZ0.030) and
HA. Although most of metabolic parameters such as fasting glucose and lipid
decreased insulin (PZ0.023) and total cholesterol (PZ0.027). In women with
profiles were significantly better in the HA group compared with the non-HA
normal BMD, we found an association between genotype carriers of allele Arg
group, bone stiffness index (BSI) in the former was lower in the latter. In both the
(Arg/ArgCArg/Gly) and decreased total cholesterol (PZ0.018). We also found
non-obese and obese groups, individuals with HA had lower waist circumference
an association between carriers of allele Gly (Arg/GlyCGly/Gly) and decreased
and BSI. Moreover, obese subjects without HA showed the highest BSI levels
of glycaemia (PZ0.010). Within women with normal BMD, we also found
among the group-s, which was especially prominent in women. Our results
inverse correlations between HDL and alkaline phosphatase (PZ0.030) and
suggest that bone strength in obese individuals may be more negatively affected
HOMAIR (PZ0.018). In women with osteoporosis, we found direct correlations
by high adiponectin levels. Further studies are necessary to confirm the effects of
between glycaemia and osteocalcin (PZ0.017) and HDL (PZ0.049).
adiponectin on bone health in subjects with obesity.
Conclusion
DOI: 10.1530/endoabs.49.EP236
Arg6Gly polymorphism of ADRB2 gene is associated with a higher risk for the
development of osteoporosis. This polymorphism also appears to modulate
directly or indirectly some metabolic parameters associated with bone
remodelling.
DOI: 10.1530/endoabs.49.EP234
EP237
Do the surgical outcomes change if the surgeon accompanies the
endocrinologist during the preoperative ultrasonography examination?
Ibrahim Kilic1, Sefika Burcak Polat2, Sevgul Faki2, Mehmet Tokac1,
Reyhan Ersoy2, Mehmet Kilic3 & Bekir Cakir2
1
Department of Surgery, Ataturk Education and Research Hospital
Education and Research Hospital, School of Medicine, Ankara, Turkey;
EP235
2Department of Endocrinology and Metabolism, Yildirim Beyazit
Bone histomorphometry and bone marrow adipocytes in premeno-
University, School of Medicine, Ankara, Turkey;3Department of Surgery,
pausal women with type 2 diabetes
Yildirim Beyazit University, School of Medicine, Ankara, Turkey.
Vicente Andrade1, Victoria Borba1, Domingos Chula1, Fellype Barreto2,
Cesar Boguszewski1 & Carolina Moreira1,2
1Endocrine Division of Feral/University of Parana - SEMPR, Curitiba,
Introduction
Brazil;2LABORATORY PRO, Histomorphometry sivision, Pro Renal
Parathyroid surgical therapy differs because the glands are small and of variable
Foundation, Curitiba, Brazil.
number and location. Although localization studies have improved greatly, we may
not reliably determine the number and location of all diseased glands preoperatively.
Ultrasonography (US) is the most widely used imaging method. In this study, we
Few studies have evaluated bone histomorphometry in type 2 diabetic patients
aimed to demonstrate how the surgical outcomes change when the surgeon
(DM2) and none has established if the disease control plays a role on bone
accompanies the endocrinologist during preoperative ultrasonography examination.
morphology and bone marrow adipocytes. The aim of this study is to present
Methods
preliminary data on bone microstructure, bone formation rate and bone marrow
This prospective study included 50 patients with primary hyperparathyroidism
adipocytes in premenopausal women with DM2 with different levels of glucose
(PHPT) who underwent a minimally invasive parathyroid adenomectomy under
control. Bone biopsy, followed by tetracycline labelling, was obtained for
local anaesthesia at our institution from January 2014 to December 2015. The
analysis of static and dynamic parameters of bone histomorphometry and volume
patients were divided in two groups. In group A, all patients underwent neck US
of bone marrow adipocytes. To date, 12 bone biopsies and 6 histomorphometry
performed by an experienced endocrinologist and the surgeon on the day of
analysis were performed in a group of women with mean age of 40.9G6.0 yrs,
operation and the location of the lesion was specified by the surgeon. Group B
mean duration of DM2 of 6.8G2.6 years and median glycosylated haemoglobin
patients were operated according to the previous US performed by the
of 8,1% (range 6.5-12.3). Initial results have shown a normal bone volume,
endocrinologist only.
reduced bone formation and an increase in adipocytes content in comparison to
Results
normal premenopausal women values at the literature. Our preliminary results
There were 25 patients in Group A and 25 patients in Group B. The two groups
suggest that bone morphology and bone marrow adipocytes content is altered in
were similar in regard to demographical features, biochemical and hormonal
premenopausal women with DM2.
parameters. Postoperative parathyroid hormone (PTH), calcium and phosphorus
DOI: 10.1530/endoabs.49.EP235
levels didn’t differ between the groups. In group A operation duration was
significantly shorter compared to Group B (25.7 min vs 45 min, PZ0.00).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
adipose tissue percentage (FMR) was measured with DEXA. SPSS 16.0 was used
Preoperative detection of hyperactive parathyroid glands is useful for minimizing
for statistical data processing.
the extent of surgical intervention, reducing operation time and decreasing the
Results
risk of perioperative complication.
Patients were 33.7G8.9 years old (meanGS.D.), BMI was 24.6G5.2 kg/m2,
DOI: 10.1530/endoabs.49.EP237
CD4C were 475 c/ml (24-1,476) and viral load was 38 600 cp/ml (927-422 000).
Four patients (6%) presented with low testosterone levels (hypogonadotropic
hypogonadism) and one with newly diagnosed subclinical hypothyroidism
requiring therapy. Significant reduction of BMD was observed in 26 patients
(37%) from which 22 had osteopenia (Z score K1 to K2.5) and four had
osteoporosis (Z score !K2.5). Reduced BMD correlated positively with low
BMI (P!0.01), while no correlation was found with viral load, CD4C, smoking,
25OHD3 and gonadal hormones’ concentrations (PO0.05).
EP238
Conclusion
Teriparatide discontinuation in a patient with post surgical
In treatment - naïve HIV-infected male patients, the most frequently observed
hypoparathyroidism: a clinical challenge
endocrine disorder is reduced BMD, which does not seem to correlate with HIV
Alessandro Brancatella, Matteo Apicella, Emilio Fiore, Giovanni Ceccarini,
infection markers. In patients with low BMI, measurement of BMD would be
Edda Vignali, Claudio Marcocci, Paolo Vitti & Eleonora Molinaro
helpful for early diagnosis of reduced bone mass and the prevention of further loss
Department of Endocrinology and Metabolism, Univesity of Pisa, Pisa,
by using the most suitable antiretroviral therapy.
Italy.
DOI: 10.1530/endoabs.49.EP239
Context
Teriparatide may represent a possible treatment for hypoparathyroidism when
oral supplementation with calcium and calcitriol fail to maintain adequate serum
calcium level (SCL). The switch from teriparitide to oral calcium and calcitriol
could be challenging and there is no consensus for clinical management.
Case presentation
EP240
A 50-year-old man was admitted at our Department for teriparatide discontinuation.
Three years before admission, the patient underwent total thyroidectomy for a
Trabecular bone score is negatively associated with bone resorbtion
multinodular goiter. Three months after thyroidectomy, the patient was admitted to
markers in patients with primary hyperparathyroidism
the intensive care unit for the onset of symptomatic hypocalcemia. Laboratory exams
Daniel Grigorie1,2, Mirela Ivan2, Andra Caragheorgheopol2, Diana Paun2 &
were consistent with hypocalcemia related to post-surgical hypoparathyroidism. The
Alina Sucaliuc1,2
patient was discharged with calcium carbonate and calcitriol therapy but in the
1Carol Davila University of Medicine, Bucharest, Romania;
following months the patient was re-admitted several times to the E.R. for the
2National Institute of Endocrinology, Bucharest, Romania.
recurrence of symptomatic hypocalcemia. Therefore in addition to the oral therapy,
teriparatide was introduced. After two years of treatment, teriparatide has been
Objectives
discontinued in accordance to the national drug administration (AIFA) authorizing
Mean TBS (Trabecular Bone Score) values are generally lower in PHPT (primary
regulations. At the admission, the physical examination was normal. Laboratory
hyperparathyroidism) patients than controls. The aim of this study was to assess
exams were notable for low SCL and an elevated serum TSH level despite high dose
TBS from spine DXA images in patients with PHPT and look at its correlates.
of Levothyroxine supplementation (250 mcg/d). After teriparatide discontinuation
Methods
SCL progressively decreased (6,5 mg/dl) with the onset symptoms of hypocalcemia,
This was a cross-sectional study conducted in an osteoporosis referral center. One
despite high doses of calcium carbonate and calcitriol. Further investigations revealed
hundred and thirty six patients with PHPT were selected from our database
an atrophic autoimmune gastritis, confirmed at gastroscopy. It was decided to switch
(2010-2016) if they had a valid LS DXA scan. The patients were both females
from calcium carbonate to calcium citrate and to modify patient’s diet. SCL slowly
(20% premenopausal) and males (12%), mean age 59.4 yrs (range 16-83), with
increased up to 8,6 mg/dl so that the patient could be discharged. In six months, no
both asymptomatic and symptomatic PHPT (mean PTH 226 pg/ml, mean serum
symptomatic hypocalcemia occurred and the SCL were stable with oral therapy.
calcium 11.3 mg/dl); a third of the patients were severely vitamin D deficient
Conclusions
(!10 ng/ml). TBS indices were derived from LS-DXA images and cutoff points
Teriparatide discontinuation in patients treated for hypoparathyroidism is
used in term of fracture risk were those previously reported.
challenging and clinically does not differ from “hungry bone syndrome” after
Results
parathyroidectomy. Furthermore calcium citrate could be an alternative to
Mean TBS values of the group was 1.26G0.12. TBS Z-score was negatively
calcium carbonate in patients with achlorhydria.
and significantly correlated with serum PTH, serum Calcium, Osteocalcin
DOI: 10.1530/endoabs.49.EP238
(rZK0.275, PZ0.005) and mostly C-telopeptide
(rZK0.314, PZ0.001).
Actually TBS values and both T and Z scores correlated negatively and
significantly with serum C-telopeptide. TBS was in the partially degraded range
but did not differ by vitamin D status, even when compared with severely
deficient patients
(35 pts, mean TBS 1.25). PTH correlated negatively with
25OHD and TBS correlated strongly (rZ0.536) with aBMD.
Conclusion
We observed a good and negative correlation between TBS and serum
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C-telopeptide which favor the notion that TBS might reflect degraded
Endocrine disorders in treatment-naïve male patients with HIV
microarchitecture.
infection
DOI: 10.1530/endoabs.49.EP240
Nikolaos Kalogeris1, Markella Nezi1, Maria Chini2, Athina Lioni2,
Vissaria Sakka2, Nikolaos Mangafas2, Styliani Kaoustou2, Marios Lazanas2
& Andromachi Vryonidou1
1Department of Endocrinology, Diabetes and Metabolism, Red Cross
General Hospital, Athens, Greece;2Infectious Diseases Unit, Red Cross
General Hospital, Athens, Greece.
EP241
Objective
Normocalcemic primary hyperparathyroidism (NPH)
To investigate endocrine disorders concerning bone metabolism, thyroid and
Cristina Corina Pop-Radu1,2
gonadal axis in treatment-naïve HIV-infected male patients.
1University of Medicine and Pharmacy, Tirgu Mures, Transilvania,
Subjects and methods
Romania;2Mures Clinic County Hospital, Tirgu Mures, Transilvania,
We studied 70 male, treatment-naïve patients (stage AZ60, stage BZ10) from
Romania.
the Infectious Diseases Unit of our Hospital. Anthropometric indices were
measured and BMI was calculated for each participant. Blood samples were
obtained after an overnight fasting for the evaluation of thyroid hormones,
Normocalcemic primary hyperparathyroidism (NPH) is characterized by normal
25OHD3, gonadotropins, total testosterone, sex hormone binding globulin
total and ionized serum calcium concentrations and consistently elevated PTH
(SHBG) levels. Free Androgen Index
(FAI) and bioavailable testosterone
levels. These patients have no obvious causes for secondary elevations of PTH,
(BAT) were calculated. Bone mineral density (BMD) in the lumbar spine and
such as renal disease, vitamin D deficiency or malnutrition. The group consisted
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
of 22 postmenopausal women, six premenopausal women, and two men, aged
Trabecular bone score (TBS) is a recent noninvasive analytical method, based
58G2 years (range 31-77) investigated between 2011 and 2016.
upon DXA images, related to bone microarchitecture or bone quality; together,
Results
TBS and DXA may evidence bone strength. Falls and osteoporotic fractures
All subjects had normal renal function and
25-hydroxyvitamin D levels
increase with ageing, while both BMD and vitamin D levels slowly decline. Data
O20 ng/ml (80% had levels O30 ng/ml); none used thiazide diuretics or lithium
about the influence of vitamin D on the TBS are scarce.
or demonstrated significant hypercalciuria. The reasons for referral included
Aim
elevated PTH discovered during the evaluation of low bone mass (nZ22), recent
To evaluate the influence of the blood vitamin D levels on the TBS in normal men.
fragility fracture (nZ2), nephrolithiasis (nZ6).
Material and methods
At the time of diagnosis, 70% had osteoporosis by BMD (measured at the lumbar
The lumbar spine BMD (g/cm2), and TBS (obtained from DXA scans) were
spine, hip or distal one-third of the non-dominant radius), 6.6% had documented
evaluated in a group of normal men more than 40 years old. Fasting blood was
fragility fractures, and
20% had nephrolithiasis. PTH was elevated, while
collected for osteocalcin, 25(OH)D and iPTH measurements. This group was
albumin-corrected serum calcium, serum phosphorus, alkaline phosphatase
divided in normal, insufficiency and deficiency vitamin D groups (ES Guidelines)
activity, and urinary calcium, were all in the mid-normal range.
and also in normal BMD, low BMD and osteoporosis groups. Total body fat and
Nine patients with positive localization studies
(cervical ultrasonography,
lean masses were also assessed by DXA. Adequate statistical tests were used
technetium 99 m sestamibi scanning) underwent successful parathyroidectomy,
(statistical significance P!0.05).
with operative findings of a single adenoma or hyperplasia. Twenty one patients
Results
who did not undergo surgery were followed for 3.1G0.3 years (annual serum
The mean (GS.D.) BMD and TBS of the vitamin D groups are shown in Table 1.
calcium, PTH and bone mineral density determinations). Hypercalcemia
Men of the deficiency vitamin D group were the heaviest and had the lowest TBS.
developed in 19% of these individuals. Two of the patients who developed
Significant relations were detected between the blood 25(OH)D vs. TBS, vs.
hypercalcemia and three additional patients with persistently normal serum
weight and vs. total fat mass but not vs. BMD.
calcium levels underwent successful parathyroidectomy. Fourteen patients were
Conclusions
without significant change in serum calcium or development of hypercalcemia,
Blood 25(OH)D levels may play an important role on the bone microarchitecture
PTH continued to remain elevated.
(by TBS) in vitamin D deficient men, as they have worse bone quality. These data
DOI: 10.1530/endoabs.49.EP241
suggest that further studies are needed on larger cohort of men and it might be
worth to investigate also elderly men with osteomalacia.
Table 1
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Groups
Normal
Insufficiency
Deficiency
Secondary hyperparathyroidism and its implication on bone mineral
Variable
(49.3%)
(37.7%)
(13.0%)
P
density in patients with different stages of chronic kidney disease
Natalia Karlovich
TBS L1-L4
1.044
(G0.14)
1.087
(G0.16)
1.079(G0.15)
0.0071
Minsk City Endocrinology Dispensary, Minsk, Belarus.
L1-L4 BMD
1.294
(G0.12)
1.323
(G0.12)
1.434
(G0.07)
NSD
g/cm2
Secondary (SHPT) is frequent in patients with chronic kidney disease and can
DOI: 10.1530/endoabs.49.EP243
predispose patients to low bone mineral density (BMD). Necessity of BMD
assessment in such patients is controversial.
The aim was to analyze BMD and PTH secretion in patients with different stages
of chronic kidney disease. We examined 311 patients, 161 f, 150 m; age 49.2G
14.4 yrs; 190 patients are on continuous dialysis due to end-stage chronic kidney
disease (mean dialysis duration 4.9G3.9 yrs), 121 patients with CKD 1-5 not on
dialysis. Serum PTH was measured and BMD was estimated by DEXA in lumbar
spine and in proximal part of femur, T score !K2.5 was classified as low BMD.
Median PTH level was 314.1 pg/ml (119.2; 770.7) in dialysis patients and 149.0
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(65.2; 259.7) in patients with CKD 1-5 not on dialysis (P!0.05). PTH was above
Neutrophil lymphocyte ratio in 6 month teriparatide therapy of
upper limit of the reference range in all dialysis patients and in 51.6% of them was
osteoporosis
300 pg/ml and higher. SHPT was revealed in all patients with CKD 4-5, in 38.1%
Bengur Taskiran1, Goknur Yorulmaz2, Guven Baris Cansu1 &
of patients with CKD 3; in 25.3% of those with CKD 1-2. In dialysis patients
Aysen Akalin2
low BMD was revealed in 24.7% of cases, significant implication of PTH level
1Yunus Emre State Hospital, Eskisehir, Turkey;2Osmangazi University,
O300 pg/ml on low BMD development was revealed. In patients with CKD 1-2
Eskisehir, Turkey.
there were no cases of low BMD, with CKD 3-19.1%, with CKD 4 and CKD
5-33.3% (P!0.05). Prevalence of low BMD was 10.7% in non-dialysis patients
with normal PTH and 29.7% - with SHPT (P!0.05).
Aim
We can assume that frequency of low BMD is 25% and higher in patients with
Low BMD and atherosclerosis may share similar underlying biological
CKD 4-5 and secondary hyperparathyroidism significantly implicates on its
mechanisms including higher serum phosphate and inflammation. Neutrophil-
development. Future investigation is required to evaluate clinical implication of
lymphocyte ratio (NLR) as a simple marker of inflammation. There are scarce
DEXA in patients with SHPT for fracture risk assessment.
data indicating improved atherosclerosis and cardiovascular events with
biphosphonate and teriparatide therapy. We aimed to evaluate NLR before and
DOI: 10.1530/endoabs.49.EP242
after
6 months of teriparatide therapy in patients with severe established
osteoporosis.
Methods and materials
Electronic data of 53 (49 female, four male) patients with severe osteoporosis and
history of fracture of femur neck and/or lumbar spine were evaluated. None of
EP243
them were previously diagnosed with rheumatoid arthritis, DM, and secondary
Impact of vitamin D on the bone quality assessed by trabecular bone
osteoporosis. Sixteen had with HT and/or other cardiovascular disease.
score in men
Results
Mário Rui Mascarenhas1,2, Ana Paula Barbosa1,2, Nuno Duarte2,
Mean age was 74G9 years, baseline 25 OH vitamin D level 25.6G17.6 ng/ml,
Ana Wessling2,3, Ana Raquel Coelho Gomes3, Carolina Faria3,
baseline NLR 2.22G0.89, 25 OH vitamin D level at 6th month 27.8G13.4 ng/ml,
Raquel Paixa˜o3, David Barbosa3, Catarina Silvestre3, José Poupino2,
NLR at 6th month 2.10G0.96.
Vânia Gomes3, Ana Sofia Osório3, Francisco Sampaio2, Jacinto Monteiro2,
Mean baseline and
6th month measurements of NLR,
25 OH vitamin D,
Didier Hans4, Manuel Bicho1 & Maria João Bugalho2,3
parathormone, ALP, ESR, and phosphorus were similar in patients with and
1Endocrinology and Metabolic Diseases, Faculty Medicine of Lisbon,
without cardiovascular disease. NLR did not change significantly after 6 months
Lisbon, Portugal;2Fracturary Osteoporosis Outpatient Clinic - Endo-
of teriparatide therapy.
crinology, Diabetes and Metabolism Department, Santa University Maria
Conclusion
Hospital-Chln, Epe, Lisbon, Portugal;3Endocrinology, Diabetes and
NLR does not change in short term teriparatide therapy and association between
Metabolism Department, Santa University Maria Hospital-Chln, Epe,
osteoporosis and cardiovascular disease cannot be settled in advanced age.
Lisbon, Portugal;4Bone Center, Lausanne University Hospital, Lausanne,
DOI: 10.1530/endoabs.49.EP244
Switzerland.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP245
Calcium & Vitamin D Metabolism
Analysis of DXA scans of males performed in clinical center of
EP247
vojvodina
Management with Cinacalcet of non-surgical primary
Bojan Vukovic1,2, Jovanka Novakovic Paro1,2, Tijana Icin1,2, Ivana Bajkin1,
hyperparathyroidism in the elderly.
Djordje Popovic1,2, Milica Medic Stojanoska1,2, Radoslav Pejin1,2 &
Juan Marti1, Jose Luis Salsamendi1, Jon Marti-Ayerdi2 & LLuis Jordana1
Edita Stokic1,2
1Hospital Zumarraga, Zumarraga, Spain;2Complejo Hospitalario Navarra,
1Clinical Center of Vojvodina, Clinic for Endocrinology, Diabetes and
Pamplona, Spain.
Metabolic Diseases, Novi Sad, Serbia;2Medical Faculty University of Novi
Sad, NOvi Sad, Serbia.
Primary hyperparathyroidism (PHPT) is a common condition. The prevalence
since the introduction of multichannel analysers is approximately 1:1000, with the
The prevalence of osteoporosis among men is not well-documented. The aim of
older female being the typical patient. PHPT is predominantly a sporadic disorder.
this cross-sectional study is to analyze results of DXA scans preformed in males
Surgery remains the only curative approach to most primary hyperparathyroidism
in Clinical center of Vojvodina between years 2009 and 2016. Form the total of
(PHPT), medical treatment with cinacalcet has been proven to be an alternative
2006 fist DXA scans performed in 7 years period there was 14.8% of males. DXA
for patients with hyperparathyroidism.
scan was indicated by the rheumatologists, internists and endocrinologists
Objective
predominantly for suspected secondary causes of osteoporosis. We divided male
Analyze treatment with cinacalcet, in older patient with primary hyperparathyr-
subjects in groups by the age of life. In the group from 20 to 50 years of life there
oidism not tributary of surgery.
was 68 subjects with average BMI 26.5G6.30 kg/m2 with average T score in L1-
Material and patients
L4 K0.8G1.4 S.D., bone mineral density (BMD) was 1.152G0.184 g/cm2, and
Between 2011 and 2015, 13 patients with PHPT who were not suitable for surgery
femur neck K0.71G1.2 S.D., BMD 0.959G0.176 g/cm2, 9 subjects had Z score
were identified. Data collected: age, gender, comorbidities, levels of calcium and
! 2 S.D. In the group form 50 to 70 year of life (average 60.38G4.82, BMI
PTH and follow-up.
27.93G5.31 kg/m2) there was 174 subjects with T score L1-4: K0.82G1.93 S.D.,
Results
BMD 1.120G0.231 g/cm2, left femur neck: K1.41G1.36 S.D., BMD 0.887G
We present 13 patients 8 women and 5 man with a mean of age 80.5G6.59 year-
0.176 g/cm2. 56 had osteopenia and 49 had osteoporosis. Group above 70 years of
old (range 71-92). Comorbidities, diabetes mellitus 50%, frailty 58%, heart
life (88 maximum, average 75.6G3.96, BMI 25.17G4.16 kg/m2) had 55 subjects
disease
40%, depression
33%, cognitive impairment
17%. Calcium levels
from whom 22 had osteopenia and 23 osteoporosis and average T score L1-L4
previous treatment was
11.85G0.28 mgr/dl and PTH
123G34 pg/ml. T
was: K0.85G2.12 S.D., BMD 1.115G0.255 g/cm2, left femur neck: K1.84G
cinacalcet 30 mg. daily was initiated, in 12 patients and 60 mgr. in one. Patients
1.25 S.D., BMD 0.829G0.161 g/cm2. Lower values of T score and BMD were
were followed for 1-4 years (2.75G1.21) calcium were adequately controlled
measured on left femur neck in older groups. There was very high percentage of
(9.98G0.78 mgr/dl), but PTH 112.4G42 pg/ml remains high, renal function was
osteoporosis and osteopenia in the oldest groups of males although all males
uncharged in all patients. Two patients died during the follow-up, not related with
referred to DXA scan were suspected to have osteoporosis.
hyperparathyroidism. Adverse events were observed in 1 patient (vomiting) that
DOI: 10.1530/endoabs.49.EP245
disappeared to diminishing doses.
Discussion
Geriatricians will readily recognize the clinical conundrum of an incidental
finding of PHPT in the older that was unexpected. Retrospective questioning may
identify some pertinent symptoms, but none strong enough on their own to have
made the diagnosis obvious prior to testing serum calcium. This group of patients
is hard to define and hence there is little published guidance on how to manage the
increasingly common clinical scenario of the frail, relatively asymptomatic, older
patient with PHPT.
Conclusions
Cinacalcet, the first available calcimimetic, increases the sensitivity of the
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calcium-sensing receptor (CaR) to circulating serum calcium, thereby safely
Biological assessment and causes of secondary osteoporosis
reducing serum calcium and PTH concentrations in patients with mild-
Aicha Bouzid & Djamila Meskine
to-moderate PHPT, intractable disease, and also parathyroid carcinoma.
Dr, Algiers, Algeria.
Cinacalcet in a reasonable and safe alternative to treatment of PHPT not tributary
of surgery.
DOI: 10.1530/endoabs.49.EP247
Secondary osteoporosis accounts for 10-20% of the causes of osteoporosis in
menopausal women. The search for a possible etiology should not be neglected
before considering the therapeutic management of any osteoporosis. There is no
consensus on the first-line biological tests to be prescribed.
Goal
Determine biological abnormalities in postmenopausal women with osteoporosis.
Patients/methods
Postmenopausal women are enrolled, the mean age is 65.5G8.9 years. 305
patients are classified as osteoporotic according to the WHO criteria (T-score
%2.5). NFS, VS, CRP, serum calcium, phosphoric acid, 24-hour calcium, total
EP248
alkaline phosphatase, parathyroid hormone (PTH), serum protein electrophoresis,
Glucocorticoids regulate expression of lung calbindin-D9k in mouse
serum creatinine, liver function test, fasting blood glucose.
Jin Yong An, Jae-Hwan Lee, Seon Yong Park & Eui-Bae Jeung
Results
Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
6.2% (19/305) patients had an abnormality.
Distribution of anomalies
Monoclonal gammopathy five cases: two myeloma, two MGUS, one unlabeled
Introduction
case
Calbindin-D9k (CaBP-9k), which is a calcium ion buffering and transporter gene,
- HPT I: seven cases (two parathyroid adenomas confirmed by the anapath)
is known to be regulated by the vitamin D and steroid hormones, and is mainly
- 1 cases rheumatoid arthritis
expressed in mammalian intestine, kidney and uterus. However, CaBP-9k
- diabetes type two unknown: six cases, one case of intolerance to carbohydrates
expression in lung has not been studied. Maintaining lung structure using
Discussion/conclusion
pulmonary surfactant is important for pulmonary gas exchange. Steroids are
In the presence of a low BMD, it is recommended that a diagnostic survey should
known to accelerate maturation of the fetal lung and secretion of surfactant.
be carried out, including physical examination, clinical examination and routine
Otherwise the relationship between pulmonary function especially in surfactant
biological examinations, in order to eliminate malignant or metabolic osteopathy
secretion and CaBP-9k expression has not been researched. In this study, we
and to investigate the causes of secondary osteoporosis. In our study targeting a
investigate the CaBP-9k expression by sex steroid hormones and glucocorticoids
population of postmenopausal osteoporotic women followed in consultation, the
in mouse lung.
discovery by biological examination of a new condition that can lead to bone
Materials and methods
demineralization is quite common.
To confirm the effect of sex steroid hormones, the immature mice age from
DOI: 10.1530/endoabs.49.EP246
14 days to 16 days were respectively injected of estrogen (E2) and progesterone
(P4) for 3 days. To confirm the effect of glucocorticoids, the mature mice age from
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
11 weeks were respectively injected of dexamethasone (Dex). ER antagonist
EP251
(ICI187,780) and PR, GR antagonist (RU486) were injected 30 min prior to
Gitelman syndrome and primary hyperparathyroidism - a rare
steroid hormones. We compared the changes in the CaBP-9k expression of each
association
group using polymerase chain reaction.
Teresa Rego, Fernando Fonseca & Ana Agapito
Results
Endocrinology Department, Centro Hospitalar de Lisboa Central, Lisbon,
In the estrogen and progesterone treated immature mice lung, the CaBP-9k gene
Portugal.
expression had no significant change in mRNA and protein level but significantly
increased in Dex treated mice lung. It is suggested that glucocorticoids may play a
role in regulation of CaBP-9k expression in lung.
Gitelman’s Syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy
Conclusion
of young adults, characterized by secondary hyperaldosteronism, hypokalemia,
Our results has significance to the regulation of CaBP-9k by Dex. By studying the
hypomagnesemia, hypocalciuria and metabolic alkalosis. It is caused by
effects on lung surfactant through the control of CaBP-9k, it may be presented as a
mutations in SLC12A3 gene. Hypercalcemia due to hypocalciuria in these
basis data of pulmonary surfactant associated disease or research.
patients is extremely rare and requires further evaluation.
DOI: 10.1530/endoabs.49.EP248
A 25-year-old normotensive female was referred to Endocrinology clinic for
evaluation of persistent hypokalemia. She presented history of malaise, fatigue,
myalgias, cramps and paresthesia. She denied diarrhea, recent treatment with
diuretics or laxatives. Her physical exam was normal. Laboratory workout
revealed: aldosterone 47.1 ng/mL (r.v. 4-31), active renin 374.7 mUI/ml (r.v. 4.4-
46.1), KC2.7 mEq/l (r.v. 3.5-5.1), 24 h urinary KC84.7 mEq/24 h (r.v. 25-125),
Mg2C0.71 mg/dl (r.v. 1.6-2.6), 24 h urinary Mg2C143.1 mg/24 h (r.v. 73-122),
Ca2C12 mg/dl (r.v. 8.4-10.2) and 24 h urinary Ca2C133 mg/24 h (r.v. 100-
EP249
300). GS was diagnosed and she was treated with spironolactone, oral KC and
Vitamin D intoxication caused hypercalcemia: Case report
Mg2C supplementation. Further investigation confirmed hypercalcemia due to
Kader Ugur1, Hakan Artas2, Mehmet Balin3, Esra Aykut4,
primary hyperparathyroidism
(parathyroid hormone
(PTH) 107.3 pg/ml (r.v.
Selcuk Demircan4, Bedrettin Orhan4 & Nevzat Gozel4
14.8-83.1)) caused by a large single parathyroid adenoma. Following
1Firat Univercity Department of Endocrinology, Elazig, Turkey;2Firat
parathyroidectomy calcium profile normalized. The sequencing of SLC12A3
Univercity Department of Radiology, Elazig, Turkey;3Firat Univercity
gene detected the variant c.602-16GOA and the mutation c.2221GOA
Department of Cardiology, Elazig, Turkey;4Firat Univercity Department of
(p.Gly741Arg), both in heterozygosity. In this context genetic study of the
Internal Medicine, Elazig, Turkey.
progenitors was required. The father presents the variant c.602-16GOA and the
mother the mutation c.2221GOA (p.Gly741Arg), in SLC12A3 gene.
Introduction
The assotiation of hypokalemia, hypomagnesemia and hypercalcemia is
Vitamin D is a fat soluble prohormone and can be produced in the body with
uncommon but potentially lethal. Current knowledge favors that hypomagnese-
adequate sunlight exposure or taken up by consumed foods or supplements.
mia in GS’s patients protects them from hypercalcemia. In this context of multiple
Recently vitamin D deficiency has been seen in pandemic. A rare disease, vitamin
electrolyte imbalances, correction of hypomagnesemia is a challenge and should
be done carefully. Like in our patient hypercalcemia’s etiology should be prompt
D intoxication is usually iatrogenic. High levels of 25(OH) vitamin D increases
diagnosed and reversed.
the intestinal calcium absorption and causes severe and refractory hypercalcemia.
In this case report we presented a patient with pancreatitis and hypercalcemia
DOI: 10.1530/endoabs.49.EP251
secondary to vitamin D intoxication.
Case
79-years-old female patient presented to emergency department with generalized
pain, lack of appetite, dry mouth, nausea, vomiting and abdominal pain. Serum
calcium level was 13.8 mg/dl. In her medical history she used 12 ampules of
vitamin D-3 in the last month. In her physical examination there was abdominal
tenderness. Laboratory findings were as follows; 25-OH vitamin D-3: 455 mg/l
(20-150), WBC: 19 570 10e3/ml (3.8-8.6), Urea: 60 mg/dl (10-50), Creatinine:
2 mg/dl (0.6-1.2), Ca: 13.8 mg/dl (8.5-10.8), phosphorus: 2.9 mg/dl (2.6-4.5),
albumin: 3.7 mg/dl (3.5-5.5), amylase: 132 U/l (28-100), Lipase: 115 U/l (7-60),
Parathormone: 28 pg/ml (19.8-74.9). Abdominal CT scan showed interstitial
EP252
oedematous pancreatitis. In the follow up, patient was hydrated with isotonic
The volume of parathyroid adenoma is related to presurgical PTH and
saline infusion. To lower the calcium levels, intravenous furosemide infusion was
25OH-D3, but not calcium levels at patients with primary
used. Calculated QTc level when serum calcium is 9.1 mg/dl, was 443 msec.
hyperparathyroidism
According to literature we could see osborn wave in the ECG but we did not.
Cristian Velicescu1, Cristina Gatu1, Alexandru Grigorovici1, Radu Danila1,
Discussion
Valentin Munteanu2, Voichita Mogos1, Carmen Vulpoi1, Cristina Preda1,
Vitamin D toxicity develops when serum levels of 25 OH vitamin D-3 levels
Simona Mogos1 & Dumitru D Branisteanu1
reach 150 ng/ml or above and daily intake should exceed 10.000 IU. In the
1University of Medicine and Pharmacy ‘Gr.T.Popa’, Iasi, Romania;
treatment, cessation of vitamin D intake and controlling of hypercalcemia is
2University of Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj, Romania.
mandatory. Limiting daily calcium intake, hydration, loop diuretics, corticoster-
oids, calcitonin and bisphosphonates can also be used. Dialysis can be performed
to those who are refractory to these treatment modalities.
Aims
Conclusion
We wanted to evaluate the correlations between the volume of the surgically
Uncontrolled and over the counter use of vitamin supplements is a common issue
removed parathyroid adenoma and the presurgical metabolic profile of patients
worldwide. Patients who need vitamin D supplements should be followed with
diagnosed with primary hyperparathyroidism.
laboratory and clinically.
Materials and methods
Prospective multicentric study, enrolling 52 patients with primary hyperpar-
DOI: 10.1530/endoabs.49.EP249
athyroidism from two medical units, proposed for surgery. Serum calcium and
PTH were evaluated in all patients before surgery, and 25OH-D3 was measured
only in the 33 patients recruited from one of the two surgery departments.
Parathyroid volume was measured immediately after excision, using the formula
of a rotating ellypsoid. Data were statistically evaluated by using Pearson
correlation analysis. Correlations were considered significant at P values lower
than 0.05.
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Results
We observed a significant correlation between the volume of parathyroid
adenomas and presurgical PTH (P!0.001) but not presurgical calcium levels at
Abstract withdrawn.
patients from the two medical units and in the whole group. Twenty-nine out of
the 33 patients diagnosed with primary hyperparathyroidism recruited from the
first medical unit had 25OH-D3 levels in the range of vitamin D deficiency or
insufficiency. 25OH-D3 was not significantly correlated with PTH or calcium
levels, but a significant negative correlation was found between the volume of the
parathyroid adenoma and serum 25OH-D3 levels (P!0.05).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
Objectives
The volume of parathyroid adenoma seems to be related to presurgical PTH and
To evaluate the efficacy and safety of cinacalcet in patients with PHPT who were
25OH-D3, but not calcium level. D hypovitaminosis is frequently found at
unfit for surgery, refused surgery or remain hypercalcaemic post-parathyroi-
patients with primary hyperparathyroidism and may contribute to particular
dectomy and not amenable to further intervention (complex PHPT).
disease profiles. Higher PTH and lower 25OH-D3 levels, as well as larger
Methods
adenomas may be accompanied by increased disease severity, or by a different
We assessed the demographic and clinical characteristics and biochemistry in 12
spectrum of disease complications.
patients seen in endocrinology and biochemistry clinics with complex PHPT at
DOI: 10.1530/endoabs.49.EP252
the commencement of cinacalcet and after approximately 1, 3, 6 and 12 months.
We also checked doses, tolerability and side effects of cinacalcet.
Results
Most patients (66.67%) needed small maintenance dose of cinacalcet once a day.
Mean baseline adjusted calcium level was 3.36 mmol/l (13.44 mg/dl) with a range
of 2.91-5.36 mmol/l (11.64-21.44 mg/dl). There was a significant reduction in
adjusted calcium levels at approximately 1 month (10.08%), 3 months (11.93%),
6 months (13.57%) and 12 months (20.17%). Calcium normalised in most patients
(83.33%), and one patient developed hypocalcaemia necessitating cinacalcet dose
reduction. All patients adhered to the treatment with two people experiencing
self-limiting nausea and vomiting.
EP253
Conclusion
Our patient cohort indicates that cinacalcet is an effective and safe alternative to
Pseudohypoparathyroidism type Ib: a case of chronic severe
surgery in patients with complex PHPT. Cost-effectiveness analyses are needed to
hypocalcaemia and seizures diagnosed in adulthood
allow more widespread use in such patients. Further studies with long-term
Ana Cláudia, Martins, Paula Bogalho & Ana Agapito
follow-up are required to assess efficacy in preventing osteoporosis and renal
Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,
complications related to PHPT.
Portugal.
DOI: 10.1530/endoabs.49.EP254
Pseudohypoparathyroidism
(PHP) is a rare group of genetic disorders
characterised by end-organ resistance to parathyroid hormone
(PTH). We
describe the case of a 34-year-old Caucasian female with severe hypocalcaemia
presenting with a first generalised seizure. Her medical history was significant for
bilateral cataract. She had three healthy children, and no family history of note.
On examination, she had positive Chvostek’s sign. Biochemical analysis showed
serum calcium 4.5 mg/dl (n.r. 8.4-10.2 mg/dl), phosphorus 5.8 mg/dl (n.r. 2.3-
4.7;mg/dl), PTH 94.7 pg/ml (n.r. 14.76-73.1 pg/ml) and vitamin D 19.6 ng/ml
(n.r.
30-100 ng/ml), with normal serum albumin and normal alkaline
phosphatase. Electrocardiogram demonstrated prolonged corrected QT interval.
EP255
Brain imaging revealed basal ganglia and cerebellar calcifications, and
Is there a threshold of Vitamin D sufficiency that can prevent secondary
electroencephalography did not show paroxysmal activity. We excluded a
hyperparathyroidism?
number of causes of secondary hyperparathyroidism based on her medical history
André Amaral1, Tatiana Nunes3, João Anselmo2 & Rui César2
and investigations, and concluded that PTH resistance would be the most likely
1Unidade de Saúde Ilha do Faial, Horta, Faial/Ac¸ores, Portugal;2Hospital
diagnosis. Since she lacked the typical clinical features of Albright hereditary
Divino Espírito Santo, Ponta Delgada, São Miguel/Ac¸ores, Portugal;
osteodystrophy and did not present with other hormones’ resistance, a genetic test
3Unidade de Saúde Ilha de São Miguel, Ponta Delgada, São Miguel,
was requested and identified abnormal methylation of the 20q13.32 region,
Portugal.
confirming the diagnosis of PHP type Ib. The patient is currently medicated with
calcium carbonate and calcitriol, maintaining a satisfactory calcium-phosphate
homeostasis. This case highlights the importance of PHP as a rare but significant
While nonskeletal benefits of vitamin D remain a matter o debate, its importance
cause of severe hypocalcaemia. The delayed diagnosis, as seen in this case, may
in bone health is known for decades. Secondary hyperparathyroidism is
result in serious consequences.
considered to play a significant role in the pathogenesis of age-related bone
DOI: 10.1530/endoabs.49.EP253
loss. In the present study we investigate the association between serum PTH,
25-hydroxyvitamin (25(OH)D) and other clinically related variables in a cross
sectional sample of patients followed in an Endocrine consultation during the year
2016. Patients with diseases or medications known to affect calcium metabolism
were excluded. 509 participants, 365 female and 145 male, were selected for
analysis. Mean ageGS.D. was 52G16 yrs (2-86); 47% were diabetics; 31%
suffered of thyroid disorders and 7% were obese. The meanGS.D. serum level of
25(OH) D was 20.4G10.2 ng/ml; 17.8G8.7 ng/ml in measurements during
winter months and 23.4G10.04 during summer. In 61 patients (12% of the
sample) with more than one determination, there was a 51.9% increase in 25(OH)
D from a mean level of 16.81G9.3 ng/ml during winter to 24.94G11.2 ng/ml
EP254
during summer months
(P!0.02). Patients treated with statins presented
significantly lower levels of
25(OH)D than non-treated patients,
15.9G
A practice review of the use of cinacalcet in primary
6.7 ng/ml and 26G10.1 ng/ml, respectively (P!0.01).This difference remained
hyperparathyroidism
statistically significant after adjusting for age, sex and disease.
Rahat Tauni1,2, Nida Ali2 & Ritwik Banerjee2
We found an inverse relationship between 25(OH)D and PTH. The best fitted line
Cambridge University Hospitals, Cambridge, UK;2Luton and Dunstable
was obtained as a logarithmic expression of 25(OH)D (rZ0.65; P!0.001). There
University Hospital, Luton, UK.
was no further significant decrease in PTH for serum levels of 25(OH)D of more
than 25 ng/ml. In conclusion, more than half of our patients were Vit D deficient
Background
(!20 ng/ml) particularly elderly people treated with statins, but serum levels of
The treatment of choice for primary hyperparathyroidism (PHPT) is surgical
25(OH)D above 25 ng/ml are needed in order to prevent secondary hyperpar-
parathyroidectomy. Cinacalcet is the first calcimimetic approved by European
athyroidism. This value can be considered as the lower limit of Vitamin D
Medicines Agency (EMA) in 2008 for use in patients with PHPT who are not fit
sufficiency in the sample studied.
for surgery or refuse surgery. British National Formulary (BNF) recommends it
DOI: 10.1530/endoabs.49.EP255
for hypercalcaemia in PHPT where parathyroidectomy is inappropriate. The main
aim of treatment with cinacalcet is to keep calcium levels at safe levels.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP256
patients is important because of the consequences of untreated hyperparathyroid-
ism, which include nephrolithiasis, osteoporosis and atraumatic fractures.
Spontaneous remission of parathyroid adenoma due to parathyroid
apoplexy: a case report
DOI: 10.1530/endoabs.49.EP257
Cem Onur Kirac, Suleyman Baldane, Suleyman Ipekci & Levent Kebapcilar
Division of Endocrinology and Metabolism, Selcuk University Faculty of
Medicine, Konya, Turkey.
Introduction
Primary hyperparathyroidism
(PHPT) is a disease that is characterized by
elevated calcium and parathyroid hormone levels. The most common cause of
PHPT is the paratiroid adenoma and the first line treatment option is surgical
EP258
removal of the adenoma. Rarely, the haemorrhage in the lesion may cause the
Parathyroid carcinoma: experience of a Portuguese centre
spontaneous remission of the disease.
Carlos Tavares Bello1, Sara Donato2, Susana Prazeres2, Helder Simoes2 &
Case report
Valeriano Leite2
A 54-year-old woman patient with fatigue was referred to our department due to
1Hospital de Egas Moniz, Lisboa, Portugal;2Instituto Portugues de
calcium level of 11.4 mg/dl (normal range: 8.4-10.2) and PTH level of 76.1 pg/ml
Oncologia Lisboa Francisco Gentil, Lisboa, Portugal.
(normal range: 15-65). Neck ultrasound examination revealed a 10!5 mm mass
lesion in the posterior-inferior region of the left lobe of the thyroid. Sestamibi
Introduction
scan showed activity in the same region with neck ultrasound. Surgical resection
Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than
of the parathyroid adenoma was planned but the patient refused surgical excision
1% of primary hyperparathyroidism cases. Apart from certain genetic mutations,
because of personal reasons. One year after the diagnosis of PHPT, her calcium
no additional risk factors are known. Diagnosis is challenging in the absence of
concentration returned into the normal range (9.4 mg/dl), at the same time neck
metastatic disease since no consensual histological criteria have so far been
MRI showed a mass with a size of 19!13 mm, which was attached inferiorly to
developed. These neoplasms typically present with severe hypercalcemia and
the left lobe of the thyroid. The mass was diagnosed as hemorrhagic parathyroid
markedly elevated serum PTH levels. Treatment is surgical and despite frequent
adenoma because the mass was imaged as a high intensity area by T2-weighted
metastatic disease at diagnosis, clinical course is usually indolent. The authors
MRI. At that time the sestamibi scan was negative. Six months after the
report the experience of a tertiary reference centre in Portugal regarding
haemorrhage of the lesion, it was seen that the calcium level rose to 11.1 mg/dl
parathyroid carcinomas.
and the PTH level was 89 pg/ml so the PHPT has been recurred.
Methods
Conclusion
Observational, retrospective study. Patients with diagnosed parathyroid carci-
Parathyroid apoplexy can lead to spontaneous remission of the PHPT but the
noma from 1999 until 2016 were included. Clinical data was obtained from
remission is usually temporary and finally recurrence of the disease could be seen.
patient’s clinical, laboratory and imaging files. Descriptive statistical methods
DOI: 10.1530/endoabs.49.EP256
were used and results are presented as mean and standard deviation.
Results
The sample is composed of ten patients (five females) with a median age of 53G
16.9 years at the time of diagnosis. Clinical presentation was heterogeneous. All
patients had hyperparathyroidism (mean 1229G642 pg/ml), nine hypercalcemia
EP257
(13.4G2.2 mmol/l) and four hypophosphatemia (2.1G0.6 mol/l). Histological
Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism:
findings: intratumoral septa (50%), vascular, capsular, perineural invasion (70%,
a comparative study
80%, 10% respectively), extraglandular extension (50%). Mitotic index was
Natalya Mokrysheva, Svetlana Mirnaya, Anna Eremkina, Julia Krupinova &
evaluated in four patients. CDC73 mutations were present in four patients.
Elena Kovaleva
Metastases were present in one patient. All patients underwent en bloc resection
Endocrinology Research Centre, Moscow, Russia.
and three received external beam radiotherapy due to recurrent loco-regional
disease. After a mean follow up of 9 years, 90% are in remission and no mortality
has been documented.
Introduction
Conclusion
Normocalcemic primary hyperparathyroidism (NPHPT) is defined as a condition
The authors describe a series of ten parathyroid carcinoma patients. Despite the
in which persistently normal serum calcium levels are observed in the presence of
clinical and biochemical severity at the time of diagnosis, most patients achieved
high levels of parathyroid hormone (PTH). NPHPT is a new entity which possibly
sustained remission. Genetic mutations were identified in a significant proportion
represents a clinically symptomatic disease and which has generated a
of patients, having important clinical implications. This series is noteworthy for
considerable scientific interest.
the good outcome of such an aggressive neoplasm.
Aim
DOI: 10.1530/endoabs.49.EP258
To compare the clinical and laboratory data between the normocalcemic and
hypercalcemic forms of PHPT.
Materials and methods
A comparative study of 357 patients with PHPT wich were separated into
normocalcemic (nZ56) and hypercalcemic (nZ301) subgroups on the basis of
their fasting serum total calcium value. Bone mineral density
(BMD) and
T-scores were evaluated by densitometry of the lumbar spine, femoral neck and
EP259
total of the radius. Nephrolithiasis and bone fractures were documented by a
review of the medical records.
Vitamin D prescribing bias in liver transplant referrals
Results
KJ Gan1, Niamh O’Sullivan2, Bernadette Hanley1, Paul Armstrong1,
Patients with NPHPT had, on average, a lower serum PTH concentration
Mark Kilbane1, Diarmaid Houlihan2 & Rachel Crowley1
150 pg/mlG115
(N
15-65, Me
114) and a lower serum calcium level
1Department of Endocrinology, St Vincents University Hospital, Dublin,
2.44 mmol/lG0.08 (N 2.15-2.55) vs hypercalcemic PHPT - 408 pg/mlG651
Ireland;2Department of Hepatology, St Vincents University Hospital,
(Me 186) and 2.89 mmol/lG0.3 respectively. There was no significant difference
Dublin, Ireland.
in urine calcium excretion. The frequency of nephrolithiasis was
27% in
normocalcemic patients and 16% in the hypercalcemic ones (P!0.05). There
Vitamin D (VD) deficiency (25 OHD ! 50 nmol/l) is common is chronic liver
were no statistical differences in relation to BMD of the lumbar spine and femoral
disease at 64%-92% regardless of aetiology. The only guidelines for routine VD
neck, but BMD significantly differed in the total radius area. BMD in the total
supplementation are for cholestatic (C) liver disease; a population considered
radius was
0.423 g/cm2
(Me 0.415), mean T-score was K2.2
S.D. of the
being at high risk of low bone mineral density (BMD). BMD decreases further
normocalcemic patients, 51.8% had osteoporosis in at least one of the three sites
following orthotopic liver transplant (OLT). To assess VD intake in an at risk
evaluated. In addition, normocalcemic patients differed from hypercalcemic
population, retrospective analysis of intake was performed in OLT patients with C
patients by lower values of markers of bone turnover osteocalcin and b-C-
liver disease; this was excellent at 81%. Prospective analysis comparing C with
telopeptide, P!0.05. 20.4% of normocalcemic patients had a previous history of
non-cholestatic (NC) patients at time of dietetics referral at OLT assessment was
fractures compared to 20.3% of hypercalcemic patients (PO0.05).
then undertaken (nZ94, 27% C and 73% NC). Median 25OHD in C patients was
Conclusion
86.7 nmol/l compared to 24.7 nmol/l in NC (P 0.001).
36% of C patients
NPHPT is at present one of the most common reasons for consultation in bone
compared to 76% of NC had 25OHD measurement of !50 nmol/l (P !0.0001).
metabolism departments, especially in postmenopausal women. Identifying these
48% of C patients compared to 16% of NC were receiving VD supplementation
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
before OLT assessment. We have observed a prescription bias at referral to
regulatory region. We present a patient who was detected PHP while following
transplant hepatology; VD is prescribed more frequently to C than NC patients
for epilepsy.
with end-stage liver disease, although both populations are at risk of reduced
Case report
BMD.
A 17 years old male patient referred to endocrinology clinic with paresthesias of
DOI: 10.1530/endoabs.49.EP259
the hands. He had under treatment due to epilepsy for 3 years. He had normal
mental activity and phenotypic features. His family history had no specialty. His
laboratory examination revealed hypocalcemia and hyperphosphatemia with a
calcium level 7.4 mg/dl (reference range, 8.5-10.5 mg/dl), phosphorus 6.8 mg/dl
(reference range, 2.5-4.5 mg/dl), albumin 4.4 g/dl (reference range, 3.5-5.2 g/dl),
magnesium 2.06 mg/dl (reference range, 1.8-2.6 mg/dl), 25 hydroxyvitamin D
EP260
(25
OHD) 64.3 ng/ml (reference range,
30-70 ng/ml) and PTH
115 pg/ml
How to differentiate primary hyperparathyroidism with D
(reference range, 15-65 pg/ml). His rest of the laboratory findings and ophthalmic
hypovitaminosis from secondary hyperparathyroidism due to D
examination were normal. Brain computed tomography scan showed basal
hypovitaminosis?
ganglia calcifications. Calcitriol and calcium supplements were started to patient
Alina-Andreea Gatu1, Cristian Velicescu1,2, Cristina Preda1,2,
whose biochemical findings support PHP diagnosis. Genetic testing of the patient
Carmen Vulpoi1,2, Simona Mogos1,2, Voichita Mogos1,2, Valentin Zaharia2,
did not show GNAS coding region mutation and we planned methylation study in
Adrian Aancute2 & Dumitru Branisteanu1,2
terms of methylation abnormality in GNAS regulatory region.
1Gr. T Popa University of Medicine and Pharmacy, Iasi, Romania;
Conclusion
2St. Spiridon Emergency Hospital, Iasi, Romania.
PHP is an uncommon cause of hypocalcemia. Blood electrolytes must be called to
mind in case of epilepsy or neurological evidence. Early diagnosis and treatment
of PHP prevent complications.
Background
D hypovitaminosis and primary hyperparathyroidism frequently coexist.
DOI: 10.1530/endoabs.49.EP261
Secondary hyperparathyroidism reactive to D hypovitaminosis is difficult to be
differentiated from primary hyperparthyroidism.
Aims
To differentiate patients with D hypovitaminosis and secondary hyperparathyr-
oidism.
EP262
Materials and methods
Long standing primary hyperparathyroidism consequences after
Prospective study involving 71 patients admitted in our department for 1 year
parathyroid surgery: fast recovery not only for bone mass
with the initial diagnosis of primary hyperparathyroidism. Serum and urinary
Cristina Stefan1,2, Amalia Arhire1, Luminita Cima1,3 & Carmen Barbu1,3
calcium and phosphate, PTH and 25OHD3 were evaluated at admission. Patients
1Endocrinology Department, Elias Hospital, Bucharest, Romania;2Ghencea
with vitamin D levels under 30 ng/ml were repleted with 2000 IU/day of 25OHD3
Medical Center, Bucharest, Romania;3Carol Davila University, Bucharest,
for 1 month and 1000 IU/day for other 5 months. Values between groups were
Romania.
compared using student’s t test. Correlations were evaluated by using Pearson
correlation analysis.
Results
Background
Forty-eight of the 71 patients had vitamin D deficiency (! 20 ng/ml) and 15 had
Primary hyperparathyroidism is usually a long evolving disease before the
vitamin D insufficiency (between 20 and 30 ng/ml), only eight having 25OHD3 of
diagnosis, thus patients who are not diagnosed by routine screening tests may
over 30 ng/ml. Both 25OHD3 and PTH levels normalized after 6 months of
have a lot of complications affecting the bone, kidney, bone marrow.
repletion with vitamin D in only 24 of the 63 patients with initial low 25OHD3
Aim
levels and they were therefore diagnosed with secondary hyperparathyroidism
Pointing out the possibility of fast recovery not only for bone mass.
(group S), whereas in the other 39 patients PTH levels remained elevated despite
Material
normalization of 25OHD3 levels, setting the diagnosis of primary hyperpar-
We present a case of primary hyperparathyroidism, a female patient 66 years old,
athyroidism associated with D hypovitaminosis (group P). Initial PTH was
sent to emergency room, dehydrated, asthenic, with important hip pain, low back
correlated with serum calcium in both groups, but with serum phosphate only in
pain. Her CaZ14.3 mg/dl, PTHO4000 pg/dl, HbZ8.5 g/dl, CT: osteolotic
group P. Initial PTH and serum and urinary calcium were significantly higher,
lesion, pubis and ischium fracture, two osteolithic lesions on the right acetabulum
whereas serum phosphate and radius BMD were significantly lower in the patients
and the S1 vertebra, bone biopsy: perytrabecullar fibrosis, aspects of bone
from group P when compared with patients from the group S (P ! 0.05).
remodeling and normal medullar celularity, DXA T score: total hip -3, L1-L4 -
Conclusions
1.8, forearm
-4.4. The complication in the moment of diagnostic were:
Patients with secondary hyperparathyroidism reactive to D hypovitaminosis are
osteoporosis, spontaneous fragility fractures, medular fibrosis with normocytic
frequent. Their PTH and electrolyte profile are only mildly modified, with a
normochromic anemia.
milder impact on bone mass than in primary hyperparathyroidism. A clear
Results
diagnosis could be, however, set only after vitamin D repletion.
Surgery was successful with the normalization of blood calcium and PTH.
DOI: 10.1530/endoabs.49.EP260
Questions were raised regarding the high level of PTH(neoplasia was taken into
account) and also the impact of medular fibrosis the on the prognosis of the
patient. After one year BMD was in age range, DXA T score: total hip -1.2, L1-L4
-0.2, forearm -2, anemia have remitted HbZ12.5 g/dl, and maintained during 2
years follow up.
Conclusion
EP261
In spite of high level of PTH and dangerous medular fibrosis, our case show
Pseudohypoparathyroidism as an etiological cause for epilepsy:
surgical recovery of bone mass but also of medular complications.
a case report
DOI: 10.1530/endoabs.49.EP262
Naile Gokkaya1, Arzu Bilen2 & Habib Bilen1
1Division of Endocrinology and Metabolism, Department of Internal
Medicine, Faculty of Medicine, University of Ataturk, Erzurum, Turkey;
2Department of Internal Medicine, Erzurum Training and Research
Hospital, Erzurum, Turkey.
EP263
Associations of nitric oxide with vitamin D and other serological factors
Introduction
in healthy adolescents
Pseudohypoparathroidism
(PHP) is a condition mimics hypoparathyroidism
Nasser Al-Daghri1, Sobhy Yakout1, Naji Aljohani2, Yousef Al-Saleh2,
biochemically with a hypocalcemia and hyperphosphatemia but differentiates
Omar Al-Attas1 & Majed Alokail1
from it an elevated parathyroid hormone (PTH) levels. PHP characterized by
1King Saud University, Riyadh, Saudi Arabia;2King Saud bin Abdulaziz
targeted organ unresponsiveness to PTH and mainly subdivided two groups. PHP
University for Health Sciences, Riyadh, Saudi Arabia.
type 1a an autosomal dominant disease related to mutations of GNAS1. This
subtype has biochemical findings and characteristic somatic phenotype known as
Albright Hereditary Osteodystrophy (AHO). AHO include short stature, round
Nitric Oxide
(NO) has been considered a very important molecule in the
face, brachydactyly, shortened metatarsals, subcutaneous ossifications and
biological system because of its interaction with other molecules for mediating
reduced intelligence. PHP type
1b has laboratory findings but do not has
various bio-pathways. Its interaction with vitamin D in particular studied well in
phenotype of AHO. This disorder caused by methylation defects of GNAS1
animal models, cell lines and patients with various diseases. However, the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
relationship between NO and vitamin D has never been studied in healthy
Ca values within the normal ranges, patients were divided into two groups
adolescents. We aimed to determine the association of NO with vitamin D and
according to their PTH values 6 months after surgey (elevated PTH (ePTH) group
other serological factors in healthy Saudi adolescents. We recruited
740
(PTH R65 pg/ml) and low PTH (lPTH) group (PTH !65 pg/ml)). Fifteen
individuals (245 boys and 495 girls) from Riyadh, Saudi Arabia. Socioeconomic
patients were classified as having ePTH and 20 as IPTH. The frequency of ePTH
status, food habits, BMI and data regarding major medical complications were
was determined as 42%. The mean pre and postoperative PTH levels in ePTH and
recoded. Blood samples were performed for estimation of vitamin D, traces of NO
IPTH groups were 265G119, 94G32 and 206G136, 39G17 pg/ml, respectively.
and other possible serological parameters. Data revealed that NO has inverse
The mean pre and postoperative 25(OH) vitamin D3 levels in ePTH and IPTH
correlation with vitamin D but showed significant and positive association with
groups were 12G7, 22G11 and 22G14, 32G12 ng/ml, respectively.
serum triglycerides and systolic blood pressure. Here, it is suggested that some
Results
unknown limiting factors may restrict the relationship of NO and vitamin D in
Although ePTH group had higher preoperative PTH values as well as lower pre
healthy individuals. Therefore, the factors which limit the NO association with
and postoperative 25 (OH) vitamin D3 levels, there was no statistically significant
vitamin D and other molecules should be investigated in vitro and in vivo.
difference between the groups. For the remaining parameters, two groups had
DOI: 10.1530/endoabs.49.EP263
similar results.
Discussion
Several hypotheses have been proposed to explain the etiopathogenesis of
persistently elevated PTH values despite normal Ca levels following parathyroid
surgery. Suggested causes of this phenomenon include 25 (OH) vitamin D3
deficiency, secondary hyperparathyroidism resulting from insufficient renal
EP264
function, stimulation of PTH secretion induced by relative hypocalcemia
Primary hyperparathyroidism in pregnancy
postoperatively, and increased bone turnover. However, this condition may also
Belgin Efe1, Goknur Yorulmaz1, Sevil Alaguney1 & Bartu Badak2
indicate possible recurrence due to multiglandular hyperplasia rather than a single
1Division of Endocrinology, School of Medicine, Eskisehir Osmangazi
parathyroid adenoma.
University, Eskisehir, Turkey;2Department of General Surgery, School of
DOI: 10.1530/endoabs.49.EP265
Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Introduction
Primary hyperparathyroidism is the most common cause of hypercalcemia in the
general population. Hypercalcemia during pregnancy can result in significant
EP266
maternal and fetal morbidity and mortality.
Primary hyperparathyroidism mimicking metastatic bone disease
Case
Ali Burkan Akyıldız1, Seda Sancak2, Nalan Okurog˘ lu1, Kerem
A 30-year-old pregnant female primigravida in the 31 weeks of gestation with
Yig˘ it Abacar1, Elif Sakcı1 & Ali Ozdemir1
complaint of obstinate constipation was admitted to our emergency department.
1Department of Internal Medicine, Fatih Sultan Mehmet Training and
In laboratory tests, hypercalcemia was detected. She was a Syrian refugee and
Educational Hospital, Istanbul, Turkey;2Division of Endocrinology and
was unable to communicate in English and Turkish. The parathyroid hormone
Metabolism, Fatih Sultan Mehmet Training and Educational Hospital,
(PTH) and albumin-corrected serum calcium levels were high. The results were
Istanbul, Turkey.
203
(12-65) pg/ml and 15.1 (8.5-10.5) mg/dl respectively. Urinary calcium
excretion rate was 440 mg/per day. Tubular phosphorus reabsorption rate was
73%, and the chlor/phosphorus ratio was 54.7. In the light of all these data,
We would like to present a case of primary hyperparathyroidism presumably
primary hyperparathyroidism was diagnosed. Ultrasound imaging revealed a
present with clinically large cystic parathyroid adenoma with multiple destructive
parathyroid adenoma (6!6!19 mm) at the inferior of the left thyroid lobe. In
skeletal lesions, which is of course referred to bone metastases.
our case we started 3000 cc salin infusion and furosemid treatment but her
Case
calcium levels didn’t decrease to safe range. Intravenous calcitonin was added to
A 58-year-old male patient was admitted to the orthopedy polyclinic with left leg
treatment but calcium levels didn’t decrease. We started to hemodialysis but still
pain and on the MR imaging performed here, multiple lytic lesions compatible
was calcium level O12.5 mg/dl. We followed up the patient in hospital until the
with metastasis to the tibia and fibula were detected. He was directed to our
baby’s lung maturation is completed. When the gestation reached the 35th week,
internal medicine clinic for further investigation. The patient had complaints of
parathyroid adenoma excision and caesarean section were performed concur-
widespread bone pain, especially the left leg which lasted for 2 months and was
rently. Post-operative calcium levels decreased. Hypocalcemia improved with
suffering from polydipsia. Biochemical tests showed elevated serum calcium
medical treatment in the newborn.
values and increased intact parathyroid hormone (iPTH), low phosphorus, high
Discussion
alkaline phosphatise, compatible with primary hyperparathyroidism. Erosive and
The main treatment modality of hyperparathyroidism is surgery but if
brown tumour like lesions were detected in bone x-ray. On PET CT imaging,
hyperparathyroidism is diagnosed in third trimester surgical approaches have
extensive, lytic and expansile lesions were observed, especially in the kranium
high risk. Because of the high risk, we trained our patient with medical treatment
and ribs. On the neck ultrasonography, a 50!30 mm sized, septated, irregular
at the hospital until safe birth time. In the postpartum interval to avoid a
contour nodule was detected in the right lobe. Thyroid fine needle aspiration
parathyroid crisis, surgery and cesarean operation were performed simultaneously
biopsy was performed. Histopathological evaluation was benign and there were
during the safe period for the baby.
no findings indicating parathyroid pathology. Parathyroid scintigraphy showed no
DOI: 10.1530/endoabs.49.EP264
lesions compatible with neck or mediastinal adenoma. Due to resistant
hypercalcemia, the patient was given bilateral neck exploration. The parathyroid
mass was localized and resected intraoperatively in the lower pole of the thyroid
nodule extending mediastinum, and histopathological evaluation was compatible
with parathyroid adenoma. Biochemical results due to hyperparathyroidism
normalized after operation and complaints resolved.
EP265
Discussion
Eucalcemic parathyroid hormone elevation after parathyroid surgery
It should be considered that primary hyperparathyroidism may have bone lesions
for sporadic primary hyperparathyroidism
that mimic bone metastasis. Especially in cases where the thyroid nodule is
Gulsah Elbuken1, Sibel Ozkan-Gurdal2, Makbule Begum Balkan2 & Sayid
visible but there is no evidence of parathyroid adenoma in parathyroid
Shafi Zuhur1
scintigraphy intrathroidal parathyroid adenomas should be considered in the
1Department of Endocrinology and Metabolism, Namik Kemal University
differential diagnosis of cystic neck lesions.
Medical School, Tekirdag, Turkey;2Department of General Surgery, Namik
DOI: 10.1530/endoabs.49.EP266
Kemal University Medical School, Tekirdag, Turkey.
Introduction
Serum parathormone (PTH) levels may remain elevated in some patients after
surgery despite achievement of normal serum Ca levels. The factors contributing
EP267
to this phenomenon have not been fully elucidated yet. In this study, we
Acute pancreatitis as the first presentation of primary
retrospectively analysed the data of patients whose serum Ca levels returned to
hyperparathyroidism
normal after parathyroid surgery in our center.
Alexandra Vieira, Marta Ferreira, Daniela Guelho, Teresa Pereira,
Patients and methods
Luis Filipe Silva, Estela Ferreira & Ana Inácio
Computer records of 35 patients who had undergone parathyroid surgery and
Leiria Hospital Center, Leiria, Portugal.
achieved normal serum Ca levels were retrospectively analysed. Despite serum
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
EP269
Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute
Prevalence of hypocalcemia in adults in Minsk, Belarus
pancreatitis, with a reported prevalence of 1.5-8%.
Elena Brutskaya-Stempkovskaya1,2, Alla Shepelkevich1 & Georg Kostin1,3
Clinical case
1Belarusian State Medical University, Minsk, Belarus;2Minsk City
A 25-year-old male patient was referred to the Endocrinology outpatient clinic for
Polyclinic N31, Minsk, Belarus;3Minsk Consulting and Diagnostic Centre,
hypercalcemia diagnosed in the context of acute pancreatitis. He had medical and
Minsk, Belarus.
surgical pathological antecedents of: clavicle fracture after car accident,
cholecystectomy and appendectomy, gastroesophageal reflux disease. Current
medications included proton pump inhibitor daily. Laboratory analysis reported
The prevalence of hypocalcemia among patients non-operated the thyroid and
serum calcium of 3.46 mmol/l (2.20-2.65), phosphorus of 0.70 mmol/l (0.81-
parathyroid glands has increased significantly with the introduction the screening
1.45) and intact parathyroid hormone of
569 pg/ml
(12-88). Biochemical
of calcemia. The main reasons for hypocalcemia are hypoproteinemia and
screening for type 1 and type 2 multiple endocrine neoplasia was performed
hypoparathyroidism.
and was negative. The neck ultrasonography showed a nodular heterogeneity with
Objective
hyperechogenic contours with cystic areas, and posteriorly and inferiorly to the
To study the prevalence of hypocalcemia in the adult in Minsk.
left lobe an hypoechogenic nodular formation, with 2.4 cm of greater axis, which
Materials and methods
may correspond to the parathyroid gland with increased dimensions. Bone
We studed 1207 people, average age 53.9G17.25 (892 women, 315 men) from 18
densitometry showed osteopenia. Sestamibi parathyroid scintigraphy revealed a
to
96 years. Examination: total calcium, total protein. Hypocalcaemia was
focus of significant radiopharmaceutical retention on the projection of the lower
detected in total calcium level !2.2 mmol/l.
left lobe pole, alteration compatible with parathyroid adenoma. A lower left
Results
parathyroidectomy and left lobectomy of thyroid was performed without
Hypocalcaemia was recorded in 40 people (3.3/100 adults), the mean age was
complications. The histopathological result confirmed the diagnosis of
42.9G17.63 years (32 women, men - 8). In the age group up to 30 years
parathyroid adenoma. At the last visit, he had normal PTH and calcemia values.
hypocalcemia was revealed in 12 cases (8.3%, in women - 10.3%); in the group
During the follow-up he had recurrent acute pancreatites episodes.
30-44 years - five cases (1.3%, in men - 4.7%, in women - 0.3%), 45-59 years -
Conclusions
three cases (1.1%, in men - 2.5%, in women - 0.5%); 60-74 years - ten cases
The authors present this case because of its rarity: hyperparathyroidism in a young
(2.5%, in men - 2.6%, in women - 2.4%); O75 years - one case (0.7%, in men -
patient whose presentation was of acute pancreatitis without the classic clinic
3.2%). The prevalence of hypocalcemia in the group up to 45 years - 6.6 per 100
manifestations of hypercalcemia.
adults. The prevalence of hypocalcemia in the group 45 years over - 1.7/100
adults. The results of the study indicate a significant occurrence of hypocalcemia
DOI: 10.1530/endoabs.49.EP267
in the age group up to 45 years (c2Z20.34, pZ0.00001).
Conclusion
The prevalence of hypocalcemia in the adult population of Minsk-city was
3.3/100 adults (33:1000). The prevalence of hypocalcemia in the age group up to
45 years was 6.6/100 adults, in the age group 45 years over was 1.7 per 100 adults.
The results of the study indicate a significant occurrence of hypocalcemia in the
age group up to 45 years.
DOI: 10.1530/endoabs.49.EP269
EP268
Gender difference in clinical presentation of primary
hyperparathyroidism
Laura Gianotti, Elena Castellano, Francesco Tassone, Claudia Baffoni,
Flora Cesario, Gianpaolo Magro, Micaela Pellegrino & Giorgio Borretta
EP270
Division of Endocrinology, Diabetology & Metabolism, S.Croce & Carle
Hospital, Cuneo, Italy.
Assessment of changing in the therapeutic attitude in patients with
primary hyperparathyrodism in conservative management after the
realization of radial densitometry
Objective
Jose Alvaro Romero Porcel, Guillermo Martinez De Pinillos Gordillo,
Primary hyperparathyroidism (PHPT) is one of the most common endocrine
Fernando Garcia Perez, Eyvee Arturo Cuellar Lloclla, Jose Ignacio
disorders, with a female to male ratio of 3:1. Currently most patients with PHPT
Fernandez Pen˜ a, Carmen Carretero Marin, Juan Manuel Garcia De Quiros,
are asymptomatic. However, data about the gender impact on the clinical
Ignacio Fernandez Lopez, Mariana Tome Fernandez-Ladreda & Maria
presentation of PHPT are lacking.
Victoria Cozar Leon
Methods
Hospital De Valme, Sevilla, Spain.
We evaluated the difference in symptoms and biochemical parameters between
men and women with PHPT in a single center series of 417 patients.
Results
Introduction and objectives
Male PHPT patients resulted significantly younger
(PZ0.046) and more
In the 4th Workshop on Primary Hyperparathyroidism, it is recommended to
frequently symptomatic than women (62.3% vs 47%, PZ0.016). Furthermore,
perform BMD by DXA of third radius as well as lumbar spine and hip DXA in the
renal stone incidence was higher in male than in female patients (50.5% vs 33%,
initial assessment and follow up of patients with primary hyperparathyroidism.
PZ0.003) while no difference was found in the incidence of osteitis fibrosa
This test is not available in many centers, which means that only T Score values of
cystica (21.5% vs 20.7%). Instead, osteoporosis, established as T score ! 2.5 at
the lumbar spine and hip are used to certify the absence of osteoporosis in
any site, was significantly predominant in women (56.5% vs 39.3%, PZ0.015)
asymptomatic patients wich conservative management is performed. Our
rather than in men. However, no differences were found in classical biochemical
objective is to evaluate if the recent addition of radius DXA has modified the
disease parameters (i.e. PTH, serum calcium, phosphorus, 24 h-urine for calcium)
management of this patients.
nor in creatinine and vitamin D levels. Finally, the proportion of patients with
Materials and methods
surgical indications (symptomatic patients and asymptomatic patients meeting
Retrospective study including patients in follow-up by primary asymptomatic
surgical criteria recommended by current guidelines) was similar in male and in
hyperparathyroidism in conservative management according to the Fourth
female PHPT patients (84,6% vs 84,9%).
Workshop criteria when radial densitometry for the first time in its evolution.
Discussion
Changes after the DXA results were evaluated.
Gender leads to a different clinical presentation in PHPT patients, male patients
Results
being usually younger and more frequently affected by a symptomatic form of the
20 patients (65.4 years G11.14, 90% women) with a follow-up of 3.95 years
disease. In addition, renal stones are significantly more frequent in men, while in
G1.97 were included. Blood calcium levels 11.05G0.45 mg/dl, mean PTH of
women osteoporosis is prevalent. On the other hand, PHPT biochemical
105.46 pg/ml G60.9. None presented lumbar and/or femoral T-Score scores
presentation seems not to be influenced by gender. Furthermore, surgical
values lower tan K2.5 DS (lumbar T K0.15 DS G2.17, femoral K0.77 DS
indication is reached equally in male and female PHPT patients.
G0.98). The radial T Score was K2.67 DS G2.45. The radial densitometry
Conclusions
results changed the clinical attitude in 70% of the patients, from the recommed
In male patients PHPT is less frequent but more commonly symptomatic than in
conservative management to surgical treatment in those with a T-Score lower
female patients. PHPT clinical presentation is influenced by gender, although
K2.5 DS in the distal radius and T-Score higher than K2.5 DS in the lumbar
there are no sex-related differences in its biochemical profile.
and/or femoral.
Conclusions
DOI: 10.1530/endoabs.49.EP268
Our study reinforces the importance of performing distal radius densitometry in
patients in which conservative management is giving to be performed, as is
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
recommended as recommended by international criteria. Lack of implementation
30.5% had severe hypercalcaemia
(cCa R3.50 mmol/l). Aetiology:
47.2%
may lead to conservative management in patients with osteoporosis.
malignancy related hypercalcaemia, 15.1% primary hyperparathyroidism, 5.6%
DOI: 10.1530/endoabs.49.EP270
secondary or tertiary hyperparathyroidism, 9.4% drug-related, 15.1% unknown.
Frailty was documented reason to withdraw further investigations in 62.5% of the
latter. Coexistent active prostate cancer and hyperparathyroidism was found in
two cases. Investigations: PTH was checked in 67.8% cases, Phosphate in 64.4%,
ALKP 100%. Of the cases with suppressed PTH, only 72.2% had serum
paraproteins checked, 55.5% urinary Bence-Jones proteins and 83.3% imaging
EP271
for malignancy. Vitamin D was only checked in 22.6%. Management: Patients
received an average of 3L intravenous fluids in the first 24 h. 62.7% received
A rare case: intrathymic parathyroid adenoma
intravenous bisphosphonates. 13.5% had less than 2L intravenous fluids prior to
Veysi Asoglu1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
bisphosphonate. Second line treatment with Cinacalcet, steroids, Furosemide or
Ebru Tastekin3, Nuray Can3, Atakan Sezer4, Funda Ustun4 &
Calcitonin was used in
20.7% cases. There were no cases of rebound
Sibel Guldiken2
hypocalcaemia.
1Trakya University, Medical Faculty, Department of Internal Medicine,
Conclusions
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
Compliance with guidelines recommendations was suboptimal in certain areas,
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
not entirely explained by the adoption of a palliative approach with focus on
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
symptom control in cases. Training opportunities will be devised locally to
University, Medical Faculty, Department of Surgery, Edirne, Turkey;
improve practice. Bisphosphonate use in the Emergency department should be
5Trakya University, Medical Faculty, Department of Nuclear Medicine,
controlled for the appropriate circumstances. Vigilance is recommended
Edirne, Turkey.
assigning causality in active malignancy, given that
11.1% of pre-existing
malignancy cases were found to have concurrent PTH driven hypercalcaemia,
Primary hyperparathyroidism in the most common cause of hypercalcemia. 87%
despite only 38.9% of them being investigated with a PTH level.
of the cases present with single adenoma, 9% of them have hyperplasia, while
DOI: 10.1530/endoabs.49.EP272
multiple adenomas and parathyroid malignancy are detected in 3 and 1% of the
cases, respectively. Although it is rare, parathyroid adenomas may be ectopic. The
most common locations for ectopic parathyroid adenomas are thymus,
tracheaesophageal cleft, carotis sheet, intrathyroidal and paraesophageal area.
In this study, we aimed to present an intrathymic parathyroid adenoma as a rare
case.
A 46-year old female patient who received hemodialysis for chronic renal failure
secondary to chronic glomerulonephritis for
7
years and then underwent
EP273
cadaveric renal transplantation in
2010 was presented for routine follow-up
Higher circulating parathyroid hormone concentration fascilitates
visit. Laboratory examination revealed urea:19 mg/dl(n:15-43),creati-
preoperative diagnostic imagings for localization in primary
nin:0.8 mg/dl(n:0.57-1.11)), calcium:11.5 mg/dl (n:8.6-10.2 mg/dl), phosphor-
hyperparathyroidism
us:2.7 mg/dl (n:2.4-5.1 mg/dl), albumin:4.2 g/l (n:3.2-4.8 g/l), iPTH:340 pg/ml
Kentaro Okamoto1, Yoshihiko Itoh1, Akiyuki Kawashima1, Aya Amano1,
(n:15-68), creatinin clerarance in 24-h urine: 82 ml/min, calcium in 24-h urine:
Kyoko Okazaki1, Hiroyuki Murabe1, Toshihiko Yokota1, Risa Yoshimoto2,
410 mg/day. Neck ultrasonography was performed, which demonstrated 12!
Akiko Sahara2, Junko Tomokuni2 & Keita Hamamatsu3
9 mm sized well-circumscribed nodular lesion with heterogeneous echo at
1Kurashiki Central Hospital, Department of Endocrinology and Rheuma-
inferior part of lower pole of left thyroid gland (thyroid nodule? Parathyroid
tology, Okayama, Japan;2Kurashiki Central Hospital, Department of
adenoma?). Femoral neck and L1-L4
vertebra were osteopenic on bone
Laboratory Medicine, Okayama, Japan;3Graduate School of Medicine
densitometry. Parathyroid scintigraphic examination detected no scintigraphic
and Faculty of Medicine Kyoto University, Department of Diabetes,
signs characteristic for parathyroid adenoma in the neck and mediastinum. The
Endocrinology and Nutrition, Kyoto, Japan.
patient underwent parathyroidectomy following surgical exploration. Histopatho-
logic examination of parathyroidectomy material revealed intrathymic para-
thyroid adenoma. The patient was scheduled for outpatientclinic follow-up with
Introduction
post-operative laboratory findings of iPTH: 38 pg/ml, Ca:9.9 mg/dl, P:2.5 mg/dl,
For minimally invasive surgery of primary hyperparathyroidism (PHPT), the
Alb:4.3 g/l, kreatinin:0.7 mg/dl.
identification of the accurate localization is required. As preoperative diagnostic
Annual incidence of primary hyperparathyroidism is 0.27%. Since Primerhi-
imagings, we perform ultrasound, technetium 99m-sestamibi scintigraphy and
perparatiroidizmin yıllık gorulme oranı
% 0.27dir. Since both thymus and
either or both of megnetic resonance imaging or computed tomography in all
parathyroid gland embrologically derive from
3rd pharyngeal cleft, ectopic
cases. The aim of the present study is to evaluate the clinical biochemical factors
parathyroid adenomas may locate within thymus. It is very important to pre-
that fascilitate preoperative diagnostic imagings for localization.
operatively determine the localisation of ectopic parathyroid adenomas to prevent
Methods
surgical errors.
We retrospectively searched the medical records of patients with PHPT who were
DOI: 10.1530/endoabs.49.EP271
admitted in our hospital from 2014 to 2016. Fifty-five patients were identified.
Four patients with parathyroid carcinoma, multiple endocrine neoplasia type 1,
familial hypocalciuric hypercalcemia, and detectable parathyroid hormone-
related protein were excluded. Fifty-one patients were included in the study. We
defined 36 patients as the ‘localized’ group, including 30 patients who underwent
curative operation and 6 non-operative patients whose suspicious adenoma was
EP272
consistently identified by two or more of diagnostic imagings. And other 15
patients were defined as the ‘non-localized’ group. We compared biochemical
Audit of emergency hypercalcaemia management in the acute
data including intact parathyroid hormone (iPTH), serum calcium, urine calcium,
medical unit
and tartrate-resistant acid phosphatase 5b.
Emanuela Bejinariu, Rahat Tauni, Tharanga Rathnayake, Vinit Shah,
Results
Shiu-Ching Soo & Ritwik Banerjee
iPTH was statistically higher in the ‘localized’ group (146 [103-195] vs. 98 [82-
Luton and Dunstable University Hospital, Luton, UK.
136] pg/ml: pZ0.010). Multivariate logistic regression analysis demonstrated
that the usefulness of preoperative diagnostic imaging was ensured only in higher
Introduction
iPTH (pZ0.014). When we set the cut-off value of iPTH to 150 pg/ml, sensitivity
We conducted a retrospective audit of emergency management of hypercalcaemia
was 48.6% and specificity was 87.5% (AUC: 0.73 [95% CI 0.59-0.87]). When we
presenting to the acute medical team and compared our practice against the
used whole parathyroid hormone (wPTH) in place of iPTH, we obtained similar
Society for Endocrinology guidelines September 2016.
results: the cut-off value 85 pg/ml with sensitivity 57.1% and with specificity
Method
87.5% (AUC: 0.84 [95% CI 0.72-0.96]).
53 adult patients with 59 corresponding medical admissions were identified from
Conclusion
tracking all biochemistry samples with corrected calcium (cCa) R3.0 mmol/l
Both iPTH and wPTH as circulating parathyroid hormone concentration are
processed between August 2015 and July 2016 trustwide. We conducted a
useful to predict whether preoperative diagnostic imagings can identify the
retrospective review of their admissions’ case records.
acurate localization of the parathyroid adenoma.
Results
DOI: 10.1530/endoabs.49.EP273
Characteristics: age 40-98 years old (median 79), 60.4% female, median length
of stay 7 days, presenting cCa range: 3.04-5.36 mmol/l (median 3.31 mmol/l).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP274
EP276
Calcifediol is more effective than cholecalciferol in the treatment of
The changing face of primary hyperparathyroidism
severe vitamin D deficiency in a patient submitted to malabsorbitive
Ifigenia Kostoglou-Athanassiou1, Alexios Travlos2, Evaggelia Vogiatzi2 &
bariatric surgery: a case report
Eleni Pantazi2
Alessandro Brancatella, Daniele Cappellani, Edda Vignali,
1Department of Endocrinology, Red Cross Hospital, Athens, Greece;
Domenico Canale & Claudio Marcocci
2Department of Endocrinology, Alexandra Hospital, Athens, Greece.
Department of Endocrinology and Metabolism, Univesity of Pisa, Pisa,
Italy.
Primary hyperparathyroidism is a disease which nowadays is being diagnosed
with increasing frequency. The diagnosis of primary hyperparathyroidism is
Context
based on routine calcium measurement, which if detected abnormally elevated
Vitamin D deficiency following malabsorptive bariatric surgery can lead to
leads to the screening of the patient for primary hyperparathyroidism. Therefore,
osteomalacia. We report a patient with severe vitamin D deficiency following
primary hyperparathyroidism is frequently detected early in the course of the
malabsorptive bariatric surgery successfully treated with calcifediol but not
disease. Consequently, severe musculoskeletal manifestations may be lacking in
cholecalciferol.
the modern world setting in patients with primary hyperparathyroidism.
Case description
The aim was to describe musculoskeletal manifestations in patients with primary
A 40-year-old woman, submitted to biliopancreatic diversion 20 years before and
hyperparathyroidism being followed up in a center of excellence in Athens.
chronically treated with 50 000 IU cholecalciferol weekly, was admitted to our
A cohort of 38 patients, 33 female and five male, with primary hyperparathyroid-
Endocrine Unit because of severe low-back pain, muscle weakness, generalized
ism aged 62.31G1.87 years, being followed up within a center of excellence in
muscular hypotrophy, associated with hypocalcemia and elevated PTH levels.
Athens was studied. Musculoskeletal manifestations were recorded in the cohort
Initial evaluation revealed low albumin-corrected serum calcium (7.4 mg/dl),
of the patients studied.
high serum PTH (240 pg/ml), bone-specific alkaline phosphatase (125 mg/l) and
Within the cohort of
38 patients with primary hyperparathyroidism being
1,25-dihydroxyvitamin D (112 pg/ml) concentrations, and undetectable serum
followed up within a center of excellence in Athens, 12 patients (31.58%) had
25-hydroxyvitamin D (!7 ng/ml). Bone mineral density (BMD) was markedly
osteoporosis, 2 (5.26%) had osteopenia, 7 (18.42%) had diffuse bone pain, 2
low. Normocalcemia was initially restored with i.v. albumin and calcium
(5.26%) had diffuse myalgia and 1 (2.63%) had suffered a wrist fracture. Within
gluconate. Treatment with calcitriol (0.5 mg three times daily) and oral calcium
the cohort studied
18
(47.37%) patients did not have any musculoskeletal
carbonate (1000 mg daily) was simultaneously started and cholecalciferol was
manifestations.
replaced with calcifediol
(125 mg
(5000 UI) daily)). During follow-up the
It appears that primary hyperparathyroidism does not have severe musculoske-
calcifediol dose was progressively tapered to 25 mg (1000 UI) daily and the
letal manifestations, such as osteitis fibrosa cystica, in the real world setting in
calcitriol dose progressively reduced and finally withdrawn. Serum biochemistry
patients followed up for the disease within a center of excellence in Athens.
normalized, BMD significantly increased and the patient’s clinical conditions
However, patients with primary hyperparathyroidism appear to have diffuse bone
progressively improved, with a substantial recovery of autonomy.
pain as well as osteoporosis, which may be complicated by a fracture in some of
Conclusions
the cases. Early detection and diagnosis of the disease seems to have altered the
Our data suggest that calcifediol migth be more efficacious than cholecalciferol
face of primary hyperparathyroidism in the real modern world setting.
for prevention and treatment of vitamin D deficiency in patients treated by
DOI: 10.1530/endoabs.49.EP276
malabsorptive bariatric surgery.
DOI: 10.1530/endoabs.49.EP274
EP277
Single center experience of intact parathyroid hormone determination
in washout samples of suspicious parathyroid adenomas
Mustafa Sahin1, Asena Gokcay Canpolat1, Elif Ediboglu2,
¸ ag˘ lar Keskin1,
EP275
S¸ ule Canlar1, Ozgur Demir1, Sevim Gullu1, Murat Faik Erdogan1,
The effect of 1,25(OH)2D3 on interferon i secretion by human
Rıfat Emral1 & Demet Corapcioglu1
mononuclear cells in vitro
1Ankara University Faculty of Medicine, Department of Endocrinology and
Lambros Athanassiou1, Andrianos Nezos1, Ifigenia Kostoglou-Athanas-
Metabolism, Ankara, Turkey;2Ankara University Faculty of Medicine,
siou2, Clio Mavragani1, Panagiotis Athanassiou3 & Michael Koutsilieris1
Department of Internal Medicine, Ankara, Turkey.
1Department of Physiology, Medical School, University of Athens, Athens,
Greece;2Department of Endocrinology, Red Cross Hospital, Athens,
Greece;3Department of Rheumatology, St Paul’s Hospital, Thessaloniki,
Introduction
Greece.
Minimally invasive surgery is an alternative surgical approach for primary
hyperparathyroidism with less surgical trauma and anesthesia complications.
Neck ultrasonography and scintigraphy are still the first step tools for localisating
Vitamin D is a secosteroid hormone known for its skeletal effects. Recently, the
parathyroid lesions. Intact parathyroid hormone (PH) determination in washout
extraskeletal effects of vitamin D are under investigation. Vitamin D is thought to
samples is really very useful when parathyroid lesions can not be easily
exert an immunomodulatory effect, having multiple effects on the immune
distinguished from thyroid lesions or sometimes lymph nodes.
system. It is known to induce immune tolerance and also to enhance the immune
Method
response to bacteria.
In our clinic, we performed ultrasonography guided parathyroid fine needle
The aim was to study the effect of 1,25(OH)2D3 on interferon I secretion by
aspiration procedure for 119 patients diagnosed with primary hyperparathyroid-
human mononuclear cells in vitro.
ism between January
2005 and January
2016. Intact parathyroid hormone
Human mononuclear cells were separated from whole human blood from healthy
determination was performed in washout samples. 80 of the study group also had
female human subjects using the Lymphoprep protocol. Subsequently they were
a parathyroid scintigraphy. All of the patients underwent parathyroid surgery.
placed in wells 106 cells/well and were cultivated for a period of 6 h at a
Results
temperature of 37 8C in a humidified environment of 5% CO2 in the presence or
In 106 of the study group had positive parathyroid hormone washout (phw) results
absence of interferon alpha 400 U, 1,25(OH)2D3 250 pmol, interferon alpha
according to blood PH levels. Significant difference was achieved in localisation
400 U and 1,25(OH)2D3 250 pmol. Subsequently the content of the wells was
of the lesion (p:0.006), serum calcium levels (p:0.01) and PHW levels (p!0.001)
centrifuged and the precipitate was treated with Trizol for RNA extraction of
between washout negative and positive group. No difference was observed in
genes known to be stimulated by interferon alpha. Real time PCR was performed
gender, age, presence of stone, levels of serum phosphorus, creatinin, alkaline
for MX1, IFIT1, IFI44 and GAPDH as a control.
phosphatase, parathyroid hormone, vitamin D and 24 h urinary calcium levels. 28
Interferon alpha was shown to stimulate genes related to interferon I secretion, i.e.
patients in the scintigraphy group had negative scan whereas 47 of them had both
it was found to have a positive feedback on its own secretion. 1,25(OH)2D3 was
scintigraphy and PHW positive. 24 of the patients had positive PHW results but
found to modulate interferon I gene augmentation induced by interferon alpha
negative scintiscans.
treatment.
Conclusion
Vitamin D is being investigated for its immunomodulatory properties. In the
The present study represents that ultrasonography combined with PHW
present study vitamin D was found to modulate the response of human
evaluation seems to be more diagnostic according to parathyroid scintigraphy.
mononuclear cells to interferon alpha treatment.
DOI: 10.1530/endoabs.49.EP277
DOI: 10.1530/endoabs.49.EP275
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP278
exclusion of other conditions, such as familial hypocalciuric hypercalcaemia.
Symptomatic patients should usually be referred for parathyroidectomy. For
Primary hyperparathyroidism due to atypical adenoma: clinical,
asymptomatic patients there are clear guidelines for surgical referral, based on the
biochemical and histological features of an Italian cohort
Fourth International Workshop (2014) recommendations. This study evaluates
Federica Saponaro1, Marina Di Giulio1, Elena Pardi1, Simona Borsari1,
current practice for diagnosing and managing primary hyperparathyroidism
Gabriele Materazzi2, Claudio Marcocci1 & Filomena Cetani1
compared to international guidelines, at a large UK teaching hospital.
1Endocrinology Unit 2, University of Pisa, Pisa, Italy;2Endocrine Surgery,
Methods
University of Pisa, Pisa, Italy.
We evaluated all new cases of PHPT seen in outpatient endocrinology clinics
between January 2014 and July 2016. Data were collected using a standardised
Primary hyperparathyroidism (PHPT) is mostly due to a benign parathyroid tumor
proforma. Data fields included demographics, biochemistry and imaging. Follow-
(99%). Some have parathyroid ‘atypical adenomas’, rare tumors with histological
up data on surgical referrals, histology and outcomes were also collected.
features of parathyroid cancer (PC) (fibrous trabeculae, thick fibrous bands,
Results
mitotic figures in parenchymal cells), without local invasion or metastasis. We
Of the
121
patients, at diagnosis,
50.4% were symptomatic. Complete
evaluated 20 patients with histological diagnosis of atypical adenomas. Patients
investigation data were available for 117. 59.8% had all relevant investigations
were 13 women and seven males (mean age: 55G13 yrs). Nineteen patients had a
performed as recommended per guidelines. Urinary calcium was conducted in
sporadic PHPT and one a Familial Isolated PHPT (FIHP). At least one of the
67.5% of patients, of those, 44.3% had inappropriate vitamin D levels at the time
following symptoms was present in 8 (40%) patients: nephrolithiasis (nZ8),
of collection. At diagnosis, 30.0% patients had renal complications and 36.3%
clinical fragility fractures
(nZ1), neuropsychiatric symptoms (nZ6). In the
had osteoporosis. 84% of the 121 met criteria for surgery, although 58.8% were
remining patients (nZ12) PHPT was asymptomatic. Osteoporosis was detected in
actually referred. The most common reasons for non-referral were patient choice
8
(40%). Preoperative imaging was positive in 16 (80%) patients. The association
(33.3%) and fitness for surgery (45.5%). On imaging, 74% had a single adenoma,
with other tumors was recorded: papillary thyroid carcinoma (nZ4), adrenal
11.7% had no obvious adenoma. 75% had positive correlation between imaging
bilateral hyperplasia (nZ1), breast cancer (nZ1), Morton’s neuroma (nZ1).
and surgical findings. 3 months post-operatively, 91% of patients had normal
Biochemical tests at baseline were: albumin adjusted serum calcium 12.4G
calcium and 68% had normal PTH.
0.8 mg/dl, PTH 204 (160-277) pg/ml and 25OHD 13.4G7 ng/ml. All patients
Conclusions
underwent PTx. The histological diagnosis was of atypical adenoma (mean
This study shows that the majority of patients with PHPT are diagnosed and
diameter 24G10.6 mm) with the following features: fibrous trabeculae in two,
investigated as per guidelines. Almost all patients had a normal calcium 3 months
thick fibrous bands in 13, capsular invasion infiltration in seven and mitotic
post operatively, suggesting surgery was curative. However, urinary calcium
figures in two. All but one patients were cured after PTx and remained
estimation was performed without the correction of vitamin D levels in a
normocalcemic (mean follow-up 5 years). One patient, with apparently sporadic
significant percentage of patients, thereby affecting accuracy of interpretation.
PHPT, had persistent hypercalcemia and he is in follow-up. This study suggests
DOI: 10.1530/endoabs.49.EP280
that PHPT due to atypical adenoma is generally asymptomatic at diagnosis, it has
a moderate-severe biochemical profile resembling that of PC, it is a sporadic
disease and shows a benign prognosis in the majority of cases. We found an
association with other tumors, that will be evaluated in further studies.
DOI: 10.1530/endoabs.49.EP278
EP281
EP279
Fahr Syndrome and idiopathic primary hipoparathyroidism - clinical
Medullary vertebral compression in primary hyperparathyroidism
case
Fedala Saida, Meskine Djamila, Kedad Lamia, Fafa Nadira & Toubal Zakia
Ana Filipa Martins1, João Martin Martins1,2 & Sónia do Vale1
Laboratory of Endocrinology and Metabolism (LEM 1), Algiers, Algeria.
1Hospital de Santa Maria - CHLN, Lisboa, Portugal;2Faculdade de
Medicina de Lisboa, Lisboa, Portugal.
We report the case of an ectopic parathyroid adenoma, revealed by a medullary
vertebral compression by a brown spinal tumor in a 44-year-old women. Physical
Introduction
examination revealed a lower limb weakness, paresthesia and radicular lower
Fahr syndrome (FS) is a neuropsiquiatric condition due to progressive basal
extremity pain. Magnetic resonance imaging (MRI) showed osteolytic vertebral
ganglia calcification. Although physiopathology is not completely understood, it
lesions suggesting metastatic localizations. A thoracic CT scan identified a
may be secondary to infectious, metabolic and genetic diseases.
mediastinal mass measuring 6.2 cm in the major axis. Biological evaluation
Case report
revealed a hypercalcemia
(135 mg/l) with very high PTH
(1896 pg
/ml),
A 65-year-old male Caucasian was referred to the outpatient endocrine
parathyroid scintigraphy confirmed the mediastinal ectopic parathyroid. The
department because of hypocalcaemia. No perioral paresthesia or tingling of
patient underwent surgical resection of the mediastinal mass that proved to be a
the fingers and toes were noticed. He complained of longstanding hand tremor and
parathyroid ectopic adenoma. She showed a remarkable improvement in her
since one year ago apathy and gait instability were evident. Past medical history
clinical condition observed
6
months after parathyroidectomy. Medullary
revealed High Blood Pressure under treatment. He also referred previous use of
vertebral compression by a brown spinal tumor in primary hyperparathyroidism
anti-convulsivant medication since he was 15 because of diagnosed epilepsy.
is rare, surgery of parathyroid adenoma improved clinical condition without
Drugs were suspended at 20th with no further seizures. No previous cervical
resection of the brown tumor, However surgical decompression may be necessary
surgery or irradiation were done. Her death mother was also diagnosed of
in some cases.
epilepsy. Besides slow and rigid movement, physical examination was otherwise
DOI: 10.1530/endoabs.49.EP279
normal, with negative Chvosteck and Trouseau. Deafness, visual field defects or
dismorphisms were absent. Analytic evaluation confirmed albumin-corrected
hypocalcemia, hyperphosphatemia, normal serum magnesium, hypoparathyroid-
ism with sufficient 25OH-vitamin D levels. Slight ferropenia and chronic renal
disease grade
2
were diagnosed. Besides Hashimoto thyroiditis, no other
endocrinopathy was evident. Ecocardiogram evidenced left auricular dilatation
and reduced global systolic function. Cystic renal disease and slight cystic
EP280
calcifications were documented on kidneys ultrasound and cervical ultrasound
Management of primary hyperparathyroidism: Experience of a large
evidenced multinodular goiter. Bone densitometry of femur and lumbar spine was
UK teaching hospital
normal. craneoencephalic TC identified bilateral simetric parenquimatous
Rebecca Sagar, Amy Longhurst & Afroze Abbas
calcifications, both supra and infratentorial, with extensive involvement of
Leeds Centre for Diabetes and Endocrinology, Leeds Teaching Hospitals,
basal ganglia. I123-SestaMIBI scintigaphy did not fixate in cervical imaging. Anti-
Leeds, UK.
NALP5 antibody was negative, as well as CASR activating mutation.
Discussion and conclusion
Background
Parathyroid hormone and calcium abnormalities are the most common metabolic
Primary hyperparathyroidism (PHPT) is a common cause of hypercalcaemia seen
disorders associated to FS. We describe a patient diagnosed of idiopathic
in outpatient endocrinology clinic. Diagnosis is based on biochemistry and
hypoparathyroidism. Basal ganglia calcifications support a long-standing
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
hypocalcemia, and chronic ion disturbance may have contributed to the absence
parathyroid carcinoma, In familial primary hyperparathyroidism, reoperative
of usual muscular complaints.
parathyroidectomy are challenging entities that require special consideration and
DOI: 10.1530/endoabs.49.EP281
expertise.
DOI: 10.1530/endoabs.49.EP282
EP282
EP283
Clinical presentations of four patients with familial isolated
When is it worthwhile to perform parathyroid SPECT/CT scintigraphy
hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome
in primary hyperparathyroidism?
Taner Bayraktaroglu1, Utku Sentosun1, Dilek Karakaya Arpaci1,
Malgorzata Trofimiuk-Muldner1,2, Anna Skalniak1,2, Lukasz Kulczynski1,2,
Ali Ugur Emre2, Mertol Gokce3, Serkan Uysal3, Rabiye Uslu Erdemir4,
Aleksandra Zapendowska-Dudek2, Aneta Budek2, Monika Buziak-
Burak Bahadir5 & Guldeniz Karadeniz Cakmak2
1,2
Bereza1,2, Anna Sowa-Staszczak1,2 & Alicja Hubalewska-Dydejczyk
1Bulent Ecevit University, Faculty of Medcine, Department of Internal
1Chair and Department of Endocrinology, Jagiellonian University Medical
Medicine, Division of Endocrinology and Metabolism, Zonguldak, Turkey;
College, Krakow, Poland;2Endocrinology Department, University Hospital
2Bulent Ecevit University, Faculty of Medcine, Department of General
in Krakow, Krakow, Poland.
Surgery, Zonguldak, Turkey;3Bulent Ecevit University, Faculty of
Medcine, Department of Chest Surgery, Zonguldak, Turkey;4Bulent Ecevit
University, Faculty of Medcine, Department of Nuclear Medicine,
Introduction
Zonguldak, Turkey;5Bulent Ecevit University, Faculty of Medcine,
Observed increasing frequencies of asymptomatic or oligosymptomatic PHP
Department of Medical Pathology, Zonguldak, Turkey.
cases may increase the rate of false negative imaging results.
Aim
To determine the level of PTH and calcium at which an enlarged parathyroid
Introduction
gland can be detected by parathyroid SPECT/CT.
Primary hyperparathyroidism is commonly treated with targeted parathyroidect-
Material and methods
omy guided by preoperative imaging and intraoperative parathormone
A retrospective analysis of 117 patients diagnosed with PHP (100 females and 17
monitoring. Despite advanced imaging techniques, failure of parathyroid
males, aged 16-88 years) was performed. In each patient parathyroid SPECT/CT
localization still occurs. Hyperparathyroidism-jaw tumor syndrome and familial
after administration of
500 MBq of 99mTc-MIBI was conducted (Siemens
isolated hyperparathyroidism are a rare autosomal dominant tumor syndrome
Symbia T16). Serum calcium and parathormone (PTH) were measured in each
characterized by hyperparathyroidism. In this report, we present four patients
patient, serum phosphate was estimated in 109 subjects. Statistical analysis was
with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor
performed with Statistica 12 Software.
syndrome, below.
Results
Case 1
Median serum calcium level was
2.77 mmol/l
(LQ and UQ - 2.66 and
A 26-year-old man with left maxillary tumoral lesion is referred. He had the
2.87 mmol/l, respectively); median serum PTH level was 122.8 pg/ml (97.2 and
elevated serum calcium and parathormon levels, osteoporosis, rena anomalia,
191.9 pg/ml); median plasma phosphate was 0.84 pmol/l (0.74 and 0.98 mmol/l).
nephrolitiasis, Acording to the diagnosis of hyperparathyroidism jaw-tumor
In
70
(59.8%) patients an enlarged parathyroid gland was detected with
syndrome, imaging modalities included neck sonography, scintigraphy, compu-
SPECT/CT. There was a statistically significant difference in PTH levels (median
terized tomography indicaed that a ectopic parathyroidal adenoma, then it was
138.15 and 114.80 pg/ml, respectively; PZ0.02) and serum calcium levels
removed by videoscopic assisted medastinoscopy with temporarily hypo-
(median2.74 and 2.67 mmol/l, P!0.01) between patients with positive and
parathyroidism.
negative parathyroid SPECT/CT. Serum phosphate levels did not differ
Case 2
significantly
(PZ0.19). Receiver-operator curves
(ROCs) were drawn to
A 43-year-old-man who is a relative of Case 1 is presented with persistent
establish PTH and serum calcium cut-off levels for positive parathyroid
myalgia-arthralgia and nausea due to hypercalcemia caused by increased
SPECT/CT imaging. Sensitivity and specificity of parathyroid scintigraphy
parathormon levels. Sonographic and scintigraphical evaluations of the neck
were 38 and 89.6%, respectively, for PTH cut-off level of 191.9 pg/ml, and 52 and
showed that multiple irregular nodules of thyroid and suspected parathyroid
79%, respectively, for serum calcium cut-off level of 2.74 mmol/l.
adenomas. Fine neddle aspiration cytology of the nodules and pathological
Conclusions
lymphadenopathy revealed a suspect of the low differentiated thyroidal
Limiting parathyroid SPECT/CT to patients with significantly increased PTH
carcinoma with lymphatic invasion. In wash-out sampling from suspected
and/or serum calcium levels, particularly if surgical treatment is not considered,
parathyroid adenoma, parathormon levels were increased. Total thyroidectomy
may decrease false negative imaging rates and allow to avoid unnecessary
with central and lateral neck dissection in addition adenomectomy with hungry
radiation exposure. More precise determination of PTH and calcium cut-off levels
bone syndrome.
requires analysis of larger patients group data.
Case 3
A 600-year-old-man who is in relations with Case 1 and Case 2 is complained
DOI: 10.1530/endoabs.49.EP283
with nausea-vomiting and lower back pain with osteoporotic fractures of left
femur and left humerus. His serum levels of calcium and parathormon are highly
increased. Imaging modalities showed a suspected lesion in the inferior region of
the left thyroidal localization. After minimal invasive intervention and selective
parathyroid sampling, the second operation included exploration and thyroid-
ectomy with 3.5 paratyhroidectomy and implantation to sternocleidomastoid
muscles were performed. Postoperatively, he had hypothyroidism with elevated
serum calcium and parathormon levels. Thereafter hybrid nuclear modalities
EP284
showed a suspected paratrakeal lesion, the case referred to reoperation with
Parathormone (PTH) as a marker of vitamin D (VitD) deficiency
radioguided parathyroid surgery.
Malgorzata Trofimiuk-Muldner1,2, Anna Skalniak1,2,
Case 4
Malgorzata Kiec-Klimczak1,2 & Alicja Hubalewska-Dydejczyk1,2
The patient was a 51-year-old man (who is a brother of Case 3) presenting without
1Chair and Department of Endocrinology, Jagiellonian University Medical
any symptoms. He had hypercalcemia (12.2 mg/dl) and hyperparathyroidism
College, Krakow, Poland;2Department of Endocrinology,
(247 pg/ml). Parathyroid lesion detected with sonography and scintigraphical
University Hospital in Krakow, Krakow, Poland.
evaluations, and it is referred to minimal invasive parathyroid adenomectomy.
Conclusion
Primary hyperparathyroidism is a common clinical problem for which the only
Introduction
definitive management is surgery. Diagnosis of the familial primary hyper-
VitD deficiency, the pandemics of which we currently observe, may result in
parathyroidism caused by CDC73 (formerly known as HRPT2) is based on the
secondary hyperparathyroidism even if not accompanied by hypocalcaemia.
biochemical findings of primary hyperparathyroidism, identification of ossifying
Aim
fibroma(s) of the maxilla and/or mandible on imaging studies, family history, and
To assess VitD levels as a cause of secondary hyperparathyroidism.
detection of a heterozygous germline CDC73pathogenic variant on molecular
Material and methods
genetic testing. The spectrum of CDC73-related disorders includes hyperpar-
257 healthy volunteers with normal kidney function (GFR! 60 ml/min) (28.4%
athyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism and
males), median age 57 years, were included. In each participant, serum calcium,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
phosphates, creatinine, PTH and total VitD levels, as well as urinary calcium in
EP286
urine morning sample, were measured. Daily calcium intake was estimated with
Diseases associated with hypercalcemia
a dietary questionnaire. Statistical analysis was performed with Statistica
Elena Brutskaya-Stempkovskaya1,2, Alla Shepelkevich2, Georg Kostin2,3,
12 Software.
Eduard Chertko2 & Janna Matsiushava2
Results
1Belarusian State Medical University, Minsk, Belarus;2Minsk City
Median VitD level in the investigated group was
21.22 ng/ml; PTH
-
Polyclinic N31, Minsk, Belarus;3Minsk Consulting and Diagnostic Centre,
41.17 pg/ml, serum calcium - 2.39 mmol/l, serum phosphates - 1.12 mmol/l,
Minsk, Belarus.
serum creatinine - 68 mmol/l, and urinary calcium - 2.69 mmol/l. Median daily
calcium intake was
689 mg. There was statistically significant negative
correlation between VitD and PTH levels (rZK0.19, PZ0.0018), independent
Introduction
of serum creatinine. This relationship was particularly significant for measure-
According to modern studies, hypercalcemia is associated with an increased risk
ments performed during autumn/winter (rZK0.34, P!0.0001), while losing its
of urolithiasis, cholelithiasis, gastritis and peptic ulcer.
significance in study subjects subgroup investigated during spring/summer (rZ
Objective
K0.06, PZ0.5153). Kruskal-Wallis ANOVA analysis showed a statistically
To study the prevalence of urolithiasis, cholelithiasis, gastritis and peptic ulcer in
significant difference in PTH levels in relation to VitD deficiency severity
patients with hypercalcemia in Minsk-city.
(predefined ranges: !10; 10-19.9; 20-29.9 and R30 ng/ml) (PZ0.0078). A
Materials and methods
significantly higher PTH level was observed in subjects with severe VitD
we studied 1207 people, average age 53.9G17.25 (892 women, 315 men) from 18
deficiency (!10 ng/ml) when compared to subgroups with VitD levels of 20-
to 96 years. Examination: total calcium, total protein, creatinine, ultrasonography,
29.9 ng/ml (PZ0.0147) and R30 ng/ml (PZ0.0401). A significant negative
fibrogastroduodenoscopy, an analysis of morbidity.
correlation was found also between serum PTH and serum calcium (rZK0.13,
Results
PZ0.0447).
Hypercalcemia has been found in 31 people, mean age was 58.39G11.6 years.
Conclusions
Urolithiasis was detected in 141 cases (in patients with hypercalcemia - in nine
Lack of significant negative correlation between serum PTH and VitD, seen
cases) cholelithiasis was detected in 107 cases (in patients with hypercalcemia -
during spring and summer confirms that appropriate sunlight exposure is
in ten cases) gastritis was detected in 397 cases (in patients with hypercalcemia -
sufficient to correct VitD deficiency. Significant increase in PTH levels is seen
in 21 cases) peptic ulcer was detected in 102 cases (in patients with hypercalcemia
mostly in subjects with particularly low VitD levels, which may be an argument
- in nine cases).
for redefining the recommended normal range of VitD.
Significant differences was detected in the prevalence of urolithiasis (c2Z8.54,
DOI: 10.1530/endoabs.49.EP284
PZ0.0035), cholelithiasis
(c2Z19.33, PZ0.00001) gastritis
(c2Z16.41,
Z15.69, PZ0.0001) in patients with hypercalcemia
PZ0.0001) peptic ulcer (c2
compared all studied patients.
Conclusion
The results of the study show an increasing risk of urolithiasis, cholelithiasis,
gastritis and peptic ulcer in patients with hypercalcemia. The results may indicate
an important role of hypercalcemia in the pathogenesis of these diseases.
DOI: 10.1530/endoabs.49.EP286
EP285
Pathological basal ganglia calcification in isolated idiopathic
hypoparathyroidism: a case report
Gordana Pemovska1, Tose Plaseski1, Biljana Todorova1,
Nadica Bozhinovska1, Marija Zivkovic1 & Radmila Nesovska2
EP287
1University Clinic of Endocrinology, Diabetes and Metabolic Diseases,
PTH levels in vitamin D deficiency
Skopje, Macedonia;2City Hospital September 8th, Skopje, Macedonia.
Merve Catak1, Derya Koseoglu2, Ozden Ozdemir Baser1 & Dilek Berker1
1Numune Education and Research Hospital, Ankara, Turkey;2Hitit
Introduction
Univercity Hospital, Corum, Turkey.
The isolated hyperparathyroidism (IHP) is a metabolism disorder characterized
by an absent or low parathormon (PTH) and hypocalcemia. It can be acquired,
Introduction
autoimmune, a result of some syndrome and as a part of a family (FIHP). FIHP is
High level of Parathormone (PTH) impair bone health by increasing the risk of
an extremely rear disease which is inherited auto somatic dominant or auto
fracture. The aim is to determine the threshold value of PTH elevation to
somatic recessive as a result of a mutation of one or several different genes.
accompany deficiency or failure of Vit D. This may be an important parameter in
Pathological calcifications in the cerebrum are a secondary form of calcification
assessing bone metabolism in clinical practice.
in patients with IHP.
Material and method
Material and methods
931 patients who were referred to the endocrinology clinic were retrospectively
We present two patients, a brother and a sister, age 44 and 42. The disease started
studied and 880 patients diagnosed with Vit D deficiency included to the study.
in both cases, with a series of epileptic attacks, the brother at the adolescent period
Patients were divided into three groups according to their vitamin D levels: !10
and the sister at age of 30. The diagnose was established based on a characteristic
ng/dL, 10-19.99 ng/dl, 20-29.99 ng/dl. The mean Ca, P, PTH, Vit D, ALP levels
symptoms: Fatigue, muscle weakness, paresthesis, convulsions, speech and
were calculated.
attitude disorder as well as cognitive deficit. The brother has cataract and the sister
RESULTS
has hirzutism and acne. Hormone and laboratory diagnostic tests. Radio
880 patients included in the study, 710 were female and 170 were male.
diagnostic on the kidneys, densitometry and psychological tests.
The mean PTH levels were 68.99, 56.10, 50.92 pg/ml when Vit D levels were
Results
!10 ng/dl,
10-20 ng/dl,
20-30 ng/dl and respectively and a statistically
The brother: PTHZ4.22 pg/ml (15-65), TCaZ1.08 (1.21-2.6), PosfZ2.01 (0.8-
significant difference was found between PTH levels (P!0.0001).
1.4 mmol/e), CaCCZ1.46 (1.3-10) mmol/l, Vit. D 14.35, Mg 0.69 (0.6-
When ROC analysis was performed, while Vit D level !5 ng/dl; PTH level was
1.1 mmol/l). Undergone cataract surgery. The sister: PTHZ1.2 pg/ml, TCaZ
O71.25 pg/ml (sensitivity 45%, specificity 78%), while the Vit D level was
1.92, PosfZ1.7. No signs for litiasa and nefrosclerosis. KT scan of the brain:
!10 ng/dl; PTH level wasO66.75 pg/ml (sensitivity 50%, specificity 77,4%),
calcification in the cerebellum, basal ganglia, par ventricular and sub cortical - M.
while Vit D level !20 ng/dl; PTH level was O61.1 pg/ml (sensitivity 40.3%,
Fahr. No signs of nefrocalcinosis. Radiology finding shows osteosclerosis of the
specificity 80.9%)
cranium, spine, long bones. Both of them have neuropsychological disorder with
Conclusion
limited intellectual capacity and light mental retardation.
As the Vit D level decreases, the calcium level decreases statistically significantly
Conclusion
while the parathormone level increases. Patients with Vit D deficiency have
IPH from an unknown etiology points to a family HypoPTH which needs to be
elevated PTH levels but PTH levels are still in the normal reference range.
confirmed by a genetic test. The tests were not performed due to financial
Prospective studies are needed to evaluate the effect of increased but still in a
limitations. Timely diagnose of IPH can prevent calcification in basal ganglia.
normal range PTH levels on bone with measurement of bone mineral density.
DOI: 10.1530/endoabs.49.EP285
DOI: 10.1530/endoabs.49.EP287
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP288
Conclusion
Endocrinologist operated US and PTH wash-out increases the number and
Renal complications in patients with chronic postoperative
success of focused surgery. Especially, patients with redo-surgery may benefit
hypoparathyroidism treated with oral calcium and active
from this procedure.
vitamin D metabolites
Filomena Cetani1, Antonella Meola2, Edda Vignali1, Giovanni Guglielmi3,
DOI: 10.1530/endoabs.49.EP289
Irene Donato4, Antonio Matrone2, Rossella Elisei2 & Claudio Marcocci2
1University Hospital of Pisa, Endocrine Unit, Pisa, Italy;2Department of
Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
3University Hospital of Pisa Medicina Preventiva del Lavoro, Pisa, Italy;
4Department of Traslational Research and New Technologies in Medicine
and Surgery, University of Pisa, Pisa, Italy.
EP290
Patients with chronic hypoparathyroidism (HypoPT) treated with oral calcium
Weight has a weak influence on calcium-phosphorus metabolism in
and active vitamin D metabolites are at risk of renal complications, because of the
HIV-patients with vitamin d deficiency
Carolina García-Figueras Mateos & Manuel Cayón-Blanco
lack of action of PTH at the renal tubule. In the present study we evaluated
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
90 patients
(68
females and
22 males; age:
51.8G14.1 yrs) with chronic
postoperative Hypo (PO-HypoPT) diagnosed since at least 3 years. All patients
were treated with calcitriol and 35 (39%) with oral calcium two patients were also
Introduction
treated with thiazide diuretics. One-hundred forty-two healthy Hospital employ-
In contrast to general population, clinical consequences related to low levels of
ers, matched for age and sex, undergoing routine medical evaluation, were used as
25-hydroxyvitamin D in HIV-infected patients with overweight are not
control. Mean levels of Alb-Ca and ionized calcium were in the normal range and
established. The aim of our study was to investigate the influence of weight on
but 39 (43.3%) patients had values that did not meet the range recommended by
clinical parameters and on calcium-phosphorus homeostasis in HIV-patients with
the recent guidelines of the European Society of Endocrinology (ESE). Serial
vitamin D deficiency.
measurements of serum calcium prior to the present evaluation were available in
Methods/design
78 patients: only 9 (11.5%) patients had all values within the recommended ESE
Prospective study of HIV outpatients treated in our hospital. Vitamin D deficiency
range, and a large proportion of patients (32, 41.0%) had values greater than the
(D-DEF) was defined as serum 25-hydroxyvitamin D below 20 ng/ml. Patients
upper recommended value. The mean serum phosphorus and creatinine levels
were classified as “overweight/obesity” if body mass index (BMI) R25 Kg/m2.
were in the normal range, but 7 (7.7%) patients had elevated values of phosphorus
Their clinical, metabolic and immunological data were compared to HIV-
and 22 (24.4%) of creatinine. The serum calcium-phosphate product was normal
individuals classified as “normal weight” (BMI: 18.5-24.9 Kg/m2).
in all patients. Forty-four (54%) patients showed increased 24-h urinary calcium
Results
excretion and 27 (30%) microlithiasis, mostly asymptomatic. Compared to the
One hundred and six HIV-infected individuals (86.8% male, mean age: 46.4G6.5
controls, patients had statistically significant lower mean serum Alb-Ca
years) were included. 51.9% were classified as “overweight/obese”. Levels of
(P!0.0001) and higher serum creatinine (PZ0.0008) and greater prevalence
vitamin D were lower in “overweight/obese”, but no significant difference was
of kidney stones (27/90 vs 7/142, P!0.0001, OR: 8.2 (3.4-19.9)). In conclusion,
observed between both groups (14.8G4 vs 15.3G1.8 ng/mL; PZ0.772). In
conventional treatment of chronic PO-HypoPT is suboptimal and associated with
overweight HIV-patients, although into the normal range, the serum phosphorus
an increased risk of renal complications. Careful monitoring of patients, as
levels were higher as compared as those without D-DEF (3.3G0.8 vs 2.9G
recommended by the ESE guidelines, should be therefore performed.
0.5 mg/dl; PZ0.04). Levels of i-PTH were also higher in overweight D-DEF
DOI: 10.1530/endoabs.49.EP288
patients (66.1G35.1 vs 48.9G19.8 pg/ml; PZ0.04). No others differences were
observed between these groups. Analyzing individuals with D-DEF only, there
was no difference in calcium, phosphorus or i-PTH levels between patients with
or without overweight.
Conclusions
In HIV-infected patients with low levels of
25-hydroxyvitamin D, BMI
R25 Kg/m2 determines subtle changes on calcium-phosphorus homeostasis
which clinical significance remains to be determined. Further follow-up studies to
establish potential clinical implications of these findings are needed.
EP289
DOI: 10.1530/endoabs.49.EP290
The results of parathormone assay in parathyroid aspirates in
preoperative localization of parathyroid adenomas for focused
parathyroidectomy in patients with negative or suspicious sestamibi
scans
Aysenur Ozderya, Sule Temizkan, Kenan Cetin, Sule Ozugur,
Aylin Ege Gul & Kadriye Aydin
Kartal Dr Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey.
EP291
Chronic hypoparathyroidism disease profile from 492 patients in the
Objective
PARADIGHMe natural history global registry
In primary hiperparathyroidism (PHPT), increasing the number of patients treated
Bart L Clarke1, Steven Ing2, Aliya Khan3, Michael Mannstadt4,
by focused parathyroidectomy should be the main objective of pre-surgical
Michael McDermott5, Rebecca Piccolo6, Michael H. Shanik7,
imaging modalities. Suspicious or negative imaging results do not always mean
Tamara J Vokes8 & John Germak9
multiglandular disease, most of the patients may single adenoma and therefore
1Mayo Clinic, Rochester, MN, USA;2Ohio State University Wexner
these patients may still benefit from focused parathyroidectomy.
Medical Center, Columbus, OH, USA;3McMaster University, Ontario,
Methods
Canada;4Massachusetts General Hospital and Harvard Medical School,
Retrospectively, we analyzed the data of 65 patients with PHPT with suspicious
Boston, MA, USA;5University of Colorado Hospital, Aurora, CO, USA;
or negative sestamibi scans who admitted at a tertiary reference center between
6Shire Human Genetic Therapies, Inc., Lexington, MA, USA;7Endocrine
January 2013 and December 2016. We excluded patients who had history of
Associates of Long Island, PC, Smithtown, NY, USA;8University of
chronic renal failure, renal transplant and multiple endocrine neoplasia. All
Chicago Medicine, Chicago, IL, USA;9Shire International GmbH, Zug,
patients underwent an endocrinologist operated ultrasonographic examination
Switzerland.
and parathyroid fine needle aspiration wash-out procedure.
Results
Of the 65 patients, 23 patients had nodular guatr disease. Fifty-four patients
PARADIGHMe is a global registry (NCT01922440) of patients diagnosed with
had positive parathormone
(PTH) wash-out results. A total of
43 patients
hypoparathyroidism (HPT) R6 months regardless of aetiology and management.
underwent surgery. Of the 43 patients, four patients had redo-surgery. Of the
Routine medical care data were entered using electronic case report forms; the
operated patients,
40 had positive parathormone wash-out results and had
36-item Short Form Health Survey was completed by patients. Baseline-recorded
successful focused surgery. All of the patients with redo-surgery had positive
data are reported for 492 patients enrolled as of 1 December 2016 from 41 centres.
parathormone wash-out results and successfully re-operated. Three patients
At baseline, 78% were women, mean (S.D.) age was 49 (17) years, and mean (S.D.)
with negative PTH wash-out results, two of them had successful bilateral neck
BMI was 29.8 (8.6) kg/m2. Medical histories included mood disorder (29%),
exploration, but a patient’s operation was not successful although bilateral neck
arthritis (16%), kidney stones (11%), fractures (8%), chronic renal disease (6%),
exploration.
and hypercalciuria (3%). 93% of patients had baseline symptom data (for the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
previous 6 months), all reported R1 symptom; the most common were fatigue
approach. The gold standard is sestamibi SPECT/CT nowadays - but fails in
(40%), paraesthesia (30%), muscle twitching (24%), anxiety (20%), brain fog
approximately 10% cases. In last 3 years some case report with 18F-choline
(17%), muscle weakness (17%), back pain (16%), and headache (16%). HPT
PET/CT were published. We describe two cases with SPECT/CT invisible
management included oral calcium in 91% (calcium carbonate, 59%) and active
parathyroid adenoma.
vitamin D in 84% (calcitriol, 94%) of patients; 7% received recombinant PTH (1-
First case was 36y/o woman, with osteopenia diagnosed after pregnancy (was
84) in a clinical trial. 62% were taking R1 concomitant medication (45% thyroid
attributed to LMWH treatment in pregnancy) and no relevant health problems.
hormone,
4% hydrochlorothiazide,
1% psycholeptics,
!1% magnesium
Mild hypercalcemia (2.7 mmol/l) was found in 2014 in context with vitamine D
supplements). Key laboratory mean (S.D.) values were PTH 1.5 (1.5) pmol/l,
deficiency and patient was referred to our department. Primary hyperparathyroid-
albumin-corrected total serum calcium 2.1 (0.3) mmol/l, phosphate 1.4 (0.3)
ism was clearly stated (serum calcium 2.9 mmol/l; PTH 130 ng/l; 25-OH-D
mmol/l, magnesium 0.8 (0.1) mmol/l, and 24-hour urinary calcium 7.2 (4.6)
vitamine 69 nmol/l), bone turnover was also slightly elevated. According to age,
mmol/day. Among 330 patients who had imaging, calcifications were reported in
osteopenia and planned pregnancy we decided for surgery, but ultrasonography
40 patients (12%): kidney (nZ12), brain (nZ9), cardiovascular (nZ7), and other
and sestamibi SPECT/CT was without any parathyroid adenoma. Patient did not
sites (nZ12). In the previous 12 months, 47% of patients had 2K3 doctor visits
agreed with surgical revision of all four glands and we choosed conservative
and 49% had R1 emergency room visit owing to HPT. Mean (S.D., range) SF-
approach. In 2015, hypercalciuria was appeared, therefore next SPECT/CT and
36v2 summary scores for physical and mental components were 45.6 (10.7;
ultrasonography was performed, with still negative results. In 2016 we used
11.2K64.2) and 48.4 (11.0; 11.9K70.3). These real-world data for 492 patients
PET/MRI with 18F-choline for the first time in our hospital
- upper left
enrolled in the PARADIGHMe registry provide valuable insight into disease
parathyroid adenoma was found (9!6 mm, SUVmax 5.8). Patient was referred to
variability, symptom burden, and HPT treatment approach.
surgery and histologic examination reveals parathyroid adenoma and patient went
DOI: 10.1530/endoabs.49.EP291
normocalcemic, normocalciuric and with normal PTH level, with continuing D
vitamine treatment due to osteopenia. No hungry bone syndrome was presented.
Second case was 59 y/o man, with primary hyperparathyroidism treated for 3
years by cinacalcet, with twice negative sestamibi SPECT/CT, repeatedly
negative ultrasonography. During the treatment was slightly hypercalcemic
(2.6 mmol/l), normocalciuric, with non-progressing osteopenia. PET/MRI
revealed 8mm left bottom parathyroid adenoma and patient was referred for
surgical resection, planned for March 2017.
EP292
Despite our limited experiences, 18F-choline PET seems to be a promising
Prevalence of cardiometabolic risk factors among Saudi Women with
diagnostic option. Using MRI instead of CT has some advantages - radiation load,
vitamin D deficiency
no risk of iodine contrast allergy and slightly better resolution in neck region.
Hanan Al Kadi1 & Eman Alissa2
DOI: 10.1530/endoabs.49.EP293
1Physiology Department, Center of Excellence for Osteoporosis Research,
King Abdulaziz University, Jeddah, Saudi Arabia;2Biochemistry
Department, King Abdulaziz University, Jeddah, Saudi Arabia.
Vitamin D deficiency is highly prevalent among Saudi women. The aim of this
study was to determine the prevalence of cardiometabolic risk factors in
apparently healthy Saudi women with vitamin D deficiency. A Retrospective
chart review was conducted in the “Center of Excellence for Osteoporosis
Research” (CEOR), King Abdulaziz University, Jeddah, Saudi Arabia. Only
healthy women 20-40 years old, with no history of previous illnesses and not on
any medications were included. Data on anthropometric measurements as well as
EP294
blood pressure (BP) were obtained. Body mass index (BMI) was calculated.
Severe hypocalcemia induced by Denosumab in a patient with
Laboratory results including fasting blood glucose (FBG), fasting lipid profile,
Osteroporosis after malabsorptive bariatric surgery
25-hydroxyvitamin D3 (25(OH)D3) and parathyroid hormone (PTH) were also
Ana Jiménez Portilla, Guillermo Serra Soler, Juan Ramón Urgeles Planella,
obtained. Vitamin D deficiency was defined as
25(OH)D3
concentration
María Soledad Gogorza Pérez, Mercedes Noval Font, Honorato
!50 nmol/l. Modified NCEP:ATPIII criteria were used to define cardiovascular
García Fernández, In˜ aki Arguelles Jiménez & Vicente Pereg Macazaga
risk factor cutoff points. A total of 305 women were included in the current
Universitary Hospital Son Espases, Palma de Mallorca, Spain.
analysis. Mean (G S.D.) age of the study group was 28.4G6.1 years and median
(IQR)
25(OH)D3 was 17.8 (11.9-28.2) nmol/l. Almost
97% of the study
participants were vitamin D deficient and 70% had values below 25 nmol/l.
Introduction
25-hydroxyvitamin D was significantly inversely associated with waist
Denosumab is a monoclonal antibody indicated in the treatment of postmeno-
circumference, systolic and diastolic BP and PTH
(PZ0.011,
!0.0001,
pausal osteoporosis. Hypocalcemia is a rare adverse effect.
!0.0001, !0.0001, respectively). Prevalence of cardiovascular risk factors
Case report
were higher among subjects who fell in the lowest tertile of 25(OH)D3 except
We present the case of a 58-year-old woman with a clinical history of bariatric
total cholesterol and low density lipoprotein cholesterol, however only higher
surgery in 2001 and osteoporosis with multiple vertebral and hip fractures. Under
PTH was statistically significant (PZ0.022). The results of the present study
treatment with Zinc sulphate, Vitamin A, 25-OH-vitamin D, calcium and iron.
confirm the high prevalence of vitamin D deficiency among otherwise healthy
She came to the A&E for general malaise, generalized weakness, paraesthesia,
Saudi women. The results also suggest that the prevalence of selected
dysarthria and weight loss of some weeks of evolution. She was admitted due to a
cardiometabolic risk factors is higher among those with low vitamin D status.
severe hypocalcemia: calcium 5 mg/dl (8.4-10.2), ionic calcium 2.5 mg/dl (4.64-
Prospective studies are needed to determine whether such deficiency will be of
5.28), phosphate 1.2 mg/dl (2.3-4.7), magnesium 2.35 mg/dl (1.6-2.6), albumin
clinical significance with advancing age in this population, and whether vitamin D
38.8 g/l (35-50), PTH 284 pg/ml (15-65), 25-OH-vitamin D 22 ng/ml (30-100),
supplementation has beneficial effects.
alkaline phosphatase 360 U/l (40-150) and normal kidney function. The ECG
showed a prolonged QT. The signs for hypocalcaemia were negative. The patient
DOI: 10.1530/endoabs.49.EP292
had received treatment with subcutaneous Denosumab 60 mg 22 days before,
with prior calcium values of 8.4 mg/dl, phosphorous 3.1 mg/dl, 25-OH-vitamin D
25 ng/ml, PTH 76 pg/ml and Ca-urine 27 mg/24 h. Treatment was started with
intravenous calcium for 8 weeks, together with oral calcium, phosphorous and
25-OH-vitamin D. The patient improved symptomatically, with a normalization
of the QT and analysis with ionic calcium 4.6 mg/dl, phosphate 3.5 mg/dl,
magnesium 2.8 mg/dl, PTH 139 pg/ml, Ca-urine 2.3 mg/dl and 25-OH-vitamin D
EP293
39 ng/ml. The treatment to discharge was oral calcium
2.5 g/day and
25-OH-vitamin D 16.000 UI daily.
18F-choline PET/MRI in patients with primary hyperparathyroidism
Conclusions
and negative sestamibi SPECT/CT - report of two cases
Hypocalcemia after Denosumab is a rare adverse effect but it can be serious. The
Michal Krcma
patients who have undergone malabsortive bariatric surgery have a greater risk. It
Department of Internal Medicine I, Faculty of Medicine in Pilsen,
is important to monitor the 25-OH-vitamin D and calcium in patients who start
Charles University, Pilsen, Czech Republic.
treatment with Denosumab and at 15 days in patients who are at the greatest risk,
as is the case of this patient.
Primary hyperparathyroidism is a common disorder which is curable by surgery.
DOI: 10.1530/endoabs.49.EP294
Exact localisation of parathyroid adenoma is essential for minimal invasive
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP295
EP297
Performance characteristics of a new Waters MassTrake Vitamin D
Tc-99m sestamibi uptake by brown tumours in a patient with primary
assay
hyperparathyroidism
Norma Breen, Leanne Davey, Declan Roche, Philip Lambert,
Daniela Dias, Daniel Macedo, Rita Santos & Valeriano Leite
Danielle Cullen & Padhraic Rossiter
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,
Water Technologies Ireland Ltd, Wexford, Ireland.
Portugal.
The Waters MassTrak Vitamin D Kit is designed for the quantitative
Tc-99m sestamibi (MIBI) imaging is able to localize parathyroid adenomas/car-
determination of serum or plasma
25-hydroxyvitamin D3
(25OHD3) and
cinomas in patients with primary hyperparathyroidism. Brown tumours are one of
25-hydroxyvitamin D2 (25OHD2), which in combination provide the total
the skeletal manifestations of long standing hyperparathyroidism and its
25-hydroxyvitamin D concentration as an aid in the assessment of vitamin D
incidence has been reported to be 3%. Radiological features of these tumors
sufficiency.
may mimic bone metastasis. There are only a few reports showing brown tumours
The MassTrak Vitamin D Kit is validated for use with the Watersw ACQUITY
uptake in the whole-body Tc-sestamibi scan.
UPLCw I-Class/Xevow TQD IVD System and the sample preparation has
We report a 72-year-old female with a previous history of right nephrectomy for
been validated using the Tecanw Freedom 100/4 EVOw Offline Automated
renal lithiasis at age 49 and a left clavicle mass fracture. A neck and thoracic
Liquid Handling system. Screening for vitamin D deficiency is recommended
computed tomography (CT) scan revealed multiple lytic lesions of the skeleton
by the Endocrine Society Clinical Guidelines- Evaluation, Treatment and
(including in the left clavicle) and a pathological mandibular fracture, suggesting
Prevention of Vitamin D Deficiency by the Task Force for all individuals at
metastatic lesions.
risk for deficiency.
18F-FDG PET scan showed multiple skeletal hypermetabolic lesions and a
Vitamin D status (Total 25OHD, which is the sum of 25OHD2 and 25OHD3)
hypermetabolic nodule close to left lower pole of the thyroid gland. The biopsy of
has been a challenge to measure accurately because the antibodies used in
the lesion in the left clavicle revealed histiocytic proliferation with multinucleated
many immunoassays do not have 100% co-specificity for both 25OHD2 and
osteoclast-type giant cells compatible with a brown tumor. Laboratory data
25OHD3.
showed an elevated serum calcium of 12.8 mg/dl (8.4-10.2), alkaline phosphatase
Precision, sensitivity, linearity, potential interferents and carryover were all
of 264 UI/l (9-36), and parathyroid hormone of 1056 pg/ml (12-65).
assessed during the development of the MassTrake Vitamin D kit and found
Tc-99m sestamibi scintigraphy showed an uptake in the inferior left pole of the
to meet the performance criteria specified for the kit.
thyroid and in multiple bone lesions. The patient underwent a left inferior
To further assess the accuracy and performance of the MassTrake Vitamin D
parathyroidectomy. Histology revealed a 20 mm parathyroid adenoma.
kit assay, Waters enrolled in the CDC Vitamin D Standardisation Certification
In this patient with a long standing hyperparathyroidism the intense uptake of
Program (VDSCP) for 25(OH)D in serum, which assesses bias and precision of
brown tumors in both18F-FDG PET scan and MIBI can mimic a parathyroid
assays relative to reference measurement procedures.
carcinoma with bone metastases.
The MassTrake Vitamin D kit calibrator materials are traceable to NIST
DOI: 10.1530/endoabs.49.EP297
SRM2972a via a documented unbroken chain of calibrations. The accuracy of
this traceability to NIST SRM2972 has been verified through participation of
the Vitamin D Standardisation Certification Program (VDSCP).
DOI: 10.1530/endoabs.49.EP295
EP298
Thyroid supression in patients with primary hyperparathyroidism may
improve pre-surgical scintigraphy localisation
Mariana Tomé1, Guillermo Martínez de Pinillos2, Eyvée Arturo Cuéllar2,
Juan Manuel García de Quirós2, Fernando García2 & Ignacio Fernández2
1
Punta de Europa Hospital, Algeciras, Spain;2Valme Hospital, Seville,
Spain.
Introduction
EP296
The cause of primary hyperparathyroidism (PHPT) is a single adenoma in 85% of
Vitamin D intoxication complicated with parathormon treatment in
cases. Scintigraphy with technetium-sestamibi (MIBI) is the test of choice for
elderly: a case report
localising adenomas in patients with PHPT, allowing minimally invasive surgery
in most patients. Some articles recommend thyroid function supression to
S Nur Boysan, Burcu Altunrende, Levent Dalar, M Eren Acik,
I Polat Canpolat, C Selcan Akdeniz & M Sait Gonen
improve scintigraphy results.
Istanbul Bilim University, Istanbul, Turkey.
Methods
A prospective study was conducted in which 8 patients were included with
diagnosis of PHPT and negative scintigraphy for adenoma localisation. These
Parathormon treatment for osteoporosis is rarely complicated with hypercalce-
patients did not have a contraindication for thyroid hormone intake. We started
mia. Vitamin D treatment with high doses frequently can cause asymptomatic
treatment with a dose of 1 mcg/Kg per day with dose titulation until achievement
intoxication.We present a case with life-threatening hypercalcemia complicated
of TSH!0.3 mU/ml. Once the objective was reached, MIBI was repeated with the
both parathormon and high-dose vitamin D.
same technique and interpreted by the same specialist in Nuclear Medicine.
A 85-year old woman hospitalized for sudden-onset confusion. In history she had
Results
coronary-artery by-pass operation and a serebrovascular accedant. She was
75% of patients were women, mean age 51.9G20.55 years.
treated with teriparatide 20 mr subcuraneously and cholecalciferol 0.25 m per oral
De los eight pacientes incluidos en el estudio, 6 eran mujeres (75%), con una edad
for one year. She had a pulmonary infection one month before admission. Since
media de 51.9G20.55 an˜os. Mean preoperative calcium level was 11.49G
vitamin D is popular in media for public health, her daughter gave three doses of
0.61 mg/dl. Mean preoperative PTH level was 146.26G97.58 ng/l. Mean TSH
300 000 IU vitamin D for infection. She has hallucinations and hypoxia. Her
level before repeating scintygraphy was 0.17G0.08 mU/ml. Thyroxine suppres-
laboratory was; Ca 15.6 mg/dl, P 3.3 mg/dl, PTH 6.88 pg/ml, 25-(OH] vitamin
sion scan was positive in four of the eight patients (50%). Only two of these four
DO 70 ng/dl, 1.25(OH]2 vitamin D 86.4 ng/l. She had also increased serum
patients underwent surgery for the moment. Minimally invasive surgery was
creatinine level. She was followed in intensive care unit fo
2 days. For
performed in these cases, confirming the existence of a parathyroid adenoma
hypercalcemia she had hydration, forced duresis, calcitonin and glucocorticoid
where the MIBI suggested. The level of calcium in these patients normalized after
therapy. Thorax CT showed bilaterally lineer atelectatic areas at basal zones. She
surgery.
continued to have nebulisation and oxygen after transmission from intensive care
Conclusiones
unit. Ejection fraction was 40% on echocardiography. She was discharged after 1
In our study suppression of thyroid function by thyroxine administration
week when serum calcium was 10.2 mg/dl and PTH was 16.37 pg/ml. Vitamin D
improved MIBI sensitivity for parathyroid adenoma localization in our patients
replacement, in elderly, could be life-threatening in megadoses. In this case,
with previous negative studies, however, a larger number of patients would be
parathormon treatment with vitamin D replacement complicated presentation.
required to confirm these results.
DOI: 10.1530/endoabs.49.EP296
DOI: 10.1530/endoabs.49.EP298
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP299
hyperuricemia (14.8 mg/dl). A 25-hydroxyvitamin D deficiency was also present
(6.5 ng/ml). The first neck ultrasound did not show abnormalities;
99mTc-
Serum vitamin D in overweight patients with normal and impaired
sestaMIBI scan was negative. Repetition of neck ultrasound revealed a left-
GFR
postero-inferior nodule likely to correspond to an enlarged parathyroid. The
Stelios Tigas1, Athanasios Kitsos2, Evangelia Dounousi2,
cytological evaluation supported this hypothesis. Pamidronate, antiemetics and
Rigas Kalaitzidis2, Anna Challa3 & Costas Siamopoulos2
volume expansion with isotonic saline reverted the clinico-laboratory condition
1Department of Endocrinology, University of Ioannina, Ioannina, Greece;
and served as a bridge to parathyroidectomy. Surgery went uneventful and a 3 cm
2Department of Nephrology, University of Ioannina, Ioannina, Greece;
inferior-left parathyroid was sent to anatomopathological examination. The final
3Pediatric Research Laboratory, Child Health Department, Ioannina,
diagnosis was parathyroid adenoma. In subsequent postoperative follow-up the
Greece.
patient was asymptomatic and had normal serum calcium levels (9.3 mg/dl) and
slightly upper-limit PTH (77.3 pg/ml).
Introduction
Conclusion
Obesity is a strong risk factor for incident chronic kidney disease
(CKD).
Despite the considerable size of the resected parathyroid, initial ultrasound failed
Furthermore, high body mass index (BMI) is consistently associated with low
to locate it. Seeking for a topographical diagnosis, a second ultrasound was
serum vitamin D in the general population. The aims of the present study were to i)
performed by a different operator in our hospital. This case highlights the
compare vitamin D metabolite levels in overweight/obese versus normal weight
importance of carefully selecting experienced centers to address parathyroid
individuals with normal to severely impaired renal function and ii) to assess the
preoperative studies. Furthermore, despite the adenoma size, its inferior location,
impact of 25(OH)D on the development of secondary hyperparathyroidism (SHPT).
and the associated severe hypercalcemia, the
99mTc-sestaMIBI scan was
Methods
negative, reminding of potential false-negative results of this method.
Serum 25(OH)D, 1,25(OH)2D, PTH, calcium and phosphate were measured in 104
DOI: 10.1530/endoabs.49.EP300
CKD outpatients with BMIO25 kg/m2. Participants were categorized according to
the eGFR (ml/min/1.73 m2): G1: R60 (nZ53), G2: 30-59 (nZ35) and G3: 15-29
(nZ16). Fifty normal-weight subjects with comparable eGFR levels composed the
control group (G1-nw - G3-nw).
Results
25(OH)D was lower in overweight/obese G1 patients compared to G1-nw (21.7G
EP301
6.5 vs 26.5G7.0 ng/ml, PZ0.02) and in G2 versus G2-nw (19.0G6.0 vs 25.0G
5.2 ng/ml, PZ0.005), whereas the level did not differ among G3 groups (15.8G
4.7 ng/ml vs 20.3G4.5 ng/ml, PZ0.49 in G3 vs G3-nw respectively). Mean
1,25(OH)2D and PTH levels were similar in obese/overweight versus normal-
Abstract withdrawn.
weight individuals in each eGFR category. Multivariate regression analysis in the
entire cohort revealed that factors independently associated with low 25(OH)D
levels were BMIO25 kg/m2, eGFR!30 ml/min/1.73 m2
and female gender
whereas low 1,25(OH)2D levels were associated with eGFR!30 ml/min/1.73 m2,
older age and increased serum phosphate. Even though serum 25(OH)D levels were
suboptimal (!30 ng/ml) in both overweight and controls and in all eGFR groups,
significant SHPT was only observed in the groups with eGFR!30 ml/min/1.73 m2.
Conclusions
Lower serum 25(OH)D but similar 1,25(OH)2D and PTH levels were observed in
overweight/obese compared to normal weight individuals and preserved or
EP302
moderately impaired renal function. Even though vitamin D insufficiency was a
Ectopic production of calcitriol by non-hodgkin lymphoma as a cause of
common feature across all eGFR categories, SHPT was only observed in those with
hypercalcemia: case report
severely impaired renal function.
Elvira Alarcón, Mariana Tomé, Carmen Bautista & Daniel González
DOI: 10.1530/endoabs.49.EP299
Punta de Europa Hospital, Algeciras, Spain.
Introduction
Hypercalcemia of malignancy usually appears in patients with osteolytic
metastasis and in those patients with humoral hypercalcemia due to secretion
of PTHrp by the tumor. Hypercalcemia due to calcitriol production by the tumor
is uncommon (!1% of cases of hypercalcemia of malignancy). It is the cause of
virtually all cases of hypercalcemia in patients with Hodgkin’s lymphoma and
approximately one third of cases in non-Hodgkin’s lymphoma. It has also been
described in some cases of ovarian dysgerminoma.
Methods
We describe the case of a patient with MALT Non-Hodgkin lymphoma admitted
to our hospital with severe hypercalcemia.
Results
EP300
Our patient was admitted to the hospital with calcium levels above 15 mg/dl.
After hydration, loop diuretics and zoledronic acid he reached calcium level of
The importance of ultrasound in the preoperative evaluation of patients
10.5-11 mg/dl but after withdrawal of intravenous hydration he presented
with primary hyperthyroidism: a case report
recurrence of hypercalcemia up to the initial values. Analytics showed very low
José Marçalo, Alexandra Araújo, Ana Wessling, Maria Raquel Carvalho &
levels of PTHi and 25-OH-Vitamin D (5.76 pg/ml, 3 ng/ml respectively). Imaging
Maria João Bugalho
tests (body CT) did not show osteolytic lesions suggestive of metastases. Given
Hospital de Santa Maria, Lisbon, Portugal.
the suspicion of humoral hypercalcemia we initiated treatment with Cinacalcet
60 mg daily and steroids (Prednisone 1 mg/kg per day) without a satisfactory
Introduction
response in reducing calcium levels. Analytical result showed undetectable levels
Primary hyperparathyroidism is the most common cause of hypercalcemia in the
of PTH-related protein (!1.1 pmol/l) and very high calcitriol levels (148 pg/ml,
outpatient setting, and a single parathyroid adenoma is usually the culprit.
N: 16-56 pg/ml). Our suspicion of calcitriol tumoral production associated with
Clinical presentation is commonly dictated by hypercalcemia. Symptoms can
lymphoma is therefore confirmed. In view of the poor response to medical
range from mild non-specific malaise and gastrointestinal disturbances, through
treatment and the need for intense hydration to maintain acceptable calcium levels
bone disease, kidney stones, cardiovascular and neuromuscular dysfunction to,
a splenectomy with cytoreductive objective
(19 cm splenomegaly) was
ultimately, coma and death. However, the vast majority of patients are
performed. After this, calcium levels reached the normal level (9.5-10.2 mg/dl)
asymptomatic.
and remained stable.
Case report
Conclusion
A 46-year-old female with a half-year endocrinology monitoring for type 2
Although tumor production of calcitriol is an uncommon cause of hypercalcemia,
diabetes and obesity, resorted to our hospital after 3 weeks’ evolution of persistent
it is usually related to lymphomas. We must think in this disorder in patiens with
nausea and vomiting. Laboratory workup showed increased PTH levels
lymphoma and hypercalcemia.
(596 pg/ml), severe hypercalcemia
(17.4 mg/dl), mild hypophosphatemia
DOI: 10.1530/endoabs.49.EP302
(2.4 mg/dl), acute kidney injury
(creatinine clearance
34 ml/min) and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP303
into consideration, since this can result from secondary hyperparathyroidism and
cause formation of calcificates.
Primary hyperparathyroidism: elective parathyroidectomy versus
Conclusions
conservative management; results of a retrospective cohort study
Vitamin D3 shout be tested in the first place during the treatment of any kind of
Melanie Nana, Holly Morgan, Natasha Shrikrishnapalasuriyar &
calcified nodular goiter, since calcificates can be caused not only by oncologic
Atul Kalhan
processes, but also secondary hyperparathyroidism.
Royal Glamorgan Hospital, South Glamorgan, UK.
DOI: 10.1530/endoabs.49.EP304
Background
The optimum management strategy for primary hyperparathyroidism remains
debatable especially in patients with mild or asymptomatic disease. We aimed to
compare the baseline characteristics and long-term outcomes of patients with
EP305
primary hyperparathyroidism who were either managed conservatively or
Pseudohypoparathyroidism (PHP) and GNAS gene mutations - clinical
underwent elective parathyroidectomy.
spectrum from PHP type 1a to pseudopseudohypoparathyroidism
Methodology
Ana Saavedra1,2, Elisabete Rodrigues1,2, Filipe Cunha1,2, Miguel Le
˜o3 &
We carried out a retrospective cohort analysis of patients with primary
Davide Carvalho1,2
hyperparathyroidism under follow-up at the Royal Glamorgan Hospital, Wales
1Department of Endocrinology, Diabetes and Metabolism of Centro
from 1995 to 2016. The baseline characteristics were recorded from case records
Hospitalar de Sa˜o João, Porto, Portugal;2Faculty of Medicine, University of
while the clinical portal was used to collate biochemical and radiological data.
Porto, Porto, Portugal;3Department of Genetics of Centro Hospitalar de São
The patients were categorised into two main groups based on management
João, Porto, Portugal.
approach (conservative treatment vs elective parathyroidectomy group).
Results
Out of a total of 336 patients with confirmed primary hyperparathyroidism,
Introduction
72
(21.4%) underwent elective parathyroidectomy. Mean duration of follow up
Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders
was shorter for the surgically treated patients as compared to the ones treated
that have in common end-organ unresponsiveness to parathyroid hormone (PTH).
conservatively (3.7 vs 5.2 years). There was no significant difference between
The most frequent form, PHP type 1, results from different genetic/epigenetic
mean calcium levels at diagnosis although the mean parathyroid hormone (PTH)
changes in the GNAS gene.
level at diagnosis was significantly higher in the surgical group (15.0 vs 11.4,
Case 1
PZ0.038). Despite age adjustment using binary logistic regression, prevalence of
Woman, 25 years-old, sent to Endocrinology from Genetics consultation after her
hypertension and ischaemic heart disease was significantly lower in patients
daughter had been diagnosed with PHP type 1a (heterozygous pathogenic variant
undergoing elective parathyroidectomy as compared to the group managed
at exon 13 of GNAS gene c.1174GOA (p.e392K)). Our patient and her father
conservatively.
present some clinical manifestations as observed in the child, suggestive of
Conclusion
Albright Hereditary Osteodystrophy (AHO), and both present the same mutation
There was a significant difference in prevalence of hypertension and ischaemic
as encountered in index case. We tested phosphocalcic metabolism of our patient
heart disease in patients managed conservatively as compared to the group who
and she presented normal serum calcium/phosphorus levels as well PTH levels.
underwent elective parathyroidectomy despite adjustment for age. The duration
Other pituitary hormones were evaluated, with normal results except elevated
of follow up for this group was relatively shorter which can potentially off-set
TSH (18.72 mUI/ml) in context of primary autoimmune hypothyroidism. Patient
costs associated with surgery. The higher PTH levels at baseline for the elective
started treatment with levothyroxine.
parathyroidectomy group may also signify a correlation of PTH levels with
Case 2
increased risk of complications. Prospective large randomised controlled trials
Male, 31 years-old (case 1 brother). He was sent to Endocrinology in December
need to be designed to assess cardiovascular outcomes comparing surgical versus
2015 for lymphocytic thyroiditis evaluation. During the physical examination, it
conservative management approach.
was recognized a phenotype suggestive of AHO, as was found in his relatives
DOI: 10.1530/endoabs.49.EP303
(round facies, brachydactyly and subcutaneous calcifications). Patient’s lab tests
showed normal serum calcium/phosphorus levels and high PTH in the context of
vitamin D deficiency. Other pituitary hormones levels were in normal range.
Patient performed genetic test - results ongoing.
Conclusion
Different pathological entities may result from mutations in the GNAS gene. PHP
type 1a is characterized by the presence of AHO and PTH resistance. However,
AHO manifestations may occur in patients without PTH resistance (pseudopseu-
dohypoparathyroidism), as in the two cases presented. This occurs when the
mutation is paternally transmitted. These cases somehow demonstrate de
EP304
complexity of GNAS gene mutations, which merited recently a new classification.
It is also highlighted that although pseudopseudohypoparathyroidism needs no
Calcium metabolism and autoimmune thyroiditis
treatment, genetic counselling should also be recommended.
Armine Khroyan1,2, Edvard Toromanyan1,2, Maria Badalyan1,2 &
Mariam Khachatryan1,2
DOI: 10.1530/endoabs.49.EP305
1Muracan MC, Yerevan, Armenia;2Armenia MC, Yerevan, Armenia.
Objectives
The objective of our - investigation is to find out the role of D3 vitamin deficiency
- and calcium in patients with autoimmune thyroiditis and calcified nodules.
EP306
Methods
Hyperparathyroidism and cardiovascular risk
The research has been carried out at
“Muratsan” University Hospital and
Daniela Amzar1, Melania Balas1, Ioana Golu1, Mihaela Vlad1,
“Armenia” Medical Center, in 2013-2016.
Ramona Sandu2 & Maria Cornianu3
80 patients (ages G4-0, of which 68 women and 12 men) with autoimmune
1Department of Endocrinology, Victor Babes University of Medicine and
thyroiditis and calcified nodules have taken part in the clinical research.
Pharmacy, Timisoara, Romania;2Department of Endocrinology,
They have been tested on TSH, FT4, anti-TPO, vitamin D3, Ca2C, PTH, as well
Emergency County Hospital, Timisoara, Romania;3Department of
as undergone a thyroid ultrasound, elastography.
Pathology, Victor Babes University of Medicine and Pharmacy, Timisoara,
Results
Romania.
TSH - 58%[, 42% N
FT4 - 60% Y, 40%N
Anti-TPO - 100%[
Background
Vitamin D3 - 84%Y, 16%N
Primary and secondary hyperparathyroidism (HP) are associated with increased
Ca2C - 94%N, 6%Y
risk for cardiovascular complications and high mortality. Risk factors correlated
PTH - 89% [, 11%N
with hypertension in HP are hyperlipidemia, glucose intolerance, insulin
Thyroid ultrasound - Calcificates proved to be present in 76% of nodules, which
resistance, vitamin D deficiency, etc. The aim of the study was to assess the
have been formed on the background of autoimmune thyroidits.
incidence of cardiovascular complications in HP.
Thyroid elastography after 6 month taking vitamin D3 13% 3b elastography is go
Material and methods
to 3a. The increased level of PTH hormone and lower vitamin D3 should be taken
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
The study included 45 patients (15 men, 30 women), with a mean age of 45 years
hypertension. He is taking amlodipine 10 mg od. He is a non-smoker and drinks
(range 21-65 years). Thirty-two patients were diagnosed with primary HP and 13
alcohol in moderation. He was admitted with right leg swelling found to be a
with secondary HP due to chronic kidney disease (stages 3 and 4). The patients
new thrombosis. Incidental finding of extreme hypercalcaemia found on bloods
were evaluated by biochemical, hormonal parameters, imagistic tests, and cardiac
with raised PTH
(CorrCa 4.23 mmol/l, PTH 83.1 pmol/l.) Patient was
sonography.
completely asymptomatic. CT imaging of chest, abdomen and pelvis
Results
demonstrated extensive above knee thrombosis, renal calculi and a large
Vitamin D deficiency was documented in all patients with secondary HP and in
thyroid nodule. However, an ultrasound and Sestamibi confirmed spectacularly
24 patients with primary HP (75%). Other metabolic disturbances and risk factors
this was an enlarged parathyroid. He was anticoagulated with heparin and then
for cardiovascular diseases were as follows: diabetes mellitus (24.4%), smoking
oral anticoagulant. He was given aggressive i.v. fluids and bisphosphonate with
(28.8%), obesity (22.2%), and dyslipidemia (46.6%). The incidence of mitral
limited effect so cinacalcet was initiated. We were still unable to control
and/or aortic valvular stenosis (caused by calcifications) was similar in the two
calcium levels and so in patient parathyroidectomy was performed. At
groups, affecting 31.1% of the patients. Hypertension prevailed in the group of
operation the gland appeared grossly enlarged and vascular. However, there
secondary HP (12 cases), as compared to primary HP (10 cases, PZ0.0002,
was no tethering to adjacent tissues and easily removed weighing 43 g. Our
Fisher’s exact test). Peripheral atherosclerotic manifestations were noted in 11
patient made a good recovery with normalisation of calcium. Histology showed
cases (24.4%). Seven patients (15.5%) experienced an acute coronary event and
features in keeping with parathyroid adenoma rather than carcinoma. On
three patients underwent PTCA procedures with stent implantation. Ten patients
review in clinic two months later he remains normocalcemic. A DEXA has
showed ventricular hypertrophy (22.2%); the incidence was similar in the two
shown osteoporosis which we expect to improve in time.
groups (eight patients with primary HP, respectively two with secondary HP).
Our case is interesting as there are features of this case in keeping with
Conclusion
parathyroid malignancy rather than adenoma and we shall discuss this.
Our study shows that hyperparathyroidism is associated with higher incidence of
DOI: 10.1530/endoabs.49.EP308
severe cardiovascular complications, occurring at younger ages as compared to
general populations.
DOI: 10.1530/endoabs.49.EP306
EP309
Hungry bone syndrome after treatment of severe primary
EP307
hyperparathyroidism
Risk factors associated with osteoporosis in beta-thalassaemia major
El Mghari Ghizlane & El Ansari Nawal
patients
Chu Med6, Marrakech, Morocco.
Elena Mirela Iancu, Alice Ioana Albu & Irina Nicolaescu
Elias University Clinical Hospital, Bucharest, Romania.
Introduction
Persistent hypocalcemia after surgery for severe hyperparathyroidism are not
uncommon and may be secondary to transient or permanent hypoparathyroidism
Beta-thalssaemia major (BTM) is a rare disease that encompasses a vast
but may also be due to bone pathology.
range of endocrinological complications, despite of the improvement of
Observation
treatment protocols. The aim of this study was to identify the clinical and
Patient of 44 years old was hospitalized for fractures of the pelvis, and shaft of left
hematological parameters associated with osteoporosis, a frequent compli-
femur, spontaneous without trauma turned out. Laboratory tests shows severe
cation found in beta-thalassaemia patients.
hypercalcaemia to 156 mg/l, serum phosphorus at 22 mg/l, elevation of PTH to
Patients with BTM were evaluated in the Endocrinology Department of
1150 pg/ml and proper renal function with a serum creatinine to 8 mg/ml. PAL is
Elias Hospital between February 2004 and March 2016. Only patients who
increased to 709 U/l.
provided written informed consent were included in the study. A complete
A spot of médiastinal fixation compatible with ectopic parathyroid adenoma was
physical and hormonal evaluation was performed on all patients, and data
seen on the MIBI scintigraphy with several brown tumors. Ectopic mediastinal
regarding treatment of hematological disease were collected. The bone
parathyroidectomy was made after medical preoperative treatment with bispho-
density was evaluated using dual energy X-ray absortiometry (DXA).
sphonates, vitamin D and active metabolite of vitamin D.
Forty-nine patients were included in the study (median age 28.37 years;
In postoperative period a severe hypocalcemia reaching 65 mg/l at the fifth day
range
12-47). We found that
35
patients
(71.4%) had osteoporosis
was observed, the PTH was (9.9 pg/ml) and PAL are increased to 560 U/l with a
documented using DXA, 16 of them (45.7%) had fragility fractures caused
lowered serum phosphorus.
by decreased BMD.
The difficulty of standardization of serum calcium despite supplementation of
Patients with osteoporosis were older (median age 31.51 vs 20.5 years,
calcium element and 1 alpha and vitamin D, high PAL and the presence of diffuse
PZ0.05) and started the iron chelation therapy at an older age compared
bone lesions guide to The diagnosis of HBS.
with subjects without this condition
(105.72 months vs 63.58 months,
Conclusion
P!0.05). Although the levels of serum ferritin were higher in patients with
HBS is a heightened greed bones for calcium. It occurs in situations of
osteoporosis (1062 vs 777 ng/ml), the difference did not reached statistical
demineralization and intense bone remodeling.
significance. Hypogonadism was significantly more frequently found in
DOI: 10.1530/endoabs.49.EP309
patients with osteoporosis (30 pts, 85.7% vs 5 pts, 14.3%) in comparison to
patients without osteoporosis
(PZ0.014). The risk of developing
osteoporosis was six times greater in hypogonadal study subjects.
Our data show that osteoporosis is a highly prevalent complication among
Romanian b-thalasaemia patients, its presence being associated with older
age, delayed initiation of iron chelation therapy and the presence of
hypogonadism.
DOI: 10.1530/endoabs.49.EP307
EP310
Clinical review of nine cases of pseudohypoparathyroidism
David Barbosa1, Brígida Robalo2, Carla Pereira2 & Lurdes Sampaio2
1
CHLN - Hospital de Santa Maria, Endocrinology, Diabetes and
Metabolism Department, Lisbon, Portugal;2CHLN - Hospital de Santa
Maria, Pediatric Endocrinology Unit, Lisbon, Portugal.
EP308
Giants walk amongst us
Objective
Raj Tanday1, Bonnie Grant1, Akin Ojo2, Edel Casey1 & Khash Nikookam1
To analyze the clinicopathological features of pseudohypoparathyroidism (PHP),
1Department of Endocrinology, King George Hospital, London, UK;
that would help clinicians to consider this rare condition in children.
2Department of Surgery, King George Hospital, London, UK.
Methods
A retrospective review of nine patients with PHP (including seven males and
three females) admitted to our hospital between 1990 and 2014 was conducted.
We present the case of a 51-year-old gentleman who had a giant parathyroid
Clinical and biochemical parameters along with epidemiological data were
adenoma. He has a past medical history of deep vein thrombosis and
extracted and analyzed.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Objective
The mean age at diagnosis was 61.8G26.1 months, ranging from 4 to 114 months.
To study the prevalence of cardiovascular disease in patients with hypercalcemia.
The most frequent clinical features were: round lunar face and obesity (77.7%),
Materials and methods
followed by brachydactyly and learning/behavior disabilities (66.7%). Subcu-
We studied 1207 people, average age 53.9G17.25 (892 women, 315 men) from
taneous calcifications, although a landmark of PHP, were only present in four
18 to 96 years. Examination: total calcium, total protein, creatinine, cholesterol
patients (44.4%). Afebrile seizures occurred in two cases, despite the majority
and triglycerides, HbA1C, ambulatory blood pressure monitoring, ECG, an
showed multiple intracranial calcifications on cranial CT scan. Laboratory tests at
analysis of morbidity
(hypertension, coronary heart disease, cardiovascular
diagnosis revealed most frequently hypocalcemia (mean 7.4G1.9 mg/dl; 8.6-
events).
10.2), hyperphosphatemia (mean 7.9G1.7 mg/dl; 2.7-4.5) and high PTH levels
Results
(mean 366.3G218.4 pg/ml; 14-72). Subclinical hypothyroidism was present in
Hypercalcemia has been found in 31 people, mean age was 58.39G11.6 years.
eight out of nine patients (88.8%) with a mean TSH of 9.45G4.2 uU/ml (0.35-
Arterial hypertension was detected in 677 cases (in patients with hypercalcemia -
5.5) and a mean free T4 of 0.95G0.1 ng/dl (0.8-1.9). Vitamin D3, and calcium
in 23 patients), coronary heart disease was detected in 599 cases (in patients with
when needed, were prescribed to all patients to prevent symptomatic
hypercalcemia - 21), acute myocardial infarction - in 52 cases (in patients
hypocalcemia and presumably to stop disease progression by lowering the PTH
with hypercalcemia - 1), acute cerebrovascular accident - in 39 cases (in patients
levels, although it is not clear whether this normalization is beneficial. Genetic
with hypercalcemia - 1).
testing was performed in six children.
Significant differences in the prevalence of arterial hypertension
(c2Z4.03,
Conclusion
PZ0.0447); in the prevalence of coronary heart disease (c2Z3.87, PZ0.046) in
PHP is a rare and heterogeneous genetic disease with a high rate of misdiagnosis
patients with hypercalcemia were detected. In the same time the differences in the
and no specific treatment. It should be considered in children presenting with a
prevalence of acute myocardial infarction
(c2Z0.09, PZ0.8) and acute
round face, obesity, brachydactyly, learning/behavior disabilities, subcutaneous
cerebrovascular accident (c2Z0, PZ1) in patients with hypercalcemia were
calcifications and subclinical hypothyroidism. Laboratory evaluation of blood
not revealed.
calcium, phosphorus, PTH and thyroid hormones should be ordered as soon as
Conclusion
possible, as well as neuroimaging and a genetic profile for further confirmation.
The results of the study show an increasing risk of arterial hypertension and
DOI: 10.1530/endoabs.49.EP310
coronary heart disease in patients with hypercalcaemia. In the same time the risk
of acute cardiovascular events is not increased. The results may suggest the
influence of hypercalcemia on the development of cardiovascular disease.
DOI: 10.1530/endoabs.49.EP312
EP311
Severe hypercalcemia revealing an atypical parathyroid adenoma
El Ansari Nawal & Bouchra Rafiq
Department of Endocrinology, Diabetology Metabolic Diseases and
Nutrition Laboratory PCIM, FMPM, Cadi Ayyad University,
UHC Mohamed VI, Marrakech, Morocco.
Introduction
EP313
Primary hyperparathyroidism is a common cause for hypercalcemia, however
Vitamin D levels in obese adults and cardiovascular risk
severe hypercalcemia remain a rare complication. The atypical parathyroid
Andreia Domingues1, Bruno Oliveira2,3 & Flora Correia2,4
adenoma is an uncommon cause to severe hypercalcemia. We report a case of a
1Hospital das Forças Armadas - Polo Lisboa: Unidade de Nutrição e
40-year-old male with very high serum calcium due to a possible atypical
Dietética e Serviço de Endocrinologia e Diabetes, Lisboa, Portugal;
parathyroid diagnosed after a spontaneous fracture.
2Faculdade de Ciências da Nutrição e Alimentac¸ão da Universidade do
Case report
Porto, Porto, Portugal;3LIAAD INESC-TEC, Porto, Portugal;4Centro
A 40-year-old male was admitted to the traumatology department for the
Hospitalar de S. Joa˜o EPE, Porto, Portugal.
management of spontaneous fracture of the humerus. The clinical history revealed
clinical symptoms of hypercalcemia
(abdominal pain, neurologic irritation,
asthenia, etc.). The initial blood work up found a severe hypercalcemia (203 mg/l)
Introduction
hypophosphoremia (23 mg/l) and high ALP. Parathyroid hormone level were of
The prevalence of vitamin D deficiency is high, and yet still little recognized and
749 pg/ml. The patient underwent a surgical en bloc resection after the
treated. Cardiovascular diseases are the leading causes of morbidity and mortality
localization of a right inferior parathyroid adenoma. Pathology showed a mixed
worldwide and the emergence of evidence with the link suggesting an association
picture consistent with possible atypical adenoma versus parathyroid carcinoma.
between vitamin D deficiency and cardiovascular risk (CVR), it is pertinent to
However, due to the absence of local structures involvement, atypical parathyroid
better understand this association.
adenoma was more likely. The immunohistochimie: paratyhroidien adenoma
Objective
atypical. The evolution was marked by the improvement of the clinical signs and
This study aimed to relate the levels of 25 (OH) D in obese patients with the
calcium normalization.
cardiovascular risk.
Conclusion
Methodology
It can be very difficult to distinguish between atypical parathyroid adenomas and
Cross-sectional observational study with a sample of 31 individuals between
parathyroid carcinomas as in our case and no clear-cut guidelines yet exist to
40
and
64
years, of both sexes diagnosed with obesity. They evaluated
differentiate the two based on histology. Close follow-up is mandatory to detect
sociodemographic data, solar exposure and use of sunscreen, skin color phototype
any local recurrence.
of skin color, sources of vitamin D, physical activity, anthropometric data,
clinical and biochemical and CVR.
DOI: 10.1530/endoabs.49.EP311
Results
The average value of 25(OH) D was 15.6 ng/ml, 71.0 and 22.6% had deficiency
and insufficiency, respectively. We observed lower levels of
25(OH) D in
smokers, those with less solar exposure time, with a higher waist-to-height ratio
and in those with lower levels of DBP. We did not find a statistically significant
Cardiovascular Endocrinology and Lipid Metabolism
association between vitamin D and CVR.
Conclusions
EP312
We found a high prevalence of vitamin D deficiency in our sample of patients
Hypercalcemia and cardiovascular disease
with obesity and a significant association with the waist-to-height ratio. Despite
Elena Brutskaya-Stempkovskaya1,2
the evidence that suggests that vitamin D deficiency is associated with an
1Belarusian State Medical University, Minsk, Belarus;2Minsk City
increased CVR, we found this association but without statistical significance. The
Polyclinic N31, Minsk, Belarus.
measurement of total 25(OH) D routinely in people with central obesity can help
identify those who are at most CVR.
Introduction
Keywords: vitamin D cardiovascular risk; obesity; SCORE; metabolic syndrome.
According to modern studies, patients with hypercalcemia have an increased
DOI: 10.1530/endoabs.49.EP313
cardiovascular risk.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Case Reports - Pituitary/Adrenal
CD was suspected. Serologic test for anti-gliadin antibodies was positive. Another
examination of the biopsy after the first endoscopy revealed extensive collagen
EP314
depositions in the lamina propria of the small bowel, giving the diagnosis of CD.
Partial gigantism: case report
Also antibodies against Transglutaminase were positive. After gluten-free diet the
Munira Karimova & Zamira Khalimova
above mentioned symptoms disappeared and patient’s anemia and blood clot
Center for the Scientific and Clinical Study of Endocrinology, Department
markers as well as parathormone and Ca level were well controlled.
of Neuroendocrinoloy, Mirzo Ulugbek str. 56, 100125, Tashkent,
Conclusion
Uzbekistan.
The presence of other immune-related diseases in our case suggests that
immunological mechanism plays a crucial role in CD. We recommend active
specific screening in older patients belonging to at risk-group like other
The aim
autoimmune disorders. Disappeared and patient’s anemia and blood clot markers
To study case of partial gigantism.
as well as parathormone level were well controlled.
Methods
To evaluate the patient’s condition we conducted hormonal and biochemical
DOI: 10.1530/endoabs.49.EP315
investigations, as well as total blood and clinical urine analysis; Doppler
sonography and multislice computed tomography were performed.
Results
STH - 25.8 mIU/l (normal range: 2.0-20 mIU/l); IGF - 2.9 mg/l (normal range
for the age: 13-100 mg/l); ALPase - 160 U/l (normal range: up to 644 U/l); total
calcium
-
2.08 mmol/l
(normal range:
2.5-3.0 mmol/l); phosphorous
-
1.42 mmol/l
(normal range:
1.3-2.26 mmol/l). Doppler sonographyof left
extremity demonstratedpresence of hyperechoic(circular) layer in the projections
of the first and second left toes.
Multislice computed tomography
(MSCT) of left extremitydemonstrated
enlargement of the first and second left toes with the metatarsal involvement.
EP316
The soft tissues of the area contain multiple poorly demarcated thin-wall cyst-like
Optic neuritis as presenting complaint in primary hypoparathyroidism
formations with cystic content density of
-120C34 HU. Cortical layers of
Muhammad Fahad Arshad1, Steven Kang1, Nauman Arif Jadoon2 &
adjacent toe or metatarsal bones demonstrated no disruptions of continuity.
Rehmat Karim2
Spacing intervals between the first and second toes and metatarsal bones are
1Doncaster Royal Infirmary, Doncaster, South Yorkshire, UK;2Hull Royal
enlarged. Middle phalanx of the second toe is laterally displaced. Boundaries of
Infirmary, Hull, UK.
bones are well defined; no disruptions of cortical layer or periosteal reaction can
be seen. The soft tissues of right extremity have no changes. Total blood and
Background
clinical urine analysis, ECG and brain MRI demonstrated no deviations.
Papilledema and raised intracranial pressure has been reported frequently in
Conclusions
patients with hypoparathyroidism but very rarely optic neuritis (1).
Due to few similar cases and limited experience for their managing, it is necessary
Clinical case
to:
We report a case of 63-year-old male who presented to ophthalmology with right-
- choose the wait and see approach. The excessive growth making a patient’s
sided visual loss and a relative afferent pupillary defect. He was diagnosed with
movements hard progresses, correcting surgical procedures and appropriate
optic neuritis and underwent MRI brain which showed bilateral white matter
footwear are necessary,
changes with the possibility of demyelination. He was initially diagnosed with
- let the closure of growth zones be accomplished for correcting surgical
relapsing-remitting multiple sclerosis by the neurologist but was later found to
reconstruction to be performed; the body part disproportionally enlarged should
have severe hypocalcaemia (adjusted calcium 1.32 mmol/l (2.20-2.60)) and
be surgically removed after that, generate a databank to generalize the results,
idiopathic primary hypoparathyroidism (PTH!0.3 pg/ml (1.6-7.2)). Cerebrosp-
and to develop drug and radiotherapy regimens.
inal fluid examination was entirely normal with negative oligoclonal bands. The
DOI: 10.1530/endoabs.49.EP314
initial MRI changes were thought to be secondary to severe hypocalcaemia as per
neuroradiology MDT and subsequently, the diagnosis of multiple sclerosis was
reversed. Although the underlying mechanism is not very clear, we believe there
is an association between optic neuritis and primary hypoparathyroidism,
especially in the absence of any other underlying cause for optic neuritis.
Conclusion
Although rare, but primary hypoparathyroidism can present as optic neuritis.
Clinical Case Reports - Thyroid/Others
Therefore, serum calcium should be checked in patients with no clear cause of
optic neuritis.
EP315
Reference
An unique case of celiac disease with hypocoagulation and secondary
1. Bajandas FJ, Smith JL. Optic neuritis in hypoparathyroidism. Neurology 1976
hyperparathyreodism in elderly patient - a case report
26(5) 451-454.
Gocha Barbakadze, Lali Tigishvili, Levan Ramishvili, Nani Tsikarishvili &
DOI: 10.1530/endoabs.49.EP316
Koba Burnadze
Enmedic Clinic, Tbilisi, Georgia.
Introduction
Celiac disease
(CD) an autoimmune disorder of the small intestine, was
considered as a disease of childhood. The symptoms can be obvious. That is the
main reason why CD is underdiagnosed in elderly patients.
Aims & Methods
The purpose of our study was to demonstrate a clinical case of CD which was
EP317
diagnosed in a 41-year-old female patient. The patient attended our clinic with
The parathyroid carcinoma in a young adult male
complains of weakness, tenderness, abdominal distension, weight loss.
Sevde Nur Firat1, Anara Karaca1, Nujen C¸ olak Bozkurt1 & Hatice Unverdi2
Laboratory tests find severe iron deficiency anemia (HB -9 g/dl, Ery- 3.1!
1Ankara Teaching and Research Hospital, Endocrinology and Metabolism,
1012/l, serum iron 4 mmol/l) and severe hypocoagolopathy (prothrombine index-
Ankara, Turkey;2Ankara Teaching and Research Hospital, Pathology,
48%, INR-2.98, but mild thrombocytopenia 130!10/l). She had suffered with
Ankara, Turkey.
these symptoms for 2 years.
Results
Number of investigations was performed. We also checked parathormone which
Introduction
revealed secondary hyperparathyroidism
(parathhormon
187 pg/ml, Ca-
Parathyroid carcinoma is a rare malignancy of the parathyroid glands. Parathyroid
1.01 mmol/l). The hemolytic anemia was excluded (haptoglobin was in normal
carcinoma may be suspected, but it usually cannot be confirmed prior to operation.
range). Stool examination revealed no pathogens.
Case
It was believed that she has these symptoms due to her anemia. After 2 weeks
A 35-year-old male was consulted to Endocrinology department with persistant
occurred the oedema of abdomen and diarrhea of 3-4 watery stools daily and
kidney stones. He was operated five times in 10 years for recurrent kidney stones.
night tremor and seizure due to hypoglycaemia
(2.3 mmol/l). Ultrasound
His lab results are as follows; Ca:13(8.8-10.6), P:2.2 mg/dl(2.5-4.5),
investigation of abdomen showed very rush peristalsis of small and large
ALP:84U/L(30-120), parathormone:179 pg/ml(14-72),
25(OH)Dvit:8.2 ug/
intestines, but no ascites, significant meteorism.
l(10-80). Urine Ca: 1159 mg/24 h(100-300), urine P:134 mmol/24 h(13-42).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Neck USG revealed 17!11!12 mm PTH adenoma with cystic components, but
Congenital fibrous dysplasia is a rare disease with a broad spectrum of
with no pathological cervical lymphodenopathies.
manifestations, including various endocrinopathies;precocious puberty,
Radionuclide scan confirmed increased parathyroid gland activity on the right
hyperthyroidism, excess growth hormone, hypophosphatemia mediated by
inferior of the thyroid gland.
FGF23.
The patient underwent right inferior parathyroidectomy. Postoperative PTH!6,
We present the case of a 33 year old male, who presented in our endocrinology
Ca:8.17,which confirmed successful remove of the pathological parathyroid gland.
service with infertility and bone pain. He was diagnosed at the age of years old
The histological findings reported marked pleomorphysm in the cells, divided by
with congenital fibrous dyplasia and suffered multiple surgeries for bone
the typical fibrotic septae and Ki-67: 4-5%. All those findings were consistent with
decompression. Blood tests showed vitamin D insufficiency (16,01 ng/ml), very
parathyroid carcinoma.
high levels of alkaline phosphatise
(919 U/l), normal levels of calcium,
After 4 months his last lab results were as follows; PTH: 57.8 pg/ml, Ca:8.8 mg/dl,
phosphorus and parathormone. Bone mineral density was low at the femoral
P:4.6 mg/dl, urine Ca: 124 mg/24 h.
neck: BMD 1.385 g/cm2, TscoreZK2.4, ZscoreZK2.3.
Conclusion
His semen analysis showed a normal aspect, volume and viscosity, but with a low
There is a challenge in the diagnosis of parathyroid carcinoma, because it is
A mobility of spermatozoa and a low percentage of normal form spermatozoa.
commonly confirmed with histological evaluation. Although, parathyroid
His testosterone was within the normal range (3,44 ng/ml), with a TSH of
carcinoma is a rare disease, it should be kept in mind even in young adults.
4,10 microUI/ml. We further performed a karyotype analysis, wich showed the
DOI: 10.1530/endoabs.49.EP317
presence of an extra X chromosome in 10% of the studied metaphases, with the
diagnosis of mosaic Klinefelter:47XXY(10%)/46 XY (90%).
This is the first description of a case with congenital fibrous dysplasia which
associates mosaic karyotype 46XY/47XXY. Although the link between the two
conditions is not known, further investigations are necessary to establish a
possible correlation between them. It remains to establish if karyotype analysis
should be a routine investigation for those diagnosed with fibrous dysplasia.
DOI: 10.1530/endoabs.49.EP319
EP318
Clinical case of atypical parathyroid adenoma with severe
hypercalcemia and multiple fragility fractures
Anna Eremkina, Natalia Mokrysheva, Julia Krupinova, Svetlana Mirnaya &
Iya Voronkova
Endocrinology Research Centre, Moscow, Russia.
Introduction
Atypical parathyroid adenoma (APA) is rarely encountered cause of primary
hyperparathyroidism (PHPT). No definite criteria are considered to distinguish
preoperatively APA from parathyroid typical adenoma or carcinoma.
The aim
To describe the clinical course of a patient with an atypical parathyroid adenoma
with severe hypercalcemia and multiple fragility fractures.
Case presentation
EP320
A 61-year-old woman was evaluated for multiple fractures, skeletal deformities,
Parathyroid nodular hyperplasia: when imaging exams fail
pain in the large joints and bones, tachycardia, oppressive chest pain. She had
Ana Sofia Osório1, José Rocha2, Carolina Faria1, David Barbosa1,
severe hypercalcemia
(calcium level
14.7 mg/dl), hypophosphatemia (serum
Ema Nobre1 & Maria Joa˜o Bugalho1
phosphate 2.1 mg/dl) with an elevated intact parathyroid hormone level of
1Serviço de Endocrinologia, Diabetes e Metabolismo; Hospital de Santa
1871 pg/ml. Ultrasonography revealed a large structure (4.7 cm) of the right
Maria; Centro Hospitalar de Lisboa Norte, Lisboa, Portugal;2Serviço de
parathyroid gland. 99mTc-sestamibi SPECT/CT showed the lesion 43!34!
Cirurgia I; Centro Hospitalar de Lisboa Norte, Lisboa, Portugal.
40 mm behind the middle and lower third of the left thyroid lobe. Renal function
was impaired, GFR
46 ml/min/1.73 m2. Whole-body Tc-99m bone scan
demonstrated multiple skeletal changes accepted as parathyroid osteodystrophy.
Introduction
As a result of the determination of severe hypercalcemia, heart rhythm
Parathyroid hyperplasia is the second cause of primary hyperparathyroidism (PH),
disturbances (permanent form of atrial fibrillation), a high risk of hypercalcemic
representing 15-20% of all cases. The scintigraphy with Tc-99m-Sestamibi is a
crisis, intravenous hydration was started with no significant effect. Patient
preoperative exam used to identify parathyroid adenomas or hyperplasia. It has a
received denosumab 60 mg s.c. She underwent a surgical resection of parathyroid
sensibility of 50-90%, which increases with larger parathyroid size. The neck
adenoma and intra-operative PTH levels fell to 20.9 pg/ml. In the postoperative
ultrasonography (US) has also an important role detecting parathyroid enlarged
period serum calcium was decreased to 8.9 mg/dl. On pathological examination,
glands with 70% sensibility. We report a case of parathyroid hyperplasia where the
the tumor consisted mainly of chief cells. Capsule invasion, peripherical vascular
imaging exams fail to detect a 40 mm parathyroid.
and perineural invasion of the adjacent tissue, high mitotic activity or large bands
Case report
of fibrosis were not observed. Ki67 immunostaining was generally positive in
75-year-old woman with osteoporosis, spontaneous bone fracture and osteoarti-
about 3% of the tumor. Tumor vessel invasion was detected in the central node
cular pain. Laboratory evaluation showed a parathormone (PTH) of 145 pg/ml
part. These changes corroborated the diagnosis of atypical parathyroid adenoma.
(range 14-72), a serum calcium of 12,0 mg/dl (range 8,6-10,2) and a phosphorus
Conclusion
of 2,2 mg/dl (range 2,5-4,5). A neck US was performed revealing a 17 mm
APA are rare and have been a challenge for diagnosis. They have some features of
hypoechogenic vascularised nodule consistent with the inferior left parathyroid,
carcinoma but lack the indisputable evidence of malignant disease like invasion
also visible in the Tc-99m-Sestamibi. Patient was submitted to inferior left
or metastases. They have unpredictable clinical course, long-term follow up is
parathyroidectomy. The intraoperative exploration conducted to the additional
prudent to assess for local recurrence and metastatic disorder to distinguish
finding of an enlarged superior right parathyroid with 40 mm also removed. The
between benign and malignant parathyroid disease.
final diagnosis was nodular hyperplasia of both glands. Retrospectively, a detailed
familial history was taken and considered negative for hyperparathyroidism
DOI: 10.1530/endoabs.49.EP318
and/or endocrine tumours. After 2 months post surgery, the patient is under
Vitamin D and Calcium and mentioned improvement in symptoms.
Conclusion
Coincidental results of an anatomic exam (US) and a functional one (Tc-99m-
Sestamibi), suggesting the involvement of a single gland, do not exclude
EP319
pluriglandular HP. Vitamin D and Calcium were started considering the bone
Congenital fibrous dysplasia and Klinefelter syndrome: coincidence
disease; discontinuation and tapering of therapy will be managed according to
or not?
calcium and PTH levels.
Maria Alexandra Grama1 & Constantin Dumitrache1,2
DOI: 10.1530/endoabs.49.EP320
1Institute of Endocrinology IC Parhon, Bucuresti, Romania;2University of
Medicine and Farmacology Carol Davila, Bucuresti, Romania.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP321
gene, suggesting the diagnosis of FHH. This mutation has never been reported in
literature or in the Human Gene Mutation Database. In the follow up of the patient
As clear as mud: an atypical case of primary hyperparathyroidism
30 mg/day cinacalcet treatment was started and increased up to 60 mg/day due to
Jessica Lai1,2, Navin Niles1,3 & Namson Lau1,4
the persistant symptomatic hypercalcemia. Plasma calcium levels were
1Liverpool Hospital, NSW, Australia;2South Western Sydney Clinical
normalized and PTH levels decreased slightly after the treatment.
School, University of New South Wales, NSW, Australia;3Macquarie
Conclusions
University Hospital, NSW, Australia;4LIVE DIAB CRU, Ingham Insitute
FHH is a rare disorder, but it is clinically important because it can be confused
of Applied Medical Research, NSW, Australia.
with asymptomatic primary hyperparathyroidism. FHH is usually asymptomatic
but rarely symptoms of fatigue, weakness, and excessive thirst and concentration
Objective
problems are experienced. Cinacalcet is potentially a useful treatment of patients
A young woman presented with marked hyperparathyroidism with post-operative
with intractable hypercalcemia caused by mutations in the CaSR gene.
course complicated by hungry bone syndrome and diagnostic and management
DOI: 10.1530/endoabs.49.EP322
challenges of ongoing hypocalcaemia with hyperparathyroidism.
Method
ML, a 32-year-old Fijian Indian female, was referred with severe hypercalcaemia,
following one-year history of migratory debilitating bone pain. Initial labs
showed corrected calcium (C.Ca) 3.17 [2.10-2.60 mmol/l], parathyroid hormone
(PTH) 305.4 [2.0-6.0 pmol/l] and 25-hydroxyvitamin D (25-VitD) of 22 [40-
EP323
80 nmol/l]. Acute management included admission for intravenous fluids and
Parathyroid carcinoma can be misdiagnosis with medullary thyroid
bisphosphonates, which normalised C.Ca. A parathyroid SESTAMIBI/CT-
cancer: how is that possible?
SPECT demonstrated a 31!9!33 mm soft tissue mass in anterior superior
Natalia Mokrysheva, Julia Krupinova, Ekaterina Pigarova,
mediastinum with focal uptake at T3. Further CT neck demonstrated 10!5!
Nadezhda Platonova, Iya Voronkova & Kirill lanschakov
5 mm mass between left common carotid and subclavian arteries.
Endocrinology Research Centre, Moscow, Russia.
Results
ML’s surgical resection of the mediastinal mass was immediately complicated by
Background
generalised bony pain, pleural effusions and despite aggressive replacement of
Hypercalcemia may stimulate thyroid’s C-cells to produce the calcitonin, that
calcium, marked hypocalcaemia
(Day
1
C.Ca
1.99); consistent with an
could lead to misdiagnosis of medullary thyroid cancer.
exaggerated ‘hungry bone syndrome’. ML has been followed closely for on-going
Clinical case
optimisation of calcium and vitamin D; three-month labs showed elevated PTH
A 47-year-old woman suffered from fracture of the left knee. She could not walk
(30.7 pmol/l), despite normalisation of 25-VitD (79 nmol/l) and improved C.Ca
and used a wheelchair. CT scan in a public hospital detected multiple bone lytic
(2.04 mmol/l). Her pre-operative DEXA scan showed T-scores: lumbar spine
changes in the ribs and vertebrae (mts?), tumor in the liver (mts?) and node in the
K5.1SD and bilateral femoral necks K5.6SD. A MRI cervical spine
thyroid gland 2.6*1.9 cm. Thyroid biopsy showed follicular neoplasia (cancer?).
demonstrated widespread lytic lesions including, a lesion in the C2 spinous
At the same time, blood analysis showed high level of serum calcitonin 190 pg/m
process and posterior pedicles, considered consistent with pathological fracture.
(0-5.5). Thus, her state was determined as the medullary thyroid cancer (MTC)
Histopathology reported a
70!65!51 mm; 41 gm mass with no invasive
with mts in bone and liver and she was sent to our center for surgery of MTC.
features. Parafibromin was positive, whilst PGP9.5 was negative; other patterns of
Medical examination uncovered primary hyperparathyroidism
(PH): total
staining were normal, making HRPT2/CDC73 mutation unlikely.
calcium - 3.78 mmol/l (2.10-2.55), PTH K1513 pg/ml (15-65) in combination
Conclusion
with 3.7*2.9*2.4 cm tumor behind the thyroid gland showed by the US exam.
This case highlights: 1) the diagnostic challenge of marked hyperparathyroidism
Osteitis fibrosa cystica was suspected after radionuclide bone imaging. Renal
with a clinical picture suggestive of malignancy, but histological evidence not
functions were impaired, GFR 10 mL/min/1.73 m2. Given the fast progress of the
supporting invasion; 2) the management issues of moderating post-operative
disease the parathyroid cancer (PC) was suspected, so “en bloc” removal of the
severe hypocalcaemia and hungry bone phenomenon; and 3) the on-going
tumor was performed. The diagnosis was confirmed by histological examination.
diagnostic and management of post-operative hyperparathyroidism with
PTH, total serum calcium levels as well as calcitonin were decreased down to the
hypocalcaemia. In summary, atypical primary hyperparathyroidism presents
reference level after the surgery. The liver biopsy shows no tumor cells. PET/CT
unique diagnostic and management challenges.
did not observe the abnormal accumulation of 18FDG in the liver and in bones.
DOI: 10.1530/endoabs.49.EP321
The patient’s condition has significantly improved 4 month after the surgery - she
can walk without a wheelchair.
Conclusions
High level of calcitonin caused by hypercalcemia in combination with nodules in
the thyroid gland can lead to incorrect diagnosis. It is important to exclude
hypercalcemia in case of high levels of calcitonin.
DOI: 10.1530/endoabs.49.EP323
EP322
Familial hypocalciuric hypercalcemia with a new heterozygous
missense mutation of CaSR gene and cinacalcet treatment
Sinem Kiyici1, Burçin Uygun1 & Orhan Gorukmez2
1University of Health Sciences, Bursa Yuksek Ihtisas Education and
EP324
Training Hospital, Department of Endocrinology and Metabolism, Bursa,
Clinical case of pachydermoperiostosis
Turkey;2University of Health Sciences, Bursa Yuksek Ihtisas Education
Munira Karimova & Zamira Khalimova
and Training Hospital, Department of Genetics, Bursa, Turkey.
Center for the Scientific and Clinical Study of Endocrinology, Department
of Neuroendocrinoloy, Republic of Uzbekistan, 100125, Tashkent,
Mirzo Ulugbek str. 56.
Introduction
Familial hypocalciuric hypercalcemia (FHH) is an autosomal-dominant genetic
disease caused by an inactivating mutation in the gene encoding the calcium
The aim
sensing receptor (CaSR). The loss of function leads to increased circulating level
To study the case of Pachydermoperiostosisis.
of PTH and subsequent hypercalcemia.
Material and methods
Case report
We report a case of a 24-year old male complaining of marked changes in
20-year-old male patient referred to our center with hypercalcemia which was
appearance due to the disfiguring thickening and wrinkling of skin, excessive
found after the syncope. His serum calcium level was
11.7 mg/dl and the
greasiness and perspiration, marked horizontal creases on the forehead, with deep
phosphorus was 2.4 mg/dl (normal: 2.5-4.5). The serum PTH was 131 pg/ml
furrows between them, increase in the thickness of eye lids, “senile expression” of
(normal: 10-65), 25-hydroxyvitamin D3: 12.2 ng/ml and 24-h urine calcium
the face, thickening of distal parts of extremities, fingers and toes. The patient is
excretion was below 200 mg/day. His calcium/creatinine clearance ratio was
unsocial, aloof and focused on his emotions.To evaluate the patient’s condition
0.005. After replacement of vitamin D, calcium/creatinine clearance ratio was
we conducted hormonal and biochemical investigations, as well as total blood and
still ! 0.01. The family screening planned for FHH. Both his 49 year-old father
clinical urine analysis; MRI of pituitary and ultrasonography of inner organs were
and 22 year-old brother had also slightly elevated PTH in spite of moderately
performed.
increased serum calcium levels. Their calcium/creatinine clearance ratios were
Results
!0.01. Patient is tested for mutations in the CaSR gene. The patient was found to
GH - 2.2 (normal range: 0-20 mIU/l); IGF -114.6 (normal range: 219-644 mg/l);
have a heterozygous missense mutation (p.Ser182Pro/c.544T OC) in the CaSR
prolactin
-
5.3
(normal range:
1-18 ng/ml), TSH
-
0.87
(normal range:
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
0.17-4.05 mIU/l), free T4 - 15.5 (normal range: 11.5-23 pmol/l). The patient was
and false positive preoperative imaging might influence the extent of preoperative
diagnosed with pituitary microadenoma, mastoiditis, ethmoiditis, and sinusitis;
evaluation and the choice of surgical approach in PHPT.
US revealed chronic cholecystitis, pancreatitis, and reactive hepatitis. Total blood
DOI: 10.1530/endoabs.49.EP326
and clinical urine analysis demonstrated no deviations. The patient presented
pachydermia of scalp with moderately painful, rough skin folds in the parietal-
occipital region, resembling cerebral gyri, thickening and enlargement of eyelids
due to hypertrophy of the cartilage tissue, dystrophic changes of the conjunctiva,
atrophy of the tarsal glands with formation of cysts and granulomas in them. The
patient is unsocial, aloof and focused on his emotions.
Conclusions
EP327
Although the prognosis for patients with pachydermoperiostosis is unfavorable,
Parathyroid carcinoma: a report of cases
and there are no specific prevention techniques, they can maintain the ability to
İlknur Ozturk Unsal, Erman Cakal, Bekir Ucan, Mustafa Calıskan,
work for a long time and live to old age if the appropriate treatment is applied (the
Esra Tutal, Melia Karakose, Muyesser Sayki Arslan & Mustafa Ozbek
latter can be achieved by a thorough medical and genetic counseling of families of
Saglik Bilimleri Universty Diskapi Yildirim Beyazit Traning and Research
patients. Some cases, severe articular syndrome may cause permanent disability.
Hospital, Ankara, Turkey.
DOI: 10.1530/endoabs.49.EP324
Background
Primary hyperparathyroidism (PHPT) is one of the most common endocrine
diseases. Parathyroid carcinoma, a rare entity, comprises a small percentage
of patients with hyperparathyroidism and represents 0.005% of all cancers and
!1% of cases of PHPT.
Material and methods
Patients was diagnosed at the Endocrinology Department of Diskapi Yildirim
EP325
Beyazit Training and Research Hospital between 2010 and 2016. Ultrasound and
Vascular dementia in a 57-year old woman with adenoma of
99mTc-Sestamibi confirmed the suspicion of a parathyroid mass. Parathyroid
parathyroid gland
gland volumes were calculated by multiplication of three diameters and the
Mubina Hodzic
constant value
0.52. Intraoperative findings and pathology confirmed the
Cantonal Hospital, Zenica, Bosnia and Herzegovina.
diagnosis of parathyroid carcinoma.
Results
Of the patients eight were female and three were male. The patient’s ages were
Dementia describes a set of symptoms such as memory loss, difficulties with
between 27-76 years. Parathyroid gland volume of two patients were lower than
thinking, problem solving or language. Vascular dementia is a second most
other cases
(respectively
8.92-10.17 ml). Despite small lesion size on
common type of dementia, rare under 65 year old. I report a case of 57- year-old
ultrasonography, these two patients have moderate-high PTH values. The
woman with diagnosed dementia vascularis in Neurology department. Beside
demographic characteristics and biochemical parameters of the patients.
neurological diagnostic methods(brain scan-CT, MRI, Color Doppler of carotids,
Conclusion
she had hypercalcaemia (2.96-3.04 mmol/l; normal range 2.20-2.60) as high
Pre-operatively, parathyroid carcinoma can be expected based on factors
calciuresis/24-hour
(concentration
6.98 mmol/l). Her parathyroid hormone is
including a larger tumor size, palpable mass, severe primary hyperparathyroidism
elevated (hyperparathyroidism) due to adenoma of right inferior parathyroid
(PTH 3-15 times the normal upper limit) and hypercalcemia (O14 mg/dl) often
gland (PTH is 95 pg/ml). Because of progression on patient’s physiological and
with renal and bone involvement by the onset of presentation. Biochemical or
clinical state, immobility, difficulty to communicate and feeding with nasogastric
ultrasonographic features (lesion size, very high serum calcium and parathyroid
tube, an operation of adenoma of parathyroid gland was not an option. She ended
hormone levels) may predict aggressive disease, but this is not always the case.
with stones in her left urether and postsurgery complications.
DOI: 10.1530/endoabs.49.EP327
Keywords: dementia vascular; adenoma of parathyroid gland; hypercalcemia;
hyperparathyroidism; parathyroid hormone.
DOI: 10.1530/endoabs.49.EP325
EP328
A rare case of giant parathyroid adenoma: diagnostic and therapeutic
aspects
EP326
Cristina Alina Silaghi1, Horatiu Silaghi2, Gheorghe Cobzac3,
Equivocal preoperative imaging including 18F-fluorocholine PET-CT
Svetlana Encică4, Romina Alina Rădi5, Daniel Tudor Cosma6, Anca Ciurea7
in primary hyperparathyroidism and nodular thyroid disease - case
& Carmen Emanuela Georgescu1
report
1Department of Endocrinology “Iuliu Hatieganu” University of Medicine
Katerina Zajickova
and Pharmacy Cluj-Napoca, Cluj Napoca, Romania;25th Departament of
Institute of Endocrinology, Prague, Czech Republic.
Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-
Napoca, Cluj Napoca, Romania;3Clinic of Nuclear Medicine, County
Emergency Hospital, Cluj-Napoca, Cluj Napoca, Romania;4Department of
66-year old woman came first for an evaluation of nodular thyroid disease.
Pathology, “Niculae Sta˘ncioiu” Heart Institute, Cluj Napoca, Romania;
Primary hyperparathyroidism (PHPT) was incidentally diagnosed during the
5Clinic of Endocrinology, County Emergency Hospital, Cluj-Napoca, Cluj
entrance lab test with total calcium
2.62 mmol/l and PTH 93 ng/l. Serum
Napoca, Romania;6Diabet, Nutrition and Metabolic Diseases Clinical
creatinine was normal and 25 OH vitamin D was 97 nmol/l. Dual-energy X-ray
Center Cluj-Napoca, Cluj Napoca, Romania;7Department of Radiology
absorptiometry was carried out and revealed osteoporosis at lumbar spine.
“Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca,
Moreover, there were two low-trauma fractures in a recent patient history.
Cluj Napoca, Romania.
Although hypercalcemia was mild, the presence of osteoporosis constituted an
indication for surgical treatment of PHPT. Neck ultrasound found a
hypoechogenic lesion of 0.2 ml behind the cranial third of the left thyroid lobe
Parathyroid adenomas (85% of cases of primary hyperparathyroidism) are usually
evocative of a left superior hyperfunctioning parathyroid gland. 99mTc-MIBI
small in size (weigh 70 mg - 1 g). Giant parathyroid adenomas (GPTA) weighing
double-phase scintigraphy was, however, negative. Due to inconclusive
more than 3.5 g are very rare, more common in males, in the 6th decade of life,
conventional imaging
18F-fluorocholine PET-CT was recommended and
generally affect one parathyroid gland, are oxyphilic and ectopic in 50% of cases.
localized four abnormal parathyroid foci suggestive of parathyroid hyperplasia
We report the case of a 53-year-old woman presented for asthenia, fatigue,
and/or multigland parathyroid disease. Basic assessment of hereditary forms of
tingling in the arms and legs without other symptoms of hypercalcaemia.
PHPT was, therefore, carried out. Prolactin, IGF1, chromogranin A and calcitonin
Laboratory analysis showed: ionized calcium 6.5 mg/dl (normal: 4.2-5.4 mg/dl),
were normal; calcium/creatinine excretion ratio was 2,2%. No relatives affected
total calcium
13.9 mg/dl
(normal:
8.8
to
10.0 mg/dl), hypophosphoremia
with hypercalcemia were found. In a postmenopausal woman with normal renal
2.0 mg/dl (normal: 2.3 to 4.7 mg/dl) and 809 pg/mL intact-parathyroid hormone
functions and sufficient vitamin D level a sporadic form of PHPT with a single
(normal:
11.0
to
67.0 pg/ml). Calcitonin, thyroxin and thyroid-stimulating
adenoma would be the most expected. The result of 18F-fluorocholine PET-CT
hormone levels were normal. Cervical ultrasonography revealed a solid
was probably modified by thyroid nodules present in both thyroid lobes. The
hypoechoic nodule located postero-inferior of the right thyroid lobe with
definitive diagnosis will be made by a surgeon during bilateral cervical
retrosternal extension. An ectopic GPTA localised in para-aortic region of
exploration. The present case shows how a combination of both false negative
superior mediastinum stretching down to the bifurcation of the trachea was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
detected using technetium-99m sestamibi scintigraphy and single photon
polyuria or polydipsia. She did not have any history of hypertension,
emission computed tomography/computed tomography
(SPECT/CT). GPTA
nephrolithiasis, renal failure or bone fracture; and she was taking risedronate
measuring 8.5!4!4.5 cm was removed via cervical approach. Histopathology
for one week for osteoporosis. On physical examination, vital signs and
indicated an atypical GPTA with main cells, oncocytic cells, follicular areas, Ki67
systemic findings were normal. Blood count revealed mild anemia
! 5% (rarely, in very small areas Ki67 was up to 10%); chromogranin and
(hemoglobin:10 gr/dl, MCV:80 fL); and in biochemical analysis, creatinine
cytokeratin AE1/3 were positive; carcinoembryonic antigen, thyroid transcription
was
0.65 mg/dl, Ca:12 mg/dl, P:2.2 mg/dl, Mg:2.07 mg/dl, albu-
factor1, and thyroglobuline were negative.
min:3.1 gr/dl, ALP:738 U/l. Hormonal parameters showed biochemical
The peculiarities of this case: GPTA but poor symptomatology of hypercalcemia and
primary hyperparathyroidism
(PTH:1938 pg/ml,
25(OH)D3:!3 ng/ml).
moderately elevated serum calcium levels; ablation of GPTA by cervical incision
BMD showed severe osteoporosis in lumbar vertebra (T score K4.0).
although mediastinal expansion; mild hungry bone syndrome postoperatively (not
There were osteopenia in bone X-rays and
“Brown tumor” in fifth
correlated with GPTA volume). In conclusion, GPTA is a very rare condition but
metacarpal bone of right hand. No nephrolithiasis or nephrocalcinosis
their size is not an argument in favour of malignancy. Cervical incision should be
were found in abdominal sonography. Neck sonography revealed a large
considered before sternotomy and thoracic/mediastinal approach.
(37!24 mm), vascular, heterogenous nodule having both cystic and solid
DOI: 10.1530/endoabs.49.EP328
areas in right lobe of the thyroid gland. 99mTc-sestamibi scintigraphy
showed MIBI uptake in the nodule, making us to define the nodule as
intrathyroidal parathyroid adenoma. Then, the patient underwent to surgery,
and right hemithyroidectomy was done; and postoperative pathological
examination confirmed the parathyroid adenoma. Postoperative calcium and
PTH levels were 7.3 mg/dl and 24.3 pg/ml.
EP329
When clinical and biochemical findings point to primary hyperparathyroid-
Autosomal dominant hypocalcemia in a Portuguese family: novel
ism, we should keep in mind that intrathyroidal nodules may be parathyroid
mutation in the calcium-sensing receptor gene
adenoma.
Vânia Gomes, Florbela Ferreira, Catarina Silvestre, Raquel Castro &
DOI: 10.1530/endoabs.49.EP330
Maria João Bugalho
Santa Maria Hospital, Lisbon, Portugal.
Introduction
Autosomal dominant hypocalcemia
(ADH) is a rare condition, caused by
activating mutations in the calcium-sensing receptor (CASR) gene. Affected
EP331
individuals have hypocalcemia with inappropriately low parathyroid hormone
(PTH) levels.
The rare cause of primary hyperparathyroidism: Parathyroid
Case report
Carcinoma
A 50-year-old woman, asymptomatic, was referred to our Endocrinology
Nagihan Bestepe1, Didem Ozdemir2, Sefika Burcak Polat2, Berna Evranos1,
department for investigation of hypocalcemia detected in routine blood analysis
Reyhan Ersoy2 & Bekir Cakir2
(serum corrected calcium was 7.4 mg/dl - normal: 8.6-10.2). There was also
1Ankara Ataturk Training and Research Hospital, Department of
hyperphosphatemia (5.4 mg/dl - normal: 2.4-5.1) and abnormally low PTH
Endocrinology and Metabolism, Ankara, Turkey;2Ankara Yildirim
(9.9 pg/ml - normal: 14-72).
Beyazit University Medicine Faculty Department of Endocrinology and
Her past medical history was irrelevant except for depression in the past. She
Metabolism, Ankara, Turkey.
denied taking any prescription. There was no history of neck surgery/radiation or
known family history of hypocalcemia. Thyroid function, morning serum cortisol
Introduction
and 24-h urinary cortisol, fasting glucose, 25-hydroxyvitamin D, renal function,
Parathyroid carcinoma (PC) is a rare endocrine malignancy which accounts for
serum magnesium, sodium and potassium were normal. Auto-antibodies against
0.005% of all cancers and less than 1% of primary hyperparathyroidism cases.
thyroid, parathyroid and adrenal gland were negative. Brain computed
This uncommon tumor usually occurs during the fifth decade of life, with equal
tomography identified basal ganglia calcifications. A few first-degree relatives
frequency in both sexes, and has an indolent but progressive course. It’s
(74-year-old mother, sisters aged 44 and 49, and 30-year-old son) were also
frequently symptomatic and patients may have high values of serum calcium and
screened for hypocalcemia. The mother and the younger sister, both
parathyroid hormone (PTH) with a palpable cervical mass. PC generally occurs as
asymptomatic, had hypocalcemia and inappropriately low PTH. The mother
a sporadic disease, and less frequently in the setting of genetic syndromes such as
also presented basal ganglia calcifications. The son and the older sister had normal
hyperparathyroidism-jaw tumor syndrome and multiple endocrine neoplasia. In
calcium levels. Genetic analysis identified a novel heterozygous CASR variant:
this study we present five different PC cases followed in our clinic.
c.2269GOA (p.Glu757Lys) in the proband, her mother and younger sister
Cases
whereas it was not identified in the son and older sister. Affected individuals
There were 2 female and 3 male patients with PC. The mean age of the patients was
started calcium replacement aiming to a low-normal calcium level (8-8.5 mg/dl).
50.4G13.7(38-65). They had presented with weakness, headache, nausea and
Conclusion
vomiting, and widespread bone pain. One of the patients had bone fracture and one
The co-segregation of the novel CASR variant with the hypocalcemic phenotype
other patient had nephrocalcinosis.The mean serum calcium, phosphorus and PTH
in the family favor its pathogenic role. Clinical investigation and diagnosis of this
levels were 15.3G2.7 mg/dl (ranging between 11.6 and 18.9 mg/dl), 2.4G0.8 mg/dl
condition can be challenging, but treatment and long-term monitoring are
and 869.4G991.9 pg/ml (ranging between 87 pg/ml and 2500 pg/ml), respectively.
essential to prevent complications, such as neurological.
Histopathologically, mean tumor size was 29.2G11.1 (15-44) mm. Plasma calcium,
DOI: 10.1530/endoabs.49.EP329
phosphorus and PTH levels were in the normal range and 36 months after surgery in 2
patients. Local recurrence was observed in 2 patients and reoperation was performed.
One other patient withlung and bone metastasis had still high serum Ca and PTH
levels despite recurrent surgeries for six times.
Conclusion
PC is usually that of a slowgrowing neoplasm and indicates progressive end-organ
EP330
damage from disturbed calcium homeostasis. While some patients present with
A case of intrathyroidal parathyroid adenoma presented with severe
mild increases in serum calcium and PTH levels, some might have very severe
25(OH)D3 deficiency, bone pain and high PTH
hypercalcemia and hyperparathyroidism. Similarly, prognosis varies from cure to
Omercan Topaloglu1, Bahri Evren1, Ibrahim Sahin1 & Bulent Unal2
life threatening unresectable and metastatic disease depending on the presentation
1Inonu University Medical Faculty, Department of Endocrinology, Malatya,
and surgical success.
Turkey;2Inonu University Medical Faculty, Department of General
Surgery, Malatya, Turkey.
DOI: 10.1530/endoabs.49.EP331
The most frequent pathology of primary hyperparathyroidism presented
with the findings of hypercalcemia is parathyroid adenoma. Some patients
EP332
having the signs of primary hyperparathyroidism may have intrathyroidal
parathyroid adenoma and it may be overlooked. We present a case of
A parathyroid adenoma presented with diffuse bone lesions and anemia
intrathyroidal parathyroid adenoma presented with bone pain.
Irem Kok, Fatma Dogan, Soner Cander, Ozen Oz Gul, Erdinc Erturk &
47-year-old female patient referred to our clinics with bone pain and she had
Canan Ersoy
no pruritus, dry mouth, dyspepsia, abdominal pain, nausea, vomiting,
Uludag University Medical School, Bursa, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Primary Hyperparathyroidism is a common endocrine disorder characterized with
EP334
high parathyroid hormone (PTH) and calcium (Ca) levels. Although most of the
Broken bones and blindness- a rare cause of osteoporosis
patients are asymptomatic, some patients may be presented with renal,
Rebecca Sagar & Afroze Abbas
gastrointestinal, musculoskeletal, neurologic or cardiovascular signs associated
Leeds Centre for Diabetes and Endocrinology, Leeds Teaching Hospitals,
with hypercalcemia or elevated parathyroid hormone related findings such as
Leeds, UK.
bone disease, nephrolithiasis, hypophosphatemia increased production of
calcitriol, hypomagnesemia, hyperuricemia and anemia. Brown tumor is one of
the manifestations of Primary Hyperparathyroidism and is more commonly found
Case History
in trabecular bone pattern of the mandible, bones of the upper and lower
A 37 year-old gentlemen was referred to metabolic bone clinic due to recurrent
extremities and ribs.
recent fragility fractures. He had several fractures throughout childhood, and
Case
these had continued to occur into his adult life. He was blind in his left eye since
A 54 year-old female with a history of recurrent nephrolithiasis was referred with
birth. He felt that this had contributed to his fractures, due to falls. There had been
fragile bones fractures. Biochemical assay revealed an increased value of serum
no other previous major health problems. His brother had a similar eye condition.
PTH 1570 pg/ml and calcium 13.5 mg/dl. The serum phosphorus level was
There were no other risk factors for osteoporosis. There was nothing of
3.4 mg/dl, ALP:14 IU/l, 25OH vitamin D:!8 mg/l.
significance to find on examination.
Direct radiographies revealed multipl lesions of the upper and lower extremities,
Investigations & Results
iliac bones, femoral heads, sacrum, sternum, ribs and vertebrae. A complete blood
DXA scan- Spine L1-L4 T-score K3.6, Left hip T-score K2.4. CTX 0.24 mcg/L
count (CBC) of the patient revealed a low hemoglobin and hematocrit levels
(normal), P1NP 34 mcg/L (normal). Spine X-rays: T11 grade 1 fracture & T4
(Hg:6.93 g/dl, Htc:20.00%). There was no evidence of neutropenia or leucopenia.
grade 2 fracture. No other secondary cause of low bone mass identified (normal
After consulting to Hematology department, it was reported that anemia was
levels of testosterone, parathyroid hormone, vitamin D, calcium, phosphate and
associated with diffuse bone lesions and it was not possible to make bone marrow
coeliac antibodies)
biopsy due to diffuse bone lesions. Follow up of anemia for recovery after
Discussion
parathyroidectomy was also suggested. Ultrasound of neck revealed mass of 3 cm
This is a case of a young man with seemingly unexplained fragility fractures and
associated with parathyroid adenoma. After erythrocytes transfusions, the patient
low bone mass. The clue to the aetiology for low bone mass was the gentleman’s
was planned for surgery.
hereditary eye condition. The eye problems are caused by a condition known as
Multipl bone lesions are common in Primary Hyperparathyroidism and Brown
Familial Exudative Vitreoretinopathy (FEVR); a rare genetic disorder affecting
tumor may also be a part of this clinical condition. These lesions are usually
retinal angiogenesis that can cause progressive visual loss. FEVR may be
localized and have a tendency for recovery of the primary disease. It should be in
mediated by mutation in LRP5 coding for the LRP5 transmembrane receptor.
mind that diffuse bone marrow lesions may be seen resulting progenitor cells
LRP5 plays a key role, alongside Frizzled protein, in the Wnt signalling pathway,
failure in bone marrow and cytopenia.
which has effects on cellular proliferation, adhesion and migration. Importantly,
Wnt signalling is also known to regulate bone mass. Therefore, it is the defect in
DOI: 10.1530/endoabs.49.EP332
this pathway that is the common denominator for this gentleman’s blindness and
bone problems. We speculate that upcoming new drugs that target Wnt signalling
in osteoporosis, such as Romosuzumab
(a Sclerostin inhibitor), may be
particularly beneficial in patients with low bone mass associated with FEVR.
DOI: 10.1530/endoabs.49.EP334
EP333
Common bone lesions may be a sign of parathyroid carcinoma in the
primary hyperparathyroidism
Soner Cander1, Ozen Oz Gul1, Pinar Sisman2 & Canan Ersoy1
1Uludag University Medical School, Bursa, Turkey;2Kars State Hospital,
EP335
Kars, Turkey.
An usual cause of post operative hypocalcemia
Fatma Mnif, Wajdi Safi, Nabila Rekik, Houcem Mrabet, Hamza Elfekih,
A 60-year-old male patient who presented with left hip and knee pain was found
Nadia Charfi, Mouna Mnif & Mohammed Abid
to be compatible with primary hyperparathyroidism (PTH:2233 pg/ml, calcium:
Department of Endocrinology, Hedi Chaker University hospital, Sfax,
15.7 mg/dl, phosphorus:
2.9 mg/dl creatinin:1.99 mg/dl,
25-OH-D:9.7 mg/l,
Tunisia.
ALP:532 mU/ml). Bone grafts of the patient showed multiple lytic lesions in
the pelvis, cranium and long-bones. Neck ultrasonography showed hypoechoic
solid nodule with cystic areas, 2!2 cm with size in the left thyroid gland inferior
Introduction
region and delayed wash-out was detected by the parathyroid scintigraphy. Bone
The otorhinolaryngologist can be confronted to multiple surprises after a thyroid
scintigraphy was suspicious in terms of metastasis. Left hemi thyroidectomy and
surgery
left inferior parathyroidectomy was performed. In thorax lytic lesions compatible
Case description
with multiple metastases in bone structures were observed. Thoracal and lumbar
We report the case of a 48 year-old woman admitted with post operative
vertebral MR imaging also showed lesions compatible with metastasis.
hypocalcaemia (after thyroidectomy?). The patient has a history of hypothyroid-
Histopathological examination revealed parathyroid carcinoma with invasion to
ism since 5 years. She then presented a cervical swelling. The ultra-sound
the thyroid gland.
confirmed the presence of a suspicious thyroid nodule measuring
4 cm. A
Primer hyperthyroidism has been increasing in recent years as a laboratory
thyroidectomy was then conducted. Post operative, the patient presented with
diagnosis the contribution of asymptomatic cases has increased. Frequent routine
symptoms of hypocalcaemia, confirmed by low level of blood calcium at
examinations have also led to the early recognition of the disease, and osteitis
1.59 mmol/. The anatomopathological examination showed no sign of thyroid
fibrosa cystica and bone lesions such as brown tumor, which are among the
tissue, along with the presence of five adenomatous parathyroid nodules. Post
complications of primary hyperparathyroidism, are increasingly rare. Primer
operative scintigraphy showed a conserved thyroid tissue, with absence of
Hyperparathyroidism is often associated with solitary parathyroid adenoma,
parathyroid glands. Hungry Bone Syndrome was confirmed led to the prolonged
hyperplasia or multiple adenomas, mostly seen with the genetic syndromes.
and severe hypocalcaemia, associated to the adenomatous aspect of the
Parathyroid carcinoma is very rare and is recognized only by the presence of
parathyroid measuring more than 6 cm. Because of the family history of pituitary
metastases or histopathologically significant invasion findings, such as those
prolactinoma, primary hyperparathyroidism and multinodular goitre and the
present in our case. Clinically, incompatibility in tumor size and serum PTH
personal history of uterine fibroma and hypothyroidism, Multiple Endocrine
levels, extremely high PTH levels may be a sign of parathyroid carcinoma. Apart
Neoplasia 1 (MEN1) was suspected. Genetic confirmation is underway.
from this, common bony lesions which are rarely seen in primary hyperparathyr-
Conclusion
oidia due to early diagnosis and noisy clinical picture can be considered as
This is the case of an asymptomatic hyperparathyroidism discovered by a severe
malignancy findings as it is in our patient. Therefore, in patients with widespread
post-thyroidectomy hypocalcaemia. This hyperparathyroidism is due to multiple
pain and common bony lesions, the patient should be carefully examined for
parathyroid adenomas misdiagnosed as thyroid nodules, and probably falls within
parathyroid carcinoma and an appropriate approach should be sought.
a multiple endocrine neoplasia type 1.
DOI: 10.1530/endoabs.49.EP333
DOI: 10.1530/endoabs.49.EP335
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP336
and lower tubular calcium reabsorption, and decreased excretion of zoledronate
due to acute renal failure. Considering the high prevalence of vitamin D
Brown tumor in a normocalcemic patient
deficiency and the sudden nature of hypocalcaemia, these and other risk factors
Pinar Sisman1, Ozen Oz Gul2, Soner Cander2, Erdinc Erturk2 &
should be considered when using bisphosphonates in order to prevent this
Canan Ersoy2
potentially fatal complication. Further studies may clarify the overall risk and
1Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,
approach to this situation.
Turkey;2Uludag University Medical School, Department of Endocrinology
and Metabolism, Bursa, Turkey.
DOI: 10.1530/endoabs.49.EP337
Background
Brown tumor of bone is a non-neoplastic lesion resulting from abnormal bone
metabolism in hyperparathyroidism. Brown tumor, as the only and initial
symptom of normocalcemic primary hyperparathyroidism is extremely rare.
Case presentation
A 69-year-old female patient was admitted to the hospital with a mass in the right
thigh. A mass lesion of the right distal femur with bone and soft tissue infiltration
EP338
was observed in the lower extremity magnetic resonance imaging (MRI). The size
Transient hyperglycemia during the course of primary
of the mass was measured as approximately 10!3.7!4.6 cm. Apart from this
hypoparathyroidism: Case study
lesion, nodular lesions were detected in various dimensions on the right femur,
Magdalena Urbanczuk1,2, Marcin Lewicki2,3, Agnieszka Zwolak2,4,
left femur and left patella. Brown tumor was detected in pathologic evaluation of
Marcin Urbanczuk5, Joanna Swirska2,4, Monika Lenart-Lipinska2,6 &
the mass of the right distal femur. The patient was examined for hyperparathyr-
Jerzy S Tarach2
oidism. Serum parathormone (PTH) level was 2698 pg/mL (reference range
1Chair and Department of Clinical Pathomorphology of Medical University
15-68), calcium level was 8.8 mg/dL (8.4-10.2), phosphorus level was 2 mg/dL
of Lublin, Lublin, Poland;2Department and Clinic of Endocrinology of
(2.4-4.4) and 25-OH D level was 10 mg/L. Vitamine D treatment was given to the
Medical University of Lublin, Lublin, Poland;3Chair and Department of
patient. 24-hour urine calcium could not be assessed because of the patient’s low
Epidemiology and Clinical Research Methodology of Medical University of
compliance. The total lomber T score was K4.7 and the femur neck T score was
Lublin, Lublin, Poland;4Department of Internal Medicine and Internal
K5.5 in the bone mineral density. Localization studies were performed and neck
Medicine in Nursing, Medical University of Lublin, Lublin, Poland;5Chair
ultrasonography and parathyroid scintigraphy revealed a parathyroid adenoma in
and Department of Family Medicine of Medical University of Lublin,
the inferior right lobe. Patient underwent parathyroidectomy surgery and in
Lublin, Poland;6Department of Laboratory Diagnostics of Medical
histopathological evaluation solitary parathyroid adenoma was observed. The
University of Lublin, Lublin, Poland.
follow-up of the patient whose postoperative PTH decreased to 161 pg/mL is
being continued.
Introduction
Discussion
Calcium ions (Ca2C) play an essential role in process of correct b-cell insulin
Cytologically, it is difficult to separate the brown tumor from any other giant cell
secretion. Hypocalcemia impairs insulin secretion leading to glucose metabolism
lesions. To prevent unnecessary surgical procedures, PTH assay is necessary in
disorders and insulin resistance.
any patient with expansive lytic lesion of the bone, even if serum calcium level is
Case study
normal.
62 -year old female patient with 18 years history of type 2 diabetes, treated with
DOI: 10.1530/endoabs.49.EP336
insulin, suspected of hypoparathyroidism, was admitted to the Department and
Clinic of Endocrinology, Medical University of Lublin because of hypocalcae-
mia. She was experiencing latent tetany signs like muscle tremors, paresthesia and
an unpleasant tingling sensation in her hands, additionally persistent dry cough.
Clinical observation and laboratory findings with classic constellation of
symptoms (hypocalcemia, hyperphosphatemia, undetectable concentrations of
parathyroid hormone (PTH), latent tetany signs, history of nephrolithiasis and of
subcortical nuclei calcifications) have confirmed the diagnosis of late onset
primary hypoparathyroidism. Significant clinical improvement following intro-
EP337
duction of calcium and active form of vitamin D supplementation were achieved.
Symptomatic bisphosphonate-induced hypocalcaemia after severe
Based on normal blood glucose levels with relatively low daily insulin
idiopathic hypercalcaemia
requirement an attempt at discontinuing insulin therapy was made. In spite of
Joana Lima Ferreira, Teresa Tavares, Rui Moc¸o & Pedro Melo
hypoglycemic therapy cessation, patient’s glucose levels remained in the normal
Hospital Pedro Hispano, ULS Matosinhos, Portugal.
range. For the purpose of diagnosis verification oral glucose tolerance test
(OGTT) was performed, and did not reveal any glucose metabolism disorders.
These observations led us to conclude that recognized hyperglycemia was
Introduction
secondary to prolonged hypocalcemia.
Bisphosphonates, generally considered as safe drugs, are potent inhibitors of bone
Conclusions
calcium outflow used to treat osteoporosis and hypercalcemia associated with
The optimal concentrations of organism’s cytosolic Ca2C are required for
malignancy. Bisphosphonate-induced hypocalcaemia is an increasingly reported
appropriate b-cell insulin release. Hypocalcemia is regarded as a factor
complication, but it has not yet been a subject of comprehensive research.
implicated in pathogenesis of glucose metabolism disorders thus normalizing
Case report
serum calcium levels allows for restoration of adequate insulin secretion.
A 65-year-old woman had a history of Crohn’s disease and ankylosing spondylitis
medicated with prednisolone and etanercept. Due to vitamin D deficiency she had
DOI: 10.1530/endoabs.49.EP338
been taking calcium and vitamin D supplementation. At a consultation she
presented with difficulty in concentration and balance, and blurred vision.
Analysis revealed severe hypercalcemia (ionized Ca2C2.18 mmol/l), elevated
serum creatinine and normal parathyroid hormone (PTH). She was treated with
intravenous fluids and a single intravenous dose of zoledronate, resulting in
calcium normalization and clinical remission. Five days later she returned for
delirium, tetany, perioral paraesthesia and carpopedal spasm. Chvostek’s sign was
positive. Hypocalcaemia
(ionized Ca2C0.97 mmol/l), vitamin D deficiency,
EP339
elevated PTH, hypomagnesaemia, hypophosphataemia and hypokalaemia were
Hyperparathyroidism jaw tumour syndrome (HPT-JT)
detected. She required intravenous calcium and long-term oral calcium and
KS Ahmed, M Sherlock, L Stassen, C Timon & ML Healy
vitamin D supplementation with gradual but sustained improvement. Densito-
1Department of Endocrinology, St. James Hospital;2Department of
metry revealed femur and lumbar spine osteoporosis. Study was negative for
Endocrinology, Adelaide and Meath Hospital;3Department of Maxillofacial
neoplasms and despite extensive study, aetiology of hypercalcemia remains
Surgery, St. James Hospital;4St. James Hospital. Department, Dublin,
unclear.
Ireland.
Discussion
This case illustrates a serious but still poorly recognized complication of
hypercalcaemia treatment. Most patients do not develop hypocalcaemia due to
Hyperparathyroidism jaw tumour syndrome (HPT-JT) is an autosomal dominant
compensatory mechanisms that could be affected in this case: vitamin D
disease with variable penetrance. Onset is typically in late adolescence or early
deficiency, diminished intestinal calcium absorption (corticoids and zoledronate)
adulthood. Primary hyperparathyroidism is typically caused by a single
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
parathyroid adenoma but parathyroid carcinoma occurs in 10-15%. Ossifying
Methods
fibroma of the mandible or maxilla occurs in 30-40%, and may be locally
We report the case of a 37-year-old man admitted to the hospital with a neck mass
aggressive. 15% of patients have renal manifestations which include polycystic
of 48 mm.
kidney disease, Wilms tumour and renal cell carcinoma. In women there is an
Results
increased risk of uterine tumours. The gene causing HPT-JT, HRPT2, is located
Our patient presented with neck pain and an hipoechogenic nodule on ultrasound
on chromosome 1q31.2a, coding for parafibromin (tumour suppressor gene)
(US) on the left side of the neck adjacent to the lower pole of the left thyroid lobe.
found in 50-75%.
An US-guided fine-needle aspiration was performed and follicular cells where
We recently identified a patient with HPT-JT which led to detection of a kindred
described. Measurement of TSH, T4L and AbTPO had a normal result. Given the
with the CDC73 pathogenic variant. A
54-year-old male presented to the
suspicion of thyroid nodule O4 cm surgical treatment was decided. While
maxillofacial services for surgical removal of a jaw tumour. Histology confirmed
waiting for surgery an US was performed and we observed markedly reduction on
an ossifying fibroma of the maxilla. During his admission he was noted to have
the size of the nodule (28 mm) and the radiologist suggested the possibility of a
hypercalcaemia (CaCC3.2 mmol/l, PTH 110 pmol/l).
parathyroid adenoma. Our patient referred prior episodes of nephrolitisis a few
On review of previous history, he described poor dentition since the age of 20, and
years ago and that he had been told to had high serum calcium levels but did not
he reported that his sister had died at the age of 35 from metastatic parathyroid
undergo further studies. We measured PTHi levels and Calcium (100,5 pg/ml;
carcinoma. Diagnosis of primary hyperparathyroidism was established and he
10 mg/dl) showing a normocalcemic hyperparathyroidism. Left thyroid
underwent parathyroid surgery with normalisation of CaCC and PTH. Histology
lobectomy was performed showing a normal left thyroid lobe, a parathyroid
was consistent with parathyroid adenoma.
cyst and ectopic thymus.
His genetic analysis detected a mutation in the CDC73 gene (Exon 7 c.664 C to T
After nodule resection PTHi levels went back to normal and calcium levels
leading to protein PArg222Ter). Family members were screened, which
remain less than 10 mg/dl.
confirmed CDC73 mutation in one daughter and one son, and 1 son was
Conclusion
mutation negative.
PCs are rare lesions and often considered as thyroid cysts. Diagnosis is best made
DOI: 10.1530/endoabs.49.EP339
by monitoring serum calcium levels and sending cyst fluid for PTH analysis.
Therefore, PCs must be included and be remembered within the differential
diagnosis of all neck masses.
DOI: 10.1530/endoabs.49.EP341
EP340
Fahr syndrome revealing a pseudohypoparathyroidism
Imen Sakka, Ibtissem Oueslati, Meriem Yazidi, Malika Chihaoui,
Fatma Chaker, Ons Rjeb & Hedia Slimane
Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.
Introduction
EP342
Fahr syndrome is a rare entity characterized by the presence of bilateral
“Pseudo or not”: differential diagnosis of hyperparathyroidism with
intracranial calcifications with predilection for the basal ganglia and dentate
severe electrolyte imbalance in transgender patient: a challenging case
nuclei. It is commonly associated with endocrine disorders, particularly
report
parathyroid and Vitamin D disturbances. Herein we report a case of
Ieva Ruza1,2 & Linda Kundzina2
pseudohypoparathyroidism revealed by Fahr syndrome.
1Riga Eastern Clinical University Hospital, Riga, Latvia;2Riga Stradins
Observation
University, Riga, Latvia.
A 29-old-year male was referred to our department for symptomatic
hypocalcemia. He showed a decrease in his school performances with memory
and concentration impairement. Computed tomography scan of the brain revealed
Introduction
bilateral, symmetric basal ganglia calcifications. Ophthalmic examination
Differential diagnosis between secondary hyperparathyroidism (SHPTH) and
showed bilateral cortical cataract.
possible pseudohypoparathyroidism can be challenging in case of insufficient
Physical examination showed positive Chvostek and Trousseau’s signs. The rest
diagnostic tools and co-existing medical conditions. We report a diagnostic road
of clinical examination was normal in particular no typical findings of Albright’s
to final diagnosis.
hereditary osteodystrophy were observed.
Case report
Laboratory investigations revealed severe hypocalcemia of
44 mg/l (normal
A 48-years old white male-to-female transgender patient was admitted to our
range: 85-105), hyperphosphatemia of 48 mg/l (normal range: 25-45), elevated
clinic for evaluation due to mental deterioration, general fatigue, slowly
parathormone level of 218 pg/ml (normal range: 15-68.3), normal renal function,
progressing bilateral upper arm and epigastric area cramps over last 2 years,
normal serum albumin and normal 25 OH Vitamin D level (46 mg/l, normal range:
pain in the lumbal area and right hip region leading to reduced mobility. No
30-80 mg/l). Thyroid function was normal. Urinary cyclic adenosine mono-
remarkable history, except crural DVT during estrogen therapy, received from
phosphate level and Gsa subunit assay were not available Considering laboratory
2004-2015 without any specialist’s supervision, not any therapy used in last year.
findings, the diagnosis of pseudohypoparathyroidism was established. Patient was
Possible previous delusion episodes since head trauma during teenage years were
put on substitutive therapy.
reported by patient’s brother. The patient was severely obese.
Conclusion
Biochemical tests revealed low calcium (1.74 mM/l [2.2-2.55]) and potassium
In the absence of chronic renal failure, the coexisting of hypocalcemia,
(3.12 mM/l
[3.3-5.5]), normal phosphate, creatinine and glucose level.
hyperphosphatemia, elevated PTH and normal vitamin D level is consisting
Preliminary suspected Cushing’s and Fahr’s syndromes were excluded after
with the diagnosis of pseudohypoparathyroidism.
seeing suppressed cortisol axis and elevated PTH (624.2 pg/ml [12-68]). No
substantial changes in other tests. No electrolyte loss with 24 h urine was seen.
DOI: 10.1530/endoabs.49.EP340
Thyroid and gonadic axis were unchanged. Head CT scan revealead no basal
ganglia calcinosis. No data of paratadenoma. In spite of high normal phosphate
level and not characteristic phenotype, our first suspected diagnosis was
pseudohypoparathyroidism. Additional tests showed low 25(OH)-vitamin-D (!
7 ng/ml [30-50]) and elevated alkaline phosphatase (320 U/l [44-147]). Pelvic
MRI showed left femoral periosteal cyst formation and right hip joint synovitis.
EP341
Though we were restricted in many diagnostic tools due to multiple factors, no
further data strongly supported evidence of pseudohypoparathyroidism.
Parathyroid cyst: the forgotten diagnosis of a neck mass
Based on these findings we suggest the final diagnosis of secondary
Esperanza Miranda, Mariana Tomé, Carmen Bautista & Daniel Gonzalez
hyperparathyroidism with severe osteomalacia. Treatment was continued with
Punta De Europa Hospital, Algeciras, Spain.
calcitriol, cholecalciferol, oral calcium. Some improvement of symptoms was
seen over the hospitalization course.
Introduction
Conclusion
The differential diagnosis of cystic cervical masses includes thyroid cyst, thymic
We would like to stress the importance of multi-focused investigation for bone-
cyst, thyroglossal duct cyst, branchial cleft cyst, bronchogenic cyst, lymphan-
metabolic problems.
gioma and parathyroid cyst (PC). PC is one of the less common causes of the
DOI: 10.1530/endoabs.49.EP342
cervical masses.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Developmental Endocrinology
were not different between groups(6.39G0.4 mmol/l vs. 6.39G0.9 mmol/l, PZ
NS). OC had a positive correlation with ucOC (rZ0.3, PZ0.03). In contrast, CRP
EP343
was not correlated with OC and ucOC (PZ0.2, PZ0.3, respectively).
Adolescent onset distal renal tubular acidosis presenting with significant
Conclusion
growth retardation without rickets
We conclude that circulating OC has a potential use as a sensitive diagnostic
Sagarjyoti Roy, Sandipan Banik, Indira Maisnam, Aniruddha Ray &
biomarker for early detection of breast cancer.
Apurba Kumar Mukherjee
DOI: 10.1530/endoabs.49.EP344
R G KAR Medical College and Hospital, West Bengal, India.
Introduction
Distal renal tubular acidosis (RTA) can have varied presentation. Onset in infancy
is usually severe. However, adolescent onset has variable presentation ranging
from hypokalemia to nephrocalcinosis, and rarely with rickets or growth
retardation. We describe a girl with distal RTA presenting with hypokalemia
and growth retardation.
EP345
Case
Gross CDC73 deletions in young patients with primary
12 year old girl presented with recurrent episodes of weakness of all four limbs
hyperparathyroidism in Russia
and failure to gain height and weight for last 4 years. There was no sensory or
Elizaveta Mamedova, Natalya Mokrysheva, Evgeny Vasilyev,
autonomic involvement. She had normal birth history and developmental
Iya Voronkova, Elizaveta Orlova, Maria Kareva, Zhanna Belaya,
milestones, no dysmorphism or bony abnormality, no sensorineural deafness
Liudmila Rozhinskaya & Anatoly Tiulpakov
and a negative family history. Nutritional status was average. Height and weight
Endocrinology Research Center, Moscow, Russia.
were below Indian Academy Of Paediatrics 3rd percentile.
Investigations
KCZ2.9 mmol/l; Urine KZ30 mmol/24 hr (increased). pHZ7.324, HCO3-Z
Introduction
12.4 meq/l, pCO2 Z23.9 mm-Hg; anion gapZ10 mmol/l Urine pH Z7.0. UAG:
Hyperparathyroidism-jaw tumour syndrome (HPT-JT) is a rare disorder, which is
Positive (28 meq/l), urine calcium:creatinine ratioZ0.63(N!0.2) ANA & ENA:
frequently characterized by the development of parathyroid carcinomas and
negative. Genetic testing not done due to non-availability CBC, LFT, serum
atypical parathyroid adenomas and, thus, severe course of primary hyperpar-
25-OH Vitamin D & iPTH, CaCC, PO3-, alkaline phosphatase, FT4/TSH, IGF-1
athyroidism (PHPT).
were all normal. X-ray of wrist: no evidence of rickets. USG Abdomen Z
Case reports
Medullary Nephrocalcinosis in both kidneys.
Two patients (1 male and 1 female, 18 y.o. and 13 y.o. at the time of diagnosis of
Diagnosis
PHPT, respectively) among a cohort of young patients (!40 y.o.) with PHPT,
Growth retardation with hypokalemic periodic paralysis in a case of distal RTA of
underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo
adolescent onset based on normal anion gap acidosis with high urinary pH with
Fisher Scientific-Life Technologies, USA) using a custom-designed Ion
positive urine anion gap.
AmpliSeqTM gene panel. NGS did not reveal any pathogenic variants in genes
Treatment
associated with familial PHPT in these two patients, but the analysis of the
She was managed successfully with intravenous potassium and is on oral sodium
sequence data by the ExomeDepth program [Plagnol V et al, 2012] allowed us to
bicarbonate 500 mg twice daily. Her clinical response is good.
assume the existence of large deletions in CDC73
gene. To confirm this
Conclusion
observation MLPA (MRC-Holland, the Netherlands) of CDC73 on ABI 3500xL
The take home points are that every child presenting with hypokalemia should be
Genetic Analyzer (Applied Biosystems, USA) was performed. In a male with
evaluated for RTA. The presentation of distal RTA can be subtle to severe. Even
severe PHPT (serum total calcium 4.49 mmol/l (2.15-2.55), ionized calcium
in the absence of bony involvement like rickets children can suffer from
2.03 mmol/l (1.03-1.29), PTH 1833 pg/ml (15-65), osteitis fibrosa cystica) and
significant growth retardation. Growth failure should be actively searched for
histological diagnosis of atypical parathyroid adenoma, a gross deletion including
even in asymptomatic patients.
the entire CDC73 gene and four additional genes (TROVE2, GLRX2, B3GALT2
DOI: 10.1530/endoabs.49.EP343
and LINK0103) was detected. In a female with severe PHPT (serum total calcium
3.57 mmol/l, ionized calcium 1.58 mmol/l, PTH 1550 pg/ml, osteitis fibrosa
cystica) and histological diagnosis of parathyroid carcinoma, the deletion of 1-10
exons of CDC73 gene was detected. The patients’ mother also had PHPT due to
parathyroid adenoma.
Conclusion
These two cases illustrate that NGS data could be successfully applied for indirect
assessment of large gene deletions which could be further confirmed by MLPA.
Search for CDC73 mutations is necessary among patients with parathyroid
carcinomas and atypical parathyroid adenomas, which could occur at any age.
Endocrine Tumours and Neoplasia
DOI: 10.1530/endoabs.49.EP345
EP344
Differential roles of carboxylated and uncarboxylated Osteocalcin in
stage I breast cancer as a diagnostic biomarker
Anara Karaca1, Nese Ersoz Gulcelik1, Filiz Bakar2, Giray Akgul3,
Zeynep Sahiner1 & Mehmet Ali Gulcelik3
1Ankara Teaching and Research Hospital, Endocrinology and Metabolism,
Ankara, Turkey;2Ankara University, School of Pharmacy, Biochemistry,
Ankara, Turkey;3Ankara Oncology Teaching and Research Hospital,
EP346
General Surgery, Ankara, Turkey.
Multiple endocrine neoplasia type 1 phenocopies: role of the genes
associated with familial primary hyperparathyroidism
Elizaveta Mamedova, Natalya Mokrysheva, Evgeny Vasilyev,
Objective
Vasily Petrov, Zhanna Belaya, Liudmila Rozhinskaya & Anatoly Tiulpakov
The finding of new biomarkers is needed to have an early diagnosis of breast
Endocrinology Research Center, Moscow, Russia.
cancer. In this study we evaluated serum levels of carboxylated osteocalcin (OC)
and uncarboxylated osteocalcin(UcOC), CRP as a diagnostic biomarker for breast
cancer.
Introduction
Design and methods
The genetic causes of development of multiple endocrine neoplasia type 1 (MEN-
Blood samples of 39 women with newly diagnosed breast cancer with stage I were
1) phenocopies remain largely unknown.
obtained before surgery and 39 age and BMI matched health women were
Aim of the study
selected as controls.
To evaluate the role of genes associated with familial primary hyperparathyroid-
Results
ism (PHPT) in the development of MEN-1 phenocopies with the combination of
The mean age was 52G7 years (PZ0.8). Circulating logOC was significantly
PHPT and pituitary adenomas (PA).
lower in breast cancer patients compared to controls (2G1.1 mg/ml vs. 3G
Materials and methods
1.23 mg/ml, P!0.05), while logCRP levels were significantly higher in breast
20 patients (19 females and 1 male) were included in the study. All patients had
cancer patients than controls (0.8 vs. K0.6, P!0.05). Serum levels of logUcOC
biochemically confirmed PHPT in combination with PA of different types of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
secretion:
15
GH-secreting,
3
ACTH-secreting,
1
PRL-secreting,
1
non-
1University Hospital of Pisa, Endocrinology Unit, Pisa, Italy;2Department
functioning PA. Median age at the time of inclusion was
61 years [Q25-
of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
Q75;min-max:57-66.5;54-79], median age at the time of PHPT diagnosis was 57
3Department of Surgical, Medical and Molecular Pathology and Critical
years [Q25-Q75;min-max:54-62;51-72], median age at the time of PA diagnosis
Area, University of Pisa, Pisa, Italy;4Fondazione Pisana Per La Scienza
was 47 years [Q25-Q75;min-max:40.5-57.5;21-61]. Five patients had mild
Onlus, Pisa, Italy.
PHPT, 15 - manifest PHPT (though it was difficult to assess the role of PHPT in
osteoporosis development due to concomitant menopause and Cushing disease in
some cases). Imaging techniques revealed: in 15 patients - solitary parathyroid
Familial Isolated Hyperparathyroidism (FIHP) is a hereditary disorder charac-
tumour, in 2 patients - two parathyroid tumours, in 3 patients parathyroid tumours
terized by primary hyperparathyroidism
(PHPT) with no evidence of other
were not visualized. In the majority
(nZ16) of patients PA was the first
endocrine disorders. Germline MEN1, CDC73 and CASR mutations have been
identified, but the majority of FIHP has still unrecognized causes. The aim of this
manifestation, only in 4 patients PHPT was diagnosed before PA. In all patients
study was to identify, by whole-exome sequencing, novel gene alterations in a
no MEN1 mutations were identified by Sanger sequencing, confirming diagnosis
large FIHP kindred. The family’s proband, her sister, brother and niece were
of MEN-1 phenocopy. Next-generation sequencing of a custom-designed Ion
affected by PHPT. The proband was negative at MEN1, CDC73 and CASR gene
AmpliSeqTM panel of genes associated with familial PHPT (MEN1, CASR,
mutations by Sanger analysis. The proband, her sister and niece were also affected
CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D) using
by papillary thyroid carcinoma, the brother had Non-Hodgkin Lymphoma and
semiconductor sequencer PGMTM Ion Torrent
(Thermo Fisher Scientific,
bladder cancer. The proband had also a moderate colorectal polyposis and the
USA) was performed. ANNOVAR was used for variant annotation.
niece a renal angiomyolipoma. We analyzed the proband, two affected and two
Results
healthy family’s members with the Illumina NextSeq550 platform. The raw data
No pathogenic or likely pathogenic variants in the abovementioned genes were
were converted using Bcl2toFastq tools. Data analysis was performed by the
identified.
SeqMule pipeline. The three affected individuals, but not the healthy relatives,
Conclusion
shared 57 rare genetic variants. A more stringent filter related to genes involved in
Mutations in the genes associated with familial PHPT are unlikely to have
hereditary cancer detected one missense variant in the APC gene (V530A) in the
any role in the development of MEN-1 phenocopies with combination of PHPT
three affected patients, subsequently confirmed by Sanger analysis. Moreover, the
and PA.
other affected relative and 2/15 healthy members carried the variant. The APC
DOI: 10.1530/endoabs.49.EP346
gene is involved in familial polyposis (FAP), an inherited disease marked by
thousands colorectal polyps. The APC variant was predicted deleterious by three
statistic model. Although the affected individuals don’t have classical FAP
features, the proband had the excision of two colonic polyps. We might speculate
that the presence of non-truncating mutation could lead to a mild colonic
phenotype, as showed in the attenuated FAP, characterized by the presence of
!100 polyps. FAP tumor spectra is highly various, in about 2% of cases papillary
EP347
thyroid carcinoma and bladder cancer have been reported.
Recurrent ectopic parathyroid carcinoma
DOI: 10.1530/endoabs.49.EP348
Julia Krupinova, Natalia Mokrysheva, Anna Eremkina, Ekaterina Pigarova
& Svetlana Mirnaya
Endocrinology Research Centre, Moscow, Russia.
Background
In most cases of parathyroid carcinoma (PC) only recurrence could be a credible
feature of malignancy.
Clinical case
At the age of 19 years a woman was diagnosed with urolithiasis. At the age of 22
EP349
years she had a surgical resection of the neck nodule at the right site in the
Parathyroid cancer - clinical presentation, prognostic factors and
projection of carotid triangle. After the histological study, ectopic parathyroid
long-term evolution
tumor was misdiagnosis with paraganglioma (material is available for review). At
Beata Jurecka-Lubieniecka1, Barbara Michalik1, Grzegorz Bula2,
the age of
37 years the patient noted deteriorating state of health: severe
Jacek Gawrychowski2, Dariusz Kajdaniuk3, Bogdan Marek3,
weakness, nausea, vomiting (10 times per day), rapid loss of body weight (10 kg
Andrzej Tukiendorf4 & Barbara Jarzab1
in 6 months). She noted the appearance of nodule in the neck to the right in the
1Department of Nuclear Medicine and Endocrine Oncology, Maria
projection carotid triangle again. A month later she was diagnosed with a primary
Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
hyperparathyroidism: total calcium - 3.0 mmol/l (2.19-2.55), PTH-786 pg/ml
Gliwice, Poland;2Department of General and Endocrinal Surgery, Bytom,
(15-65). CT-scan showed two tumors sized up to
3.3*1.7 cm;
3.2*1.3 cm
Silesian Medical University, Katowice, Poland;3Department of Pathophy-
between right m. sternocleidomastoideus and the common carotid artery. The
siology and Endocrinology, Silesian Medical University, Katowice, Poland;
next day the hypercalcemic crisis developed (total calcium - 5.33 mmol/l) and
4Department of Epidemiology and Silesia Cancer Registry, Maria
therefore, ectopic parathyroid tumors were urgently resected in our center. PC
Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
was diagnosed after a histological examination. At the age of 47 years the local
Gliwice, Poland.
recurrence was diagnosed: total calcium - 3.51 mmol/l, PTH-450 pg/ml. PET/CT
showed a focus with the pathological accumulation of 18FDG in singles upper
jugular lymph node on the right at the level of C3-4, 16,7*19,7 cm. After another
Background
surgery, the tumor went through the immunocytochemical analysis which showed
Parathyroid carcinoma (PC) is a rare endocrine malignancy affecting 0.5-5% of
a diffuse intensive expression of PTH, Ki-67- 15%.
all patients with primary hyperparathyroidism. Due to the rarity of PC there is still
Conclusions
lack of prognostic implications of the disease and clear consensus regarding
The diagnosis of PC is challenging due to the lack of credible diagnostic criteria.
management. Our purpose was to evaluate prognostic factors and treatment
The treatment of choice in PC is an en bloc resection of the mass with total
outcomes of patients treated at the Department of Nuclear Medicine and
ipsilateral thyroid loboistmectomy and central compartment lymphadenectomy
Endocrine Oncology.
and timely detection and resection of mts.
Methods
The target group covered 44 patients with parathyroid carcinoma treated in years
DOI: 10.1530/endoabs.49.EP347
1995-2016 at the department of Nuclear Medicine and Endocrine Oncology.
Results
All the patients were treated surgically, 17 of them repeatedly, however, only in
19 patients the en bloc resection was performed, 25 patients underwent only
parathyroidectomy. During an average 10-year-observation among all the patients
operated non-radically the recurrence of the disease appeared. Deaths occurred
EP348
only in this group, despite radio- and chemotherapy. An interesting clinical
Exome analysis of a large family with familial isolated primary
observation are benefits resulting from cinacalcet treatment: taking the medicine
hyperparathyroidism (FIHP) and multiple cancers
for 2-4 years resulted in stabilization and ever remission of the disease in four
Filomena Cetani1, Elena Pardi2, Simona Borsari2, Federica Saponaro2,
patients with metastasis. To predict outcome histopathology results, biochemical
Liborio Torregrossa3, Chiara Mazzanti4, Paolo Aretini4, Marco La Ferla4,
and clinical features were analyzed. Due to a limited number of patients, a
Sara Franceschi4, Francesca Lessi4, Prospero Civita4 & Claudio Marcocci4
parametric Weibull’s regression was adopted. Among the analyzed risk factors
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
distant metastasis and organ complications, mainly renal failure were statistically
in G (1.29G0.12 g/cm2 vs 1.23G0.02 g/cm2 (PZ0.5). Ribs BMD were higher in
crucial in patients survival. Occurrence of distant metastasis increases the risk of
group 1 children compared to group 2 (B 0.72G0.08 g/cm2 vs 0.59G0.06 g/cm2
early death seven times (HR Z6.82, PZ0.02) whereas in renal failure the risk
(PZ0.02); G 0.71G0.05 g/cm2 vs 0.65G0.06 g/cm2 (PZ0.05)). There were no
increases nine times (HR Z8.92, PZ0.008).
significant differences in hand BMD (G 0.87G0.10 g/cm2 vs 0.85G0.13 g/cm2
Conclusions
(PZ0.836); B 0.93G0.14 g/cm2 vs 0.85G0.15 g/cm2 (PZ0.360)); total (G
In patients with parathyroid carcinoma, definition of prognostic factors and the
1.18G0.09 g/cm2 vs 1.11G0.13 g/cm2 (PZ0.29); B 1.17G0.13 g/cm2 vs 1.06G
role of the radiation, chemotherapy and cinacalcet treatment still has to be
0.14 g/cm2 (PZ0.21)) in obese children compared to control. A significant
elucidated. In our analysis distant metastases and renal failure were critical factors
increase in Ca levels were in obese B compared to control (2.48G0.07 vs 2.41G
regarding increased risk of death.
0.001 mmol/l (PZ0.001)) with no differences in G (2.43G0.09 vs 2.41G
DOI: 10.1530/endoabs.49.EP349
1.2 mmol/l (PZ0.86)). There were no differences in P (G 1.23G0.22 vs 0.95G
0.64 mmol/l (PZ0.78); B 1.32G0.27 vs 1.30G0.18 mmol/l (PZ0.85)), and AlP
(G 108.06G26.66
vs
85.13G65.64 IU/l
(PZ0.46); B
217.93G57.24
vs
157.27G26.41 IU/l (PZ0.68) in two groups.
Conclusions
A significant increase in ribs and legs BMD, Ca levels were found in children with
obesity compared to normal weight control.
DOI: 10.1530/endoabs.49.EP351
EP350
A suspicious case of multiple endocrine neoplasia
Teresa Alves Pereira1, Inês Furtado2, Ana Amado1, Lia Ferreira1,
Raquel Almeida1 & Isabel Palma1
1Endocrinology Department, Centro Hospitalar e Universitário do Porto,
Porto, Portugal;2Internal Medicine Department, Centro Hospitalar e
Universitário do Porto, Porto, Portugal.
Paediatric Endocrinology
EP352
Introduction
Multiple endocrine neoplasia (MEN) syndromes are rare entities characterized by
Progressive osseous heteroplasia in a child with
the occurrence of tumors involving two or more endocrine glands in a single
pseudohypoparathyroidism type I
patient. These syndromes are classified as type 1 or 2 according to specific
Madalina Vintila, Iuliana Gherlan, Cristina Dumitrescu, Anda Dumitrascu
phenotypic characteristics. MEN2
encompasses three different subtypes:
& Camelia Procopiuc
MEN2A, MEN2B and familial medullary thyroid carcinoma. More recently a
CI Parhon National Institute of Endocrinology, Bucharest, Romania.
syndrome related to mutations in the CDKN1B gene has been described - the
syndrome of multiple endocrine neoplasia 4. It is characterized by tumors of the
Introduction
parathyroid and pituitary glands.
Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive
The case
heterotopic ossification
(HO), from skin and subcutaneous tissues into deep
A 36-years-old woman was submitted to parathyroidectomy and adrenalectomy
skeletal muscles. Most cases are caused by heterozygous inactivating mutations
in September/2010 due to suspected parathyroid adenoma and pheochromocy-
of GNAS gene. Related disorders are Albright hereditary osteodystrophy (AHO),
toma, both confirmed posteriorly by histology. The patient did not have a positive
pseudohypoparathyroidism (PHP), and primary osteoma cutis. Distinction from
family history of pheochromocytoma, parathyroid adenomas or thyroid medullary
other GNAS-based conditions is made by the extension of HO from superficial to
carcinoma and, furthermore, genetic testing for MEN1 and MEN2 was negative.
deep tissues in POH.
Genetic investigation for MEN
4
is pending. After surgery PTH levels
Case report
normalized. However, there is a slow increase in PTH levels since 2012 and
We present the case of a 10-year-old girl who came to medical attention at
sestamibi scintigraphy shows signs of right parathyroid adenoma.
3-months of age for lumbar and scapular subcutaneous ossifications. The biopsy
Conclusion
confirmed osseous metaplasia of the connective tissue. The ossification process
This case is highly suggestive of a MEN 2A due to the symbiotic appearance of
progressed in size, depth and area, up to painful swelling and mechanical
parathyroid adenoma and pheochromocytoma in the same patient. A negative
compression in the shoulder. She underwent surgical resection of the scapular
genetic test, however, raises suspicion for a possible different diagnosis - MEN4
lesion at 3-years of age but the ossification recurred 2 years later. There were no
or even another genetic mutation.
congenital hallux valgus or other skeletal deformities. She had clinical features of
DOI: 10.1530/endoabs.49.EP350
AHO: round facies, flat nasal bridge, short neck, brachydactyly, obesity. Lab tests
revealed mild elevated TSH (4.98 mU/ml) at 5-years of age and later, at 8-years of
age, elevated parathyroid hormone
(395.9 pg/ml) with hypocalcemia
(CaZ
8.1 mg/dl) and hyperphosphatemia
(PZ7.18 mg/dl). She was diagnosed as
Endocrine Tumours and Neoplasia
having PHP most probably type Ia/c based on the typical clinical findings of AHO
phenotype and biochemical profile. She received treatment with calcitriol and
EP351
levothyroxine. Follow-up examinations revealed moderate progression of the
Bone mineral density in obese children
heterotopic ossifications and favourable clinical course with spontaneous puberty
Hanna Mikhno1, Anzhalika Solntsava1, Olga Zagrebaeva1 &
and no other hormone resistance identified yet at age of 12.
Natalia Vasilieva2
Conclusions
1Belarusian State Medical University, Minsk, Belarus;2Republican Center
Overlapping features of POH and PHP type I can be present, as part of the
of Medical Rehabilitation and Balneotherapy, Minsk, Belarus.
spectrum of the heterogeneous GNAS related disorders. Awareness and
distinction of these conditions are important for appropriate management.
Aim
DOI: 10.1530/endoabs.49.EP352
To evaluate bone mineral density (BMD) and its relationship with calcium (Ca)
and phosphorus (P) metabolism in children with obesity.
Methods
We examined 105 children in the University Hospital (Minsk) from 2011 to 2015
yrs. Their anthropometric parameters (height, weight, BMI) were determined.
Body composition with evaluating of mineral component were made by dual
energy X-ray absorptiometry with the calculation of feet, hands, spine, ribs, hips
BMD (g/cm2), Z-test. The levels of Ca and P, alkaline phosphatase (AlP) were
Steroid Metabolism C Action
determined. All children were divided into two groups: group one - children with
obesity (nZ75, boys(B)/girls(G) Z47/28, age 15.34G2.12 yrs, BMI 32.7G
EP353
5.3 kg/m2; group 2 - normal-weight control (nZ30, B/GZ19/11, 15.08G2.47
Genetic variations in the HSD11B1 gene in patients treated with
yrs (PZ0.3), 19.4G2.4 kg/m2 (PZ0.0001)).
glucocorticoids show associations with bone mineral density
Results
Heide Siggelkow1,2, Martina Blaschke1,2, Gabriele Armbrecht3,
Legs BMD were increased in boys with obesity (0.94G0.11 g/cm2 vs 1.13G
Friederike Thomasius3, Oliver Bock3, Mladen Tzvetkov4, Claus-C Gluer5
0.17 g/cm2 (PZ0.03)) compared to control group without significant differences
& Dieter Felsenberg3
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Clinic of Gastroenterology and Gastrointestinal Oncology, University
glucocorticoids due to rheumatoid arthritis or asthma (64%), or other rheumatic,
Medical Center, Gottingen, Germany;2MVZ Endokrinologikum, Gottingen,
gastrointestinal or pulmonary disorders. An equivalent glucocorticoid dose was
Germany;3Center for Muscle and Bone Research, Charite, Berlin,
calculated for the different glucocorticoids used. BMD of the spine or femoral
Germany;4Institute of Clinical Pharmacology, University Medical Center
neck, and the number of fractures and falls were correlated to the HSD11B1
Gottingen, Gottingen, Germany;5Section Biomedical Imaging, Department
SNPs.
of Radiology and Neuroradiology, MOINCC, Kiel, Germany.
Results
BMD, the number of fractures and falls did not show an association with daily or
cumulative equivalent dose or type of glucocorticoid. Since the three genetically
Introduction
linked SNPs in intron 5 of the 11b-HSD1 gene - rs11811440, rs1000283, and
Physiological glucocorticoids play an essential role in bone formation but can
rs932335 HSD11B1 highly correlated, only rs11811440 was further analyzed. In
cause osteoporosis if present in excess. The key enzyme converting inactive
patients treated with the glucocorticoids prednisolone or methylprednisolone the
cortisone into the active cortisol and vice versa is
11-beta-hydroxy-steroid-
presence of the A-allele was associated with lower BMD levels.
dehydrogenase (11b-HSD1). We have reported that genetic variations in the
Discussion
HSD11B1 gene correlate with increased cortisol levels in dexamethasone
Our results suggest that in patients treated with glucocorticoids the function of
suppression and with changes in bone mineral density
(BMD) suggesting
11b-HSD1 is dependent on HSD11B1 polymorphisms. Hence, inactivation of
individual differences in 11b-HSD1 activity caused by polymorphisms. In this
prednisolone or methylprednisolone by 11b-HSD1 would be the crucial step for
study we investigated the effect of HSD11B1 SNPs on BMD in patients on
BMD levels in glucocorticoid-treated individuals.
glucocorticoid therapy.
DOI: 10.1530/endoabs.49.EP353
Methods
In
246 patients treated with different glucocorticoids the HSD11B1
SNPs
rs11811440, rs1000283
und rs932335
were determined. Patients received
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations: Diabetes,
Obesity and Metabolism
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Calcium & Vitamin D Metabolism
can be useful to alleviate either a medical condition diagnosis confirmation or
unraveling of its etiology.
EP354
Aim
We present a case 30 years old male, presented with nausea, vomiting and diffuse
abdominal pain. Three months before hospital admission, patient was
Abstract withdrawn.
unsuccessfully treated for painful, reddish skin lesions
5mm in diameter,
dispersed on abdominal wall, arms and legs, interpreted as ‘viral papillomata’.
Out of mentioned skin lesions-eruptive xanthomata, hypotension, light abdominal
tenderness and moderate distention, other physical examination was normal.
Results
Laboratory findings revealed lipemic serum, elevated inflammatory, pancreas and
liver necrosis markers, hyperglycemia, hyponatremia and hypocalcaemia.
Performed imaging procedures (ultrasound and computed tomography) showed
enlarged pancreatic body and tail, and left pleural effusion. Lipemic serum and
eruptive xanthomata taken together with other case findings pointed to life-
threatening acute pancreatitis caused by mixed dyslipidemia, obviously serious
Cardiovascular Endocrinology and Lipid Metabolism
(lipids could not be measured initially). In association with aggressive pancreatitis
EP355
management, nil-by-mouth treatment with plasmapheresis successfully lowered
lipids and enabled their measurement (triglycerides 19.9 mmol/l and cholesterol
Metabolic syndrome in digestive neoplasms
10.8 mmol/l). After plasmapheresis, diet and fibrate, triglycerides and cholesterol
Soumaya Mrabet, Nour Elleuch, Aya Hammami, Hanen Jaziri,
levels were 4.04 and 3.99 mmol/l, respectively. Patient was referred to lipid
Aida Ben Slama, Ahlem Braham, Salem Ajmi, Mehdi Ksiaa & Ali Jmaa
clinic, gastroenterologist and surgeon (formed pancreatic cyst).
Sahloul University Hospital, Sousse, Tunisia.
Conclusions
Adequately interpreted eruptive xanthomata can act as a shortkey for faster
Introduction
confirmation of acute pancreatitis. Treatment of serious pancreatitis and
The metabolic syndrome (MS) is a real public health problem on a global scale.
dyslipidaemia is done at the same time. Plasmapheresis, as well lifelong diet
People with MS are at increased risk not only for cardiovascular diseases but also
and pharmacotherapy later, are the mainstay for management of dyslipidaemia
for neoplasia. The aim of our study is to determine the prevalence of MS in
that caused pancreatitis (presumably mixed one).
patients with digestive neoplasia and to study the impact of MS on the
DOI: 10.1530/endoabs.49.EP356
epidemiological, clinical profile and prognosis of digestive neoplasms.
Material and methods
This is a retrospective study including patients with digestive neoplasia who were
hospitalized in our department between January 2015 and June 2016. For all
patients, BMI, waistline, systolic and diastolic blood pressure, HDL cholesterol,
triglycerides, and blood glucose levels were determined. A MS was defined
according to the criteria of the International Diabetes Federation IDF 2005.
Results
78 patients were included (40 men and 38 women), with an average age of 61.7
years (between 28 and 89 years). The digestive neoplasias found were: colorectal
cancer (CRC) (nZ21.27%), hepatocellular carcinoma (CHC) on cirrhosis liver
(nZ18.23%), gastric cancer (nZ13.16.7%), Cholangiocarcinoma (nZ10.12.7%),
pancreatic cancer (nZ9.11.5%), oesophageal cancer (nZ3.8%), small bowel
lymphoma and a Cancer of the gall bladder in two cases each (nZ2.6%). The mean
tumor size at diagnosis was 6.2 cm (1.5-18 cm). The tumor was metastatic in 26
cases (33.3%). MS was present in 29 cases (37.2%). The analytical study found that
EP357
MS was more frequently found in female patients (50% versus 25%, PZ0.022),
Metformin and changes in blood pressure and heart rate in lean patients
older patients (68.2 years versus 58 years, PZ0.001) and having a CRC (57%
with polycystic ovary syndrome (PCOS)- preliminary study
versus 29%, PZ0.027). However, the presence of a MS did not influence the
Marta Kialka1, Tomasz Milewicz1, Marek Klocek2 & Rita Tomczyk1
average survival of patients (10.3 months versus 8 months, PZ0.138).
1Department of Gynecological Endocrinology, Jagiellonian University,
Conclusion
Medical College, Cracow, Poland;2Department of Cardiology and
In our study, more than one-third of patients had MS. It was associated with an
Hypertension, Jagiellonian University, Medical College, Cracow, Poland.
older age, the female sex and the CRC. However, diagnosis and management of
MS remains difficult in these patients because of the malnutrition and weight loss
caused by the disease.
Introduction
The aim of our study was to assess the value of blood pressure and heart rate using
DOI: 10.1530/endoabs.49.EP355
the 24-h blood pressure monitoring (ABPM) before and after treatment with
metformin to patients with polycystic ovary syndrome (PCOS) and normal lean.
Material and methods
20 patients received metformin 1500 mg/day in three divided doses. ABPM was
performed to each patient with PCOS twice: before and after 6 months of
treatment with metformin.
Results
EP356
In patients with PCOS and normal lean after treatment with metformin we
Dyslipidemia-associated skin lesions as a short key for etiology
observed: statistically significant lower systolic blood pressure
(120.2G
unraveling and management of life-threatening acute pancreatitis
22.33 mmHg vs 113.22G21.43 mm Hg, PZ0.0248); lower systolic blood
in young male
pressure of daily measurements (127.1G32.13 mmHg vs 116.1G22.08 mmHg,
Zoran Gluvić1, Bojan Mitrovi
´1, Vladimir Samard
ˇic´1, Jelena Tica Jevtić1,
PZ0.0062); reduction in average arterial pressure MAP daily measurements
Marina Vujović1, Vesna Popović-Radinovic´1, Aleksandar Stanojević2 &
(95.52G22.76 mmHg vs
88.36G16.41 mmHg, PZ0.048); oscillometric
Esma R. Isenovi
´3
pressure reduction (96.27G27.93 mmHg vs 87.82G21.61, PZ0.0004 mmHg);
1Division of Internal Medicine, Department of Endocrinology, Zemun
oscillometric pressure reduction of daily measurements (102.1G27.93 mmHg vs
Clinical Hospital, School of Medicine, University of Belgrade, Zemun,
91.85G21.61 mmHg, PZ0.0032); oscillometric pressure reduction in the
Serbia;2Division of Internal medicine, Department of Gastroenterology,
measurement of the night
(88.81G24.85 mmHg vs 82.22G20.54 mmHg,
Zemun Clinical Hospital, School of Medicine, University of Belgrade,
PZ0.0089). In women after treatment with metformin has also been observed
Zemun, Serbia;3Laboratory for Molecular Endocrinology and Radio-
higher average heart rate (65.82G13.48/min vs. 70.71G16.04/min; P !0.01).
biology, Institute for Nuclear Sciences ‘Vinča’, University of Belgrade,
The calculations included 500 measurements.
Belgrade, Serbia.
Conclusion
Treatment with metformin in patients with PCOS and normal lean leads to lower
Background
blood pressure and increases the frequency of heart rate.
After the gall bladder stones and alcohol abuse, dyslipidemia is among most
DOI: 10.1530/endoabs.49.EP357
frequent causes of acute pancreatitis, especially in youngsters. Some clinical signs
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP358
characterized by: higher (P!0.05) serum TCH, lower (P!0.05) hepatic TCH
and its biosynthetic precursors, lower (P!0.05) hepatic7a-hydroxycholesterol
Screening for type 2 diabetes mellitus as a method of secondary
but elevated (P!0.05) 27- and 24- hydroxycholesterol in comparison to YA IC.
prevention of cardiovascular lesions
Both GEN and DAI decreased (P!0.05) hepatic 27-hydroxycholesterol, with no
Lev Prystupiuk, Liudmyla Naumova, Maksym Prystupiuk,
effect on any other parameter of cholesterol metabolism. We obtained age-related
Iuliia Onofriichuk & Marianna Naumova
reduction of serum estradiol, which was reversed by both soybean phytoestro-
Bogomolets National Medical University, Kyiv, Ukraine.
gens. In conclusion, age-related dyslipidemia was associated with reduced
7a-hydroxycholesterol, main intermediate of neutral pathway, and higher
In patients with type 2 diabetes mellitus (T2DM), cardiovascular lesions are 3-4
27—hydroxycholesterol, main intermediate of alternative acidic pathway of
times more often than in non-diabetics. Screening for T2DM in 1564 people from
Chol degradation to bile acid. Both GEN and DAI lowered hepatic
27-
all Ukraine revealed that 12% had HbA1c at 6.1-6.4% and 16% had HbA1c above
hydroxycholesterol, which might be associated with elevated serum estradiol
6.5%. Those with HbA1c above 6.5% were examined for BMI, glycemia, total
concentrations. Further research is needed to examine this possibility.
cholesterol, HDL-C, non-HDL-C. Dyslipidemia was defined as total cholesterol
DOI: 10.1530/endoabs.49.EP359
over 5.20 mmol/l, HDL-C - less than 1.02 mmol/l for males and less than
1.29 mmol/l for females. Total cholesterol averaged
6.41G0.03 mmol/l in
screened men and 6.23G0.01 in women. HDL-C was respectively 1.89G0.08
and
1.88G0.07 mmol/l. Whereas non-HDL-C was
4.60G0.02
and
3.38G
0.05 mmol/l respectively. As for total cholesterol, objects were divided into the
following groups (in mmol/l): 5.2; 5.3-6.5 and over 6.5. Males with these
indicators were distributed:
38%, 57%, 5%; females - 28%, 64% and 8%
respectively. According to correlation of total cholesterol to fasting glucose, men
with glycemia under 6.1 mmol/l had cholesterol 5.70G0.01 mmol/l, those with
glycemia 6.2-7.8 mmol/l had cholesterol 5.90G0.05 mmol/l and those with
glycemia over 7.8 mmol/l had cholesterol 5.99G0.04 mmol/l. While in women,
cholesterol levels were (mmol/l): 4.86G0.03, 6.50G0.03, and 7.50G0.03 in
EP360
relation to the above mentioned levels of glycemia. In accordance with division of
Awareness and prevalence of metabolic syndrome among high-risk
BMI into normal weight, overweight and obesity, cholesterol levels in males were
individuals attending internal medicine clinics across Jordan
(mmol/l): 5.81G0.06, 6.12G0.04 and 6.10G0.05 respectively, while in females
Rania Efaishat1, Rana Abu Farha2 & Eman Alefishat3
5.48G0.04, 5.56G0.02 and 5.77G0.01. Consequently, dyslipidemias were found
1Medical Supply Department, Directorate of Royal Medical Services,
in 70% of our group with T2DM of both sexes. They are induced by increase in
Amman, Jordan;2Department of Clinical Pharmacy and Therapeutics,
non-HDL-C, correlate with degree of compensation of diabetes and with BMI.
Faculty of Pharmacy, Applied Science Private University, Amman, Jordan;
Therapeutic correction of dyslipidemias in patients with T2DM should be:
3Department of Biopharmaceutics and Clinical Pharmacy, Faculty of
normalization of glycemia and body weight. Screening for T2DM and its active
Pharmacy, The University of Jordan, Amman, Jordan.
treatment are most suitable method of secondary prevention of cardiovascular
lesions caused by T2DM.
DOI: 10.1530/endoabs.49.EP358
Purpose
To examine the prevalence and awareness of metabolic syndrome (MetS) in high-
risk individuals attending 30 internal medicine clinics in Amman, Jordan, and also
to evaluate the various factors associated with increased risk of MetS among
them.
Methods
This retrospective cross-sectional study was carried out across Amman, Jordan
from October to December
2014. During the study period,
900 high-risk
individuals (with hypertension, diabetes, central obesity and/or dyslipidemia)
were recruited from thirty internal medicine clinics in Amman, Jordan. Data
collection forms were filled based on patient interview and medical case file.
Results
The prevalence of MetS among high-risk individuals was around 40% (361/900),
with around 79% (284/361) of MetS patients unaware of their condition. Older
age, lower income and family history of premature cardiovascular diseases were
EP359
associated with a higher prevalence of MetS.
Conclusion
Soybean phytoestrogens reduce 27-hydroxycholesterol concentration in
Although MetS was found to be highly prevalent among high-risk individuals in
the liver of middle-aged female rats
this study, the awareness of the condition in this group is very poor. These
Branka
ˇ oši
´-Jurjevi
´1, Sne
ˇana Jankovic´2, Dieter Lutjohann3, Ivana Jarić1,
findings support the need for educational programs that involve both health care
Marko Miler1, Branko Filipovic´1, Vladimir Ajdžanović1 &
providers and patients. These programs should especially target those at risk of
Verica Miloševi
´1
MetS, in order to improve awareness of the concept of MetS.
1Institute for Biological Research ‘Siniša Stanković’, University of
Belgrade, Belgrade, Serbia;2Institute for Science Application in
DOI: 10.1530/endoabs.49.EP360
Agriculture, University of Belgrade, Belgrade, Serbia;3Institut fur Klinische
Chemie und Klinische Pharmakologie Universitatsklinikum Bonn, Bonn,
Germany.
Hypercholesterolemia is associated with athero-thrombotic disease, a leading
cause of mortality worldwide. Advances in both dietary and pharmacological
interventions contribute to prevention and treatment of modifiable risk
factors.Purified soybean phytoestrogens, isoflavones genistein
(GEN) and
daidzein (DAI), were reported to exert moderate cholesterol-lowering effect. In
EP361
this research first we studied age-related modifications in hepatic cholesterol
Nine months of practice in California - self-referrals in endocrinology
metabolism and serum estradiol concentration of acyclic middle-aged (MA)
Jelena Maletkovic
female rats. Then we tested if purified isoflavones may prevent or reverse these
UCLA, Los Angeles, California, USA.
changes. Serum and hepatic total cholesterol (TCH), bile acid and cholesterol
precursors were determined by comparing data obtained for MA with young adult
(YA) intact (IC) females. Effects of subcutaneously administered GEN or DAI
Objective
(35 mg/kg per daily during four weeks) to MA rats were evaluated vs vehicle
A great number of patients are self-referred to endocrinologist. Most of these
(sterile olive oil) - treated MA females. After decapitation, perfused rat livers and
patients had some research of their symptoms and have a specific diagnosis that
serum were used to determine total cholesterol (TCH), its oxidative metabolites
they want to investigate.
(7a-, 27- and 24-hydroxycholesterol) and precursors (lanosterol, desmosterol,
Methods
dihydro-lano sterol and lathosterol), using gas chromatography/mass spec-
A retrospective chart review of 628 new consults conducted in one outpatient
trometry. Serum estradiol was determined by ECLIA. MA IC females were
endocrine office at University of California, Los Angeles was conducted.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
possible FH were 18.4%, 66.0% and 15.6%, respectively. Although the majority
Of the 628 new patients 326 were referred by another physician and were
of the patients (93.9%) were aware of their high LDL-C levels, only about half of
excluded from further review. Of 302 self-referred patients 248 patients had a
them (nZ75, 51.0%) were under treatment. Of all the patients who were
preexisting endocrine diagnosis and were excluded. The remaining 54 patients
interviewed, 21% (nZ31) had never taken, and 28% (nZ41) had stopped taking
were seeing endocrinologist for the first time and these patients were included in
lipid-lowering drug.
further study. Most common complaints were: weight gain (78% of patients),
Conclusion
fatigue
(72%), cold intolerance (46%), heat intolerance (31%), constipation
The results of this pilot study show that, undiagnosed or undertreated FH patients
(24%). Other common complaints observed were hair loss, low libido, erectile
can practically be detected from the high LDL-C registries of the Hospital
dysfunction, anxiety, palpitations, weight loss, hirsutism, acne, muscle weakness,
Laboratories. Nationwide implementation of this method may help us reach and
stretch marks, buffalo hump and polydipsia. When asked if they had a specific
manage these high-risk patients.
hormone abnormality in mind most of the patients reported that their main
DOI: 10.1530/endoabs.49.EP362
concern is hypothyroidism (69%), high cortisol level (13%), low testosterone
(10%), low cortisol
(5%), hyperthyroidism
(5%), diabetes insipidus
(4%),
diabetes mellitus (2%). After conducting endocrine studies based on presenting
symptoms none of the 54 patients were found to have confirmation of suspected
diagnosis. Four patients were found to have elevated TPO antibodies but thyroid
functions tests were normal. Six patients were found to have diabetes mellitus that
was previously not diagnosed or suspected. Two patients were found to have
elevated cholesterol.
Discussion
Common problems lead to online research that offers a number of endocrine
conditions as a possible underlying problem. With access to subspecialist care
oftentimes unnecessary work-up is done.
Conclusion
A longer period of investigation would add valuable data in determining the
impact of self-referrals on subspecialty practices as well as health care in United
EP363
States in general.
The effect of admission hyperglycemia on clinical outcome of ischaemic
DOI: 10.1530/endoabs.49.EP361
stroke patients
Vina Yanti Susanti1, Iswandi Darwis2 & Fidha Rahmayani3
1
Internal Medicine Department, Universitas Gadjah Mada/Sardjito General
Hospital, Yogyakarta, Indonesia;2Resident on Internal Medicine Depart-
ment, Universitas Gadjah Mada/Sardjito General Hospital, Yogyakarta,
Indonesia;3Resident on Neurology Department, Universitas Gadjah
Mada/Sardjito General Hospital, Yogyakarta, Indonesia.
Background and objective
Hyperglycemia exacerbates multiple deleterious derangements and this process
would influence the clinical outcome in diabetic patient. The objective of this
study is to know the effect of admission hyperglycemia on clinical outcome of
ischamic stroke patients admitted in Sardjito General Hospital.
Method
Observational cohort study over
5 months’ period from August 1-2016 to
EP362
December 31-2016 was done. All patients 18 years old and above, admitted as
stroke ischaemic patients in Sardjito General Hospital Yogyakarta were screened.
Identifiying underdiagnosed or undertreated patients with familial
In order to qualify, patient were subjected to initial random blood sugar
hypercholesterolemia from the central laboratory registries
determination upon admission and monitored to 48-72 h. Capillary blood glucose
Cem Haymana1, Hamza Berlik2, Yalcin Gunes2, Orhan Enes Tuncez2,
was monitored using blood glucose monitor device by Bayer. Hyperglicemia
Cihat Aytekin2, Zafer Tapikara2, Huseyin Guzel2, Ozlem Ozturk3,
status is blood glucose above 200 mg/dl. Clinical outcome was evaluated and
Cem Barcin4, Taner Ozgurtas3, Omer Azal1 & Alper Sonmez1
recorded using The National Institutes of Health Stroke Scale (NIHSS) on day 1
1Department of Endocrinology and Metabolism, Gulhane Training and
and discharge. Participants who are below 18 years old, previously stroke, or
Research Hospital, Ankara, Turkey;2Gulhane School of Medicine, Health
those with acute co-morbid disease like acute myocardial infarction, pneumonia,
Sciences University, Ankara, Turkey;3Department of Biochemistry,
or critical infection, ketoacidosis diabeticum, hyperglicemia hyperosmolar state
Gulhane Training and Research Hospital, Ankara, Turkey;4Department of
were all excluded. All patients managed according to guidelines for stroke and
Cardiology, Gulhane Training and Research Hospital, Ankara, Turkey.
hyperglycemia.
Result
Objective
Sixty four eligible subjects admitted at Sardjito General Hospital, 12 (19.35%)
Familial hypercholesterolemia
(FH) is a life-threatening genetic disease
were hyperglycemia and 50 (80.65%) normoglycemia. The mean value of blood
associated with elevated low density lipoprotein cholesterol
(LDL-C) and
glucose at admission are 153.45C69.09 mg/dl. Patients who have worsening
premature coronary heart disease that is globally underdiagnosed and
clinical outcome at dischare are 18 (29.03%) based on NIHSS. Six patients
undertreated. This study aimed to search for the demographical characteristics,
(44.44%) who had hyperglicaemia had worsening clinical outcome and four
awareness and treatment adherence of underdiagnosed or undertreated FH
patients (9.09%) did not have worsening clinical outcome (P-value 0.003; OR 8;
patients from the records of the central biochemistry laboratory.
min 2 001-max 31 988).
Methods
Conclutions
Patients with a central laboratory measurement of LDL-C O250 mg/dl were
Hyperglicaemia at admission have correlate with worsening of clinical outcome
identified. Patients with older than
18 years without secondary causes of
ischaemic stroke patients.
dyslipidemia were called by medical students and interviewed about demographic
Keywords
characteristics, awareness of dyslipidemia and treatment adherence.
Hyperglycemia; Ischaemic stroke patients; The National Institutes of Health
Results
Stroke Scale.
A total of 147 patients
(mean age 51.7G16.6 years, 59.2% female) were
DOI: 10.1530/endoabs.49.EP363
interviewed. The mean LDL-C levels were 292.8G49.9 mg/dl. According to the
Dutch Lipid Clinic Network Criteria, the patients with definite, probable and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP364
the heart rate (HR) hardly changed at this constant rate. Since, saliva lactate levels
in an AT training are independent of heart rate and mostly of effort intensity.
Deleting genomic region of Hsd17b1 in mice results into a hypomorphic
Naglu allele, and consequently to a phenotype mimicking a lysosomal
DOI: 10.1530/endoabs.49.EP365
storage disease
Heli Jokela1, Janne Hakkarainen1, Pirjo Pakarinen1,2, Suvi Ruohonen1,
Fuping Zhang2 & Matti Poutanen1,2
1University of Turku, Turku, Finland;2Turku Center for Disease Modeling,
Turku, Finland.
EP366
Abstract
Hydroxysteroid
17-beta dehydrogenase
1
(HSD17B1) is an enzyme
The effect of tocilizumab - an interleukin-6 receptor antagonist - on
catalyzing the reduction of estrone
(E1) to estradiol
(E2), as well as
lipid levels in rheumatoid arthritis
androstenedione (Adione) to testosterone (T). To elucidate the physiological
Ifigenia Kostoglou-Athanassiou1, Lambros Athanassiou2,
function of HSD17B1, we generated knockout mice with disrupted Hsd17b1
Aikaterini Tzanavari2, Charoula Katsavouni2, Markos Kostopoulos2,
Dimitrios Pantelidis2 & Panagiotis Athanassiou2
gene using targeted ES cells (clone 10231) obtained from KOMP repository
1Department of Endocrinology, Red Cross Hospital, Athens, Greece;
(www.komp.org). In these ES cells the whole coding region of Hsd17b1 was
2Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece.
replaced with LacZ/Neo cassette, expressing the reporter gene. As
previously shown by us, the homozygous Hsd17b1-LacZ/Neo females
were found to be subfertile and have a defect in pseudopregnancy
Tocilizumab is an interleukin-6 receptor antagonist used in the treatment of
maintenance, likely caused by the imbalance in ovarian steroid synthesis.
rheumatoid arthritis
(RA). It is known to induce remission and inhibit
In addition, the Hsd17b1-LacZ/Neo males present with a metabolic
radiographic progression in RA. Tocilizumab may be administered either
phenotype, including reduced adipose mass, increased lean mass and lipid
intravenously or subcutaneously. Its effect on lipid levels and the cardiovascular
accumulation in the liver. During the characterization of the metabolic
risk has not been fully investigated. The aim was to study the effect of tocilizumab
phenotype, it became evident that the expression of N-acetyl-alpha-
i.v. on disease activity, lipid levels and cardiovascular risk in RA patients.
glucosaminidase
(Naglu) gene, located
8399-739
bp upstream of the
Tocilizumab was administered i.v. once monthly in 25 patients with RA for a
Hsd17b1 transcription start site, was severely reduced (13-40-fold) in all
period of 1 year. Inflammation indices, ESR and CRP and lipid levels were
tissues analyzed in Hsd17b1-LacZ/Neo mice. Furthermore, similar results
measured before and 1 year after tocilizumab administration. The DAS28 disease
were obtained from Hsd17b1-LacZ mice after removing the Neo cassette or
activity index was also calculated.
by crossing the Hsd17b1-LacZ/Neo mice with transgenic mice constitutively
Inflammation indices ESR and CRP decreased from 34.3G4.04 mm/h and 2.02G
expressing human HSD17B1. Deficiency of the Naglu gene causes the
0.34 mg/dl before to
8.3G1.62 mm/h and
0.27G0.07 mg/dl, respectively
accumulation of glycosaminglycans
(GAGs) in several tissues, and
(P!0.001) after tocilizumab administration. The DAS28 disease activity index
accordingly, GAG accumulation was observed in all the above mentioned
decreased from 5.02G0.26 to 2.42G0.26 after tocilizumab (P!0.001). Total
mouse models lacking the genomic region coding for Hsd17b1.
cholesterol and HDL cholesterol increased from 207.4G8.53 mg/dl and 57.68G
Furthermore, biochemically and morphologically similar metabolic pheno-
2.65 mg/dl before to 231.08G12.30 mg/dl and 72.51G4.76 mg/dl, respectively
type, mimicking lysosomal storage disease, was observed both in Naglu
(P!0.001) after tocilizumab administration, LDL cholesterol and triglyceride
knockout mice (with the presence of active HSD17B1), and all the mouse
levels increasing from 128.6G7.45 mg/dl and 108.48G7.83 mg/dl before to
models lacking 2.3 kb long genomic region of Hsd17b1 gene. Thus, the data
136.17G9.39 mg/dl and 130.58G15.82 mg/dl, respectively
(P!0.001) after
indicate the presence of a strong Naglu enhancer inside the Hsd17b1 gene,
tocilizumab. No acute cardiovascular events were recorded during the study.
and the metabolic phenotype in mice lacking the Hsd17b1 genomic region is
Tocilizumab administered i.v. in patients with RA was shown to decrease
caused by the off target effect.
inflammation indices and disease activity. Lipid levels increased significantly.
DOI: 10.1530/endoabs.49.EP364
However, total cholesterol increased in parallel with HDL cholesterol.
Cardiovascular events were not observed during the study period. It appears
that tocilizumab may be accompanied by lipid level alterations, cardiovascular
risk not increasing as the adverse effects of total cholesterol may be counteracted
by HDL cholesterol.
DOI: 10.1530/endoabs.49.EP366
EP365
Salivary lactate levels during anaerobic threshold (AT) training
Hugo Ogando Berea1, Laura Toba Estevez1, Juan Fandin˜o Gómez1, Yolanda
Diz Chaves1, Jose Luis García Soidán2, Lucas Gonzalez Matías1 & Federico
Mallo Ferrer1
EP367
1Labendo, Cinbio, Vigo University, Campus Lagoas-Marcosende s/n 36310
Homocystein-significant marker of metabolic syndrome and
Vigo, Spain;2Faculty of Educational Sciences and Sports, University of
atherosclerosis risk
Vigo, Campus a Xunqueira, s/n 36005 Pontevedra, Spain.
Branko Sreckovic1, Vesna Dimitrijevic-Sreckovic2,7, Ivan Soldatovic3,7,
Hristina Janeski4, Nenad Janeski5, Jasna Gacic1, Mirjana
6,7
Sumarac-Dumanovic2,7 & Igor Mrdovic
Anaerobic threshold (AT) is defined as the point of maximum intensity at which
1Clinical Center Bezanijska Kosa, Belgrade, Serbia;2Clinic for
lactate is being produced but does not accumulate in blood during exercise.
Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia,
Training at this intensity is common in athletes. Lactate is currently regard as
Belgrade, Serbia;3Institute for Medical Statistics and Informatics, Belgrade,
indicator of effort intensity. It is usually quantified by reflectometry of capillary
Serbia;4University Children’s Hospital, Belgrade, Serbia;5Clinical
blood. This procedure although not very invasive, may be annoying during
Hospital Center Zemun, Belgrade, Serbia;6Clinic for Cardiovascular
repeated measurements. Saliva is proposed as an alternative sample.
Diseases, Clincal Center of Serbia, Belgrade, Serbia;7Faculty of Medicine,
The objective of the present study is to quantify the variation of salivary lactate
Belgrade University, Belgrade, Serbia.
levels during AT training, in order to prove its usability in this field.
10 male subjects (32G2.96 years) performed a treadmill test recording intensity
(watts/min), VO2 and heart rate (HR) to determine AT. After two days resting
Background
they performed 6 running series of 1km at AT rhythm with 2 minutes of resting
Obesity is followed by insulin resistance (IR) and low grade inflammation. In
between series. Saliva samples by Salivette system (SARSTEDT, Germany) and
patients with metabolic syndrome
(MS) and clinicaly evident vascular
HR were taken at pretest, the end of each series, and 3, 6 & 9 min of resting after.
complications homocystein values are higher. Hyperhomocysteinemia correlates
Eating, smoking, drinking (except water) or teeth brushing was forbidden in 2 h
with hyperinsulinemia and IR, resulting in oxidative stress, which causes
previous to start.
endothelial lesions and dysfunction, promoting atherosclerosis and hypertension.
Salivary lactate concentrations increased significantly from 1st to 3rd series
Objectives
(PZ0.002). Afterwards, a plateau of saliva lactate concentration was observed in
To examine homocystein levels in patients with and without MS, and find
all subjects up to the end of the series (4th-6th). After a small reduction, an
correlation between factors of MS and homocystein values.
additional increase in saliva lactate was also consistently observed after 6 min of
Methods
rest. HR hardly changed during the exercise series. Since we can conclude that:
The study included 76 obese individuals (age over 30, BMI O25 kg/m2) classified
The salivary lactate was increased according to the accumulated workload despite
into two groups: I- with MS (35 patients); II- without MS (41 patients). OGTT
exercise was performed at constant intensity (AT). That was confirmed because
was used to evaluate the extent of glucoregulation disorder. IDF classification was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
applied for diagnosing MS. Si MS risk score by Soldatovic I et all 2016 was used.
exists between CAC with coronary vascular disease (CVD), Agatston score being
IR was determined by HOMA IR. Serum CRP was measured by immunometric
an independent predictor of CVD. Including CAC may improve CV risk
assay. Microalbuminuria was determined immuno-nephelometrically. Homo-
prediction in addition to conventional risk factors. The AIM of our study was to
cistein was determined by immunoassay FPIA-Abbot.
assess CAC in subjects with prediabetes (preDM) at the beginning of the long
Results
term follow-up for occurrence of cardiovascular disease.
Patients with MS had increased WC:(I-110.6G15.4, IIG15.4 cm), BMI:(I-
Methods
35.3G6.6, II-30.4G7.4 kg/m2), blood pressure (I-136.4G13.9 /90.5G9.5, II-
After diagnosing preDM with oral glucose tolerance test and HbA1c, ECG was
118.4G12.2/78.1G9.7 mmHg), glycaemia
(I-5.4G1.6, II-4.8G0.8 mmol/l),
performed and subjects were evaluated for CVD risk. Score charts were used to
HOMA IR (I-8.8G9.4, II-5.3G3.8 mmol/mU per ml), triglycerides (I-2.17G
calculate the CVD risk. Thereafter, all subjects were appointed for multislice CT
0.95, II-1.45G0.7 mmol/l), CRP (I-7.0G0.0, II-3.7G3.8 mg/l), microalbumi-
to obtain the CAC.
nuria (I-87.4G81, II-56.4G56.9 mg/24 h), homocysteine (I-13.0G3.2, II-11.8G
Results
3.7 mmol/l) and decreased HDL (I-1.07G0.2, II-1.35G0.35 mmol/l). Statistical
70 subjects with preDM were screened for CVD. CAC score of 0 was present in
significance between groups was found for WC, BMI, systolic and diastolic
32 subjects. Minimal calcifications with a CAC score of 1-10 AU were present in
pressure, triglycerides, HDL-cholesterol (P!0.01) and CRP, Apo B, HOMA IR
12 subjects with pre DM. Moderate calcification of11-100 AU were present in 15
(P!0.05). Correlations: Homocysteine with systolic and diastolic pressure, Apo
subjects. Nine subjects had significant calcifications with 101-400 AU. Two
B and hyperlipoproteinemia (P!0.05). Si MS risk score with homocysteine
subjects had a CAC score of 100 AU which meant significant calcifications. Score
(P!0.01), rZ0.263.
risk below 2% was present in only 19 subjects, while a score risk of 15% and more
Conclusion
was present in 23 subjects. No significant correlation was found between Score
Abdominal obesity, hypertension, hypertriglyceridemia, inflammation factors,
charts and CAC. However, a trend of finding more calcifications in those with a
IR, homocystein and microalbuminuria as markers of endothelial dysfunction
10% and above Score risk was noted.
were increased in patients with MS. Correlation of homocystein values with si MS
Conclusion
risk score indicates that it is significant co-founding factor of MS. Correlation of
An approach to risk assessment that combines the traditional risk factor-based
homocystein with hypertension and hyperlipoproteinemia indicates importance of
paradigm with a more personalized atherosclerosis-imaging model may be
homocystein as significant marker for atherosclerosis.
appropriate for high risk individuals, such as subjects with pre diabetes.
DOI: 10.1530/endoabs.49.EP367
DOI: 10.1530/endoabs.49.EP369
EP368
Graft vs host disease and insulin resistance after bone marrow
transplantation
EP370
Panagiotis Athanassiou1 & Ifigenia Kostoglou-Athanassiou2
Cardiometabolic risk and female sexuality: focus on clitoral vascular
1Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece;
resistance
2Department of Endocrinology, Red Cross Hospital, Athens, Greece.
Elisa Maseroli1, Egidia Fanni1, Sarah Cipriani1, Irene Scavello1,
Francesca Pampaloni1, Cesare Battaglia2, Massimiliano Fambrini1,
Graft vs host disease is a disorder in which the graft, i.e. bone marrow, attacks the
Edoardo Mannucci1, Emmanuele A Jannini3, Mario Maggi1,4 &
host after bone marrow transplantation. It has various manifestations, one being
Linda Vignozzi1,4
skin and muscle involvement with cutaneous sclerosis and diffuse muscle pain.
1University of Florence, Florence, Italy;2University of Bologna, Bologna,
The aim was to describe the case of a patient with graft vs host disease
Italy;3Tor Vergata University of Rome, Rome, Italy;4Istituto Nazionale
complicated by insulin resistance and metabolic syndrome, after bone marrow
Biostrutture e Biosistemi, Rome, Italy.
transplantation for the treatment of acute lymphoblastic leukemia.
A patient, male, aged 2.5 years old, developed acute lymphoblastic leukemia. He
The relation between sexual and cardiovascular health in women is not well
was treated and the disease went into remission. At the age of 7 years, the patient
defined. Clitoral colour Doppler ultrasound
(CDU) with assessment of the
had a recurrence. He was found to be compatible with his elder brother and bone
pulsatility index (PI), reflecting resistance to blood flow, has been proposed as an
marrow transplantation was performed. During the following months the patient
objective measurement of sexual functioning. We aimed to investigate the
developed a skin eruption, diffuse cutaneous sclerotic lesions, muscle edema and
associations between clitoral PI and cardiometabolic risk factors. Seventy-one
pain.
adult heterosexual women attending our clinic for sexual dysfunction were
He was treated with thalidomide and cyclosporine and clinical manifestations of
consecutively recruited. Clitoral PI was positively correlated with BMI
graft vs host disease improved. Diffuse skin and muscle involvement improved.
(P!0.0001), waist circumference (WC; P!0.0001), glycaemia (PZ0.029),
The patient developed hypertriglyceridemia and insulin resistance. Metformin
insulin (PZ0.002), homeostatic model assessment index (PZ0.005), triglycer-
and fenofibrate were administered. The patient developed also hypothyroidism.
ides (PZ0.011), total cholesterol (PZ0.010), and LDL-cholesterol (PZ0.016).
Thyroxine was administered. At the age of 29 the patient developed psoriasis like
All relations, with the exception of glycaemia, retained statistical significance
lesions in the maxilla and the external genital organs.
after adjusting for age, smoking habit, and years since menopause (P!0.0001 for
In conclusion, the case of a patient is described with graft vs host disease after
BMI, WC and triglycerides; P!0.05 for all other associations). Analysis of
bone marrow transplantation for the management of acute lymphoblastic
covariance, after adjusting for confounders, showed that women with obesity or
leukemia. Graft vs host disease may have various clinical manifestations. In the
metabolic syndrome (MetS) showed significantly higher PI values (obesity:
case described skin and muscle involvement, along with insulin resistance and
PZ0.001; MetS: PZ0.019). In particular, a stepwise increase of PI was found as
metabolic syndrome were the predominant manifestations.
a function of increasing MetS components (PZ0.007). Clitoral PI was negatively
DOI: 10.1530/endoabs.49.EP368
associated with Female Sexual Function Index arousal
(PZ0.014) and
satisfaction
(bZK0.289, PZ0.026) scores and positively associated with
Middlesex Hospital Questionnaire somatized anxiety symptoms, even after
adjusting for confounders (PZ0.011). A positive association also was observed
between PI and the Body Uneasiness Test (BUT) positive symptom distress index
(PZ0.039) and BUT for dislike of the womb, genitals, and breast (P!0.0001;
EP369
P!0.0001; P!0.0001, respectively). After introducing WC as another covariate,
Coronary artery calcium score in prediabetes - preliminary results
the associations between clitoral PI and the BUT positive symptom distress index
Milica Marjanovic Petkovic1, Ivana Sasic3, Miljanka Vuksanovic1,2 &
and BUT dislike of the womb, genitals, and breast retained statistical significance
Teodora Beljic Zivkovic1,2
(PZ0.038 for positive symptom distress index; P!0.0001 for dislike of womb,
1Zvezdara University Medical Center, Belgrade, Serbia;2Belgrade
genitals, and breast). Clitoral vascular resistance is positively associated with
University School of Medicine, Belgrade, Serbia;3Institute of
MetS (in particular insulin resistance), decreased sexual arousal, body image
Cardiovascular Diseases Dedinje, Belgrade, Serbia.
concerns, and increased somatized anxiety symptoms. Further studies are needed
to establish whether treatment of metabolic abnormalities might improve clitoral
CDU indices and sexual outcomes.
Introduction
Coronary artery calcium (CAC) is examined through multislice CT. Calcifica-
DOI: 10.1530/endoabs.49.EP370
tions indicate late-stage subclinical coronary atherosclerosis. An association
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP371
EP373
Metformin and changes in serum lipid profile in lean patients with
The role of leptin signalling in the development of cardiovascular
polycystic ovary syndrome (PCOS)
diseases in obesity
Marta Kialka1, Tomasz Milewicz1, Anna Wajda1, Patrycja Czekanska1,
Stephanie Simonds & Michael Cowley
Barbara Zdzierak1 & Sandra Mrozinska2
Monash University, Melbourne, Victoria, Australia.
1Department of Gynecological Endocrinology, Jagiellonian University,
Medical College, Cracow, Poland;2Department of Metabolic Diseases,
Cardiovascular diseases are the greatest cause of death globally. Obesity
Cracow, Poland.
significantly increases the risk for the development of cardiovascular diseases.
However research does not under stand the physiological and molecular
Introduction
connections of these diseases. We have identified that the hormone leptin in
The aim of our study was to assess the values of total cholesterol, HDL-C, LDL-C
obesity plays a key role in elevating blood pressure in obesity. However recent
and triglycerides before and after treatment with metformin in patients with
findings in humans treated with leptin in the disease state of lipodystrophy, did not
polycystic ovary syndrome (PCOS) and normal lean.
result in the elevation of blood pressure. In the research present here we suggest
Material and methods
that one reason as to why leptin fails to increase blood pressure in lipodystrophy
32 patients received metformin 1500 mg/day in three divided doses. Lipids
patients is that plasma leptin concentration in not increasing high enough. For the
measurements were performed to each patient with PCOS twice: before and after
development of cardiovascular complications in obesity plasma leptin concen-
6 months of treatment with metformin.
tration needs to increase significantly to concentrations similar to that of obese
Results
animals (ten times the concentration measured in lean animals). In rodents we
In patients with PCOS and normal lean after treatment with metformin we
dose dependently demonstrate the differing effects of concentrations of leptin on
observed: statistically significant lower LDL-C levels (4.16G0.79 mmol/l vs
changes in body weight, food intake, brown adipose tissue temperature, blood
3.4G0.86 mmol/l, P!0.05) and triglycerides levels (1.8G0.53 mmol/l vs 1.12G
pressure and heart rate. We can demonstrated in obese hypertensive mice that
0.64 mmol/l, P!0.05). We observed an increase in HDL values and a decrease in
changes to the signaling components of specific neurons within the Dorsomedial
total cholesterol values, but these changes were not statistically significant (1.5G
Hypothalamic leptin receptor expressing neurons in the brain can substantially
0.71 mmol/l vs
1.71G0.69 mmol/l, PZ0.09;
5.87G0.92 mmol/l vs
5.69G
change leptin’s influence on cardiovascular control. Hence we can control in
0.97 mmol/l, PZ0.11).
rodents the development of hypertension in obesity, via manipulating the
Conclusion
responsiveness of leptin receptor responsive neurons. We are mapping the
Our study showed that treatment of 1500 mg metformin for about 6 months
connections of this specific subset of neurons and are gaining a true understanding
among PCOS women result in improvement in serum lipids. We observed a
on how the adipose derived hormone leptin plays a key role in the development of
significant decrease in LDL-C and triglycerides values after metformin treatment.
cardiovascular diseases.
DOI: 10.1530/endoabs.49.EP371
DOI: 10.1530/endoabs.49.EP373
EP372
Prevalence of major cardiovascular risk factors among people living
EP374
with HIV in a low risk country for cardiovascular disease
Influence factors on lipid profile among patients with rheumatoid
Carolina García-Figueras Mateos & Manuel Cayón-Blanco
arthritis
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
Manuel Cayón-Blanco1, Carolina García-Figueras Mateos1,
Raúl Menor-Almagro2 & Mario H Cardiel Ríos3
1
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain;
Introduction
2Universitary Hospital Virgen del Rocío, Seville, Spain;3Hospital Dr.
It is well known that the prevalence of major cardiovascular risk factors has
Miguel Silva, Morelia, Mexico.
increased in HIV-infected people since improvement of antiretroviral therapy.
Currently, Spain is defined as a ‘low risk country’ for cardiovascular diseases
(CVD) by 2016 European Guidelines on cardiovascular disease prevention. The
Introduction
objective of this study is to assess the prevalence and characteristics of CVD risk
Patients with rheumatoid arthritis (RA) face an increased risk of developing
factors and risk for CVD in a cohort of HIV-infected adults living in the South of
premature cardiovascular disease and limited ability to modify risk factors such
Spain according to current guidelines.
exercise or dietetic habits. Influence of exercise, dietetic habits or treatment on
Methods/design
lipid profile has been little studied in patients with RA. Here we aim to determine
Cross-sectional study. Measurements included anthropometry, blood pressure,
differences in lipid profile between two cohorts of patients with RA with different
fasting lipids and glucose assessment. Demographic, clinical, immunological, and
habits and patterns of treatment.
antiretroviral therapy data were obtained from electronic medical records. 10-year
Methods/design
risk of heart disease or stroke was calculated using the SCORE- European low
Cross-sectional study. Lipid profiles of 50 RA out-patients from South Spain were
risk chart.
compared with 50 age and sex matched controls from Central Mexico. Traditional
Results
risk factors were analyzed such as overweight or obesity, smoking status and
218 patients were evaluated. Hypertriglyceridemia was the most prevalent
hypertension. Glucose and lipid profiles as well as dietetic habits and physical
disturbance (44.3%) found, followed by low HDLc levels (41.7%). 8.7% of the
activity were recorded.
cohort had hypertension and 6.9% had type 2 diabetes. 68.5% were current
Results
smokers. High risk (10-year risk of fatal CVD O10%) was found in 13.3% of the
RA patients from Spain were more likely to practice physical activity (66.7% vs
cohort. People at higher risk were mostly men (100% vs 81%; PZ0.005), had
33.3%; PZ0.001), had lower BMI
(24.9G4.6 kg/m2
vs
26.7G3.6 kg/m2;
higher BMI (25G2.3 vs 23G2.7 kg/m2; PZ0.04) and had a lower CD4 count
PZ0.004). No significant differences in smoking status, prevalence of diabetes
(405.5G156.2/mm3 vs 551.5G211.7/mm3; PZ0.035) and were more likely to
(steroid induced diabetes or type 2 diabetes), alcohol consumption or mean dose
receive protease inhibitors (48% vs 30%; PZ0.04).
of steroid treatment were found. Regarding to lipid profile, Mexican patients had
Conclusions
lower levels of LDLc (86G31.5 vs 128.7G24.9 mg/dl; P!0.001) In contrast, the
According to our results, the prevalence of major risk factors for CVD is high in
European population had lower levels of triglycerides (124.9G14.6 vs 145.3G
HIV-infected patients of our area, especially among those with worse immunity
3.6 mg/dl; P!0.001) and higher HDLc (60.5G12.8 vs 52.1G21.4; P!0.005).
and higher BMI. Physicians should screen their patients for metabolic and
Conclusions
cardiovascular risk at the regular visits to reduce CVD risk among people with
In patients with RA, exercise can modulate lipid profile favourably irrespective of
HIV. Changes in antiretroviral therapy to more metabolic neutral antiretroviral
corticoid dose or steroid induced diabetes. More accurate studies focusing on
drugs may also be considered.
specific nutrients would be useful to confirm our results.
DOI: 10.1530/endoabs.49.EP372
DOI: 10.1530/endoabs.49.EP374
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP375
obtained with a high fat diet (HFD), treatment with the dual FXR/TGR5 agonist
INT767 reduced visceral adipose tissue (VAT) accumulation, insulin resistance,
hypercholesterolemia and nonalcoholic steatohepatitis (NASH). In liver, INT767
reduced the high macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory)
Abstract withdrawn.
ratio observed in MetS. Furthermore, INT767 increased the expression of: IL10
and FOXP3, markers of M2 macrophage and Treg cell, respectively; PPARa,
marker of hepatic fatty acid metabolism; VAMP4 and Syntaxin5, markers of lipid
droplet formation; IRS1
and STAMP2, markers of insulin signaling while
decreased lipogenesis markers. Moreover histomorphological sign of NASH were
significantly improved by INT767.
MetS induced insulin resistance, which shows VAT derangements like adipocytes
hypertrophy and reducted GLUT4 translocation to membrane. Treatment with
INT767 counteract these VAT alterations and induced the expression of brown
adipocytes markers. The analysis of preadipocytes
(rPADs) obteined from
INT767-treated rabbit and HFD rabbit revealed that INT767 improved insulin
sensitivity and mitochondrial ultrastructure and dynamic whereas reduced
superoxide production. In rPADs, when compared to HFD, INT767 increased
EP376
the expression of CIDEA and TMEM (brown fat markers); TFAM and NRF1
Oxidative stress and metabolic profiles assessment after melatonin and
(mitochondriogenesis markers); SDHB (membrane respisatory chain marker) and
irbesartan co-administration in a novel pharmaceutical formulation
MFN2 and FIS1, (mitochondria fusion/fission markers).
Cristina Manuela Dragoi, Alina Crenguta Nicolae, Daniela Elena Popa,
To conclude, INT767 significanlty improves NASH and VAT alterations induced
Ion-Bogdan Dumitrescu, Andreea Letitia Arsene, Corina Grigore &
by HFD, restoring insulin sensitivity and inducing the differentiation of rPADs to
Cristina Elena Dinu-Pirvu
a metabolically healthy phenotype.
University of Medicine and Pharmacy ‘Carol Davila’, Faculty of Pharmacy,
DOI: 10.1530/endoabs.49.EP377
Bucharest, Romania.
The concurrence of glucose intolerance, hypertension, dyslipidemia and obesity
has been termed metabolic syndrome. Each component of the metabolic
syndrome is an independent risk factor for cardiovascular disease and diabetes
type 2, the combination of these risk factors elevating the rates and severity of
cardiac pathology.
The therapeutic use of irbesartan, a selective blocker of the AT1 receptors,
administered in arterial hypertension, coronary heart disease and diabetic
nephropathy, is extremely important due to the presence of these receptors both
centrally and in the periphery.
Melatonin is an endogenous indoleamine hormone synthesized by the pineal
gland. Melatonin release into the circulation is augmented in darkness and
decreased during exposure to light, and facilitates the synchronization of the
body’s physiologic systems to circadian patterns. Melatonin shows properties of a
EP378
powerful antioxidant, at sufficiently high concentrations as a direct radical
Prevalence of metabolic syndrome and its relation to physical activity
scavenger, but, at lower, near-physiological levels, as a regulator of redox-
and nutrition in Azerbaijan
relevant enzymes, suppressor of prooxidant excitatory and inflammatory
Afruz Mammadova1,2, Selen Yilmaz ݸikhan3, Aylin Acikgoz4 &
processes and as a mitochondrial modulator. Increased oxidative stress has
Okan Bulent Yildiz1,5
emerged as playing a central role in metabolic syndrome and its component
1Department of Internal Medicine, Hacettepe University School of
pathologies and may be a unifying factor in the progression of this disease.
Medicine, Ankara, Turkey;2Azerbaijan Medical University Therapeutic
In the present study, we evaluated in a hamster experimental model, the influence
Training Clinic, Baku, Azerbaijan;3Department of Biostatistics, Hacettepe
of irbesartan and melatonin, co-administered in a novel pharmaceutical
University School of Medicine, Ankara, Turkey;4Department of Nutrition
multiparticulate formulation, on metabolic markers and oxidative profile. Our
and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara,
results depicted blood glucose, serum cholesterol and triglycerides lowering
Turkey;5Division of Endocrinology and Metabolism, Hacettepe University
effects, being maximum for the new formulation irbesartan and melatonin,
School of Medicine, Ankara, Turkey.
revealing a potentiating effect of the two drugs. On the oxidative status, the new
formulation presented a tremendous decreasing effect, due to the simultaneous
release in the bloodstream the two medicines, depicting a synergic unique effect,
Aim
reasoning the use of the two molecules in a single pharmaceutical formulation.
Metabolic syndrome is a major public health challenge associated with an
DOI: 10.1530/endoabs.49.EP376
increased risk for cardiovascular disease and type 2 diabetes. The prevalence of
metabolic syndrome in Azerbaijan is unknown. The purpose of this study was to
examine the prevalence of metabolic syndrome and its relation to physical
activity and nutrition in a representative sample of adult population in Azerbaijan.
Methods
The study population consisted of 288 adults, 20 years of age and over, from
Guba, Azerbaijan recruited between January and April of 2016 by random
EP377
sampling in line with the gender and age distribution.
Revised NCEP/ATP III criteria were used to define metabolic syndrome and
The dual FXR/TGR5 agonist INT-767 counteracts nonalcoholic
prevalence estimates of each individual component were determined. Physical
steatohepatitis and visceral adipose tissue dysfunction in a rabbit model
activity and food consumption were assessed with validated questionnaires and
of high fat diet-induced metabolic syndrome
their relations with components of metabolic syndrome were evaluated.
Paolo Comeglio2, Ilaria Cellai2, Sandra Filippi1, Annamaria Morelli5,
Results
Erica Sarchielli5, Luciano Adorini4, Mario Maggi2,3 & Linda Vignozzi2,3
The participants were 159 women and 129 men (mean GS.D. age of 43.1G15.2 y
1Interdepartmental Laboratory of Functional and Cellular Pharmacology of
(range
20-83 y)). Overall prevalence of metabolic syndrome was
28.4%.
Reproduction, Department of Neuroscience, Phychology, Drug Research
Abdominal obesity was the most common individual component (49% and 85.4%
and Child Care, University of Florence, Florence, Italy;2Sexual Medicine
in whole population and in those with metabolic syndrome respectively).
and Andrology Unit, Department of Experimental and Clinical Biomedical
Interestingly, it was also the only component that was more common in women
Sciences, University of Florence, Florence, Italy;3I.N.B.B., Rome, Italy;
than men (P!0.05 for both whole population and patients with metabolic
4Intercept Pharmaceuticals, New York, USA;5Department of Experimental
syndrome) whereas the other components did not show a gender difference. The
and Clinical Medicine, University of Florence, Florence, Italy.
odds ratio for having metabolic syndrome was 0.56 (95% CI, 0.34-0.95) in
moderate-high physical activity group compared to low physical activity group
The nuclear Farnesoid X receptor (FXR) and the G protein-coupled bile acid
suggesting a reduced risk of metabolic syndrome with increased physical activity.
receptor
1
(TGR5) are bile acids receptors that play a key role in energy
Total calorie intake, protein, fat and carbohydrate consumption did not show a
metabolism. In an animal model of non-genomic metabolic syndrome (MetS),
significant difference in participants with and without metabolic syndrome.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
Informed Consent Forms, the intermittent interstitial glucose reading device
Metabolic syndrome in Azerbaijan is common and associated with low physical
(IPro2 - Medtronic/USA) was implanted and simultaneous electrocardiographic
activity. Preventive measures should be taken to address this public health
recording was performed by the Holter system (Cardios Systems/Brazil). The
problem and related risk factors in the country.
patients were monitored for hypoglycemia
(defined as interstitial glucose
DOI: 10.1530/endoabs.49.EP378
value !70 mg/dl according to the International Diabetes Federation without
any induction for this occurrence and arrhythmia detection for 24 hours. Twenty-
two patients were studied. From these eight patients (36.3%) did not have
hypoglycemia: two patients (25%) also had no arrhythmia, while six patients
(75%) had arrhythmias interpreted as non-significant. Hypoglycemic events were
detected in the other 14 patients (63.7%), corresponding in this scenario from 4%
(55 minutes) to 68% (16 hours) of total monitoring time. In this group, seven
patients (50%) presented no arrhythmia, while the other seven patients (50%) had
some non-significant arrhythmia that is common in non-diabetic subjects, being
more prevalent as ventricular and supraventricular extrasystoles, isolated/paired
with low frequency and sinus tachycardia. In the evaluated group, we find no
EP379
relation between episodes of hypoglycemia and clinically relevant cardiac
arrhythmia.
Isolated low HDL-Cholesterol in patients with type 2 diabetes about
168 cases
DOI: 10.1530/endoabs.49.EP380
El Ansari Nawal, Habra Bahia & El Mghari Ghizlane
Endocrinology, Diabetes and Metabolic Diseases Mohammed the 6th
University Hospital, Faculty of Medicine, Cadi Ayyad University,
Marrakesh, Morocco.
Introduction
Lipid abnormalities in diabetics both quantitative and qualitative contribute to the
increased cardiovascular risk.
EP381
Aim
Family hypercholesterolemia: about 4 cases
The aim of this study is to determine the prevalence of isolated hyoHDLémie in
Aicha Bouzid & Djamila Mineesk
type 2 diabetics and assess cardiovascular risk in two populations of type 2
Dr, Algiers, Algeria.
diabetes with and without Low HDL-Cholesterol isolated.
Patients and methods
Familial hypercholesterolemia (HF) is a rare hereditary dyslipidemia charac-
Prospective study started in diabetic patients seen in diabétologic consultation at
terized by a major elevation of LDLc, cutaneo-tendinous xanthomas and
the University Hospital of Marrakech.
atheromatous manifestations. This anomaly exposes a high vascular risk, more
Preliminars Results
than 50% for men and 30% for women, occurring early.
One hundred and sixty eight patients were identified, 72% female, The average
Observations
age of patients was
55 years, average duration of diabetes was
7 years,
We report four cases of HF from the same family, three girls and one boy and
hyoHDLémie was found in 40.4% of cases (68 patients), the prevalence of
whose parents are affected by hypercholesterolemia. The average age of patients
isolated hyoHDLémie is estimated at
26.19%
(44
cases), with overall
is 11 years. Only the eldest siblings present tendon xanthomas. The mean total
cardiovascular risk estimated at more than 20% in the group of patients with
cholesterol is 3.45 g/l, the average LDLc is 2.80 g/l, the mean HDLc level is
isolated Low HDL-Cholesterol.
0.37 g/l, the average triglyceride level is 1.30 g/l. The search for vascular and
Discussion
cardiac repercussions was negative outside aortic narrowing in the elder. For lack
Lipid disturbances are widely studied in diabetic patients, but few studies have
of means the genetic diagnosis could not be made.
examined the Low HDL-Cholesterol isolated. In diabetic patients, current
Discussion
treatment guidelines target low-density lipoprotein cholesterol (LDL-C) with
Xanthomas were the main manifestation in this family. The presence of these
statins. In patients with elevated TGs, non-HDL-C is considered a secondary
clinical signs led to the prescription of a biological check-up in search of a lipid
target of therapy. Despite the use of statin therapy in diabetes, a significant
perturbation and of early vascular pathologies. Familial hypercholesterolemia
number of fatal and nonfatal coronary heart events still occur, indicating the need
to target other modifiable risk factors for coronary heart disease, including Low
results from a lack of binding and internalization of LDL through the LDL
receptor. Identification of the mutation should be systematically performed.
HDL-Cholesterol. This study shows a high prevalence of isolated diabetics
Genetic diagnosis provides diagnostic certainty and facilitates family screening.
correlated with cardiovascular risk also important that the interests of the target
Low HDL-Cholesterol by lipid-lowering therapy to reduce cardiovascular
DOI: 10.1530/endoabs.49.EP381
morbidity and mortality in diabetics.
DOI: 10.1530/endoabs.49.EP379
EP382
Description of an educational intervention lifestyle program in reducing
cardiovascular risk factors
EP380
Eduardo Oliveira
Can hypoglycemic episodes in type 1 diabetics trigger cardiac
Universidade Estadual do Pará, Belém, Pará, Brazil.
arrhythmias?
Goals
Kelly Regina Lainetti, João Pimenta, Márcio Faleiros Vendramini &
The purpose of this article is to describe an educational program of lifestyle
José Luiz B. Cassiolato
intervention rather successful, taught for 25 groups of customers of a private
Hospital do Servidor Público Estadual, São Paulo/SP, Brazil.
hospital in Amazon, for a total of 2,215 individuals between 2008 and 2014, 1448
being female and male 767 and briefly assess its results in relation to some of the
Type 1 diabetes mellitus (DM1) accounts for 5 to 10% of DM cases, and can
main risk factors.
occur both in childhood and adults. Studies show an association between severe
Methods
hypoglycemia and increased vulnerability to cardiac arrhythmias due to
The PVS - Programa Vida Saudável, promotes evaluations and individual and
conduction disorders, interval ST-segment changes, and even sudden death.
group counselling, consisting of two phases, the first being, with eight meetings of
The aim of this study is to evaluate the occurrence of cardiac arrhythmias during
the group with the multidisciplinary team in 12 weeks, followed by the second
episodes of hypoglycemia. A prospective study with DM1 patients under insulin
phase, with monthly meetings during 52 weeks for a total of 15 months. Clinical
therapy for at least 5 years, aged 18-60 years, of both sexes. Before study
evaluations occur with individual counselling and laboratory dosages at the
initiation, all patients underwent a two-dimensional echocardiogram and
beginning and end of each phase, as well as an assessment of reaction to the end of
laboratory tests, and those who did not present structural heart disease or any
each of the sessions. The goals of the intervention were presented progressively
hormonal alterations that could cause arrhythmias, were included. The study was
and easy to perform encouraging the adoption of habits and health principles,
approved by the Research Ethics Committee of the Institution and after signed the
widely established.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
80/50 mmHg. Biochemistry revealed fasting glucose:95 mg/dl, Na:127 mmol/l,
We analyse those who obtained 75% or more of the meetings frequency
K:5.35 mmol/l, Hb:16.6. CT abdomen showed normal adrenal gland morphology
(nZ1723) in 15 months and as controls, those who did the assessments and
with no local masses or infectious pathology. Pituitary MRI demonstrated
exams, however, did not participate in the educational program
(nZ132).
enlarged heterogeneous gland with 9 mm height, probably due to high ACTH
Preliminary results showed a significant evolution in the percentage of each risk
levels. All findings were consistent with Addison disease, which was confirmed
factor in patients with blood glucose reduction, improvement in cholesterol, with
with morning cortisole of 2.44 mg/dl (normal range 6-22), ACTH: 1250 pg/ml
reduction in LDL-c reduction in triglycerides, reduction in blood pressure and
(0-46).
weight reduction.
Once Addison’s disease had been confirmed, other autoimmune diseases
Conclusion
regarding APS were undertaken. Subclinic hypothyroidism with automimmune
Based on studies of the data, this program of health education (PVS) presented a
thyroiditis; TSH:8
(0.4-5.3), fT4:
0.9 ng/dl
(0.6-1.25), anti-TPO:1016 IU/ml
good adhesion of the customers and proved to be effective to reduce the risk levels
(0-9) was detected. Despite his normoglycemia; C-peptit:1.69 ng/ml, fasting
in its active participants.
insulin:22.3 uIU/ml, A1c:5.6%, he had high anti-GAD and anti-islet cell
DOI: 10.1530/endoabs.49.EP382
antibodies, widely used as a diagnostic and predictive tool for type 1 diabetes
mellitus, indicating that he may develop type 1 diabetes mellitus in future.
After a week of steroid replacement his physical discomforts were alleviated with
improved electrolytes.
Discussion and Conclusion
Herein, we reported an uncommon case, who had complete two-glandular
deficiency with third component; predicted type 1 diabetes. This patient is being
monitored closely on glycaemic state. Therefore, once an autoimmune disease is
identified, the early screening for antibodies against associated disease such as
anti-TPO, GADA, ICA, and antibodies to 21-hydroxylase is crucial, which
EP383
facilitate the diagnosis of further disorder at an early stage.
Role of lactate dehydrogenase-A (LDH-A) in atherosclerosis
DOI: 10.1530/endoabs.49.EP384
Keun Gyu Park, Yeon Kyung Choi, Kwi Hyun Bae & Jung Beom Seo
Kyungpook National University Hospital, Dae Gu City, Republic of Korea.
Pathological proliferation and migration of vascular smooth muscle cells
(VSMCs) has been implicated in the pathogenesis of accelerated atherosclerosis
in patients with diabetes mellitus. Increased aerobic glycolysis is a key feature of
cellular phenotypes including cancer and immune cells. However, it remains
largely unknown about the role of aerobic glycolysis in atherogenic phenotype of
VSMCs. Here, we investigated the role of lactate dehydrogenase-A (LDH-A),
which is a key enzyme for glycolysis, on proliferation and migration of VSMCs.
Clinical Case Reports - Thyroid/Others
Activation of VSMCs with platelet-derived growth factor (PDGF) or fetal bovine
EP385
serum (FBS) resulted in cellular proliferation and migration and increased
glycolytic activity accompanied by the increased expressions of glucose
Insulin autoimmune syndrome (Hirata Disease) triggered by a tyrosine
transporter 1 (GLUT1), hexokinase (HK) 2 and LDH-A in primary rat VSMCs.
kinase inhibitor drug in a Latin American patient
Through wound healing assay, actin stress fiber staining and transwell migration
Susana Mallea Gil, Carolina Ballarino, Daniel Lotero Polesel,
assay, we observed that both pharmacological inhibition (oxamate) and siRNA-
Maria Teresa Kleine, Emilio Batagelj & Nicolas Picon
mediated knockdown of LDH-A
(siLDH-A) effectively inhibited cellular
Hospital Militar Central, Buenos Aires, Argentina.
migration. Oxamate reduced PDGF stimulated glucose uptake, lactate production,
ATP production and NAD/ nicotinamide adenine dinucleotide (NADH) ratio.
Hirata syndrome is a rare cause of spontaneous hypoglycaemia, more prevalent in
Nicotinamide mononucleotide (NMN), nucleotide precursor of NADC, partially
Japanese population, very infrequent in Caucasian patients. It has been described
but significantly recovered oxamate treatment or siLDH-A induced inhibition of
that it can be triggered by medication with sulfhydryl compounds or a-lipoic acid.
VSMC proliferation and migration, suggesting NADC involvement in LDH-A
A 73-year-old male patient was sent to the Endocrinology Division in December
mediated VSMC proliferation and migration. Taken together, this study shows
2015 because he had been presenting with episodes of sweating, palpitations and
that enhanced aerobic glycolysis in PDGF- and FBS-stimulated VSMCs plays an
feeling hungry for
6
months; these symptoms improved when he ate
important role in their proliferation and migration and suggests that LDHA can be
carbohydrates. In the last 15 days before his visit, the episodes worsened, every
a potential therapeutic target for the prevention of vessel lumen constriction in the
3 hours. The patient had a history of a synchronous bilateral clear cell renal
course of atherosclerosis or restenosis.
carcinoma, the right kidney was removed in 2007, and the left renal carcinoma
DOI: 10.1530/endoabs.49.EP383
was not surgically removed because he presented worsening of a large
thoracoabdominal aortic aneurysm and the patient refused to be operated due to
the high risk involved in this surgery. He was treated with sunitinib, but this drug
was switched to sorafenib because of adverse effects in 2008. In 2013, he
presented cancer progression and he began treatment with pazopanib but there
was no response and the oncologist decided to switch to axitinib 10 mg/day in
Clinical Case Reports - Pituitary/Adrenal
2014. A year later the patient began with endocrine symptoms. Pancreatic CT
EP384
and MRI were normal. Lab tests: glycaemia 41 mg%, insulin O 1000 uU/ml
(N: 0-12) C-peptide: 5.4 ng/ml (N: ! 2.6). Insulin antibodies were performed:
Prediction of type 1 diabetes in autoimmune polyglandular syndrome
O50 U/ml (N: !1) which confirmed the diagnosis of Hirata disease. Axitinib
type 2
was stopped immediately and fractional eating was indicated. The hypoglycaemic
Anara Karaca, Nese Ersoz Gulcelik, Tulay Omma, Isilay Taskaldiran,
episodes became progressively less frequent and some days there were no
Sevde Nur Firat & Nujen Bozkurt
episodes. HLA analysis revealed the HLA-DRB1*04:15 allele. As the patient
Ankara Teaching and Research Hospital, Endocrinology and Metabolism,
improved, insulin antibodies were repeated but they remained elevated. The
Ankara, Turkey.
patient had renal cancer progression and died a year after.
Conclusions
Introduction
Episodes of hypoglycaemia with very high levels of insulin in a non-diabetic
Autoimmune Polyglandular Syndrome (APS) is a very rare endocrinopaty,
patient suggest a probable autoimmune origin. This is the first report of Hirata
characterized by the coexistence of at least two glandular autoimmune mediated
disease triggered by Axitinib, a drug not previously involved in this syndrome.
diseases. In this case a patient presented with hyperpigmentation of the whole
Another novel finding is that HLA phenotype results in HLA-DRB1*04:15 allele,
body, significant weight loss for last 6 months.
which has not been described before neither in Asian nor in European patients and
Case
this may be due to the fact that this patient is Latin American.
A-49 year old male were refered to our deparment with loss of appetite, fatigue,
DOI: 10.1530/endoabs.49.EP385
nausea, weight loss and with marked buccal pigmentation. Blood pressure was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP386
EP388
Fulminant diabetic ketoacidosis complicating nivolumab
Diabetic patient with suppurative thyroiditis caused by Salmonella
immunotherapy
enterica complicated with acute kidney injury
Ploutarchos Tzoulis1, Justin Stebbing2, Elly Baker1, Daniel Heaton1 &
Aleksandra Hernik1, Ewelina Szczepanek-Parulska1, Bogusz Falkowski1,
Richard Corbett1
Hanna Komarowska1, Anna Wejman-Matela2, Michal Drews2 &
1Whittington Hospital, London, UK;2Imperial College/Imperial Healthcare
Marek Ruchala1
NHS Trust, London, UK.
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan
University of Medical Sciences, Poznan, Poland;2Department of General,
Endocrine and Gastrointestinal Oncological Surgery, Poznan University of
A 56-year-old woman, recently commenced on immunotherapy as second-line
Medical Sciences, Poznan, Poland.
treatment for advanced non-small cell lung cancer, presented at the hospital
critically unwell with severe diabetic ketoacidosis (DKA) (glucose 47 mmol/l,
blood ketones 7.5 mmol/l, pH 6.95, bicarbonate 6.6 mmol/l). One week prior to
Incidence of acute thyroiditis is about 0.1% of thyroid gland conditions requiring
presentation, she was clinically well with random glucose of
6.1 mmol/l.
surgical treatment. Main pathogen causing acute thyroiditis is Staphylococcus
Following admission to Intensive Care Unit, she responded well to standard
aureus while Salmonella enterica is extremely rare.
treatment for DKA and discharged on basal bolus insulin regime. Her anti-GAD
Herewith we report a 61-year-old obese woman with sore throat and fever. She
antibodies were
12 kU/l
(0-5 kU/l), while islet cell antibodies and serum
had chronic atrial fibrillation, hypertension, and well-controlled type 2 diabetes
C-peptide were undetectable. Nivolumab has been recommenced without the
mellitus (HbA1C 5.5%) for 3 years (on metformin and gliclazide). Her medical
development of other immune-mediated phenomena to date.
history was negative for thyroid and renal disorders. Ultrasound examination
Besides metastatic lung adenocarcinoma diagnosed 3 years ago, she had no
(US) of the neck demonstrated mixed solid/cystic lesion. Moreover, empirical
personal/family history of diabetes mellitus (DM), while venous glucose had been
therapy with clindamycin was introduced (1.2 g/day) and the patient was referred
normal at numerous measurements. She was initially treated with Pemetrexed and
to the endocrinonogy department. On admission she was weakened and
Cisplatin followed by Pemetrexed as maintenance chemotherapy which was
dehydrated. Physical examination revealed restricted, swollen, tender and painful
discontinued due to side-effects two months prior to her emergency presentation.
lesion in the lower part of the neck. Laboratory tests indicated inflammation, acute
At that stage, Nivolumab every 2 weeks was initiated. She has maintained good
kidney injury and hyperthyroidism. Fine-needle aspiration biopsy (FNAB) of the
radiological and clinical response to treatment.
lesion was performed. Cytological diagnosis was consistent with acute thyroiditis,
Nivolumab is an anti-PD-1 monoclonal antibody and as a checkpoint inhibitor
while microbiologically Salmonella enterica was identified as pathogenic factor.
acts as an immunomodulatory antibody that augments the anticancer immune
Blood and stool cultures were negative for Salmonella. Neck CT revealed thyroid
response through downregulation of T-cell inhibition. Immunotherapy has a
lesion 6.8 cm in size. Patient received adequate therapy for acute kidney injury
beneficial effect in an increasing number of tumour sites, but is associated with
(most probably clindamycin-induced). I.v. treatment with ceftazidime according
immune-mediated endocrinopathies. Development of new-onset type 1 DM after
to antibiogram and thiamazole was administered. The patient was qualified for
receiving anti-PD-1 antibodies, especially as single agent, is extremely rare.
incision and percutaneous drainage. She was discharged after
11 days of
This patient developed fulminant type 1 DM leading to severe DKA and remains
hospitalization presenting significant clinical improvement. A year later on US six
insulin dependent. Both endocrinologists and oncologists need to recognise this
mixed solid/cystic lesions of size below 1 cm were visualized, benign on FNAB.
potentially life-threatening complication and to monitor patients for hyperglycae-
She remains clinically and biochemically euthyroid. Typical infections with
mia prior to and periodically during immunotherapy. Further studies examining the
Salmonella concern gastrointestinal tract, while conditions associated with
pathophysiology and natural history of immunotherapy-associated diabetes are
atypical infections are: HIV infection, transplant recipients, diabetes mellitus,
warranted in order to guide optimal patient monitoring and management.
thyroid gland disorders
(e.g. multinodular goiter, after FNAB), anatomical
DOI: 10.1530/endoabs.49.EP386
abnormalities
(piriform sinus fistula), corticosteroid therapy, advanced age,
neoplastic disease and contact with breeding animals. The only risk factor for
acute thyroiditis in our patient was diabetes mellitus, although it was well-
controlled.
DOI: 10.1530/endoabs.49.EP388
EP387
Dyslipidemia and antiretroviral therapy: a case report
El Meghari Ghizlane, Elbahi Meryam, Rafii Sana & El Ansari Nawal
Faculty of Medecine and Pharmacy, Marrakech, Morocco.
Introduction
EP389
The use of highly active antiretroviral therapy in 1996 helped greatly reduce the
Improved xanthomas after leptin replacement short therapy in
morbidity and mortality in patients infected by HIV. Very quickly, secondary
congenital lipodystrophy patient
metabolic complications to this same treatment have been described.
Antonio F Oliveira-Filho1, Irla A Dantas4, Renata N Velloso3,
Dyslipidemia occupy a large part of these complications and give the patients
Sofia N P de Oliveira2, Diego F F Candido4 & Adriana Nunes3
an atherogenic profile favouring the occurrence of acute coronary events. We
1Paraiba Health State Department, Campina Grande, Brazil;2Federal
report a case that illustrates the lipid abnormalities associated with anti retroviral
University Campina Grande, Campina Grande, Brazil;3Federal University
treatment.
Rio Grande Norte, Natal, Brazil;4Faculty of Health Sciences, Joao Pessoa,
Case report
Brazil.
The subject was 54 years old woman, diabetic for 8 years, without history of
hypertension or smoking, BMI was 29 Kg/m2, diagnosed as HIV infected for 1
year, treated by antiretroviral therapy. Her initial lipid profile reveals a moderate
Berardinelli-Seip syndrome is an autosomal recessive disorder characterized by
hypertriglyceridemia of 2.5 g/l, total cholesterol was 1.7 g/l and HDL cholesterol
generalized lipoatrophy, extreme insulin resistance with dyslipidaemia in
was 0.3 g/l. High plasma viral loads persisted after 6 months of antiretroviral
childhood and development of diabetes and hepatic steatosis in adolescence.
therapy, thus the patient was considered to have a treatment failure. The control of
The metabolic derangements can be severe and lead to substantial comorbidities,
her lipid profil, after 2 months of a second-line combination therapy, reveals an
including acute pancreatitis, hepatic cirrhosis, and premature cardiovascular
aggravation of her previous dyslipidemia with a severe hypertriglyceridemia of
disease. Other manifestations can include polycystic ovarian syndrome,
6.36 g/l, an hypercholesterolemia of 2.72 g/l and HDL cholesterol was 0.4 g/l.
acanthosis nigricans, and eruptive xanthomas. Lipodystrophy syndromes have
Discussion
caught interest because adipose tissue has been found to secrete a variety of
While the retroviral infection itself, especially at the AIDS stage, is responsible
cytokines/hormones such as leptin, adiponectin, resistin, and many others. Here
for an increase in triglycerides and a decrease in total cholesterol, antiretroviral
we describe a dramatic response to treatment with leptin. A 15-year-old girl was
therapy exacerbates abnormal lipid metabolism. This is mainly dyslipidemia with
given the diagnosis of Berardinelli-Seip congenital lipodistrophy syndrome
predominant hypertriglyceridemia, associated with an increase in total cholesterol
(BSCL). She presented generalized lipoatrophy, muscle hypertrophy, xanthomas
and LDL-cholesterol; HDL-cholesterol is either lowered or slightly modified,
in elbows legs and soles, umbilical hernia, hirsutism, hyperphagia, acanthosis
these abnormalities are partly due to increased hepatic synthesis of large VLDL
nigricans and hepatomegaly. Her BMI was 20.67 kg/m2, body fat was 5.72%, and
and decreased purification of remnants rich in triglycerids. The Knowledge of
BMR was 1 440.3 Kcal. Computer tomography revealed hepatic steatosis, one
lipid abnormalities induced by antiretroviral treatment is critical for better patient
cyst on the right kidney, and absence of subcutaneous and adipose tissues. Patient
management between infectiologist, biologist and endocrinologist.
had difficult to manage metabolic parameters, requiring 300U of insulin and
DOI: 10.1530/endoabs.49.EP387
combined therapy. She started a leptin-replacement therapy (1 ml/day). After ten
days, her xanthomas became vanished, cholesterol levels decreased from 550 to
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
196 mg/dl, and triglycerides
5.000
to
840 mg/dl. She observed progressive
Conclusions
reduced fasting blood glucose and insulin dose simultaneously with improvement
The clinical features of this syndrome was according to those described in the
in clinical signs, symptoms and quality of life. In a ten days course, leptin
literature. Metabolic and endocrine disorders should not be interpreted as isolated
replacement showed to be able to manage metabolic state of the patient and
pathology, but as possible pathogenetic factors. We underline the essential role of
xanthomas.
MRI in detecting the disease correlated with intense headache. The neurological
DOI: 10.1530/endoabs.49.EP389
symptoms and psychiatric symptoms were correlated with the severity of internal
frontal hyperostosis and cortical atrophy.
DOI: 10.1530/endoabs.49.EP391
EP390
Resistant hypertension in an obese type 2 diabetic male with obstructive
sleep apnea: resolution with CPAP, weight loss and Dulaglutide
EP392
Claudia Arnas-Leon1, Ana Delia Santana-Suarez1, Alba Rodriguez-Perez2,
Continuous glucose monitoring in glycogen storage disease type Ia - a
Manuel Nivelo-Rivadaneira1, Agnieszka Kuzior1, Sara Quintana-Arroyo1,
major improvement for patients
Carmen Acosta-Calero1 & Francisco Javier Martinez-Martin1
Diana Martins1, Diana Oliveira1, Carla Baptista1, Sandra Paiva1,
1Endocrinology and Nutrition, Hospital Doctor Negrin, Las Palmas de Gran
Nuno Vicente1, Luís Cardoso1, Adriana Lages1, Mara Ventura1,
Canaria, Spain;2Internal Medicine, Hospital Doctor Negrin, Las Palmas de
Nelson Cunha1, Sónia Moreira2, Hugo Clemente2, Helder Esperto2 &
Gran Canaria, Spain.
Francisco Carrilho1
1Department of Endocrinology, Diabetes and Metabolism of Coimbra
Hospital and Universitary Centre, Coimbra, Portugal;2Department of
A 49-year-old male was referred to our Hypertension Clinic with uncontrolled
Internal Medicine of Coimbra Hospital and Universitary Centre, Coimbra,
hypertension, treatment Valsartan/Amlodipine/Hydrochlorothiazide 80/10/25 mg
Portugal.
C Doxazosine 4 mg. Mean home BP was 156/103 mmHg. Personal history:
dyslipidaemia, central obesity and type 2 diabetes, with mild diabetic retinopathy,
persistent microalbuminuria and preserved renal function. Treatment: Metfor-
Introduction
min/Sitagliptin
1000/50 mg BID; Pravastatin/Fenofibrate
40/160 mg. Height
Glycogen storage disease (GSD) type Ia (von Gierke’s disease) is an inherited
172 cm, weight 112 kg, BMI 37.8 kg/m2, waist 126 cm, clinic BP 165/99, HR 77;
metabolic disorder of glycogen metabolism, caused by defects in the glucose-6-
unremarkable physical exam except abdominal adiposity. Glycemia 132 mg/dl,
phosphatase complex, with associated risk of severe hypoglycemia within 3-4 h
HbA1C
7.2%, Cr
0.92 mg/dl, GFR
(CKD-EPI)
97 ml/min per
1.73 m2,
after a meal.
Cholesterol
166
mg/dL
(HDL 38, LDL 96), Triglycerides
161
mg/dl,
The aim of the present study was to evaluate the efficacy of continuous glucose
Albuminuria 126 mg/g Cr; TSH, Metanephrines, Aldosterone, PRA and ratio
monitoring (CGM) system in determining the magnitude of hypoglycemia in
were normal. Heart US: normal function, mild LVH (PW and IVW 14 and
patients with GSD type Ia.
13 mm). 24 h. ABPM: Awake BP 157/96, Sleeping 146/89, non-dipper.
Methods
The treatment changed to Perindopril/Indapamide 8/2.5 mg, Eplerenone 50 mg
We retrospectively analyzed data from three patients with GSD type Ia, who
and Doxazosine 4 mg. Four months later, the patient had lost 2.5 kg with
underwent CGM with iProTM2 CGM device (Medtronic, Northridge, CA), over a
diet/exercise, but BP and HbA1C had not improved. Dulaglutide 1.5 mg/week was
7.0 days period, under real life conditions.
substituted for Sitagliptin. The patient’s wife reported heavy snoring with
Results
apparent pauses, and the patient was referred to polysomnography. A severe OSA
A total of 5.520 glucose data points were analysed. Concerning to low glycemic
was diagnosed, and CPAP was initiated.
excursions (!70 mg/dl), we identified 15 episodes (three of them below 55 mg/dl
Six months later, weight was 98.5 kg (IMC 33.1 kg/m2); waist 114 cm, and home
and reaching 40 mg/dl in one case). Most of the episodes of hypoglycaemia were
and office BP were normal. New ABPM: Awake 132/76, sleeping 116/69, dipper.
asymptomatic and occurred 3 or more hours after meals or during the nocturnal
Glycemia was 114 mg/dl, HbA1C 6,7%, Cr 0.91 mg/dl, GFR 98 ml/min per
period. The individual CGM analysis revealed a mean area under the curve of
1.73 m2, Chol. 153 mg/dl (HDL 43, LDL 79), Trigl. 156 mg/dl, Albuminuria
blood glucose below 70 mg/dl (AUC!70) respectively of 0.1, 0.5 and 0.8. One
23 mg/g Cr. New heart US: PW and IVW 11 and 10 mm.
patient presented with important glycemic variability: MAGE 3.11 (reference
The diagnosis was resistant hypertension with target-organ damage (albuminuria,
range 0.0-2.8).
LVH) associated to OSA, plus type 2 diabetes, central obesity, and dyslipidemia.
Conclusions
With CPAP, weight loss and Dulaglutide, BP and glycemic control were achieved
The analysis of continuous glucose monitoring data revealed significant periods
and target-organ damage was reversed.
of asymptomatic hypoglycemia and provided better perception into glycemic
DOI: 10.1530/endoabs.49.EP390
variations therefore, it may serve as a safe and useful tool for the long-term
management of patients with GSD type Ia. We suggest that CGM can be used as
an instrument to detect hypoglycemia, especially in the nocturnal period, helping
patients with GSD to modify their nutritional regimens if necessary.
DOI: 10.1530/endoabs.49.EP392
EP391
Morgagni-Stewart-Morel Syndrome in a 61-years patient: case report
Mihaela Stanciu
Lucian Blaga University of Sibiu, Sibiu, Romania.
EP393
Introduction
Diabetes mellitus: one train may hide another
Morgagni-Stewart-Morel syndrome is a disorder defined by the presence of
Sara Vandewalle1,2, Nike Van Doninck1 & Peter Coremans1
internal frontal hyperostosis, variably associated with metabolic disorders,
1AZ Nikolaas, Sint-Niklaas, Belgium;2Ghent University Hospital, Ghent,
endocrine and neuropsychiatric disorders. Hyperostosis frontalis interna (HFI)
Belgium.
is a morphological change of the frontal bone like a single or multiple bilateral
nodules on the inner lamina, characteristically sparing the diploe and the midline
calvaria.
A 26-year-old Chinese male with autism spectrum disorder and mental
Case presentation
retardation, was referred to start insulin therapy for uncontrolled diabetes
We present a 61-years old women with hypertension and diabetes mellitus (with
mellitus (DM) (HbA1c: 9%; C-peptide: 1.75 ng/ml; anti-GAD AB: negative)
oral antidiabetic therapy), obesity, osteoporosis; also the patient was operated in
treated with oral antidiabetic drugs since 2012.
2005 for a multinodular goiter (total thyroidectomy), treated with L-thyroxin
Clinical examination revealed a tall man with overweight and truncal obesity in
100 mg per day. She was referred to our department for severe frontal headache
light of his ethnicity. We withheld facial dysmorphism with hypertelorism, scarce
which she had suffered for several years, with gradually worsened, failing to
facial hair, and clinodactyly. He had a true gynaecomastia and acanthosis
respond to nonsteroidal anti-inflammatory drugs in last six months and a history
nigricans. Tanner genital stage was IV, however testicular volume was !4 ml.
of psychotic disorders. MRI demonstrated the internal hyperostosis frontalis with
Blood results showed hypergonadotropic hypogonadism
(LH:14.1 U/L,
compression of the cerebral cortex and a small image in the pituitary gland, which
FSH:25.3 U/L, testosterone: 195 ng/dl, free testosterone: 5.71 ng/dl). Additional
is now under observation.
genetic testing showed 48 XXYY karyotype.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Based on medical questionnaires, DM is described in 18% of 48 XXYY males.
A 45-year-old female presented with recurrent episodes of neuroglycopaenic
Following pathophysiological mechanism is proposed: low tota l and free
symptoms 6 years after Roux-en-Y gastric bypass surgery. Her symptoms
testosterone levels are associated with truncal obesity leading to metabolic
occurred during both the fasting and postprandial state. She had a history of
syndrome, insulin resistance and DM. Abdominal obesity and high C-peptide
Rheumatoid Arthritis. Her symptoms did not response to a complex carbohydrate
levels in our patient are arguments in favor of insulin resistance as possible
diet or Acarbose use.
etiological factor. Based on the pathophysiology, metformin and testosterone
Whipple’s triad was demonstrated during a 72 h fast; symptomatic hypoglycae-
could be considered as therapy. Our patient was initially treated with basal-bolus
mia
(1.8 mmol/l) occurred which resolved with glucose administration.
insulin therapy in combination with metformin to enhance insulin sensitivity.
Simultaneous C-peptide, IGF1, IGF2 and insulin samples were requested during
Although in-hospital blood glucose curves were perfect, global metabolic control
the hypoglycaemic episode.
remained poor (HbA1c: 8.5%) due to compliance problems partially by the
The Insulin level was 10 pmol/l, IGF1 level was 11.6 nmol/l, the IGF2 level was
complexity of treatment. Therefore therapy was simplified to a combination of
36.3 nmol/l, IGF2/I ratio was 3.1 (!10), C-peptide level was !94 pmol/l, GH
basal insulin and metformin. Metabolic control remained however poor. Some
was 7.5 mg/l and Sulphonlylurea screen was negative.
data suggest that testosterone treatment might improve metabolic control by
Ketones was
‘Zero’ confirming an insulin independent mechanism for
increasing skeletal muscle mass and decreasing abdominal obesity. In our patient,
hypoglycaemia. Hydroxcholoroquine for Rheumatoid Arthritis was discontinued
there was however no amelioration of metabolic control after start of testosterone.
which led to complete resolution of her symptoms.
Adequate DM therapy is complicated by mental retardation seen in 48 XXYY
This is the first case of severe hypoglycaemia in a patient who did not have
making it difficult to use complex insulin schemes. It seems reasonable to use
diabetes, who underwent bariatric surgery and developed hypoglycaemia due to
metformin in treatment as insulin resistance seems to play a role in the
hydroxycholoroquine therapy with complete resolution of symptoms on
pathophysiology.
discontinuing hydroxychloroquine.
DOI: 10.1530/endoabs.49.EP393
This case demonstrates the need for a structured approach to the evaluation of
hypoglycaemia. Roux-en-Y gastric bypass surgery is associated with subsequent
development of hypoglycaemia which can respond to a complex carbohydrate
diet or acarbose therapy. The lack of response however should prompt a thorough
evaluation. The demonstration of an insulin independent mechanism for
hypoglycaemia excluded post gastric bypass hypoglycaemia as a cause and
EP394
prompted a review of the medication list. Hydroxcholoroquine is associated with
Endocrine manifestations of Woodhouse-Sakati Syndrome - a
the development of hypoglycaemia and cessation resulted in complete resolution
Portuguese case
of symptoms which were occurring at a frequency of 3-4 times per week resulting
Diana Oliveira1, Sandra Paiva1, Pedro Louro2, M Carmo Macário3,
in termination of employment and driving.
Joa˜o Durães3, Diana Martins1, Mara Ventura1, Adriana Lages1,
DOI: 10.1530/endoabs.49.EP395
Nelson Cunha1 & Francisco Carrilho1
1Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital
and University Center, Coimbra, Portugal;2Medical Genetics Unit, Coimbra
Hospital and University Center, Coimbra, Portugal;3Neurology
Department, Coimbra Hospital and University Center, Coimbra, Portugal.
EP396
A case report of insulin autoimmune syndrome in a Caucasian
Introduction
Jaroslaw Jendrzejewski, Lukasz Obolonczyk, Martina Leczycka &
Woodhouse-Sakati Syndrome (WSS) is a very rare autossomic recessive disorder
Krzysztof Sworczak
caused by mutations in DCAF17 gene that primarily affects the endocrine and the
Medical University of Gdansk, Gdansk, Poland.
nervous systems. It is associated with hypogonadism, diabetes mellitus,
hypothyroidism, sensorineural hearing loss, alopecia and extrapyramidal findings.
Treatment is symptomatic and managed by multidisciplinary teams. Less than
The Insulin Autoimmune Syndrome (IAS) also called Hirata’s disease consists of
80 cases are reported to date.
hypoglycemia, high insulin concentration and presence of anti-insulin antibodies.
Case report
IAS is the third leading cause of spontaneous hypoglycemia among Japanese
We describe a 29-year-old woman with dysmorphic facial features, alopecia, mild
population. The syndrome is exceptionally rare among Caucasians, with !50
intellectual disability and sensorineural hearing loss, referred to the Endo-
cases described in literature.
crinology department for primary hypothyroidism with negative thyroid
In this report we showcase a 67 year-old female patient. She presented with
autoantibodies, hypergonadotrophic hypogonadism with ovaries not visualized
paroxysmal sweating, daily fatigue and weakness with no triggering factors for
on pelvic ultrasound and diabetes mellitus diagnosed at 19 years of age. She was
these symptoms. Her blood glucose levels during those episodes were below
under treatment with levothyroxine, drospirenoneCethynyl estradiol and oral
50 mg% measured by using a standard home glucometer device. Prolonged 72 h
glucose lowering agents. Worsening of metabolic control led to start of insulin
fast test showed extremely high insulin-glucose-ratio with moderate elevation of
therapy. Week positivity for Islet-cell cytoplasmic autoantibodies and positive
C-peptide levels. CT scans did not reveal any significant masses in the abdomen.
glutamic acid decarboxylase autoantibodies were detected. IGF1, GH, prolactin,
The subsequent laboratory analysis showed high levels of anti-insulin antibodies
cortisol and ACTH were normal. Progressive neurologic deficits included
with low insulin recovery by using polyethylene glycol precipitation method.
dysarthria, dysphagia, lower limb dystonia and spastic tetraparesis. Brain MRI
After treatment with low glycemic index diet and prednisone the average
showed generalized leukodystrophy. She was the only child of a consanguineous
glycemia has increased with the remission of the symptoms. There have been no
couple. Common genetic, metabolic and mitochondrial disorders were excluded.
incidents of hypoglycemia since the establishment of the treatment.
WSS was suspected. Sequencing of DCAF17 gene detected the homozygous
Our report indicates that at IAS should be considered in the differential diagnosis
variant c.1091C2TOC, not previously described in literature. However, since it
of spontaneous hypoglycemia in Caucasians. The treatment might lead to the
affects the splice donor site of intron 10 and probably causes exon 10 skipping, it
remission of the symptoms.
is likely to be pathogenic.
DOI: 10.1530/endoabs.49.EP396
Discussion
When in presence of several endocrine disorders associated with multisystem
involvement, it is fundamental to look for genetic disorders. Accurate clinical
evaluation allows genetic diagnosis and counseling. A new homozygous variant
of the DCAF17 gene was found in this case. The pathogenic mechanisms of the
disease are still unclear; diabetes-related autoimmunity is not found in previously
EP397
described cases. Also unlike other described cases, IGF1 was within normal
Acquired generalized lipodystrophy associated with latent autoimmune
limits. Endocrine consequences of WSS need frequent follow-up.
diabetes mellitus in adults: a new metabolic phenotype
Federica Ferrari1, Marianna Maranghi2, Giovanni Ceccarini1,
DOI: 10.1530/endoabs.49.EP394
Silvia Magno1, Caterina Pelosini1, Margherita Maffei1, Paolo Vitti1,
Marcello Arca2 & Feruccio Santini1
1
Obesity and Lipodystrophy Center at the Endocrinology Unit, University
Hospital of Pisa, Pisa, Italy;2Department of Internal Medicine, Medical
Specialties, University La Sapienza, Rome, Italy.
EP395
Hypoglycaemia due to hydroxychloroquine in a patient who underwent
Roux-en-Y gastric bypass surgery
Introduction
Kamrudeen Mohammed & Altayeb Abdalaziz
Acquired generalized lipodystrophies (AGL) are rare syndromes characterized by
Hull Royal Infirmary, Hull, East riding of Yorkshire, UK.
complete loss of subcutaneous adipose tissue and very low serum leptin levels.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
AGL are complicated by severe insulin resistance, diabetes mellitus, dyslipidemia
EP399
and fatty liver. In most patients evidence exists of an autoimmune etiology.
Extensive venous thrombosis of the upper extremity in a newly
Case report
diagnosed type 2 diabetic female
We herein describe the case of a Caucasian woman who was diagnosed with
Daniel-Tudor Cosma1, Cristina Alina Silaghi2,5, Vlad Florin Bontea3,
lipodistrophy at 5 years of age, when she began to develop a gradual loss of
Calin Homorodean3,5, Horatiu Silaghi4 & Ioan Andrei Veresiu1,5
subcutaneous adipose tissue. At the age of
20
years insulin-resistance,
1Center for Diabetes, Nutrition and Metabolic Diseases Cluj-Napoca,
hypertriglyceridemia and fatty liver were evident; diabetes mellitus was
Cluj-Napoca, Cluj County, Romania;2Endocrinology Clinic, Cluj-Napoca,
diagnosed when she was 28-years old, and 3 years after insulin therapy became
Cluj County, Romania;31st Internal Medicine Clinic, Cluj-Napoca,
necessary in order to improve metabolic control of the disease. Genetic testing
Cluj County, Romania;45th Department of Surgery, ‘Iuliu Hatieganu’
were negative for PPARG and LMNA/C mutations, ruling out the principal forms
University of Medicine and Pharmacy, Cluj-Napoca, Cluj County,
of congenital lipodystrophies. She came to our attention at the age of 35 years. At
Romania;5‘Iuliu Hatieganu’ University of Medicine and Pharmacy,
clinical examination a generalized loss of subcutaneous fat that included the face
Cluj-Napoca, Cluj County, Romania.
and the extremities was observed. Laboratory tests showed a poor glicemic
control. HbA1c was 85 mmol/mol on high doses of insulin (150UI/die). Nuclear,
PMScl, Gastric Parietal Cell, and high titer Glutamic Acid Decarboxylase
Upper extremity deep vein thrombosis (UEDVT) is not infrequent and accounts
autoantibodies were detected.
for approximately 14% of deep vein thrombosis. The risk of pulmonary embolism
Discussion
is lower than in lower extremity DVT and prompt diagnosis is essential to select
AGL are frequently associated with other autoimmune disorders. The coexistance
those patients who deserve anticoagulant treatment. Previous studies indicated
with type 1 diabetes is very rare, but the association with a latent autoimmune
that type 2 diabetes (DM) patients carried greater risk of DVT development or
diabetes mellitus in adults
(LADA) has never been reported before. This
recurrence than the general population.
association generates an unusual metabolic pattern characterized by severe
A 49-years old female, with no previous medical history, was admitted to our
insulin-resistance due to ectopic-lipid accumulation and severe diabetes due to an
center via Emergency Room (ER) for optimizing glycemic control. At admission:
absolute insulinopenia. For these reasons the management of the metabolic
altered general status, bradylalia, bradypsychia, generalized edema, marked
syndrome in this case is extremely difficult and the association of insulin with
fatigability, BPZ140/90 mmHg, pulseZ96 b/min, holosystolic murmur in the
human recombinant leptin therapy seems to be more efficient than conventional
mitral area. Lab findings revealed: BGZ401 mg/dl, glycosuria
(1 g/dl),
drugs. This case shows the need to screen all patients presenting with an AGL for
proteinuria (300 mg/dl), low serum iron, mild normochromic and normocytic
associated autoimmune disorders including type 1/LADA diabetes.
anemia, high INR and NT proBNP levels, hypocalcaemia, low HDL cholesterol,
DOI: 10.1530/endoabs.49.EP397
slightly elevated CRP, cholestasis syndrome and A1cZ14.01% was consistent
with a sever glycemic imbalance in the last 3 months. Intravenous insulin infusion
and few boluses were needed to correct the hyperglycemic values followed by
initiation of a basal regimen with glargine insulin and metformin. On 3rd day
since admission, edematous swelling and cyanosis of the right arm with collateral
circulation at the shoulder girdle was observed. The echo-Doppler showed a
massive thrombosis from brachial to the brachiocephalic and internal jugular vein
and the CT pulmonary angiogram thrombi at the level of segmental arteries
bilaterally. Treatment with LMWHs was initiated and the patient was transferred
to the Cardiology department with a favorable outcome. The screening for
EP398
thrombophilia emphasized hyperhomocysteinemia and a slightly elevated S
protein activity.
Humalog Mix50w massive overdose for suicidal purpose: a case report
Our case illustrates an extensive UEDVT and pulmonary embolism in a newly
Daniel-Tudor Cosma1, Cristina Alina Silaghi2,5, Horatiu Silaghi4,5,
diagnosed type
2 diabetic patient. The modifications in the thrombophilia
Mihaela Mocan3,5 & Ioan Andrei Veresiu1,5
screening together with the hypercoagulable state induced by hyperglycemia
1Center for Diabetes, Nutrition and Metabolic Diseases
might have led to the development of this extensive UEDVT.
Cluj-Napoca, Cluj-Napoca, Cluj County, Romania;2Endocrinology Clinic,
Cluj-Napoca, Cluj County, Romania;31st Internal Medicine Department,
DOI: 10.1530/endoabs.49.EP399
Cluj-Napoca, Cluj County, Romania;45th Department of Surgery, ‘Iuliu
Hatieganu’ University of Medicine and Pharmacy, Cluj-Napoca, Cluj
County, Romania;5‘Iuliu Hatieganu’ University of Medicine and Pharmacy,
Cluj-Napoca, Cluj County, Romania.
EP400
Intentional insulin overdose in diabetic patients is a rare critical situation. The
Early association of three autoimmune disorders in a young male with
severity is due to numerous neurological complications, electrolyte disturbances,
polyglandular autoimmune syndrome type IIIA
liver and lung damage or death.
Daniel-Tudor Cosma1, Cristina Alina Silaghi2,5, Mihaela Mocan3,5,
A 76-years old female, with significant cardiac pathology, diagnosed with type 2
Horatiu Silaghi4 & Ioan Andrei Veresiu1,5
diabetes and treated with Humalog Mix50w 0-0-24 U/day, is admitted to our
1Center for Diabetes, Nutrition and Metabolic Diseases Cluj-Napoca,
center via ER (emergency room) after an episode of severe hypoglycemia after
Cluj-Napoca, Cluj County, Romania;2Endocrinology Clinic, Cluj-Napoca,
administration of 1500U Humalog Mix50. She arrived in the ER one hour after
Cluj County, Romania;31st Internal Medicine Department, Cluj-Napoca,
the overdose with a glycemic value of 111 mg/dl after 50 ml of glucose 33% and
Cluj County, Romania;45th Department of Surgery, ‘Iuliu Hatieganu’
500 ml 10% glucose. At admission: altered general status, profuse sweating,
University of Medicine and Pharmacy, Cluj-Napoca, Cluj County,
multiple injection sites across her abdomen and thighs. Labs exams revealed:
Romania;5‘Iuliu Hatieganu’ University of Medicine and Pharmacy,
hypocalcaemia, hypokalemia, slightly elevated creatinine and BUN, mild
Cluj-Napoca, Cluj County, Romania.
normochromic, normocytic anemia, A1cZ6.29%. An infusion of 10% glucose
was begun at 1 L/h. The glucose infusion rhythm and concentration was adjusted
according to the glycemic profile with a total duration of infusion of 46 h.
Polyglandular autoimmune syndromes (PAS) are a heterogeneous group of rare
Besides, multiple boluses of glucose 33% were needed to avoid the hypoglycemic
diseases characterized by autoimmune activity against more than one endocrine
events. Hypocalcaemia and hypokalemia were corrected by intravenous (i.v.)
organ, although non-endocrine organs can be affected. In PAS III, autoimmune
administration of calcium gluconate and potassium chloride. Psychological
thyroiditis occurs with another organ-specific autoimmune disease, but the
evaluation diagnosed depression and recommended a psychiatric consult. On day
syndrome cannot be classified as PAS I or II.
3 since admission, the patient’s general condition worsened significantly with
A 29-years old man was refer to our center for diagnostic confirmation with the
severe hypotension (requiring continuous positive inotropic infusion), liver and
following complaints: xerostomia, polyuria, polydipsia, nocturnal enuresis, 10 kg
renal failure and she was transferred to the ICU. Despite intensive care
weight loss in the last 2 months, blurred vision and marked fatigability. One week
maneuvers, the patient died of cardiac arrest through electromechanical
before admission the lab exams revealed: blood glucose (BG) of 527 mg/dl,
dissociation.
severe dyslipidemia, glycosuria, ketonuria and a basal bolus regimen with insulin
Insulin overdose requires intensive and prolonged glycemic monitoring to prevent
glargine and lispro was started. Labs findings displayed: BGZ276 mg/dl,
recurrent hypoglycemia. The dose is correlated with a prolonged hypoglycemic
moderate hypertriglyceridemia, glycosuria, low sodium and chloride and the
risk higher than that deduced from the pharmacokinetics of insulin administered.
A1cZ17.73% was consistent with a sever glycemic imbalance in the last 3
To our knowledge this case represents the largest overdose with Humalog
months. The specific antibodies for type 1 diabetes (GAD, ICA, IA2, anti-insulin)
Mix50w ever reported.
were negative and the C peptide was low. The screening for other autoimmune
DOI: 10.1530/endoabs.49.EP398
diseases was positive for thyroiditis (high TPO antibodies) and celiac diseases
(high IgA anti-transglutaminase antibodies) and were confirmed by thyroid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
ultrasound, gastroscopy
(paving stone duodenum) and histopathological
preservation of muscle mass and induction of satiety in non-bariatric subjects.
examination. In order to improve the glycemic control, the insulin doses were
Therefore, we investigated the effects of dietary protein, assessed by amino acid
adjusted according to the glycemic values and carbs ingestion. Nutritional
composition, on satiety, hunger and gastrointestinal hormones after gastric bypass
education was conducted emphasizing the importance of gluten-free diet and
surgery.
correct estimation of the carbs intake. The lipid profile normalized after
Methods
normoglycemia was achieved.
Participants who previously had undergone primary gastric bypass surgery were
Despite the lack of specific antibodies, the patient profile, lab exams and
studied during an oral Mixed Meal Tolerance Test (MMTT). Satiety and hunger
association with other autoimmune diseases support the diagnosis of type 1
were assessed every 30 min by means of a visual analogue scale. Blood samples
diabetes. The zinc transporter-8 (ZnT8) antibodies are not yet available in our
were collected at baseline, every 10 min during the first half hour and every
country. The evolution in these cases may be unpredictable and requires the
30 min till 210 min after the start. The plasma samples were assessed for 24
concomitant treatment of all the conditions involved in order to achieve the
amino acids including derivatives and four gastrointestinal hormones.
therapeutic success.
Results
DOI: 10.1530/endoabs.49.EP400
30 female and 12 male subjects aged 48G11 years, 31-76 months after surgery
with total weight loss of 30G9% completed the MMTT. After ingestion increases
in satiety, the hormones PYY, active GLP1, inactive GLP1 and most amino acids
were observed, while hunger, ghrelin and citrulline declined. Satiety scores above
the median were associated with increased plasma levels of PYY, active and
inactive GLP1. Hunger scores below the median (indicating less hunger) were
associated with increased levels of PYY and a reduced attenuation in ghrelin.
Higher concentrations of several plasma levels of amino acids especially
Developmental Endocrinology
histidine, serine, arginine, glutamine and glycine were observed in subjects
EP401
experiencing more satiety, higher levels of PYY, active or inactive GLP1.
Nutritional status in ambulatory patients by Medicine Laboratory
Additional analyses are underway.
Francisco Javier Merida De La Torre & Nieves Bel Pe
˜a
Conclusions
Health Management Area Serrania, Medicine Laboratory, Ronda, Malaga,
Our exploratory analysis shows positive associations between various plasma
Spain.
amino acids in groups with differences in satiety and gastrointestinal hormones.
This provides new insights to optimize the outcomes of bariatric surgery.
DOI: 10.1530/endoabs.49.EP402
Nutritional status has an important effect on the progression of any disease, not
only in hospitalized patients, even more in ambulatory patient of primary care.
Although there are many systems of evaluating nutritional status, they are costly
and subject to variability amongst individuals. The Medicine Laboratory can
correctly perform a nutritional evaluation in a quick an efficient manner.
Objective
Diabetes (to include Epidemiology, Pathophysiology)
Analyze the nutritional status by CONUT nutritional evaluation method
performed by the Medicine Laboratory in ambulatory patients of primary care
EP403
our Health Management Area in 2016.
The fatty acid profile in diabetic children
Materials and methods
Cíntia Castro-Correia1, Sara Sousa2, Sónia Norberto3, Cristina
The CONUT method for nutritional evaluation was used. This method is based on
Delerue-Matos4, Valentina Domingues2, Manuel Fontoura1 &
determining undernutrition according to levels of total lymphocyte count total
Conceição Calhau3,4
cholesterol and serum albumin. During the study, the results of rutinary blood
1Hospital S João - Unidade Endocrinologia Pediátrica, Porto, Portugal;
tests were used, not additional bllod tests were performed. The focus was a sample
2Requimte/LAQV-GRAQ - Instituto Superior de Engenharia, Instituto
size of all patient admitted in primary care centers, nZ1454 patients. Statistics
Politécnico do Porto, Porto, Portugal;3Department of Biochemistry, Faculty
data: accepted error 3.5%, C.I. 99%. The frequency of nutritional risk was
of Medicine, University of Porto, Centro de Investigac¸ão Médica, Porto,
calculated analysed alongside data on patients’ sex, age.
Portugal;4CINTESIS - Center for Research in Health Technologies and
Results
Information Systems, Porto, Portugal.
1454 patients were studied, 68.5%were not undernourished, 27,4% were mild
undernourished and 4,1% were moderate or severe undernourished. The mean age
of patients was 57.9 years, 60.9% were women and 39.1% were men. 6.7% of men
Several studies have shown a link between pro-inflammatory activity and the
were moderate or severely undernourished, only 2.3% of women studied were
presence or relative deficit of some fatty acids. A low amount of omega 3 fatty
moderate or severely undernourished. The statistics differences by gender were
acids, appears to promote an inflammatory profile. The omega 6 fatty acids have
significatives.
also the same effect. It is well known that a chronic low-grade inflammation is
Conclusion
associated to several diseases, namely, diabetes. The follow-up of children and
The nutritional evaluation performed by the Medicine Laboratory is an effective
young people with Type 1 diabetes involves the periodic evaluation of their
tool to evaluate nutritional status and take corrective measures. Although there are
lipidic profile, however it is not done regularly the evaluation of the profile on the
many experiences in CONUT nutritional evaluation in hospitalized patients, we
concentration of different types of fatty acids.
think that this method is useful in primary care too.
Objective
To characterize, and compare, fatty acids profile in children with Type 1 diabetes
DOI: 10.1530/endoabs.49.EP401
and healthy children.
The authors observed that the ratio of omega 6/omega 3 fatty acids was higher in
the control population. Omega 6 levels were higher in the diabetic children
compared to the control group. Several other differences in free fatty acid
composition were observed.
EP402
Conclusion
Satiety, hunger and gastrointestinal hormones after a test meal in
Our findings showed higher levels of alpha-linolenic acid, EPA and DHA, as well
patients after gastric bypass surgery: an association with amino acids
as mono and polyunsaturated fatty acids in diabetic children. This fact is
Merel van den Broek1, Loek de Heide1, Nic Veeger2,3, Marloes Emous5 &
attributed to pharmacological therapy and nutritional management of these
André van Beek4
children. These findings reinforce the importance of a precocious nutritional
1Department of Internal Medicine, Medical Center Leeuwarden,
attention and intervention in the diabetic child treatment.
Leeuwarden, The Netherlands;2Department of Epidemiology, University of
DOI: 10.1530/endoabs.49.EP403
Groningen, University Medical Center Groningen, Groningen, The
Netherlands;3Department of Epidemiology, Medical Center Leeuwarden,
Leeuwarden, The Netherlands;4Department of Endocrinology, University
of Groningen, Groningen, The Netherlands;5Department of Surgery,
Medical Center Leeuwarden, Leeuwarden, The Netherlands.
EP404
Background
Sitagliptin use may reduce oral cancer risk in patients with type 2
Nutrition is essential in achieving maximal treatment success after bariatric
diabetes
surgery, and is simultaneously beneficial for avoiding long-term complications.
Chin-Hsiao Tseng
Dietary protein could have an important role, because of its positive effects on
National Taiwan University Hospital, Taipei, Taiwan.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
Objectives
Whether sitagliptin may affect oral cancer risk has not been investigated.
To analyze the prevalence of episodes of diabetic decompensation in patients
Methods
admitted in Orthopedic Surgery and Traumatology (OST) area.
The reimbursement database of the National Health Insurance in Taiwan was
Material and methods
used. Diabetic patients newly treated with sitagliptin
(nZ50033) or other
Descriptive analysis of patients admitted to OST Service who presented
antidiabetic drugs (nZ277038) within 1999-2008 were followed for oral cancer
abnormally high or decreased blood glucose levels according to the criterion of
until December 31, 2011. The treatment effect was estimated by Cox regression
the Orthopedic Surgeon who performed the consultation.
adjusted for propensity score (PS) or using PS weighting by inverse probability of
Results
treatment weighting approach.
From June 2008 to December 2014, 1486 consultations were sent to Internal
Results
Medicine, Cardiology or Endocrinology, regarding patients admitted to the OST
The overall hazard ratios suggested a
20% lower risk without statistical
area who had suffered some type of medical decompensation during admission.
significance. In tertile analyses, the PS-adjusted hazard ratios for the first
Of these patients, 437 (29.4%) had a documented history of DM. The reason for
(!6.53 months), second (6.53-14.00 months) and third (O14 months) tertile of
consultation was poorly controlled DM in 124 patients (8.3%), with 111 patients
cumulative duration were 1.382 (0.899, 2.125), 0.908 (0.566, 1.456) and 0.464
(89.5%) presenting hyperglycemia and 13 (10.5%) presenting hypoglycaemia.
(0.272, 0.789), respectively; and were 1.324 (0.864, 2.030), 0.871 (0.545, 1.394)
However, since the consultations were made by the Orthopedic Surgeon who
and 0.447 (0.263, 0.760), respectively, for PS-weighted.
requested it, after the initial evaluation of all these patients, the diagnosis of
Conclusions
poorly controlled DM was only considered in 108 patients (7.4% of the total
Sitagliptin may reduce oral cancer risk when the cumulative duration is O14
decompensated patients), since the rest, despite presenting glycemia above 125 on
months.
fasting, were considered controlled taking into account their particular clinical
situation. This implies an actual decompensation of 24.7% of patients with
DOI: 10.1530/endoabs.49.EP404
known DM.
Conclusions
DM is a cause of medical decompensation in 8.3% of patients admitted to OST.
One in four known diabetics had abnormal blood glucose levels.
Together with previous studies in which we concluded that approximately one in
EP405
six known hypertensive patients is decompensated during admission to surgical
Does a first-degree family history of diabetes impact placental vascular
areas, we suggest that an early evaluation of blood glucose and blood pressure
circulation and placental inflammatory response?
performed by Cardiology, Endocrinology or Internal Medicine could be
Jacob Bar
beneficial in terms of morbidity.
WMC and Tel Aviv University, Tel Aviv, Israel.
DOI: 10.1530/endoabs.49.EP406
Background
Experimental and clinical studies have demonstrated that heritability of diabetes
is associated with marked hyperinsulinemia, impaired endothelial function, and
inflammatory up-regulation. However, no studies have examined whether a
EP407
family history of diabetes effects placental maternal and fetal vascular circulation,
Episodes of poorly controlled diabetes in 173 patients admitted in
or placental inflammatory response. The present study was designed to investigate
Vascular Surgery
the impact of first-degree family history of diabetes (FHD) on placental vascular
María Molina Vega1, Pilar Losada Mora3, Alfonso M Garrido Castro2,
circulation and inflammatory lesions.
Jose M García Almeida1, Juan L Carrillo Linares2, Miguel Damas Fuentes1,
Methods
Carmen Rodríguez García1 & Cristina Díaz Perdigones1
402 pregnant women were divided into two groups according to presence of of
1Endocrinology, Hospital Virgen de la Victoria, Malaga, Spain;2Internal
first-degree FHD: Group 1 included 255 subjects without FHD, Group 2 included
Medicine, Hospital Virgen de la Victoria, Malaga, Spain;3Cardiology,
145
subjects with FHD. Placental histology was performed for vascular
Hospital Virgen de la Victoria, Malaga, Spain.
circulation and inflammation lesions of maternal and fetal origin.
Results
Maternal vascular supply
(MVS) abnormalities of the placental bed was
Introduction
significantly higher in subjects with FHD, compared to group 2 (33% vs 52%,
Episodes of poorly controlled diabetes (DM) are one of the most frequent medical
P!0.005). Fetal vascular supply (FVS) abnormalities as well as maternal and
complications during hospitalization in the elderly population.
fetal inflammatory lesions (MIR and FIR) did not differed significantly between
Objetives
groups. In the logistic regression analysis, FDH is an independent and significant
To analyze the prevalence of episodes of diabetic decompensation in patients
predictor predictor of maternal vascular supply abnormalities (PZ0.001) and
admitted to the area of Vascular Surgery and Angiology (VS).
more than doubles risk of this outcome
(OR 2.084, 95% CI 1.337-3.247,
Material and methods
PZ0.001). Gestational diabetes incidence was significantly higher in subjects
Descriptive analysis of patients admitted to the VS Service who presented
with FHD.
abnormally high or decreased blood glucose levels according to the criteria of the
Conclusion
Vascular Surgeon who performed the consultation.
We demonstrated that first-degree family history of diabetes is associated with an
Results
increased rate of maternal vascular malperfusion abnormalities.
From February 2011 to December 2014, 173 consultations were sent to Internal
Medicine, Endocrinology or Cardiology regarding patients admitted to the VS
DOI: 10.1530/endoabs.49.EP405
area who had suffered some type of medical decompensation during admission.
Of these patients, 94 (49.1%) had a documented history of DM. The reason for the
consultation was ‘poorly controlled DM’ in 8 patients (4.6%) of whom had
hyperglycemia 4 (50%) and hypoglycemia, 4 (50%) as well as ‘control of vascular
risk factors’ in 18 (10.4%). However, after analysis of all patients, only 22
(12.7%) were diagnosed as decompensated DM in the discharge report. This
implies a real decompensation of 23.4% of patients with known DM.
EP406
Conclusions
Episodes of poorly controlled diabetes in 1486 patients admitted in
DM is a single cause of medical decompensation in 4.6% of patients admitted to
Orthopedic Surgery and Traumatology
VS. However, associated with decompensation of other vascular risk factors, one
María Molina Vega1, Pilar Losada Mora3, Alfonso M Garrido Castro2,
out of four known diabetics had abnormal blood glucose levels.
Jose M García Almeida1, Juan L Carrillo Linares2, Miguel Damas Fuentes1,
Together with the previous studies in which we conclude that approximately one
Carmen Rodríguez García1 & Cristina Díaz Perdigones1
in six known hypertensive patients is decompensated during admission to surgical
1Endocrinology, Hospital Virgen de la Victoria, Malaga, Spain;2Internal
areas, we suggest that an early evaluation of blood glucose and blood pressure
Medicine, Hospital Virgen de la Victoria, Malaga, Spain;3Cardiology,
performed by Cardiology, Endocrinology or Internal Medicine could be
Hospital Virgen de la Victoria, Malaga, Spain.
beneficial in terms of morbidity and hospital stay, since previous studies
associate the diabetic uncontrol in patients admitted to Vascular Surgery to an
average stay 9 days superior compared to non-diabetics.
Introduction
Episodes of poorly controlled diabetes (DM) are one of the most frequent medical
DOI: 10.1530/endoabs.49.EP407
complications during hospitalization in the elderly population.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP408
5. Ulysses SAFEGUARD IT now reports all insulin incidents monthly which are
discussed as part of Quality Improvement. A monthly junior doctor insulin/
Postprandial triglyceride responses and insulin resistance among night
prescription error alert (Aug’15) now mandates all error discussions with
shift health care workers
Educational Supervisors helping them reflect/learn from mistakes (11 insulin
Kiranmala Keithellakpam, Aslam Mohd, Brijesh Mishra, Rajat Jhamb &
incidents in Jan/Feb’16 vs 19 in Nov/Dec’15).
Madhu Sri Venkata
Thus, over a relatively short period of 1 year, we have shown that our simple, yet
Diabetes, Endocrinology and Metabolism Centre, Department of Medicine,
helpful, safety innovations can be very effectively applied to reduce diabetes
University College of Medical Sciences, New Delhi, Delhi, India.
errors, improve staff knowledge & satisfaction. Our approach can be easily
replicated by any NHS Trust to improve overall safety in insulin and diabetes
Background
management.
A higher cardiometabolic risk has been reported in night shift workers. Post
DOI: 10.1530/endoabs.49.EP409
prandial hypertriglyceridemia
(PPHTg) is recognized as an independent
cardiovascular risk marker. Few studies have shown that acute disruption of
circadian rhythm is followed by significantly altered insulin secretion and lipid
tolerance.
Aim and objectives
In this study we compared the postprandial triglyceride (PPTG) responses to
standard oral fat meal between health care night shift workers and non- night shift
EP410
workers to ascertain if it contributes to cardiometabolic risk in them.
Heterozygote c.313delC (p.H105TfsX11) mutation of Glucokinase gene
Methods
in patient with Waardenburg syndrome type 1
20 health care night shift workers (R4 night duties/month for last one year), aged
Huseyin Anil Korkmaz
20-40 years with normal glucose tolerance (NGT) following a 75 g glucose
Division of of Pediatric Endocrinology, Balikesir Ataturk State Hospital,
OGTT and 20 age and sex matched non-night shift workers who had not done
Balikesir, Turkey.
night duty in the last one year or ever were recruited. Anthropometric, OGTT,
HbA1c (%), insulin, HOMA-IR, HOMA-b (%), fasting lipids parameters and
inflammatory markers (IL-6 & Hs CRP) were measured. PPTG responses were
Background
obtained after a standard fat meal given at 8 am, and sampling done every two
Waardenburg syndrome is known as an inherited disorder associated with
hours for next 8 hours, that is at 0, 2, 4, 6 and 8 h and compared between the two
sensorineural deafness and pigmentary abnormalities affecting the skin, hair, and
groups.
eye. There are rare case reports of Waardenburg syndrome with diabetes mellitus
Results
in the literature.
Night shift and non-night shift workers were matched for age (29.70G3.92 years
Case
vs 29.70G2.23 years) and sex (M:F 12:8 vs 12:8). The duration of night shift
A 9-years-old boy from consanguineous family was admitted to pediatric
exposure was relatively short
(4.2G3.3 years) among cases. There was no
endocrine department because of fasting and postprandial hyperglycemia. In the
significant difference between the two study groups with respect to anthropo-
medical history, it was learned that his aunt and uncle had brilliant blue iris,
metric, glycaemic, fasting lipids parameters or inflammatory markers. However,
fasting and postprandial hyperglycemia. On physical examination; Height:
2 h postprandial glucose in health care night shift workers was comparatively
131.5 cm (10-25p), Height SDS: K0.76, Weight: 28.9 kg (25-50p), Weight SDS:
higher than non-shift workers (103.8G18.53 mg/dl vs 91.5G19.96) though it just
K0.29, Body mass index: 16.72, Body mass index SDS:0.16. On physical
fell short of statistical significance (PZ0.50). PPTG measures - PPTG area under
examination, the patient with a brilliant blue iris had dystopia canthorum, skin
the curve (TG AUC) and TG peak values were comparable in both the groups.
hypopigmentation, synophrys, broad nasal root, hypoplasia alae nasi and mild
PPTG response showed significant positive correlation with fasting insulin and
sensorineural hearing loss. When our patient was evaluated for Waardenburg
HOMA-IR indicating insulin resistance, and HOMA-b (%) indicating insulin
syndrome clinical criteria, Waardenburg syndrome was diagnosed with
secretion in night shift health care workers but not in others. There was no
Waardenburg Consortium. Blood glucose was 148 mg/dl (75-100), insulin was
significant correlation of PPTG parameters with any other clinical, biochemical
19.1 IU/ml (2-18) and serum C-peptide level was 3.72 ng/ml (1.1-4.4). HbA1c
and inflammatory measures.
value was 6.2%, anti insulin antibody was 0.01 U/ml (0-0.5U), anti-GAD was
Conclusions
!1 U/ml (! 1 U/ml) and islet cell antibody was negative. When our patient was
Postprandial triglyceride burden is significantly associated with insulin resistance
evaluated for maturity onset diabetes of the young, MODY type 2 was diagnosed
in night shift workers even with a relatively short duration of night shift,
with heterozygote c.313delC (p.H105TfsX11) mutation in glucokinase gene.
DOI: 10.1530/endoabs.49.EP408
Repaglinide was started for controlling blood glucose levels and blood glucose
regulation was achieved.
Conclusion
We reported the case of a patient with Waardenburg syndrome accompanied by
glucokinase gene mutation, To the best of our knowledge, we believed the first
reported Waardenburg syndrome patient with these concomitant disorder.
Keywords: Waardenburg syndrome type
1; glucokinase gene; MODY;
EP409
hyperglycemia.
Improving safety in diabetes management and reducing insulin errors
DOI: 10.1530/endoabs.49.EP410
in hospital - practically achievable or a utopian fantasy?
Wyn Burbridge, Lynne Braycotton, Amar Puttanna, Mahender Yadagiri,
Dee Ilsley, Sagnik Mukhopadhyay, Karthik Munichoodappa & Parijat De
Sandwell & West Birmingham NHS Trust, Birmingham, UK.
EP411
42 insulin related incidents were reported within our Trust in 2014. Subsequent
GLIS3 rs7020673 and rs10758593 polymorphisms interact in the
Root Cause Analysis revealed numerous insulin errors, hyperglycemia
susceptibility for type 1 diabetes mellitus
mismanagement and highlighted significant deficits in diabetes knowledge
Daisy Crispim1,2, Guilherme Duarte1,2, Tais Assmann1,2, Cristine Dieter1,2,
amongst nursing staff. To address the above issues, new safety interventions were
Bianca de Souza1,2 & Luis Canani1,2
introduced and five key outcomes are:
1Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,
1. A new stand-alone insulin prescription chart introduced May’15 has seen
Rio Grande do Sul, Brazil;2Post-graduation Program in Medical Sciences:
insulin incidents decrease from 60 (Apr’14 - May’15) to 37 (June’15 - Apr’16).
Endocrinology, Faculdade de Medicina, Universidade Federal do Rio
2. A new, abbreviated DKA protocol and DKA App launched Aug’15 has shown
Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
significant clinical benefits and crucially, helped earlier discharge by 3.2 days
(audit of 40 patients (13 between May - July’15 and 27 between Aug’15
Background and Aims
- Mar’16).
The transcription factor Gli-similar 3 (GLIS3) plays a key role in the development
3. A mandatory new “6 steps to insulin safety online module” introduced for all
and maintenance of pancreatic beta-cells as well as in the regulation of Insulin
junior doctors & nurses (Dec’15) - 91 staff have already completed the module.
gene expression in adults. Accordingly, genome-wide association studies
Our CCG has recently introduced this successful module for care home staff.
identified GLIS3 as a susceptibility locus for type 1 diabetes mellitus (T1DM)
4. Daily Hypoglycemia email alerts and Precision (Abbott) web database
and glucose metabolism traits. Therefore, the aim of this study was to investigate
introduced to specifically target & educate problem wards. A number of changes
the association of the rs7020673 (G/C) and rs10758593 (G/A) single nucleotide
have been already made as a result.
polymorphisms (SNPs) in the GLIS3 gene with T1DM in a Brazilian population.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
Wolfram syndrome, rare neurodegenerative disorder, is known to be DIDMOAD
Frequencies of the rs7020673 and rs10758593 SNPs were analyzed in 503 T1DM
(diabetes insipidus, diabetes mellitus, optic atrophy and deafness). There are rare
patients (cases) and in 442 non-diabetic subjects (controls). Genotyping was
case reports of Wolfram syndrome with chronic renal failure in the literature.
performed using Real-Time PCR and TaqMan MGB probes (Thermo Scientific).
A 19-year-old male patient was admitted to our pediatric emergency department
Haplotypes constructed from the combination of these SNPs were inferred using a
because of headache, chest pain and diurnal and nocturnal enuresis. He had been
Bayesian statistical method.
diagnosed with diabetes mellitus at
13 years of age
(Plasma glucose was
Results
386 mg/dl, urinary ketone negative, normal blood gases, serum C-peptide level
GLIS3 rs7020673C allele frequency was 47.3% in T1DM patients and 45.1% in
0.1 pmol/ml (0.15-1.10) and HbA1c value of as 9.6%) and had received four
the non-diabetic group (PZ0.365), while the rs10758593A allele was present in
doses of regular insulin (0.9 U/kg per day) treatment. Anti-insulin antibody was
43.3% of cases and 41.1% of controls (PZ0.341). Genotype distributions of these
3 U (0-8 U), anti-GAD 0.4 U/ml (!1 U/ml), and islet cell antibody negative at
SNPs were in agreement with those predicted by Hardy-Weinberg Equilibrium in
the diagnosis. In addition, fundus oculi examination had demonstrated bilateral
controls (all PR0.05), and did not differ significantly between groups (PZ0.468
optic atrophy and no sign of diabetic retinopathy at 13 years of age. He was the
and PZ0.279, respectively). In addition, frequencies of rs7020673
and
sixth child of apparently healthy consanguineous parents, born at full-term by
rs10758593 SNPs did not differ between groups under dominant, recessive or
normal vaginal delivery. Family history disclosed that his uncle, aunt and sister
additive inheritance models (all PR0.05). However, frequency of three or more
had diabetes mellitus. Physical examination: weight: 31 kg (!3 percentile),
minor alleles of the analyzed SNPs in haplotypes was higher in T1DM patients
height: 136.5 cm (!3 percentile), blood pressure: 160/80 mmHg and pulse rate
compared to non-diabetic subjects (6.2 vs 1.6%; PZ0.001). Presence of R3
96/dk. He had bilateral blindness. High renal function tests (BUN:78 mg/dl,
minor alleles remained independently associated with risk for T1DM after
creatinine: 4.7 mg/dl), serum electrolytes (Na: 133.7 mmol/l, K: 4.2 mmol/l, Cl:
adjustment for T1DM high-risk HLA DR/DQ haplotypes, age and ethnicity (ORZ
103.7 mmol/l, serum calcium: 8.4 mg/dl serum phosphorus: 8 mg/dl) and high
3.68 95% CI 1.22 - 11.12). Moreover, levels of glycated hemoglobin were higher
parathyroid hormone (PTH: 321.63 pg/ml range, 15 to 65) suggested chronic
in T1DM patients carrying the rs10758593A allele than patients with the G/G
renal failure. Urinary ultrasound imaging disclosed small kidney size. Glomerular
genotype (8.9G2.1 vs 8.2G2.0; PZ0.038). In conclusion, our results indicate
filtration rate was calculated as 13 ml/min/1.73 m2. Audiometric examination for
that the rs7020673 and rs10758593 SNPs interact in the predisposition for T1DM.
Wolfram syndrome revealed bilateral sensorineural hearing loss. A known
DOI: 10.1530/endoabs.49.EP411
homozygous mutation (Y508fsX541, c.1523_1524delAT) in exon 8 of WFS1 was
found in the proband.
We reported a case with Wolfram syndrome accompanied by chronic renal
failure. Early diagnosis and appropriate management for Wolfram syndrome
would prevent development of complications.
DOI: 10.1530/endoabs.49.EP413
EP412
Vitamin D level in naïve Type2 Diabetes Mellitus in Fayoum University
Hospital
Eman Fahmy1 & Mohamed Mashahit2
1Faculty of Medicine, Helwan University, Cairo, Egypt;2Faculty of
EP414
Medicine, Fayoum University, Cairo, Egypt.
Hypoglycaemia in hospital is associated with longer hospital stay and
decline of renal function
Ricardo Fonseca, João Sequeira Duarte, Carlos Bello, Ricardo Capitão,
Vitamin D deficiency has become a worldwide problem, although vitamin D
Francisco Sousa Santos, Catarina Roque, Cátia Ferrinhos &
deficiency had associated with increased insulin resistance, obesity and HbA1c in
Carlos Vasconcelos
patients with T2D.
Hospital Egas Moniz, CHLO, Lisbon, Portugal.
It is uncertain whether vitamin D deficiency causes diabetes or its due to
confounding. The active metabolite 1a,25-dihydroxyvitamin D3 may affect the
receptors of pancreatic b-cells and hence affect insulin secretion, also it may have
Background and aims
impact on insulin sensitivity.
Hypoglycemia is a common complication of diabetes treatment and it’s
Several trials revealed that vitamin D improved glycaemic control in T2DM
associated with poor outcomes. A link between severe hypoglycemia and renal
patients. However, the outcome of these trials often was not clinically relevant.
dysfunction was suggested. No studies evaluated the impact of hypoglycemia of
The aim of this study is to reveal to the relation between vitamin D and naïve type
inpatients in microvascular or macrovascular complications. The aim of our work
2 DM. This is a case control study that was conducted on 90 Egyptian diabetic
was to study the evolution of renal function between admission and final visit, and
subject of both gender their ages was between 25 to 70 years, Exclusion criteria
the impact of nephropathy in the presence of hypoglycemia in inpatients.
are, post-menopausal females, pregnant & lactating females, presence of mal-
Materials and methods
absorption disorders like Crohn’s disease, celiac disease and cystic fibrosis,
Retrospective, observational study of consecutive patients with type 1 (nZ13)
presence of any endocrinal disorder, presence of renal and hepatic disorders.
and 2 Diabetes (nZ85), admitted to the medical specialties ward between 2011
First group included 47 naïve type 2 diabetic patients (HbA1C above 7) including
and 2015 (nZ106 admissions), who had their capillary glycemia written in the
51.1% male diabetic and 48.9% female diabetic patient and 46 healthy control
medical record (nZ14410). We evaluated the renal function (glomerular filtration
including 47.8% male subject and 52.2%female subjects.
rate determined by CKD-EPI formula; glicemic variability
(STD) and
The 47-diabetic group their mean age was 40G0.5 years and their mean BMI was
albuminuria) at admission and at the final visit as outpatients. We used
28G3.6 while the 26 control subjects their mean ages is 42G7.8 years and their
descriptive statistics
(Median G std), t-test and non-parametric tests for
mean BMI was 28G3.8.
continuous variables and Chi-squared distribution for categorical variables.
Vitamin D level was 22.47G10.5 and 23.57G9.7 ng/ml in diabetic group and in
Results
control group respectively, there were no statistically difference when comparing
We report 56 admissions with hypoglycemias, which were compared to 50
vitamin D level between the two groups. In this study, we found a negative
admissions without hypoglicemias in the same period. There were no differences
correlation between vitamin D level and hyperglycemia.
in the distribution of gender (64% were females), age (60.9G1.6 years), diabetes
Also, we found a positive correlation between vitamin D level and age, while
type (12.2% were type 1) or diabetes duration (5.0G1.0 years). In patiens with
vitamin D level was negative correlated with Body mass index.
hypoglicemia we found significant differences in glicemic variability (84 vs
DOI: 10.1530/endoabs.49.EP412
56 mg/dl, P!0.01), in GFRe at admission (94 vs 83 ml/min/1.73 m2, PZ0.03),
GFRe decline (25 vs 7 ml/min/1.73 m2, PZ0.03), and longer hospital stay (13 vs
6 days, PZ0.006).
Conclusion
Despite having the known limitations of a retrospective study, and some
heterogenecity of the population mainly in diabetes duration, we found significant
associations between occurrence of hypoglicemia during hospitalization and
longer hospital stay and decline of renal function. Other study design would be
required to investigate if it is only a marker of fragility or if hypoglycemia may
EP413
have a role in progression of microvascular complications, as suggested by some
Association of wolfram syndrome with chronic renal failure in a boy
investigators.
Huseyin Anil Korkmaz
DOI: 10.1530/endoabs.49.EP414
Balikesir Ataturk State Hospital, Balikesir, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP415
EP417
Could we prevent insulin induced lipohypertrophy in diabetic patients?
Epidemiological and clinical study of diabetes in immigrants from
Natalya Volkova, Ilya Davidenko, Maria Porksheyan, Alexander Zibarev &
Bangladesh in Athens versus Greek patients
Alexey Harlamov
Georgios Papadakis1, Thomas Zambelis2, Kostas Konstantopoulos3 &
Rostov State Medical University, Rostov-on-Don, Russia.
Stylianos Chatzipanagiotou4
1STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;2Department of
Neurology, Aeginition Hospital, Athens, Greece;3Department of
Introduction
Hematology, Laikon University Hospital, Athens, Greece;4Department of
Lipohypertrophy (LH) is a chronic complication of diabetes mellitus that caused
Medical Biopathology, Aeginition Hospital, Athens, Greece.
by frequent subcutaneous injections of insulin. Nowadays, on the basis of results
of ultrasonography of subcutaneous fat prevalence of LH in diabetic patients is
still high.
Objectives
Design
Diabetes risk for Asians is related to a greater tendency to adiposity, which
The aim has been to develop prevention of insulin induced LH in diabetic
increases insulin resistance. Various studies have highlighted the fact that people
patients. This study was done on 140 diabetic patients who had been under the
from South Asia have a younger age of onset of diabetes, greater upper-body
treatment with insulin a mean 8 years. On first stage all patients were divided into
adiposity and lower body mass index (BMI) and higher risk compared to those
two groups. First - 117 patients with LH, second - 23 diabetics without LH.
from other nations. Greece has experienced a large wave of immigration from
Further, all known LH risk factors were statistically processed using Spearman’s,
Asian countries, especially Bangladesh. The purpose of this study was to explore
Gamma rank correlation coefficients. Results were statistically significant when
the ethnic differences and special needs that must be taken into account when
P!0.05. On second stage 65 patients from first group were divided into two
treating patients with different cultural background.
subgroups. First - 50 patients with LH and corrected risk factors, second (control)
Methods
- 15 diabetics with LH and uncorrected risk factors. Ultrasonography of
A total of 166 randomly selected immigrants with diabetes from Bangladesh were
subcutaneous fat were used in assessing new LH in these subgroups after 3 and
compared with 123 randomly selected Greek Caucasian patients with diabetes.
6 month.
Results
Results
Patients from Bangladesh had a mean duration of living in Greece of 10.34G6.2
As a result, 10 factors from 23 were remained after statistic analysis on first stage.
years. The Bangladeshi group was younger compared with the Greek group
Statistically insignificant parameters were eliminated (PO0.05). On next stage, in
(44.05G8.1 vs 48.75G9.2 years old, PZ0.009) and had an earlier age at onset of
first subgroup only two patients (4%) had new LH, while in second - 9 diabetics
diabetes (39.3G7.3 vs 41.7G10.1 years old, PZ0.025). The reported duration of
(60%) had new pathologic areas of subcutaneous fat after 3 month. And in first
diabetes was lower in the Bangladeshi group (4.86G4.5 vs 7.34G6.21 years,
subgroup only 6 patients (12%) had new pathologic areas of subcutaneous fat,
P!0.05). The Bangladeshi group had a significantly lower BMI (24.19G3.3 vs
while in second - 12 diabetics (80%) had new LH after 6 month.
29.04G8.7 kg/m2, PZ0.01), and waist circumference (92.2G8.9 vs 103.1G
Conclusions
15.7 cm, P!0.001). Bangladeshi group had a slightly worse, but not statistical
Nowadays, primary prevention of LH is necessary for diabetic patients under the
significant, glycemic control as compared with the Greek group (A1CZ7.74G
treatment with insulin. There were stated that only 10 risk factors strongly
1.6% vs 7.55G1.7%, PZ0.3). A significant number of Bangladeshis stated that
influence on LH progress. Correction of these risk factors doesn’t lead to
they rarely checked their self-monitoring blood glucose as compared with the
development of new subcutaneous fat pathological changes and could be used to
Greek group (1.26G2.6 vs 8.87G9.9 times per week, P!0.01). There were also
prevent LH in diabetic patients in clinical daily practice.
no significant differences between the two groups for most laboratory findings,
DOI: 10.1530/endoabs.49.EP415
although Bangladeshis had higher mean levels of glucose (190.3G72 vs 160.8G
81 mg/dl, PZ0.4), cholesterol (199.8G44.4 vs 178.86G44.9 mg/dl, PZ0.9),
LDL (129.3G33.2 vs 110.62G33.9 mg/dl, PZ0.8) and triglycerides (231.4G
213 vs 181.95G166 mg/dl, PZ0.07). In the Bangladeshi group, the mean HDL
level was significantly lower as compared with the Greek group (33.99G9.4 vs
44.05G10.43 mg/dl, PZ0.037).
Conclusions
Bangladeshi immigrants are less likely to engage self-care behaviors and have
worse glycemic control and less access to medication, laboratory test and
healthcare units.
DOI: 10.1530/endoabs.49.EP417
EP416
Relation between serum leptin concentration and insulin resistance
syndrome in patients with type 2 diabetes mellitus
Tamer Shebl, Nour El Dein Abd El Azeem & Hosny Abd El Kareem
Alazhar Univesity, Assuit, Egypt.
Type 2 diabetes mellitus is known for its morbidity and mortality all over the
globe. It has been demonstrated in recent studies that abnormal levels of
EP418
adipocytokines may contribute to insulin resistance and type 2 diabetes.
Vitamin D levels in newly diagnosed type I diabetes mellitus and
Objectives
relationship with organ specific autoimmune disorders
The aim of the present study was to assess the relation between serum leptin levels
Belgin Efe1, Gonca Akdere2 & Goknur Yorulmaz1
and insulin resistance syndrome in type 2 diabetic patients.
1ESOGU Faculty of Medicine Department of Endocrinology, Eskisehir,
Methods
Turkey;2ESOGU Faculty of Medicine Department of Internal Medicine,
Eighty persons were enrolled in this study and were divided into two groups.
Eskisehir, Turkey.
Twenty healthy persons as a control group and 60 patients with type 2 diabetes
mellitus as a disease group. The disease group were further divided into those who
have evidence of metabolic syndrome (30 patients), and those who do not (30
Based on the effects of Vitamin D on immune system it has been suggested that
patients). Parameters like age, sex, anthropometric measurements and
vitamin D may play a role in the pathogenesis of type I diabetes mellitus (T1D)
biochemical indicators such as fasting and post prandial blood sugar, HbA1c,
and other organ specific autoimmune disorders. In our study, we aimed to show
lipid profile, leptin and fasting insulin were determined.
the effect of Vitamin D deficiency in the development of newly diagnosed T1D
Results
and other autoimmune disease that may associated with T1D such as autoimmune
Higher Leptin and insulin levels were observed in patients with metabolic
thyroid disease (ATD), celiac disease, Addison’s disease, vitiligo and atrophic
syndrome (P!0.001).
gastritis. In addition to 50 newly diagnosed T1D patients and 60 healthy controls,
Conclusion
we evaluated the data of the formerly diagnosed 50 T1D patients. The frequency
High serum leptin is a good indicator and could provide a minimally-invasive
of vitamin D deficiency in newly diagnosed T1D patients was found 88%. 30% of
marker for early detection of the insulin resistance syndrome.
these patients were anti parietal cell antibody (APA) positive which is marker for
Keywords
pernicious anemia,
24% of had ATD, 10% of was positive for anti-tissue
leptin concentration; insulin resistance syndrome; type 2 diabetes mellitus.
transglutaminase IgA which is marker for celiac disease and 2% of had vitiligo.
DOI: 10.1530/endoabs.49.EP416
Levels of 25(OH)D were statistically significant lower in newly diagnosed T1D
patients with positive APA than patients with negative APA. Frequency of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
vitamin D deficiency was 66.7% in healthy controls and 84% in formerly
The aim
diagnosed T1D patients. When we considered all T1D patients, we found the
To evaluate the efficacy of Nucleo CMP Forte
(Cytidine
- 5’- disodium
frequency of ATD was 25%, frequency of positive APA was 28%, frequency of
monophosphate and Uridine - 5’- trisodium triphosphate) in the combined
positive anti-tissue transglutaminase IgA was 10% and frequency of vitiligo was
treatment of patients with DPNP.
2%. We found that ATD and predisposition of celiac disease were much frequent
Methods
in T1D patients than healthy controls. Vitamin D levels were found lower; in
It was examined 59 (41-79 years old) patients with type 2 DM and DPNP. They
patients with T1D than healthy controls; when we evaluate all subjects we found
were compared into two groups: A - 30 patients received standard treatment, B -
that patients with ATD had lower vitamin D levels than patients without ATD and
29 diabetics additionally were taken Nucleo CMP Forte (1 capsule three times a
also patients with ATD and positive APA had lower vitamin D levels than patients
day). Patients filled questionnaire of life quality EQ-5D-3L
(Ukraine 2004,
without ATD and negative APA.
EuroQol) on the first and tenth day of treatment. We used non-parametric test c2
DOI: 10.1530/endoabs.49.EP418
to evaluate efficacy of therapy. Significance was set at P!0.05.
Results
All patients revealed positive changes after 10 days of treatment. Thus, the
problems with walking decreased in 16.6% of the group A patients (c2Z1.164.
PO0.05) and 33.3% (c2Z6.171, P!0.05) of the group B, the relief in
performing of daily activity was marked by 25% (c2Z2.286, PO0.05) and 50%
(c2Z2.859, PO0.05) of ones respectively, pain/discomfort bothered less than
25% (c2Z4.267, P!0.05) patients of the group A and 33.3% (c2Z6.171,
EP419
P!0.05) of the group B, anxiety/depression decreased in 58.3% (c2Z6.063,
Is secreted frizzled-releated protein 4 (SFRP-4) a possible biomarker
P!0.05) and 66.7% (c2Z6.954, P!0.05), respectively.
for b cell dysfunction?
Conclusion
Suleyman Baldane1, Suleyman Ipekci1, Sedat Abusoglu2, Ali Unlu2 &
Patients of both groups noted the positive effect of treatment. Usage of Nucleo
Levent Kebapcilar1
CMP Forte in the combined treatment of patients has more expressed positive
1Division of Endocrinology and Metabolism, Selcuk University Faculty of
influence on problems with walking.
Medicine, Konya, Turkey;2Department of Biochemistry, Selcuk University
DOI: 10.1530/endoabs.49.EP420
Faculty of Medicine, Konya, Turkey.
Introduction
SFRP-4 is a recently described inflammatory cytokine influencing insulin
secretion from human b cells as an extracellular modulator of Wingless (Wnt)
pathway. The aim of this study is to compare serum SFRP-4 levels in patients with
normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2
diabetes (T2DM), and to investigate its relation with other parameters.
Methods
The study included 152 patients who applied to the endocrinology outpatient
EP421
clinic of our hospital. Eighty-two patients who had history of T2DM constituted
Effect of glucose ingestion on serum fractalkine levels in healthy
the T2DM group. Patients who underwent OGTT within the last three months
subjects and diabetic patients
were categorized in either IGT (nZ34) or NGT (nZ36) groups according to their
Suleyman Baldane1, Ismail Can Kendir2, Suleyman Ipekci1, Gulsum Tekin3,
test results. All patients provided blood samples between 08 am and 09 am
Ali Unlu3 & Levent Kebapcilar1
following overnight fasting. Fasting insulin, fasting glucose, HbA1c and SFRP-4
1Division of Endocrinology and Metabolism, Selcuk University Faculty of
levels were measured.
Medicine, Konya, Turkey;2Department of Internal Medicine, Selcuk
Results
University Faculty of Medicine, Konya, Turkey;3Department of
T2DM group had significantly higher serum SFRP-4 levels compared to BGT and
Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey.
NGT groups (0.282 ng/ml vs
0.183 ng/ml, PZ0.001; and
0.282 ng/ml vs
0.170 ng/ml, PZ0.004, respectively). In comparison of BGT and NGT groups,
although serum SFRP-4 levels were higher in BGT group, the difference was not
Introduction
statistically significant (0.183 ng/ml vs 0.170 ng/ml, PZ0.630). SFRP-4 level
Current studies suggest that fractalkine (FKN) could be a pathogenic factor
showed significant positive correlation with fasting glucose (rZ0.274, PZ0.001)
associated with adipocyte dysfunction and type 2 diabetes (T2DM) and have
and HbA1c (rZ0.291, PZ0.002) levels.
shown that FKN serum levels are increased in T2DM patients. The aim of this
Conclusion
study was determined as evaluating the change of FKN levels that will occur with
Progressive b cell dysfunction is observed during the normal course of T2DM,
oral glucose tolerance test (OGTT).
and inflammatory cytokines are held responsible. Recent studies have
Methods
demonstrated the association between increased SFRP-4 expression on b cells
The study included 67 patients to whom OGTT was applied. The patients with the
and reduced insulin release. Additionally, studies have found an association
history of diabetes mellitus, malignity or inflammatory disease were excluded. All
between serum SFRP-4 levels and high fasting glucose level and impaired insulin
subjects were given 75 g of glucose orally after an overnight fasting and blood
sensitivity in non-diabetic individuals. We found increased serum levels of SFRP-
samples were taken for glucose and FKN levels at 0 and 120 min. According to
4 in patients with T2DM in our study, and SFRP-4 level was positively correlated
OGTT results, the patients were divided into the groups of NGT (nZ33) and
with fasting glucose and HbA1c levels in the whole study group. We think our
newly diagnosed T2DM (nZ34).
results support the idea that increased plasma SFRP-4 levels may be a good
Results
indicator of b cell dysfunction and insulin resistance.
The basal level of FKN (OGTT at 0 min) was found to be significantly higher in
DOI: 10.1530/endoabs.49.EP419
T2DM group than NGT group (0.374 ng/ml vs 0.259 ng/ml, PZ0.012). The FKN
level at 120 min of OGTT was significantly higher also in T2DM group compared
to NGT group (0.367 ng/ml vs 0.229 ng/ml, PZ0.001). No significant changes in
FKN levels during OGTT were observed in both T2DM and NGT groups (0 and
120 min change) (0.374 ng/ml vs 0.367 ng/ml, PZ0.433 and 0.259 ng/ml vs
0.229 ng/ml PZ0.06, respectively). A significant positive correlation was noted
between the levels of FKN and glucose at
120 min of OGTT (rZ0.331,
PZ0.006).
Conclusion
EP420
Acute hyperglycemia or food intake is known to lead to an increase in circulating
The clinical efficacy of the nucleo CMP forte usage in the combined
levels of many inflammatory cytokines such as IL-1, IL-6, TNF-a. Fractalkine
treatment of diabetic peripheral neuropathy
(FKN) is a recently defined inflammatory cytokine. The results of our study, there
Larysa Martynyuk, Nadiya Makarchuk, Mykola Shved & Lesia Mykhailiv
was no change of serum FKN levels during OGTT in T2DM and NGT patients but
I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
there was a significant correlation between the levels of FKN and glucose at
120 min of OGTT. We believe that long-term studies with broad participation and
serial measurements are needed to determine the role of FKN in the pathogenesis
Introduction
of T2DM.
The protocols of medical care of diabetic peripheral neuropathy (DPNP) are
developed but positive effect cannot be achieved in all patients. New medications
DOI: 10.1530/endoabs.49.EP421
in DPNP have to be studied.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP422
Conclusion
Prediabetes and T2D were detected in the majority of patients undergoing
Epidemiological features of type 1 diabetes in children and adolescents
coronary angiography without previously known glycemic disorders. Therefore,
in the Republic of Armenia
HbA1c should be determined in all patients hospitalized for possible CAD,
Yelena M Aghajanova, Gayane M Bayburdyan, Lusine V Navasardyan,
regardless of the history for diabetes.
Renata L Markosyan & Lusine G Kalantaryan
Yerevan State Medical University, Yerevan, Armenia.
DOI: 10.1530/endoabs.49.EP423
Background
Diabetes is the most prevalent chronic metabolic disorder in children and
adolescents, and incidence rates for both type-1 and type-2 diabetes are increasing
worldwide. In recent years, the number of patients with type 1 diabetes is
increasing mainly due to children under 5-years-old.
Objective
To study the epidemiological indicators of T1DM among children of the Republic
EP424
of Armenia (RA) from 2007 to 2016. Methods: Retrospective analysis of the
The relation between type II diabetes and chronic depression in
Republican Children’s Endocrinology Center database using conventional
primary care practice in Jordan
statistical methods.
Abdallah Alzoubi, Renad Abu Naser, Ady Khasawneh & Aws Khasawneh
Results
Jordan University of Science and Technology, Irbid, Jordan.
During the period 2007-2010 in Armenia there was a relatively stable incidence
of diabetes in children 0-18 years: 7.1 in 2007, 6.45 in 2008, 6.3 in 2009 and 6.8
in 2010 (per 100 000 child population), while during 2010-2016 period increased
Diabetes is a major health problem that affects 8.5% of adults worldwide,
incidence is seen (6.7 in 2011, 9.4 in 2012, 8.7 in 2013, 9.99 in 2014, 10.69 in
and 13.2% of adults in Jordan. Studies suggest a bidirectional relationship
2015). The study of age-specific morbidity in children with T1DM in RA showed
between diabetes and chronic depression. Diabetic patients are twice as
that the maximum incidence in different years was at the age of 5-9 or 10-14
likely to suffer from depression that is symptomatically worse when
years. According to the Republican Children’s Endocrinology Center data
compared to nondiabetic individuals. Depressed diabetics suffer from poor
rejuvenation of type 1 diabetes can be traced. Mean age of patients in 2007 was 11
glycemic control and increased risk of diabetes complications. Because little
years. In 2014 mean age was 8.9 and 9.8 in 2016. The incidence rate in children of
is known about the bidirectional relationship between diabetes and chronic
younger age group (0-4 years) increased from 2.24 in 2007 to 5.05 in 2010, 7.14
depression in Jordan, we screened for depressive disorders among diabetic
in 2014 and 5.8 in 2016 (per 100 000 child population).
patients using the Patient Health Questionnaire-9 (PHQ-9) and screened for
Conclusions
diabetes among depressed individuals by measuring their HbA1c, in a cross-
In RA an increased incidence of type 1 diabetes among children and adolescents
sectional study design. A total of
146 diabetic patients (74 males, 72
is seen. The highest incidence occurs in the age groups 5-9 and 10-14 years.
females) participated in the study, with a mean age of 56G8.5 years. Almost
Further studies are needed to look into the cause of these changes.
60% of participants were uncontrolled for diabetes (HbA1c R 7%) with a
DOI: 10.1530/endoabs.49.EP422
mean HbA1c of 8.9%G1.7 and a mean PHQ-9 score of 6.2G5.5. The
remaining 40.4% were controlled for diabetes (HbA1c % 7%) with a mean
HbA1c of 6.1G0.6 and a mean PHQ-9 score of 6.7G4.5. The prevalence of
chronic depression (PHQ-9 score R 10) among diabetic patients was 27.4%.
No correlation was found between PHQ-9
scores and HbA1c levels
(Spearmen’s rZK0.03, PZ0.75). Additionally, 20 depressed patients were
recruited from the psychiatry clinic with a mean age of 41.7G8.3 years, and
were then screened for diabetes by measuring HbA1C levels. None of these
EP423
was found to be diabetic, with a mean HbA1C of 5.4%G0.4. In conclusion,
High incidence of glucose metabolism disorders in patients undergoing
our results thus far deny a correlation between depression and diabetes.
coronary angiography without history of diabetes
However, our future plan of examining the effect of treating depression on
Stavroula A Paschou1, Sotirios Kiokas2, Grigorios Avdikos2,
glycemic control and diabetes complications, and the effect of improving
Efstathios Lazaris2 & Andromachi Vryonidou1
glycemic control on the severity of depression, might improve our
1Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital,
understanding of this relationship.
Athens, Greece;22nd Department of Cardiology, Hellenic Red Cross
DOI: 10.1530/endoabs.49.EP424
Hospital, Athens, Greece.
Introduction
The aim of this study was to investigate the incidence of glycemic disorders in
patients undergoing coronary angiography with no prediagnosed type 2 diabetes
(T2D), as well as the association of the glycemic status with the extent of the
coronary artery disease (CAD).
EP425
Patients and methods
Anti-islet cell antibodies in a sample of Egyptian females with
We studied 170 consecutive patients (134M/36W), 63.9G13.1 (23-95) years old,
gestational diabetes and its relation to development of type 1 diabetes
with not known T2D, who underwent coronary angiography. HbA1c was
mellitus
measured and patients were classified into 3 groups accordingly: i) normal
Hanan M Amer1, Rania S Abd elbaky1, Merhan S Nasr1, Laila M Hendawy1,
HbA1c!5.7%, ii) prediabetes HbA1c 5.7-6.4%, and iii) T2D HbA1c R6.5%.
Mohamed O Taha2 & Wessam A Ibrahim1
The presence of other risk factors for CAD was recorded, while the extent of CAD
1Ain Shams University Division of Endocrinology and Diabetes, Cairo,
was examined. Vessel disease (VD) was defined when stenosis was O70%.
Egypt;2Ain Shams University Division of Gynecology and Obstetrics,
Results
Cairo, Egypt.
From the total of 170 patients, 19.4% (33/170) presented normal HbA1c, 17.6%
(30/170) prediabetes and 63% (107/170) were diagnosed with T2D. Patients with
normal HbA1c were 60.5G16.7 years old, with BMI 29.1G5.2, 18.2% (6/33)
Background
were women, 48.5% (16/33) had hypertension, 36.4% (12/33) dyslipidemia,
Gestational diabetes mellitus is any degree of glucose intolerance with first
while 21.2% (7/33) had history of CAD. Of these, 33.3% (11/33) showed no VD,
diagnosis during pregnancy; it affects 3-10% of pregnancies. The presence of
33.3% (11/33) one VD 21.2% (7/33) two VD, 6% (2/33) three VD and 6% (2/33)
diabetes-related autoantibodies has shown to be able to predict the development
left main along with another one VD. Patients with prediabetes were 65.9G11
of type 1 diabetes before hyperglycemia arises.
years old, with BMI 29.6G5.1, 6.7% (2/30) were women, 63.3% (19/30) had
Aim of work
hypertension, 43.3% (13/30) dyslipidemia and 20% (6/30) had history of CAD.
To recognize the prevalence of islet cell antibodies among a sample of Egyptian
Of these, 30% (9/33) showed no VD, 30% (9/30) one VD, 6% (5/30) two VD and
females with gestational diabetes and its possible relation of development of Type
23.3% (7/33) three VD. Patients with T2D were 64.4G12 years old, with BMI
1 diabetes within 1 year.
23.8G2.6, 26.2% (28/107) were women, 69.2% (74/107) had hypertension,
Design and methodology
52.3% (56/107) dyslipidemia, while 24.3% (26/107) had history of CAD. Of
Our cross sectional study was conducted on 150 Egyptian pregnant females with
them, 42.1% (54/107) showed no VD, 27.1% (29/107) one VD, 17.8% (19/107)
gestational diabetes aged
19-39 years diagnosed by 75-g 2-h oral glucose
two VD, 11.2% (12/107) three VD and 1.9% (2/107) left main along with another
tolerance test. All females were subjected to full history, thorough clinical
one VD.
examination and laboratory measurement of anti-islet cell antibodies, those
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
females with positive antibodies were followed up 6 months and 1 year after
antidiabetic medications, insulin, herbal substances. However, in our history, we
delivery for their fasting insulin, fasting blood glucose and 2 h post prandial
learned that pregabalin and alfalipoic acid were given to the patient considering
levels.
neuropathic pain and proton pump inhibitors for dyspeptic complains. Physical
Results
exam revealed a healthy-appearing middle-aged male with BMI of 21.4. Initial
The prevalence of pregnant females with gestational diabetes having positive anti
tests showed low venous blood glucose
(44 mg/dl), high insulin levels
islet cell antibodies was (44%), the prevalence of females diagnosed to have
O1000 mIU/ml, C-peptide 15.6 ng/ml. To rule out pancreatic or extrapancreatic
diabetes mellitus was (37.88%) 6 months and (51.52%) 1 year postpartum.
insulinoma; abdominal ultrasound, abdominal computer tomography scan,
Conclusion
abdominal MRI and Ga-68 DOTATATE PET/CT was performed. The results
Gestational diabetes can be of type 1 diabetes due to islet cell antibodies and not
did not show an evidence of insulinoma. Intra-arterial calcium stimulation test
only type 2 diabetes due to increased insulin resistance
was also performed to rule out insulinoma but the results were inconclusive. Anti-
Keywords
insulin antibody test was performed for the differential diagnosis and it was
Pregnancy; Gestational diabetes; anti-islet cell antibodies; Type
1 diabetes;
positive. The symptoms associated with low glucose levels and high serum insulin
Type 2 diabetes; Insulin resistance
levels along with positive anti-insulin antibody lead us to the diagnosis of insulin
DOI: 10.1530/endoabs.49.EP425
autoimmune syndrome. According to the current literature suggesting the
relationship between insulin autoimmune syndrome and alpha lipoic acid and
proton pump inhibitors we discontinued that drugs and started alpha glucosidase
treatment and nutritional management. During the follow up the patient did not
report a hypoglisemic episode.
Conclusion
EP426
Insulin autoimmune hypoglycemia is a rare cause of endogenous hyperinsuli-
A retrospective analysis of the impact of new diagnostic criteria for
nemic hypoglycemia. It is a condition that should be kept in mind in patients who
gestational diabetes mellitus on the endocrinology service at a tertiary
have very high levels of insulin and who can not detect a specific focus through
hospital
imaging modalities.
Thaw Dar Htet1, Alice Lam2, Iouri Banakh2, Rumes Sriamareswaran1,
DOI: 10.1530/endoabs.49.EP427
Samuel Wu1, Jasmina Felsinger1, Kati Mattheisson3 & Elisabeth Nye1
1Department of Medicine, Peninsula Health, Melbourne, Australia;
2Department of Pharmacy, Peninsula Health, Melbourne, Australia;
3Department of Endocrinology, Peninsula Health, Melbourne, Australia.
EP428
Background
Incidence estimate of type 1 Diabetes in Youth in Dhaka
The prevalence of gestational diabetes mellitus (GDM) may increase with the
Ana Balsa1, Bedowra Zabeen2, Graham Ogle3, Samin Tayyeb2 &
implementation of revised diagnostic criteria
(as recommended by the
Kishwar Azad4
International Association of the Diabetes and Pregnancy Study Groups) aimed
1Serviço de Endocrinologia Centro Hospitalar Baixo Vouga, Aveiro,
at identifying pregnancies at increased risk of adverse perinatal outcomes. There
Portugal;2Department of Changing Diabetes in Children, Bangladesh
are clear implications for health-care services in terms of resources and the
Institute of Research and Rehabilitation of Diabetes, Endocrine and
associated cost-benefit relationship. Our study analysed the impact on clinic
Metabolic Disorders, Dhaka, Bangladesh;3International Diabetes
visits, the initiation of insulin treatment and fetal and maternal outcomes.
Federation Life for a Child Program, Sydney, Australia;4Bangladesh
Methods
Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh.
A retrospective cohort study was conducted. The medical records of patients with
GDM referred to Diabetes in Pregnancy Clinic were reviewed, comparing two
12-months periods: March 2012 to February 2013 (period 1) and March 2015 to
Introduction
February 2016 (period 2), before and after implementation of the new criteria.
Analysis of epidemiologic patterns in diabetes helps with understanding of
Maternal and fetal outcomes were analysed for six months of each period.
etiology, natural history and current and future needs. Bangladesh is a low-
Results
middle-income, densely populated country where there is limited information
165 GDM patients attended the clinic in period 1 vs 323 patients in period 2.
regarding incidence of childhood diabetes.
Insulin treatment increased significantly in period
2, from
34.2
to
53.1%
Aim
(PZ0.002). The mean number of Endocrinologist consultations (government
To assess the type of diabetes in children and young adults in Dhaka, Bangladesh,
billed) increased from 3.6 to 4.2 (PZ0.006) and with a Diabetic Educator from
from July 2011 until June 2016, and estimate minimum incidence of type 1
1.6 to 1.8 (PZ0.006). The rate of caesarean sections (CS) in patients with GDM
diabetes (T1D).
increased from 31.1% in period 1-47.0% in period 2 (PZ0.038). The number of
Methods
neonates grouped as “Small for Gestational Age” (SGA) increased in insulin-
Retrospective study using clinical records from Diabetic Association of
treated patients in period 2 vs period 1 (17 vs 0, P!0.001) but the number of
Bangladesh (BADAS) clinics in Dhaka and affiliated satellite centers in other
“Large for Gestational Age” neonates was similar (6 vs 5, PZ1).
districts. Subjects under
25 years
(y) diagnosed in the study period were
Conclusion
identified. Diabetes type was classified according to clinical evaluation.
The new GDM diagnostic criteria have impacted on existing health-care
Demographic information was obtained from the 2011 population census and
resources with a corresponding increase in costs with minimal evidence of
extrapolated using the estimated growth rate. Incidence was calculated for the
clinical benefits. Hospital systems will need to plan for the increased demands on
area surrounding the main clinics (Dhaka District) to minimize any ascertainment
pregnancy-related diabetes services.
bias.
DOI: 10.1530/endoabs.49.EP426
Results
Were identified 2347 subjects. Type of diabetes was more fully characterized for
those !18 years (1634 cases), and showed 1437 (87.9%) T1D, 151 (9.2%) type 2,
23 fibrocalculous pancreatic diabetes (1.4%), 5 (0.3%) neonatal, 18 (1.1%) other
types. For T1D incidence estimation a total of 526 subjects were ascertained. The
mean Dhaka district incidence rate for subjects !25 y was 1.24/100 000 per y
EP427
(males 0.92, females 1.71) and 0.96/100 000 for !15y (males 0.63, females 1.55)
Insulin autoimmune syndrome-a case report
. By age group, incidence/100 000 was 0.27 (0-4y), 0.60 (5-9y), 2.46 (10-14y),
Elif Sevil Alaguney, Belgin Efe, Goknur Yorulmaz, Berat Acu &
1.86
(15-19y), 1.44 (20-24y). No secondary ascertainment could be done, but
Insaf Durmus
ascertainment in Dhaka Division was estimated to be at least 95%.
Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey.
Discussion
The support to BADAS by the Changing Diabetes in Children and IDF Life for a
Child Programs have centralized care and permitted tracking of diabetes cases in
Introduction
young people in Bangladesh. T1D is commonest, but other forms occur which
Hypoglycemia is a medical emergency that can have many different causes in
could benefit from different management: further typology studies are warranted.
etiology. Autoimmune hypoglycemia in patients with very high insulin levels
T1D had a female preponderance. Peak T1D onset is at 10-14 y, as in developed
should also be considered in the differential diagnosis.
nations.
Case
A 50-year-old man was admitted to our clinic for investigation and treatment of
DOI: 10.1530/endoabs.49.EP428
hypoglycemic episodes. He did not have any evidence for the use of oral
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP429
EP431
Is thiol/disulfide homeostasis related to parity and gravidity in
Vascular dementia and type 2 diabetes: incidence and outcomes in
gestational diabetes?
elderly patients in a ten year study
Faruk Yildiz1, Cemile Bicer2, Mahmut Senyurt1, Murat Alisik3
Nuria Mu
˜ oz-Rivas1, Francisco Javier del Can˜ izo-Gómez1,
& Ayse Carlioglu1
Manuel Méndez-Bailón2, Ana López-de Andrés4, José María de
1Regional Training and Research Hospital, Erzurum, Turkey;2Faculty of
Miguel-Yanes3, Valentín Hernández-Barrera4, Javier de Miguel-Díez3
Medicine, Yildirim Beyazit University, Ankara, Turkey;3Ataturk Training
& Rodrigo Jiménez-García4
and Research Hospital, Ankara, Turkey.
1Hospital Universitario Infanta Leonor, Madrid, Spain;2Hospital Clinico
san Carlos, Madrid, Spain;3Hospital Universitario Gregorio Mara
˜ ón,
Madrid, Spain;4Universidad Rey Juan Carlos, Madrid, Spain.
Purpose
The purpose of this study was to evaluate the relation gestational diabetes mellitus
(GDM) and the thiol/disulfide balance, used as a marker of oxidative stress, by
Background
measuring that exchange using a novel technique.
To describe trends in the incidence and outcomes for vascular dementia in elderly
Material/Methods
patients with and without type 2 diabetes (T2DM) in Spain between 2004 and
Thirty one subjects diagnosed with GDM and 30 healthy pregnant women were
2013.
included in the study. Thiol/disulfide homeostasis concentrations were measured
Methods
by a newly developed method in this study. After native thiol, total thiol and
We used National Hospital Discharge Data to select all patients aged 70 years or
disulfide levels were determined; measures such as disulfide/ native thiol,
over discharged from hospital with a vascular dementia primary diagnosis.
disulfide/total thiol, and native thiol/total thiol were calculated.
Discharges were grouped by diabetes status (T2DM or non-diabetic). Incidence
Results
was calculated overall and stratified by diabetes status and age groups. We
Fasting blood glucose (FBG) levels (P!0.001), 50-g glucose load values (OGTT
analyzed diagnostic and therapeutic procedures, patient comorbidities, infectious
50)
(P!0.001), parity (0.002) and gravidity (PZ0.005) were significantly higher
complications, length of hospital stay and in-hospital mortality (IHM).
and native thiol (P!0.001) and total thiol levels (P!0.001) were significantly
Results
lower in patients with GDM compared to control subjects. We found negative
We identified a total of 170.607 admissions for vascular dementia (34.3% with
correlations between native and total thiols and FBG and OGTT 50. Parity and
T2DM). The adjusted incidence was higher among people with T2DM over the
gravidity had a significantly negative correlation between the disulfide, the
study period. We found a higher incidence in men than women in all years
disulfide/native thiol ratio, the disulfide/total thiol ratio, had a positive correlation
studied. T2DM was positively associated with vascular dementia hospitalization
between the native thiol/total thiol ratio. Low native thiol and total thiol levels in
(IRR 2.14, 95% CI). Mean age at admission was higher than 80 years for all
patients with GDM were found to be independent of age, gestational weeks and
groups and more than 70% has a Charlson Comorbidity Index (CCI) R2.
bmi in multivariate regression analyse.
Pneumonia was significantly associated with a higher mortality (OR: 2.59; 95%
Conclusion
CI 2.52-2.67). We found that percutaneous endoscopic gastrostomy (PEG) was
It can be concluded that oxidative stress is increased in patients with GDM, can
associated to lower IHM (OR: 0.37, 95% CI 0.31-0.45) while parenteral nutrition
play a pathophysiological role in the development of GDM and this increase is not
had the opposite effect
(OR: 1.29,
95% CI 1.18-1.41). Diabetes was not
associated age, gestational weeks and bmi. However, studies with larger sample
associated with a higher IHM (OR: 0.99, 95% CI 0.93-1.06). For the entire
sizes are needed in this area.
sample, time trend analyses showed a significant decrease in mortality in patients
DOI: 10.1530/endoabs.49.EP429
admitted for vascular dementia (OR: 0.98, 95% CI 0.97-0.99).
Conclusions
Incidence rates were higher in T2DM patients. Men have significant higher
incidence rates than women. Pneumonia and parenteral nutrition were associated
with mortality while PEG was associated to survival. The presence of diabetes is
not associated with a higher IHM during admission with vascular dementia.
DOI: 10.1530/endoabs.49.EP431
EP430
Endocrine factors associated with postprandial hypoglycaemia in
patients with cystic fibrosis: a pilot study
Yasir Elamin1, Rachel Crowley1,2, ED Mckone1, Patrick Twomey1,2,
Siobhan Hatton1, Julie Martin-Grace1 & S Kearns1
EP432
1St. Vincent’s University Hospital, Dublin, Ireland;2University College
Study of the glycemic control in the hospitalized patient
Dublin School of Medicine, Dublin, Ireland.
Lucía Vera Pacheco2, Lorena Rentero Redondo1, Carles Iniesta Navalón1,
Amparo Meoro Avilés1, María Teresa Gallego García1,
Postprandial hypoglycaemia in patients with cystic fibrosis (PWCF) is frequently
Cristina Del Peso Gilsanz1, María Amparo Egea Valera1,
reported but poorly understood. The aim of this pilot study was to investigate the
Noelia Victoria García-Talavera Espín1 & M. Bienvenida Gómez Sánchez1
aetiology of postprandial hypoglycaemia in PWCF. Serum cortisol, insulin and
1University Hospital Reina Sofía, Murcia, Spain;2University Hospital
C-Peptide were measured at the 2 hour timepoint of the annual glucose tolerance
Rafael Mendez, Lorca, Murcia, Spain.
test in 32 PWCF not known to have CF-related diabetes. Hypoglycaemia was
defined as glucose ! 3.3 mmol/l. Patients were classified as Normal glucose
Objective
tolerance (NGT; nZ17), Post prandial hypoglycaemia (PPH; 6) and Abnormal
To evaluate the degree of compliance of the glycemic objectives in non-critic-
glucose tolerance (AGT; 9-3 CF related diabetes, 4 impaired fasting glucose and
hospitalized patient and determinate the factors associated to the lack of
2 impaired glucose tolerance). There was a difference in insulin level at 2 hours
compliance of the aforesaid objectives.
between groups (PZ0.007, Wilcoxon); subanalysis showed a difference between
Material and method
AGT (mean 48.9 mu/l) and PPH groups (16.6 mu/l)(P 0.003) and between AGT
Retrospective observational study in hospitalized patients during 2014. Adult
and NGT groups (28.4 mu/l) (P 0.015). Of the PPH cases none had symptomatic
patient age
18 or older, who had at least two points of care de glucose
hypoglycaemia. Three PPH cases with cortisol ! 500 nmol/l underwent short
measurements
(capillary blood glucose) during their hospitalization, were
synacthen test (SST); 2 had a cortisol post-SST O 550 nmol/l. One patient
included. By the revising of the computerise-clinic-history, sociodemographic,
showed suboptimal response with a cortisol level at 416 nmol/l and is undergoing
clinic and administrative datum were obtained. The results of the glycaemia were
further investigation. There were no differences between groups in body mass
obtained from electronic devices.
index (median 22.1 kg/m2) or lung function. PPH occurred in 19% of the cohort
Results
and was associated with detectable insulin at the 2 hour OGTT timepoint,
2610 patients were included, 54.6% were men. The average age was 71.9G14.2
suggesting the possibility of dysregulated insulin release. AGT patients had
years old (73.7% older than 65 years old). The 73.5% of the patients were
higher insulin levels than NGT cases, suggesting relative rather than absolute
hospitalized in medical service. The main diagnoses when they were hospitalized
insulin deficiency in this cohort of PWCF.
were related with breathing system (20.1%), circulatory system (18.8%) and the
DOI: 10.1530/endoabs.49.EP430
central nervous system
(11.1%) diseases. The main chronic diseases were
diabetes
(60.9%), Chronic kidney disease
(18.9%), chronic obstructive
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
pulmonary disorder (COPD) (18.4%) and the congestive heart failure (CHF)
EP434
(17.6%). 49846 glycaemia were analysed (95.8% pre-prandial, 2.9% postprandial
The importance of islet antigen-2 and glutamic acid decarboxylase
and
1.3% night-time) with average values of
176.7G73.9 mg/dl,
250.2G
antibodies in proper diagnosis of diabetes mellitus at the age R30 and
108.2 mg/dl and 203.2G95.3 mg/dl respectively (P!0.001). The 66.7% fulfil
!70 years
at least one of both stablished criterion. 43.0% of patients had a pre-pandial
Aiste Kondrotiene1, Evalda Danyte2,3, Rimantas Zalinkevicius3 &
mean glycemic !140 mg/dl, 66.4% of patients had a random blood glucose
Rasa Verkauskiene2,3
!180 mg/dl. No differences in hospital stay among patients with good and poor
1Lithuanian University of Health Sciences, Medical Academy, Kaunas,
glycemic control (11.1G11.2 versus 10.34G9.4 days) (PZ0.081) were found.
Lithuania;2Department of Endocrinology, Kaunas clinics, Hospital of
The factors associated to the lack of compliance of the objectives were diabetes
Lithuanian University of Health Sciences, Kaunas, Lithuania;3Institute of
(OR:5,0[IC95%:
4.1-6.1]), the CHF
(OR: 1.5[IC95%:1.2-1.8]), the COPD
Endocrinology, Medical Academy, Lithuanian University of Health
(OR:1.3[IC95%:
1.0-1.6]) and the urgent hospitalization
(OR:2.1
[IC95%:
Sciences, Kaunas, Lithuania.
1.6-2.8]).
Conclusions
The glycemic control in hospitalized patients is far from adequate although we did
Objective
not find differences in hospital stay between patients with / without good glycemic
Misclassification of type 1 (T1DM) and type 2 diabetes mellitus (T2DM) is quite
control. We need to update the existent insulinization protocol because with the
common and crucial to choice of appropriate therapy. The aim of the study was to
current, the 33.3% of patients do not meet the goals.
evaluate the correspondence of islet antigen-2 (Anti IA2) and glutamic acid
DOI: 10.1530/endoabs.49.EP432
decarboxylase (Anti GAD65) antibodies with clinical diagnosis.
Methods
The Anti IA2 and Anti GAD65 were measured in 583 patients (337 males and 246
females) diagnosed with T1DM or T2DM with not typical manifestation at the
age R30 and !70 years. The data for analysis was collected from medical files.
Results
245
(42.02%) cases had primary diagnosis of T1DM, and 338 (57.98%) - T2DM.
One or both positive antibodies were found in 271 patients (group I), and all
negative in 312 (group II). The mean age at onset of diabetes mellitus was
42.55G9.29 yrs in group I vs. 41.83G8.53 yrs in group II; PZ0.33. One or both
antibodies were found in 141 patients with primary diagnosis of T1DM (odds
ratio (OR) 1.84 (95% CI 1.69-2.01, sensitivity 57.55%), 77 males (OR 0.92 (95%
CI 0.83-1.04, sensitivity 49.01%) and 27 females (OR 6.16 (95% CI 5.34-7.11,
EP433
sensitivity 71.28%). 208 patients with T2DM had negative antibodies (OR 2.56
(95% CI 2.38-2.77, sensitivity 61.54%), 63 males (OR 3.81 (95% CI 3.45-4.22,
Hypoglycaemia: Prevalence and factors associated in the
sensitivity 66.13%), and 67 females (OR 1.61 (95% CI 1.44K1.81, sensitivity
old-hospitalized patient
71.28%).
Lucía Vera Pacheco1, Lorena Rentero Redondo2, Carles Iniesta Navalón2,
Conclusion
María Teresa Gallego García2, Amparo Meoro Avilés2,
The presence of antibodies corresponded to primary diagnosis in 49.01% to
Cristina Del Peso Gilsanz2, María Amparo Egea Valera2, Noelia Victoria
71.28% at the age R30 and !70 years.
García-Talavera Espín2 & Ma Bienvenida Gómez Sánchez2
1University Hospital Rafael Mendez, Lorca,Murcia, Spain;2University
DOI: 10.1530/endoabs.49.EP434
Hospital Reina Sofía, Murcia, Spain.
Objective
To determine the hypoglycaemia prevalence in an old-patient hospitalized and to
stablish the factors associated with its appearance and to study the association
between the hypoglycaemia with the stay in hospital and the mortality during the
hospitalization.
EP435
Material and method
The increase in unsaturated fatty acids is related with an
A retrospective study in which all patients, older than 65 years old that were
hospitalized during 2014 and at least two glycemic control have been realised,
anti-inflammatory profile in the hypothalamus of non-diabetic
were included. By the revising of the computerise-clinic-history, sociodemo-
IRS2-deficient mice
graphic, clinic and administrative data were obtained. The degree of comorbidity
Vicente Barrios1, María Vinaixa2, Laura M. Frago1, Sandra Canelles1,
(Charlson index) was calculated which classified it in three levels: absence,
Ángela M. Valverde3, Jesús Argente1 & Óscar Yanes2
1Department of Endocrinology, Hospital Infantil Universitario Nin˜o Jesús,
moderate and high. The results of the glycaemic were obtained from electronic
Instituto de Investigación La Princesa and CIBERobn, Instituto de Salud
devices.
Carlos III, Madrid, Spain;2Centre for Omic Sciences, Universitat Rovira i
Results
Virgili and CIBERdem, Instituto de Salud Carlos III, Tarragona, Spain;
1924 patients were included, 51,0% were men. The average age was 78,8G7,9
3Alberto Sols Biomedical Research Institute (CSIC/UAM), and CIBERdem,
years old. The 86,8% of the patients were urgent hospitalized and the 74,1% of the
Instituto de Salud Carlos III, Madrid, Spain.
patients were hospitalized in medical services. The main diagnoses when they
were hospitalized were related with breathing system (23,0%), circulatory system
(19,4%) and the central nervous system (11,2%) diseases. The Charlson index
Background
was 5,6G3,6, showing up the 98,4% a high comorbidity. The 8,7% of the patients
IRS2-deficient
(IRS2-/-) mice are considered a good model to analyze the
presented at least one hypoglycaemia episode during the hospitalization, of which
development of diabetes as some of them present an increase in glycemia
the
26,3% presented more than two hypoglycaemia episodes during their
comparable to that observed in diabetes onset in humans, whereas a high
hospitalization.The factors associated to the appearance of any hypoglycaemia
proportion of these mice do not develop diabetes. Energy homeostasis regulation
episode were the hemiplegia (OR:1,7[IC95%:1,0-2,9]), and the chronic kidney
by the hypothalamus can be disturbed by an inflammatory environment, which
disease (OR:1,2[IC95%:1,0-1,4]. The patients hospitalised in medical services
predisposes an individual to the onset of diabetes. Saturated fatty acids induce
had also more hypoglycaemia risk than the ones hospitalized in surgery services.
hypothalamic dysfunction, whereas unsaturated fatty acids mediate several anti-
(OR:1,5[IC95%:1,1-1,4]. The median stay was 11,1 days (range: 3-107), without
inflammatory actions.
finding differences between patients with and without hypoglycaemia (12,1G
Objectives
10,9 versus 11,0G10,4 days; PZ0,181).As for overall mortality was 7.3%, and
Our aim was to determine the pattern of fatty acids in the hypothalamus of non-
no differences between the group of patients with / without hypoglycemia were
diabetic IRS2-/- (ND) and diabetic IRS2-/- (D) mice and its possible association
found (4.2% vs 7.6%; PZ0.108).
with hypothalamic inflammation.
Conclusions
Methods
The hypoglycaemia episodes in elderly patients were low comparing it to the
We studied 18 male mice including controls, ND and D mice. We analyzed
other studies and they were associated with chronic diseases such as the renal
enzymes involved in the generation of NADPH, fatty acid synthesis and
disease and the hemiplegia.Contrary to what you would expect, hypoglycemic
regulation of energy homeostasis by western blotting and pro- and anti-
episodes were not related to mortality or hospital stay.
inflammatory chemokines/cytokines by multiplexed bead immunoassay. Meta-
DOI: 10.1530/endoabs.49.EP433
bolomic studies were performed by proton nuclear magnetic resonance (H-NMR)
after extraction of hypothalamic metabolites in organic solvents.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Introduction
Malic enzyme was increased in ND mice and fatty acid synthase in D and ND,
Gestational Diabetes Mellitus (GDM) has been associated with complications
with a greater increase in ND. Acetyl-CoA carboxylase was inhibited and AMPK
both in the neonate and in the mother; including increased risk of Type 2 Diabetes
activated in D mice, with no changes in ND mice. Among the studied
Mellitus (DM2), obesity, and cardiovascular disease. Fibroblast growth factor 21
chemokines/cytokines, monocyte chemoattractant protein-1, fractalkine and
(FGF21) is a key regulator of glucose and lipid metabolism. Recently, the
interleukin (IL)-2 were increased in D and IL-4 en ND mice. Metabolomic
relationship between FGF21 and metabolic component diseases such as diabetes
studies revealed an increase in the levels of u3-fatty acids, phosphatydil-
mellitus and obesity has been demonstrated. In addition, FGF21 mRNA and
ethanolamine, linolenic acid and MUFA plus PUFA in the hypothalamus of ND
protein levels, as well as soluble levels of this molecule, have been reported to be
mice with respect to controls. A negative correlation of the analyzed metabolites
increased in patients with GDM compared to normoglycemic pregnant women.
with fractalkine and a positive correlation with IL-4 was observed.
Objective
Conclusion
To associate FGF21 serum levels with metabolic profile of patients with GDM.
The favorable hypothalamic lipid profile suggests a beneficial role against
Material and methods
hypothalamic inflammation in non-diabetic IRS2-/- mice.
Twenty patients with GDM and fifteen clinically healthy pregnant women were
DOI: 10.1530/endoabs.49.EP435
included; serum FGF21
levels were determined by ELISA, and glucose,
triglycerides, total cholesterol, HDL, LDL and VLDL values were measured.
Results
Our results shown that serum levels of FGF21 are significantly higher in the group
of patients with GDM compared to the control group (313.72G84.58 vs 116.46G
31.41 pg/mL, PZ0.013). The values of triglycerides, cholesterol and VLDL
EP436
showed a similar behavior between groups; while HDL levels were higher in the
Epidemiological indicators and prevalence of risk factors of diabetes
control group. Serum FGF21 levels positively correlated with triglyceride values
type 2 among the inhabitants of Almaty city and Almaty region of
(rZ0.344, P$0.05) and postprandial glucose (rZ0.356, P$0.05). There was no
Kazakhstan
correlation between total cholesterol, HDL, LDL and VLDL levels and FGF21
Laura Danyarova, Akmaral Tashmanova & Zhanmedet Shyman
levels in our study group.
Scientific-Research Institute of Cardiology and Internal Diseases, Almaty,
Conclusion
Kazakhstan.
The FGF21 molecule may play an important role in the GDM pathophysiology,
since it alters the metabolic profile, both glycemic and lipid, of these patients.
Relevance
DOI: 10.1530/endoabs.49.EP437
The main risk factors for developing diabetes type 2, such as obesity, overeating
and a sedentary lifestyle are common to a variety of chronic non-infectious
diseases.
Purpose of the study
Investigate the source of epidemiological indicators, risk factors for type
2
diabetes based on cross-sectional study of the population of Almaty city and
Almaty region of Kazakhstan.
Methodology
The material for the research were population at the age of 18-69 years living in
EP438
Almaty city and Almaty region. The study was conducted in three stages:
interviews with respondents, physical measurements and laboratory tests.
Site-specific cancer risk in people with type 2 diabetes: Nationwide
Results of the study
population-based cohort study in Korea
Analysis of the survey results on a national basis has revealed a significant
Du-Hyong Cho2, Ju-Young Jang1, Suk Kyeong Kim1, Dong-Lim Kim1
prevalence of diabetes among Russians (15.35%) compared with the Kazakhs
& Kee-Ho Song1
(4.9% r$0.01), with other Asian ethnic groups (10.7%, r$0.05). But compare the
1Konkuk University School of Medicine, Seoul, Republic of Korea;2School
results of Russians with other European nationality (8.3%) and Ukrainians (7.1%)
of Medicine, Eulji University, Daejeon, Republic of Korea.
have not showed significant differences (PO 0.05). The age has been proved as
a significant risk factor in the development of type 2 diabetes, and the ratio is 1:
Background
9
(OR Z9.266), ie in the age group over 45 years the risk of developing type
Many studies indicated an increased cancer incidence and cancer mortality in
2 diabetes increases by 9 times. Genetic inclination of diabetes refers to a group of
subjects with diabetes mellitus. But most of studies have been surveyed in western
the absolute risk of diabetes; the analysis showed that the 271 respondents pointed
countries and have problems in applying the results to Korean. We aimed to
to first-degree relatives with diabetes history, where diabetes occurred in 14.8%.
evaluate the site specific cancer risk of diabetic patients in Korea over 30 years,
The remaining 1304 people had no family history of diabetes, and diabetes among
and investigate causal relationship and temporal relationship by analyzing the
them was 5.8%. The ratio is almost 1: 3 (OR Z2.920). Risk factors, obesity, blood
organ-specific cancer risk in diabetics according to duration.
pressure, concomitant cardiovascular disease, glucose and cholesterol in the
Methods
blood plasma. Comparison of these factors in the groups of respondents with
Using a database provided by NHIS, we conducted a retrospective, population-
diabetes and without diabetes showed significant differences in body mass index
based cohort study for adults over 30 years from January 1, 2005 to December 31,
(BMI), blood pressure, both systolic (SBP) and diastolic (DBP). The values of all
2013. We calculated the hazard ratio (HR) for each cancer by using Cox
parameters in patients with diabetes were significantly higher than in those
regression. And we compared HR for each cancer according the duration of
without diabetes
(P!0.05). The survey revealed that people with diabetes
diabetes divided in to 6month, 6months to 3years and more than 3years to verify
compared with those without diabetes suffer the hypertension 2 times harder,
the possibility of detection bias or reverse causation.
ischemic heart disease - more than 3 times, myocardial infarction occurs 6 times,
Results
stroke - 4 times more often.
The incidence of total cancer per 1,000 Subjects with diabetes was higher than
Conclusion
with non-diabetes group. Hazard ratio(HR) for cancer of pancreas, liver, kidney,
Analysis of risk factors for type 2 diabetes of the population has confirmed the
bladder, colorectum, thyroid, lung, stomach and leukemia were significantly
impact of such factors as race, age and genetic inclination on the prevalence of
higher in diabetes group after adjusted. HR for cervix, endometrium and breast
diabetes.
cancer in female diabetes group were higher than those of non-diabetes group. HR
DOI: 10.1530/endoabs.49.EP436
for laryngeal cancer in male was higher in diabetes group. The total cancer risk
was higher in ! 6 months of diabetes duration (HR 2.03; 95% confidence interval
[95% CI]. 1.99-2.07), whereas the hazard ratio decreased with increasing
duration of diabetes, raging from 1.19 (95% CI, 1.18-1.21) between 6 months and
3 years to 1.12 (95% CI, 1.11 to 1.13) at over 3 years, but remained significantly
EP437
higher than the non-diabetic group. HR for pancreas, liver, colorectum, prostate
and endometrium were higher in diabetes group for entire duration of diabetes.
Association of FGF21 soluble levels with metabolic profile in
When excluding diabetes duration less than
6months, HR for stomach,
Gestational Diabetes patients
colorectum, liver, pancreas, kidney, bladder, thyroid, prostate, endometrium
Cristian A. Saucedo-Toral1, María L. Lazo-de-la-Vega-Monroy1,
and cervix showed similar pattern including diabetes duration less than 6 months.
Martha E. Fajardo-Araujo1, Manuel A. Espinosa-Nava1, Francisco J.
Conclusion
Anaya-Torres2, Lorena del R. Ibarra-Reynoso1 & Yeniley Ruiz-Noa1
Cancer incidence risk increases in T2DM patients, and the phenomenon is more
1Universidad de Guanajuato, León, Guanajuato, Mexico;2Clínica Médica
prominent in short durations, i.e. shortly after diagnosis of diabetes. As the
Campestre, León, Guanajuato, Mexico.
duration increases, incidence risk of cancer varies depending on the site of cancer
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
and patient’s gender. Thus, in diabetes patients, cancer screening should be
metformin during postpartum period were accepted as type 2 DM and were not
individualized regarding duration of diabetes, sex, and the site of cancer.
given OGTT. According to 75 g OGTT; with their basal average being (101.83G
DOI: 10.1530/endoabs.49.EP438
10.77 mg/dl) and 2nd hour glucose average being (124.66G39.53 mg/dl), 11
(34.3%) patients were not diagnosed with diabetes. Thirteen (36.11%) patients
were diagnosed with impaired fasting glucose, three (8.33%) with impaired
glucose tolerance, three (8.33%) with impaired fasting glucose and impaired
glucose tolerance, six (16.67%) with type 2 DM.
Discussion
Our study included pregnant women who had not been diagnosed with DM in the
beginning of their pregnancy who later on were diagnosed with GDM during
EP439
pregnancy. We followed them during their postpartum period. With these results,
Erosio interdigitalis blastomycetica- discrete and early sign for
it is found necessary to follow and evaluate the postpartum period of the patients
diabetes mellitus
diagnosed with GDM during pregrancy with regard to Type II DM progress.
Anca E. Chiriac & Doina Azoicai
DOI: 10.1530/endoabs.49.EP440
University of Medicine and Pharmacy, ‘Grigore T Popa’, Iasi, Romania.
Erosio interdigitalis blastomycetica is a special form candidiasis commonly
seen in the third web space of digits, but can spread to all web spaces.
Diagnosis is clinically suspected in the presence of maceration and
ulceration, erythema, sometimes associated with pain. The main predispos-
EP441
ing condition is chronic maceration (for example in launderers), irritant
Diabetic nephropathy in type 1 diabetes mellitus
chronic agents and prolonged moisture affect skin barrier with subsequent
Ines Barka, Nesrine Chikhrouhou, Amel Maaroufi, Maha Kacem,
colonization of Candida spp. Direct mycological examination and fungal
Molka Chaieb & Koussay Ach
culture certify the diagnosis and exclude similar clinical disorders, mostly
Department Endocrinology, Farhat Hached University Hospital, Sousse,
irritant contact dermatitis and psoriasis. Erosio interdigitalis blastomycetica
Tunisia.
is frequently diagnosed in daily practice especially in diabetes patients. We
present cases series of erosio interdigitalis blastomycetica as initial sign of
undiscovered diabetes mellitus. Suspicion of diabetes should be made in any
case of erosio interdigitalis blastomycetica. Screening for diabetes is
Nephropathy is a serious complication of Type 1 diabetes mellitus (T1DM)
mandatory in case of erosio interdigitalis blastomycetica.
with a grave prognosis after the onset of proteinuria. End stage of renal
DOI: 10.1530/endoabs.49.EP439
disease remains the major cause of excess morbidity and premature
mortality in patients with T1DM. The aims of the present study were to
investigate the prevalence of diabetic nephropathy and to evaluate risk
factors for its development among patients developing T1 DM. Seventy six
patients with T1DM history over 20 years were included in our study. We
analysed the occurrence and risk factors of diabetic nephropathy.
Microalbuminuria and macroalbuminuria were defined as urinary albumin
excretion 31-299 mg and 300 mg, respectively, per 24 h in at least two of
EP440
three consecutive samples, kidney failure was defined as a glomerular
Postpartum Tip 2 DM follow-up after gestational diabetes mellitus
filtration rate (GFR) !30 ml/min/1.73 m. The following risk factors were
Seda Sancak1, Ali Ozdemir2, Kerem Yi
˘it Abacar2, Ayhan C¸ elik3,
considered: sexe, diabetic control
(HbA1c) and duration, hypertension,
Nalan Okurog˘ lu2, Ya¸ar Sertba¸2 & Hasan Aydin4
smoking. A total of 76 patients were enrolled: 43 men and 33 women, the
1Fatih Sultan Mehmet Training and Educational Hospital, Division of
mean age and the mean diabetes duration was 39.9 years G9.5 (24-61
Endocrinology and Metabolism, Istanbul, Turkey;2Fatih Sultan Mehmet
years) and
28.18G5.9 years respectively. During follow-up, persistent
Training and Educational Hospital, Departmant of Internal Medicine,
microalbuminuria developed in four patients (5.3%); macroalbuminuria
Istanbul, Turkey;3Fatih Sultan Mehmet Training and Educational Hospital,
developed in seven patients
(9,2%) and kidney failure in
12 patients
Division of Obstetrics and Gynecology, Istanbul, Turkey;4Yeditepe
(15.8%). the risk of diabetic nephropathy was significantly higher in men
University Hospital, Division of Endocrinology and Metabolism, Istanbul,
than in women (PZ0.012). Our study suggests that several potentially
Turkey.
modifiable risk factors predict the development of nephropathy in type 1
diabetic patients.
Purpose
DOI: 10.1530/endoabs.49.EP441
GDM is defined as any degree of carbonhydrate intolerance that is first diagnosed
during pregnancy. Patients diagnosed with GDM are expected to have
complications such as Type II DM, obesity, hypertension in the long term.
Prevalence of GDM diagnosis during pregrancy changes between 2 and 10%. Our
purpose is to revaluate the OGTT of the patients diagnosed with GDM, with
regard to their postpartum Type II DM progress.
Materials and methods
EP442
450 pregnant women who were not diagnosed with diabetes in the beginning of
Diabetes and smoking: epidemiological study in two ethnic groups
their pregrancy were included to the study, who had consulted to our clinic
Georgios Papadakis1, Thomas Zambelis2, Kostas Konstantopoulos3
between 2012 and 2014. Seventy-two of those quitted the study willingly, 20 of
& Stylianos Chatzipanagiotou4
those quitted during follow-up, 12 of those quitted due to spontaneous abortion in
1STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;2Department of
the first trimester. 346 remaining patients were included to the study. After 75 g
Neurology, Aeginition Hospital, Athens, Greece;3Department of Haema-
OGTT, GDM screening was made to those patients between 24th and 28th weeks
tology, Laikon University Hospital, Athens, Greece;4Department of
of their pregrancy. With 75 g OGTT, 61 patients were diagnosed with GDM.
Medical Biopathology, Aeginition Hospital, Athens, Greece.
They were reevaluated with regard to their postpartum Type II DM progress. But
36 of these 61 patients were made 75 g OGTT. Two of those became pregnant
again, two of those moved out of the city, 21 of those could not be reached; thus,
Objectives
they could not be reevaluated. Among the patients diagnosed with GDM, 29 of
Smoking tobacco is a risk factor for several diseases and has been increasing in
them were followed with diet, four of them with basal and short-acting insulin,
many developing countries. Smoking cessation counseling should be a routine
two of them only with basal insulin, one of them only with short-acting insulin.
component of diabetes care. The aim of the present study was to examine the
Three of those who were followed with diet and one of those who were followed
association between smoking status in two different groups of patients with
with basal and short-acting insulin were followed with metformin during
diabetes: Immigrants from Bangladesh who live in Greece and Greek-born
postpartum period. None of the patients used insulin during postpartum period.
subjects.
Results
Methods
Patients called postpartum in the mean month period 20.82G5.66. Mean age
A total of 166 immigrants with diabetes (122 with Type 2 and 44 with Type 1
average of the patients was 32G5. Postpartum BMI was 29.10G5.47 kg/m2.
diabetes mellitus) from Bangladesh were compared with 123 Greek Caucasian
HbA1c average of the patients was 5.77G0.39%. Four patients who were using
patients (82 with Type 2 and 41 with type 1 diabetes mellitus). Patients from
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Bangladesh had a mean GS.D. duration of 10.34G6.2 years of living in Greece. A
Background
questionnaire was formulated and pilot-tested for the comprehensibility of
Low serum testosterone (LST) is associated with some chronic diseases, changes
questions by both ethnic groups. Interviews were conducted, a physical
in body composition and resistance to insulin. Diabetes is one condition that has
examination followed and blood samples for plasma glucose and HbA1c were
high prevalence of LST.
collected. Demographic characteristics and diabetes-related information was
Objetive
collected.
To determine the prevalence of LST in men with diabetes and its relationship with
Results
age, anthropometric and biochemical data.
A total of 40 (24.1%) patients from Bangladesh and 58 (47.2%) patients from
Material and methods
Greece were smokers, 18 (10.8%) patients from Bangladesh and 37 (30.1%)
A cross-sectional study of 65 men with type 1 and type 2 diabetes was conducted,
patients from Greece reported that they were ex-smokers at the time of
with age ranging from 25 to 73 years. Clinical data was obtained from clinical
examination and interview, whereas 108 (65.1%) patients from Bangladesh and
records, like disease duration, diary insulin dose, retinopathy, hypertension and
28
(22.8%) patients from Greece never smoked
(P!0.001). Patients from
medication. Biochemical parameters evaluated were: total testosterone (TT), free
Bangladesh reported less tobacco use than Greek patients
(5.61G11.91 vs
testosterone (FT), gonadotropins, prolactin, glycated haemoglobin (A1C), urinary
24.77G24.20 pack-years, P!0.001).
albumin/creatinine relation. LST was considered TT !3.0 ng/ml.
Conclusions
Results
Most immigrants reported less tobacco use than native Greeks. Higher education
Mean age was 51.9G19.9 years, 60% had type 2 and 40% type 1 diabetes and the
is associated with less smoking prevalence in both ethnic groups. Patients living
mean disease duration was 15.6G10.2 years. 76.9% had body mass index (BMI)
alone were more likely to smoke than those who live with families. Employed
R25 kg/m2. Twenty-seven patients (41.5%) had LST, 6 (23.1%) in type 1 group
persons had a lower smoking prevalence than unemployed persons in both ethnic
and 21 (53.8%) in type 2. In patients under 40 years-old 5 (26.3%) had LST.
groups. Smoking is associated with higher glucose and HbA1c values in both
In multiple linear regression model TT was associated with BMI (b K0.355,
ethnic groups. From the literature tobacco smoking is related to insulin resistance,
PZ0.005) and age (b K0.255; PZ0.044) and no associations were found with
systemic inflammation, decreased b-cell function and pancreatic inflammation.
FT. However, patients with FT!15 pg/ml had a significantly higher A1C, 8.40G
Understanding some culturally relevant predictors of tobacco use among different
1.71% vs 7.54G1.38% (PZ0.029). BMI R25 kg/m2 was associated an increased
ethnic population might assist health care providers in designing successful
risk of LST (odds ratio (OR): 6.50; 95% confidence interval (CI) 1.33-31.83),
smoking control programs, especially for patients with diabetes.
such as antiplatelet medication (OR: 5.83; CI: 1.40-24.23).
DOI: 10.1530/endoabs.49.EP442
Conclusion
In this sample we found a high prevalence of LST in men with diabetes, similar to
data described in other studies. Age and BMI were correlated with testosterone
levels such as in men without diabetes, and no association was observed with A1C
levels. Only FT! 15 pg/ml was associated with higher A1C. To clarify this
relation, more data is needed.
DOI: 10.1530/endoabs.49.EP444
EP443
Prevalence of hyperglycemia in patients hospitalized in the health area
of cuenca (Spain)
José Pérez-Rodríguez, Lidia Guerra-Navarro, Mubarak Alramadan,
Paula García-Notario, David Martín-Iglesias, Santiago Aranda-Regules
& Dulce Calderón-Vicente
Virgen de la Luz Hospital, Cuenca, Spain.
EP445
Vitamin D and testosterone in diabetes mellitus: cross-sectional
study results
Introduction and objectives
Nelson Cunha1, Leonor Gomes1,2, Diana Martins1,2, Diana Oliveira1,2,
Hyperglycemia is a common problem in hospitalized patients, that increases
Adriana Lages1, Mara Ventura1, Lúcia Fadiga1, Diana Catarino1 &
infections, mortality, costs and the hospital stay. The objective of this study is to
Francisco Carrilho1
know the prevalence of hyperglycemia in our hospital.
1Endocrinology, Diabetes and Metabolism Department, University Hospital
Methods
of Coimbra, Coimbra, Portugal;2Faculty of Medicine of University of
We designed a cross-sectional observational study. We included patients admitted
Coimbra, Coimbra, Portugal.
in the hospital every 3 days in 2 months. We excluded patients younger than
15 years, stays less than
3 days and those of the pediatric, gynecological,
emergency and intensive care services. We collected the data from these patients
Background
the third day of admission and at discharge. We defined hyperglycemia as two or
In the recent years, Vitamin D role has grown in cardiovascular and inflammatory
more capillary glucose values greater than 140 mg/dl.
diseases, and some relations were made with low serum testosterone (LST) levels.
Results
It is equally known that in patients with diabetes, the prevalence of LST is higher.
A total of 328 patients (173 females and 155 males) were included, with a median
Objetive
age of 73 years. The 75% were in medical services and 25% in surgical services.
To determine the prevalence of low levels of vitamin D and its relation with LST
The main reason for admission was infection (26%), followed by organ failure
in men with diabetes.
(12%). 33% (109) patients had hyperglycemia. Of these patients, 71.6% (78) were
Material and methods
known diabetics, while 28.4% (31) were not known diabetics. The median age of
A cross-sectional study of 65 men with type 1 and type 2 diabetes was conducted,
patients with hyperglycemia was 80 versus 68 years old in patients without
with age ranging from 25 to 73 years. Clinical data was obtained from clinical
hyperglycemia.
records, such as disease duration, diary insulin dose, retinopathy and
Conclusions
hypertension. Biochemical parameters were: 25-hydroxi-vitamin-D (25[OH]D),
The prevalence of hyperglycemia in our hospital is higher than another areas,
total testosterone (TT), free testosterone (FT), gonadotropins, prolactin, glycated
probably due to a higher mean age in our population. Almost one third of patients
haemoglobin (A1C). Low levels of 25(OH)D were considered when !30 ng/ml
with hyperglycemia were not diabetic. Therefore hospitalization is an opportunity
(insufficiency
20-29 ng/ml and deficiency!20 ng/ml) and LST when TT
to diagnose and treat adequately these patients.
!3.0 ng/ml.
DOI: 10.1530/endoabs.49.EP443
Results
Mean age was 51.9G19.9 years and the mean disease duration was 15.6G10.2
years, 60% had type 2 and 40% type 1 diabetes. 76.9% had BMI R 25 kg/m2.
Forty-two patients
(64.6%) had low vitamin D levels (40% had 25(OH)D
20-29 ng/ml and 24.6% had 25(OH)D!20 ng/ml). In multiple linear regression
model, low levels of 25(OH)D were associated with triglycerides (b K0.314;
EP444
PZ0.011) and FT (b 0.273; PZ0.03) when adjusted for age, BMI and disease
Testosterone levels in men with diabetes mellitus. What relation?
duration. Men with low levels of vitamin D had significantly lower FT (15.82G
Nelson Cunha1, Leonor Gomes1,2, Diana Martins1,2, Diana Oliveira1,2,
9.53 vs 22.72G10.72 pg/ml; PZ0.013) and higher serum triglycerides (164.1G
Adriana Lages1, Mara Ventura1, Lúcia Fadiga1, Diana Catarino1 &
122.1 vs 104.9G45.2; PZ0.029). Mean A1C was 8.07G1.61% vs 7.48G1.40%,
Francisco Carrilho1
respectively, but was not significantly different (PZ0.250).
1Endocrinology, Diabetes and Metabolism Department, University Hospital
Conclusion
of Coimbra, Coimbra, Portugal;2Faculty of Medicine of University of
In this sample, the prevalence of low levels of vitamin D was similar to data
Coimbra, Coimbra, Portugal.
described in other studies (52-77%). When adjusted for age, BMI and disease
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
duration, these levels of vitamin D were associated with higher serum
Objectives
triglycerides and lower free testosterone, which may indicate the metabolic
T helper1 (Th1) cells were determined to have important roles in the development
effects of this vitamin in patients with diabetes.
of type 2 diabetes (T2D). We aimed to investigate relationship between Th1
DOI: 10.1530/endoabs.49.EP445
cytokines (IFN g, IL-2 and TNF-a) and T2D.
Material and methods
The study included 32 newly diagnosed type 2 diabetic patients (T2DPs) who had
not begun to take antidiabetic agents except from insulin and 30 healthy subjects
(CG) who did not have glucose intoerance (fasting or after glucose load). Serum
IFN-g, IL-2 and TNF-a levels were measured using ELISA method. Serum levels
of those ctokines in T2DPs were compared with those in controls.
Results
EP446
TNF-a levls of T2DPs were higher (P!0.05) than those in controls. There were
The relationship between serum uric acid and insulin resistance and
no differences between the IFN-g and IL-2 levels of T2DPs and controls
sensitivity parameters in Turkish type 2 diabetes mellitus patients
(PO0.05).
Betul Ekiz-Bilir1, Bulent Bilir2, Neslihan Soysal-Atile1 & Gulsah Elbuken3
Conclusion
1Tekirdag State Hospital, Endocrinology and Metabolic Diseases Division,
TNF-a levels increase in T2D. Decreased insulin action in T2D may be due to the
Tekirdag, Turkey;2Namik Kemal University, Medical Faculty, Internal
increased TNF-a levels, since TNF-a has been suggested to down regulate the
Medicine Department, Tekirdag, Turkey;3Namik Kemal University,
tyrosine kinase activity of the insulin receptor.
Medical Faculty, Internal Medicine Department, Endocrinology and
DOI: 10.1530/endoabs.49.EP447
Metabolic Diseases Division, Tekirdag, Turkey.
Summary
Hyperuricemia is associated with glucose metabolism disorders clinically. In this
study, we evaluated the relationship between serum uric acid concentrations and
some insulin resistance/sensitivity parameters in Turkish type 2 diabetes mellitus
patients.
EP448
Methods
Adipocytokines, incretins, insulin resistance and body composition
The anthropometric and laboratory data of 87 type 2 diabetes patients of both
coherence in women with previously diagnosed gestational diabetes
sexes
(35
male,
52
female) were evaluated retrospectively. HOMA-IR
mellitus
(homeostatic model of insulin resistance) and QUICKI (quantitative insulin
Migle Francaite-Daugeliene & Dzilda Velickiene
sensitivity check index) measurements were made by the formulae of [glucose
Lithuanian University of Health Sciences, Kaunas, Lithuania.
(mg/dl)
! insulin (mu/ml)]/405 and 1/[log ins (mu /ml)Clog glu (mg/dl)]
respectively.
Results
Introduction
The mean age of the patients were 54.4G11.2 (minimum 20, maximum 77) years.
Adipose tissue is a major source of adipocytokines. It plays an important role for
The serum uric acid values ranged from 1.7 to 9.6 with a mean of 4.82G1.39.
the development of insulin resistance (IR). Data implicate that incretins enhance
HOMA-IR values ranged from 0.51 to 25.99 with a median of 3.27G2.57.
insulin sensitivity. One aspect of the pathophysiology of gestational diabetes
QUICKI values ranged from 0.25 to 0.43 with a median of 0.32G0.04. There was
(GDM) is IR. The relationship between adipocytokines, incretins and GDM might
a positive and significant correlation between serum uric acid and insulin levels
be closely associated.
(rZ0.301; PZ0.005). There was a negative and significant correlation between
Aim
serum uric acid and A1c and glucose levels
(rZK0.372; PZ0.000 and
To evaluate the coherence of adipocytokines (adiponectin and leptin), incretins
rZK0.313; PZ0.003). The correlation of uric acid to age, diabetes duration and
(GLP-1, GIP), insulin resistance and BMI in women with previously diagnosed
body mass index did not reach statistical significance. Although the correlation of
GDM.
uric acid to HOMA-IR and QUICKI values did not reach statistical significance
Methods
(rZ0.128; PZ0.236 and rZK0.128; PZ0.236), HOMA-IR values increased
We examined 126 women with previously (16-43 years ago) diagnosed GDM.
but QUICKI values decreased with increasing uric acid levels.
BMI, incretins, adipocytokines were evaluated. IR was calculated with HOMA-
Conclusion
IR index. Data expressed as meanGS.D. for parametric data or median (min-max)
Although the correlations did not reach statistical significance, serum uric acid
for non-parametric data. ANOVA was used to compare data between groups of
levels are positively correlated to insulin resistance parameter (HOMA-IR) and
three or more variables. Non-parametric data correlation analysis was performed
negatively correlated to insulin sensitivity parameter (QUICKI) as expected. The
using the Spearman’s correlation coefficient. The results were considered
small sample size of our cohort might be responsible for this statistical
statistically significant at P!0.05.
insignificance. The negative correlation of serum uric acid to glucose and A1c
Results
might be related to increased renal excretion of uric acid together with glucose
Women’s average age was 53.52G8.34 years (39-77 years). The coherence
due to osmotic diuresis. These results must be confirmed with larger studies.
between adipocytokines, incretins and BMI was observed: increased BMI
DOI: 10.1530/endoabs.49.EP446
determined decreased adiponectin (rZK0.361, P!0.01), and increased leptin
(rZ0.838, P!0.01) either incretins concentrations (GIP rZ0.270, PZ0.01 and
GLP-1 rZ0.167, PZ0.21). HOMA-IR was higher in obese women (rZ0.641,
P!0.01). Data analysed in different BMI categories (normal weight/overweight/
obese): adiponectin (26.8(12.2-76.8)/21.4 (10.8-54.4)/17.9 (5.2-41.6), P!0.01),
leptin (5.9(0.2-16.1)/12.5(3.8-122.1)/24.7(11.1-74.9), P!0.01), GIP (0.8(0.2-
2.9)/0.97(0.2-5.2)/1.29(0.2-18.2), PZ0.145), GLP-1
(0.06(0.04-21.7)
/0.06(0.04-6.1)/0.06(0.04-18.2), PZ0.517), HOMA-IR
(2.2(0.5-4.7)/2.5(0.4-
EP447
6.4)/4.6(1.2-27.2), P!0.01). No significance between adiponectin and GIP,
Relationship with T helper 1 cytokines and type 2 diabetes
GLP-1 was defined (rZK0.152, PZ0.156/rZ0.02, PZ0.824). Women with
Havva Gonca Tamer1, Ozge Telci Caklili2, Ilkay Kartal3, Kagan Gungor4
lower adiponectin had higher HOMA-IR (rZK0.22, PZ0.03). The correlation
& Hasan Huseyin Mutlu5
between leptin and GIP, GLP-1, HOMA-IR
(rZ0.3, PZ0.05/rZ0.231,
1Division of Endocrinology and Metabolism, Department of Internal
PZ0.03/rZ0.697, P!0.01) was observed. The positive correlation between
Medicine, Medeniyet University, Goztepe Training and Research Hospital,
GIP, GLP-1 and HOMA-IR (rZ0.388, P!0.01/rZ0.352, PZ0.001) was found.
Istanbul, Turkey;2Department of Internal Medicine, Medeniyet University,
Conclusion
Goztepe Training and Research Hospital, Istanbul, Turkey;3Division of
Adipocytokines and incretins are closely linked to the amount of fat tissue in the
Endocrinology and Metabolism, Department of Internal Medicine,
body: increased BMI correlates with decreased adiponectin and increased
Medeniyet University, Goztepe Training and Research Hospital, Istanbul,
leptin/incretins levels in women with previously diagnosed GDM. HOMA-IR
Turkey;4Division of Endocrinology and Metabolism, Department of
is closely associated with leptin and incretins.
Internal Medicine, Medeniyet University, Goztepe Training and Research
DOI: 10.1530/endoabs.49.EP448
Hospital, Istanbul, Turkey;5Department of Family Medicine, Medeniyet
University, Goztepe Training and Research Hospital, Istanbul, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP449
assays: chromogranin at 10 times normal and Metanephrine at 3.33 times normal,
abdomino-pelvic ultrasound finds a supra-renal mass supplemented by pelvic CT
The coherence of carbohydrate metabolism and metabolic parameters
recovering an oval tissue formation measuring
46.8!36.5 mm Enhancing
(adipocytokines, incretins, insulin resistance) in women with previously
intensely after injection of contrast medium, evoke a pheochromocytoma
diagnosed gestational diabetes mellitus
confirmed by a MIBG scintigraphy which finds a focus of intense hyperfixation
Migle Francaite-Daugeliene & Dzilda Velickiene
of the tracer radio corresponding to a right adrenal neurectodermal tumor of
Lithuanian University of Health Sciences, Kaunas, Lithuania.
52!36 mm. In search of other pathologies coming within the framework of a
multiple endocrine neoplasia the assessment of extension is without anomaly.
Introduction
Patient is programmed in surgery for a management
There is growing evidence that gestational diabetes mellitus (GDM) significantly
Conclusion
increases the risk of adverse consequences, the most significant of which is a
In patients with pheochromocytoma
35% are diabetic, the diagnosis of
predisposition to the development of metabolic syndrome and diabetes mellitus
pheochromocytoma in the diabetic may be responsible for a glycemic imbalance
(DM). The reasons why some women develop DM, while the others not, are still
and this considerably alters the management.
studied. The relationship between various metabolic parameters and GDM might
DOI: 10.1530/endoabs.49.EP450
be closely associated.
Aim
To evaluate the coherence of carbohydrate metabolism and metabolic parameters
(adipocytokines, incretins, insulin resistance) in women with previously
diagnosed GDM.
Methods
We examined 126 women with previously (16-43 years ago) diagnosed GDM.
EP451
BMI was evaluated. Fasting plasma glucose (FPG) was examined for women with
Unacylated ghrelin does not seem to influence glucose homeostasis in
DM. OGTT was performed for carbohydrate metabolism testing for the rest.
obese women
Women assigned to different groups: NG - normal glucose, IFG-IGT - impaired
José Silva-Nunes1,2, Miguel Brito2, Carina Silva2, Ana Oliveira2 &
fasting glucose/impaired glucose tolerance and DM group. Incretins, adipocyto-
Luisa Veiga2
kines were evaluated. IR was calculated with HOMA-IR index. Data expressed as
1Endocrinology Department - Curry Cabral Hospital, CHLC, Lisbon,
meanGSD for parametric data or median (min-max) for non-parametric data.
Portugal;2Research Group in Genetics and Metabolism - Lisbon School of
ANOVA was used to compare data between groups of three or more variables.
Health Technology, Lisbon, Portugal.
Non-parametric data correlation analysis was performed using the Spearman’s
correlation coefficient. The results were considered statistically significant at
P!0.05.
Background and Aim
Results
Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially
Women’s average age was 53.52G8.34 years (39-77 years). Age differed in
considered as a non-functional peptide, soon after UAG has been associated to a
separate carbohydrate metabolism groups (PZ0.001). Carbohydrate metabolism
negative action on energy balance, suppression of hepatic glucose production and
was set for 58%: IFG-IGT for 16.7%, DM for 41.3% patients. The correlation
decrease in circulating levels of insulin. The aim of this study was to analyze the
between adipocytokines, incretins and FPG was evaluated: higher FPG was seen
association between the serum levels of UAG and glucose metabolism parameters
in women with lower adiponectin (rZK0.186, PZ0.037), higher leptin levels
in obese women, independently from the eventual interference of adiposity.
(rZ0.340 P!0.01) as well as incretins concentrations (GIP rZ0.368, P!0.01
Material and Methods
and GLP-1
rZ0.05, PZ0.004) and HOMA-IR (rZ0.656,P!0.01). Data
One hundred lean and 254 obese Caucasian women were studied. Each woman
analysed in different carbohydrate metabolism groups (NG/IFG-IGT/DM): BMI
was characterized for total body weight, body mass index (BMI), waist and hip
(26.7
(18.8-52.2)/27.9
(20.1-52.9)/34.8
(20.5-52.9), PZ0.001), adiponectin
circumferences, glucose at fasting and 2 hours after an oral glucose tolerance test
(21.6
(10.3-76.8)/18.7 (9.9-54.4)/17.7 (5.2-52.9), PZ0.07), leptin (14.7 (0.2-
(OGTT), fasting insulin, glycated hemoglobin
(HbA1c), and UAG. Insulin
74.9)/10.9 (2.2-48.6)/19.6 (1.6-66.3), PZ0.327), GIP (0.8(0.2-12.1)/0.8 (0.2-
resistance was assessed by the homeostasis model assessment (HOMA-IR).
5.2)/0.07 (0.05-21.7), PZ0.416), GLP-1 (0.06 (0.04-16.6)/0.07 (0.04-5.4)/0.07
Obese women were classified in three glycemic status subgroups (normogly-
(0.05-21.7), PZ0.044), HOMA-IR (2.3 (0.5-4.7)/2.4 (1.4-7.2)/4.5 (0.5-27.2),
cemia, prediabetes and diabetes) according to HbA1c and glucose values.
P!0.01).
Results
Conclusion
When compared with the lean group, significantly lower UAG levels were
Age, BMI, adipocytokines, incretins and IR are closely linked to the carbohydrate
observed in obese women when compared with the lean group (350.2G251.9 vs
metabolism: IFG-IGT and DM was more frequently seen in elder overweight/obese
219.2G149.7 pg/ml; P!0.001). However, no significant difference was observed
women, having lower adiponectin, higher GLP-1
concentration and higher
through obesity classes I to III. UAG levels were not significantly different among
HOMA-IR.
glycemic status subgroups and did not show any direct association with glucose,
DOI: 10.1530/endoabs.49.EP449
insulin, HOMA-IR, or HbA1c values.
Conclusions
Although the level of the unacylated form of ghrelin shows an association with
anthropometrics it seems not to be involved in glucose homeostasis.
DOI: 10.1530/endoabs.49.EP451
EP450
Instable diabetes revealing pheochromocytoma
Samir Ait Abderrahmane, Imad Boulmarka, Mounia Chenegreha,
Lila Brakni, Samia Ouldkablia & Brahim Oudjit
HCA, Kouba, Algeria.
EP452
Influence of a part of Korean red ginseng on blood glucose control and
complication markers of type 2 diabetic NSY rats
Introduction
Jung Hye Kim, Kahui Park, Sang Bae Lee, Ji Hong You, Yusik Kim,
Pheochromocytomas are secreting tumors, producing catecholamines (dopamine,
Jong Suk Park, Ji Sun Nam & Chul Woo Ahn
noradrenaline and adrenaline), responsible for arterial hypertension; Pheochro-
Gangnam Severance Hospital, Seoul, Republic of Korea.
mocytoma in the diabetic may be responsible for an unbalanced glycemic and this
considerably modifies the management. We present the case of a patient for whom
the diagnosis of pheochromocytoma was posed before a glycemic imbalance.
Objective
Clinical case
Ginsenoside or saponin, is considered as the major bioactive component
A 70-year-old patient is hospitalized for unexplained unstable diabetes mellitus
mediating the therapeutic properties of Korean red ginseng (KRG). However,
(Several episodes of severe hypo-hyperglycaemia per week with a 7.5% Hba1c. It
the exact physiological mechanism underlying anti-diabetic effects is still not
is diabetes mellitus evolving for 20 years, marked by instability of glycemic
fully Clarified. More than 30 different saponins together account for only about
figures For
3 years, during his hospitalization for management of severe
3-4% of KRG, thereby, it is assumed that non-saponin fraction of KRG also carry
hypertension was discovered associated with headache and slimming.Infectious
potential anti-diabetic effects; however, there is no study reporting the
and inflammatory balance without anomaly, no lipodystrophy, in search of
differentiated effects of saponin and non-saponin fractions of KRG on glycemic
endocrinopathy responsible for this hypertension and unstable diabetes Biological
indications and hyperglycemia-associated complication markers.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
adressin MAdCAM-1, chemokine receptors CXCR4 and CCR7. Sphingosine-1-
12-week-old male Nagoya-Shibata-Yasuda (NSY) mice were allocated into 4
phosphate receptors S1PR1 activate T-cell exit from MLN.
groups: control group given standard rodent diet (SRD) or treatment groups given
Methods
either Korean red ginseng extract (KRG), saponin fraction from KRG extract
We use RT-PCR method for investigating of mRNA expression levels of genes
(Spn) or non-saponin fraction from KRG extract (NSpn) admixed in SRD. The
MAdCAM-1, CXCR4, CCR7 and S1PR in MLN of the offspring of rats with
targeted administration doses of KRG, Spn and NSpn were all 200 mg/kg/day; all
experimental gestational diabetes. To determine the level of target genes was
mice were fed assigned regimens for 24 weeks. Parameters for glycemic control,
performed RT-PCR in real-time by thermocycler CFX96e Real-Time PCR
blood lipid profile, inflammation, oxidative stress, and anti-oxidant enzymatic
Detection Systems. The relative level of gene expression were studied with rat
activities were measured.
reference genes GAPDH by the methodDDCt. Statistical analysis were conducted
Results
using available software «Bio-Rad CFX Manager 3.1» (Bio-Rad, USA).
KRG had positive effects on glycemic control by attenuating the increase in FBG
Results
at 24-week and by increasing glucose clearance and insulin response during i.p.
Expression analysis of homing receptors in MLN revealed an expected significant
GTT as compared to control. KRG also attenuated increases in TNF-a, oxidized
increasing of CCR7 and MAdCAM-1 mRNA in offspring of animals with EGD,
LDL (oxLDL), advanced glycation end-products, and accumulation of
indicating the activation of the immune cells in the GALT, which is accompanied
malondialdehyde in skeletal muscle. Spn had a positive effect on insulin response
by intensification of lymphocytes homing and confirms the involvement of these
while NSpn attenuated oxLDL as compared to control.
receptors in the pathogenesis of diabetes. We were unable to detect changes in the
Conclusion
mRNA levels of another regulator - CXCR4 in MLN of the offspring of rats with
This study showed that anti-diabetic properties of KRG are not mainly mediated
EGD. Increased expression level of S1PR1 mRNA of MLN lymphocytes in the
by saponin, but the therapeutic potentials of KRG may be due to the orchestral
offspring of animals with diabetes confirms its important role in the progression of
effects of both saponin and non-saponin.
diabetes.
DOI: 10.1530/endoabs.49.EP452
Conclusions
Signals of chemokine receptors affect the activation of different Th cells subsets
and we may assume their pivotal role in the development of autoimmune diseases,
particularly diabetes mellitus. The revealed changes evidence of abuse of
formation of peripheral immunological tolerance and can trigger the development
of AID in the offspring of mothers with EHD.
DOI: 10.1530/endoabs.49.EP454
EP453
The prevalence of diabetic neuropathy, painful diabetic neuropathy and
the at risk diabetic foot in Qatar
Tarik Elhadd1, Georgios Ponirakis2, Khaled Ashawesh1, Khaled Dukhan1,
Adel Badie Abou Samra1 & Rayaz Malik1,2
1Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;
2Weil Cornell Medical College, Doha, Qatar.
EP455
Study of expression of genes mTOR, Foxp3, IL1b and IL17A in
Objective
parapancreatic adipose tissue of rats with streptozotocin-induced
To define the prevalence of Diabetic Peripheral Neuropathy (DPN), painful
diabetes and after metformin administrations
diabetic neuropathy (PDN) and the at risk diabetic foot in 2 out of the 3 National
Denis Putilin, Alex Kamyshny & Vita Kamyshna
Diabetes Centres in Qatar.
ZSMU, Zaporozhye, Ukraine.
Methods
712 people with Type-1 & Type-2 diabetes recruited from Alwakra Hospital and
Introduction
Hamad General Hospital underwent assessment for DPN & PDN using the
mTOR is not only a central regulator of lipid metabolism, controlling the
Neurothesiometer and the DN4 questionnaire, respectively.
processes of adipogenesis and lipolysis, but also a regulator of immunometabo-
Results
lism of immune cells infiltrating the adipose tissue. In its turn, the level of
The average age, duration of diabetes, systolic BP, BMI, HbA1c were: 52.2G
progression of diabetes is largely limited by Treg subpopulation, the complexity
0.49, 10.8G0.32 years, 132.6G1.26 mmHg, 32.2G0.52 kg/m2 and 8.3G0.11%,
and heterogeneity of which is confirmed by the detection of numerous tissue-
respectively. The prevalence of DPN and PDN were 31% and 36%, respectively.
specific Tregs, including the so-called VAT Tregs (visceral adipose tissue CD4C
However, 4 in 5 adults with DPN and 9 in 10 adults with PDN were undiagnosed.
Foxp3C regulatory T cells). Therefore, the purpose of the work was to find out
One in ten adults with diabetes were at high risk for diabetic foot ulceration (VPT
the level of expression of mRNA genes of mTOR, Foxp3, IL1b and IL17A in
O25) and had not been diagnosed. Patients with DPN were significantly older
parapancreatic adipose tissue of rats with experimental streptozotocin-induced
(57.1G0.73
v 49.8G0.62, P!0.0001), had a longer duration of diabetes
diabetes after introduction of metformin.
(14.34G0.57 v 9.1G0.36, P!0.0001), higher systolic blood pressure (139.8G
Methods
2.25 v 129.2G1.46, PZ0.001) and higher creatinine (118.6G16.76 v 70.9G2,
We use RT-PCR method for investigating of mRNA expression levels of genes
PZ0.007), but no difference in HbA1c (8.6G0.21 v 8.2G0.13), vitamin D
mTOR, Foxp3, IL1b and IL17A. To determine the level of target genes was
(23.7G1.7 v 23.3G0.9) or B12 (344.7G39.17 v 323G21.3).
performed RT-PCR in real-time by thermocycler CFX96e Real-Time PCR
Conclusion
Detection Systems. The relative level of gene expression were studied with rat
The overall prevalence of DPN, PDN and those at risk of foot ulceration in Qatar
reference genes GAPDH by the methodDDCt. Statistical analysis were conducted
are comparable to that reported in Europe and the US. However, an alarmingly
using available software «Bio-Rad CFX Manager 3.1» (Bio-Rad, USA).
low proportion of patients are diagnosed and treated for DPN and PDN. There is a
Results
need for a systematic screening for DPN and PDN in Qatar. Age, duration of
the development of diabetes causes the transcriptional activation of the gene of
diabetes, blood pressure and high creatinine are risk factors for DPN.
the protein kinase mTOR, does not affect the expression of mRNA of Foxp3,
DOI: 10.1530/endoabs.49.EP453
increases the level of expression of mRNA of proinflammatory cytokines IL1b
and IL17A. At the same the introduction of metformin in diabetic rats inhibits the
expression of mRNA of mTOR and increases the level of transcriptional activity
of the gene Foxp3 in parapancreatic adipose tissue.
DOI: 10.1530/endoabs.49.EP455
EP454
Changes in gene expression MADCAM1, S1PR1, CXCR4 and CCR7 in
offspring of rats with experimental gestational diabetes
EP456
Tanya Prozorova, Alex Kamyshny & Vita Kamyshna
Response to stroke in diabetic versus non-diabetic patients. Should
ZSMU, Zaporozhye, Ukraine.
Diabetes education systematically include advise on stroke symptoms
and the correct response to them?
Introduction
Paloma González-Lázaro1, Julia Silva-Fernández1, Rafael García-Ruiz2,
Mesenteric lymph nodes (MLN) is a major transition point for recirculating
Rosa García-Ruiz3, Francisco Javier Gómez-Alfonso1, Florentino Del
lymphocytes of GALT. Homing of lymphocytes in MLN is regulated with
Val-Zaballos1, Belvis Torres-Arroyo1 & Carolina González-Pereira4
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Endocrinology Service. Mancha Centro Hospital, Alcázar de San Juan,
Conclusion
Spain;2Neurology Service. Manca Centro Hospital, Alcázar de San Juan,
This study showed no association between the rs1746661
and rs3480
Spain;3Internal Medicine, Marina Salud Hospital, Denia, Spain;4Unit Care
polymorphisms and GDM; however, the rs1746661T mutated allele seems to
Department, Hospital Universitario central de Asturias, Asturias, Spain.
be associated with increased SBP in pregnant women independently of GDM.
DOI: 10.1530/endoabs.49.EP457
Introduction
Stroke is the second cause of death in the world and the first cause of disability. It
is also the second cause of Diabetes-related death. The success of reperfusion
therapies is time-dependent, with most delays being patient-related. We
investigated the response to stroke in diabetic patients (DM), as their risk of
stroke is increased by 1,8-6 times.
Material and Methods
EP458
Consecutive patients with acute stroke or transient ischemic attack were
The relations of apelin with the carbohydrate metabolism in
prospectively included. Sociodemographic and clinical data, time from stroke
hypertensive patients with type 2 diabetes or without it
onset to decision to seek medical attention (Decision delay (DD)) and to hospital
Sergiy Koval, Kostiantyn Iushko & Tatyana Starchenko
arrival (Prehospital Delay (PD)) and first medical contact (FMC) were obtained.
L.T.Malaya Therapy National Institute of the NAMS of Ukraine, Kharkiv,
Decision to call the 112 Emergency Services (112-ES) within the first 15 min was
Ukraine.
considered the correct decision.
Results
Purpose
382 patients were included. 138 (36,1%) were diabetic. DD was ! 15 min in 41
The aim of the study was to evaluate the relationships of apelin with the
(29,7%) DM vs 57 (23,4%) non-diabetic patients (non-DM) (PZ0,17). FMC was
parameters of the carbohydrate metabolism in hypertensive patients with type 2
112-ES in 20 (14,5%) DM vs 50 (20,5%) non-DM (PZ0,14), and a correct
diabetes (T2D) and without T2D.
decision was made in 13 (9,4%) DM vs 32 (13,1%) non-DM (PZ0,28). PD was
Methods
!60 min in 14 DM vs 29 non-DM. No significant differences were found after
The study involved 93 patients with hypertension grades 2-3 combined with T2D
adjustment for potential confounders.
or without it (45 men and 48 women) in age from 43 to 70 years old. The
Conclusions
investigation complex included measuring levels of fasting blood glucose, fasting
Response to stroke symptoms in DM was not different to non-DM, while carrying
blood insulin with insulin resistance index calculation
(HOMA), glycated
a greater load of vascular risk factors and a higher risk of stroke. Even more,
hemoglobin (HbA1c). The blood level of apelin was tested using an Enzyme-
although not significant, the use of the 112-ES was quite lower in DM. We
linked immunosorbent assay. Two groups of patients were formed:
1.
propose to systematically incorporate information on stroke risk, symptoms,
hypertensive patients with T2D (nZ63), 2. hypertensive patients without T2D
consequences and how to respond to stroke into DM education.
(nZ30). The control group consisted of 14 practically healthy volunteers.
DOI: 10.1530/endoabs.49.EP456
Results
The levels of apelin in both groups were significantly lower than in control group
-
0,882(0,788;0,924) ng/ml in hypertensive patients with T2D and
0,886(0,846;0,937) ng/ml in hypertensive patients without T2D versus
1,097(0,944;1,171) ng/ml in healthy volunteers
(P!0,001
and P!0,01
respectively). The significant difference in apelin levels between patients with
T2D and without T2D has been not found (PO0,05). The hypertension patients
with T2D had significant negative correlations of the apelin with HbA1c
(rZK0,45, P!0,05), insulin (rZK0,48, P!0,05) and HOMA (rZK0,47,
P!0,05). The patients without T2D had significant positive correlations of
the apelin with insulin (rZ0,71, P!0,001) and HOMA (rZ0,76, P!0,001). The
EP457
levels of apelin were significantly higher in the patients without T2D, but with the
The T allele of the rs1746661G/T polymorphism in FNDC5 (irisin) gene
insulin resistant
(HOMAO2,77), than in patients without T2D and normal
is associated with increased systolic blood pressure
HOMA - 0,937(0,916;1,112) ng/ml versus 0,851(0,839;0,884) ng/ml, P!0,001.
Leticia A. Brondani, Ana Paula Bouças, Tais S. Assmann, Angela
Conclusion
J. Reichelt, Sergio Martins-Costa, Leticia S. Weinert, Sandra P. Silveiro,
The presented data are confirmed the compensatory increasing of the antidiabetic
Bianca M. de Souza & Daisy Crispim
apelin factor in the initial manifestations of carbohydrate metabolism disorders
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
and its subsequent decline is associated with the development of the T2D.
DOI: 10.1530/endoabs.49.EP458
Background
Gestational diabetes mellitus (GDM) is a risk factor for type 2 diabetes and both
conditions are characterized by insulin resistance (IR) and decreased insulin
production by pancreatic beta-cells. FNDC5 gene encodes a type I membrane
protein that is proteolytically processed to form a hormone secreted into the
blood, termed irisin. After induction by exercise, irisin activates profound
changes in the subcutaneous adipose tissue, stimulating browning and UCP1 gene
EP459
expression. This causes a significant increase in total body energy expenditure
Maturity-onset diabetes of the young type 5 (mody 5): a case report
and resistance to obesity-linked IR. Studies have shown that circulating irisin is
Carlos Silva Vaca, Elena García Fernandez, Juan Carlos Romero Rodriguez
decreased in women with GDM and the FNDC5 gene is also expressed in the
& Guillermo Martinez
human placenta. Thus, genetic variants in FNDC5 gene may be associated with
Hospital Universitario 12 de Octubre, Madrid, Spain.
DGM.
Objective
To evaluate if the polymorphisms rs3460A/G and rs1746661G/T in the FNDC5
Introduction
gene are associated with GDM and/or its clinical features.
MODY 5 is a rare type of dominantly inherited diabetes mellitus. It is asociated
Methods
with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene. They
We analyzed 132 pregnant women without GDM (controls) and 219 pregnant
are mostly missense mutations that produce truncated proteins with a variable
women with GDM (cases). Polymorphisms were genotyped by Real-Time PCR
clinical spectrum that encompasses among others: kidney, genital and pancreatic
using TaqMan MGB probes. Haplotypes constructed from the combination of
abnormalities.
rs1746661 and rs3480 polymorphisms were inferred using the Phase 2.1 program.
Case-report
Results
A 35 years-old man without relevant medical history, presented with acute
Genotype and allele frequencies of the rs1746661 and rs3480 polymorphisms did
hypergycemia (541 mg/dl) and ketosis but wihout metabolic acidosis. He had had
not differ significantly between cases and controls (PO0.05). The haplotype
cardinal symptoms for a 2-week period before presentation. Further investigation
frequencies also did not differ between the two groups (PZ0.913). Interestingly,
revealed a diagnosis of early onset diabetes in his mother, three siblings and a
patients carrying the T allele of the rs1746661 polymorphism had higher values of
niece who also had undergone nephrectomy due to polycystic kydney disease.
systolic blood pressure (SBP) than patients with the A/A genotype (127.2G18.7
Laboratory workout revealed acute renal injury
(MDRD4 57.2 ml/min per
vs 122.9G17.3 mm/Hg; PZ0.004), adjusting for the use of antihypertensive
1.73 m2) and elevated liver enzymes with a cholestatic pattern (Gamma-GT
medications.
74U/l; Alkaline Phosphatase 154 U/l; Bilirrubin 1.7 mg/dl), both resolved before
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
discharge. No other abnormalities were detected. Abdominal US was normal.
malnutrition and sarcopenia were different in diabetic patients compared with the
During hospitalization, the patient progressively achived adecuate glucose and he
group of non-diabetics.
was discharged with a basal-bolus insulin regimen, pending on the results of
Methods and material
pancreatic autoimmunity, and the performance of a magnetic cholangioreso-
A total of 312 institutionalized elderly people volunteers with a mean age of O65
nance. During follow-up the patient showed no evidence of islet-cell antibodies
years were selected, being
207 women and 105 men. They had preserved
nor glutamic acid decarboxylase autoantibodies (Anti GAD65 0.46 IU/ml, Anti
functional capacity and absence of cognitive impairment. Anthropometric
IA2 2.13 U/ml, anti insulin 0.51 U/ml), a C- peptide of 237 ng/ml and the
variables were measured, test of physical performance were carried out and
magnetic cholangioresonance that revealed aplasia of the dorsal pancreas. The
muscle mass was determined by bioelectrical impedance analysis (BIA). For the
diagnosis of MODY 5 diabetes was made after a genetic study for detecting HNF-
diagnosis of sarcopenia, the criteria recommended by the European Working
1beta gene mutations confirmed a missense mutation (M_000458.2:c.884GOA -
Group on Sarcopenia in Older People (EWGSOP) were used, which consist of
p.Arg295His-) in the DNA-binding homeodomain. The insulin was progressively
using the presence of both low muscle mass and low muscle function (strength or
withdrawn and metformin was introduced.
performance), and the method to evaluate if the patients had malnutrition was the
Conclusion
Mini Nutritional Assessment test.
MODY 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-
Results
1B is warranted in young patients with an AD pattern family history of diabetes
The prevalence of type 2 diabetes mellitus in this population was 21.15%, being
particularly when pancreatic atrophy, kidney or genital abnormalities are present.
57.6% of them women and 42.4% men (P 0.089). There were statistically
DOI: 10.1530/endoabs.49.EP459
significant differences in the variables age, weight, BMI, arm circumference,
tricipital skinfold and abdominal circumference, between diabetic and non
diabetic people, being all this variables higher in the diabetic group. According to
the results of the MNA test, the prevalence of malnutrition in the diabetic group
was of 52.2%, while in non diabetic people was 44% (P!0,05), and with regards
to the prevalence of sarcopenia, there were statistically significant differences
between the non diabetic group, in which the prevalence of sarcopenia was
27.3%, and diabetic people, with a higher prevalence (36.58%).
EP460
Conclusion
New-onset diabetes after transplantation (NODAT): an evaluation of
The prevalence of type 2 diabetes was 21.15%, which was higher in women than
risk factors in renal transplantation
in men, without statistically significant differences. Moreover, there were
Raquel Almeida, Andreia Campos, La Salete Martins & Jorge Dores
significant differences in the anthropometric parameters evaluated and the
Centro Hospitalar do Porto, Porto, Portugal.
prevalence of malnutrition and sarcopenia was higher in the diabetic group.
DOI: 10.1530/endoabs.49.EP461
Background
The identification of patients with high risk of diabetes mellitus (DM) after renal
transplantation in the pre-transplantation period is crucial for the prevention of
this pathology and reduction of the risk of cardiovascular morbidity and mortality.
With this study we intended to identify the risk factors for NODAT in renal
transplantation.
EP462
Methods
All patients submitted to renal transplantation at Centro Hospitalar do Porto
New onset diabetes after transplantation (NODAT): frequency and
between 01/01/2009 and 12/31/2013 were retrospectively evaluated. Patients with
characterization of patients in renal transplantation
history of DM, transplantation of more than one organ, younger than 18 years at
Raquel Almeida, Andreia Campos, La Salete Martins & Jorge Dores
transplantation, and patients with less than 6 months of follow-up were excluded.
Centro Hospitalar do Porto, Porto, Portugal.
DM was defined according to WHO criteria. To identify risk factors for DM, two
groups were formed: people with diabetes (DMC) and without diabetes (DMK).
Background
Results
The identification of patients with NODAT in renal transplantation is essential to
Of the 556 patients undergoing renal transplantation, 247 patients were excluded
establish adequate treatment and to reduce cardiovascular risk and graft failure.
and 309 patients were eligible for the analysis. A total of 68 patients (22%) with
With this study we intended to evaluate the frequency of NODAT and to
DM criteria were identified, with a mean time to onset of the disease of 8.9G15.3
characterize patients with NODAT in renal transplantation.
months posttransplant. Patients were followed for an average of 4.2G1.5 years
Methods
(DMC) and 4.2G1.8 years (DMK). DM C patients were significantly older at
All patients submitted to renal transplantation at Centro Hospitalar do Porto
the time of transplantation (54.1G11.5 vs 45.7G13 years, P!0.001), had higher
between 01/01/2009 and 12/31/2013 were retrospectively evaluated. Patients with
frequency of family history of DM (30.9% (P!0.001), higher obesity rate (17.6%
a history of DM, transplantation of more than one organ, younger than 18 years at
vs 4.6%, P!0.001) and higher deceased-donor rate (86.8% vs 75.5%, PZ0.048).
transplantation, and patients with less than 6 months of follow-up were excluded.
There was no statistically significant difference between groups in recipient sex
DM and intermediate hyperglycemia were defined according to WHO criteria.
distribution, donor age and sex, renal disease etiology, immunosuppressive
Patients with hyperglycemia in the postoperative period were considered diabetic
therapy used or HCV/CMV infection occurrence.
only if they maintained criteria 3 months after transplantation.
Discussion and conclusion
Results
The only modifiable pre-transplant risk factor found is obesity, whereby a healthy
Of the 556 patients undergoing renal transplantation, 247 patients were excluded
lifestyle and weight loss should be encouraged within the specific limitations of
and 309 patients were eligible for the analysis. DM screening was performed on
patients with end-stage renal disease. Since cardiovascular diseases are the main
all patients by assaying fasting blood glucose; No patient performed PTGO; 88
cause of morbidity and mortality in these patients, a tight control of all vascular
patients (28.5%) had no recorded HbA1c. The mean follow-up time was 4.2G1.7
risk factors is required.
years; 99 patients (32.4%) presented alterations in glucose metabolism: 68 (22%)
DOI: 10.1530/endoabs.49.EP460
DM criteria,
17
(5.5%) fasting glucose anomaly and
14
(4.5%) transient
postoperative hyperglycemia. The mean time to onset of DM was 8.9G15.3
months, with 73.5% of the diagnoses performed in the first 6 months after
transplantation. The diagnosis was established through fasting glycemia in 51
patients (75%), HbA1c in 13 (19%) and typical symptoms in 4 (5.9%). Of the 60
patients currently undergoing follow-up, 15 (25%) were without anti-diabetic
EP461
drugs, 22 (36.7%) with non-insulin anti-diabetics and 23 (38.3%) with insulin.
Malnutrition and sarcopenia in diabetic institutionalized older people:
The mean values of fasting blood glucose and HbA1c are 113G33 mg/dl and
are there differences with non diabetic people?
6.8G1.4%, respectively.
Beatriz Lardiés-Sánchez1, Alejandro Sanz-París2, Guayente Verdes-Sanz3
Discussion and conclusion
& Leticia Pérez-Fernández2
We believe that the prevalence of DM found is underestimated considering the
1Royo Villanova Hospital, Zaragoza, Spain;2Miguel Servet Hospital,
use of fasting glycemia as a preferential screening method, which is not very
Zaragoza, Spain;3Obispo Polanco Hospital, Teruel, Spain.
sensitive to the diagnosis of DM in patients undergoing corticosteroid therapy.
PTGO would be a valuable complementary diagnostic test to increase diagnostic
Backgrounds and aims
sensitivity, especially in patients with fasting blood glucose anomalies or classic
The aims of the study were, on the one hand, to analize the prevalence of type 2
risk factors for DM.
diabetes mellitus in a population of institutionalized older people and, on the other
DOI: 10.1530/endoabs.49.EP462
hand, to evaluate if the anthropometric parameters and the prevalence of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP463
Conclusion
The evaluation of modified HOMA-IR and HOMA-islet indices before the start of
Incidence of diabetic ketosis and ketoacidosis in Caucasian adults with
intensive GC treatment and during OGCT may improve early detection of risk
type 2 diabetes mellitus: a population-based study
Petra
´
aći
´1, Ivan Kruljac2, Miroslav
´
aćic´2, Božidar Perić2,
groups for serious CMDs - IGT and DM.
Maja Filipovi
´-Grči
´2, Gorana Miroševic´2 & Milan Vrkljan1,2
DOI: 10.1530/endoabs.49.EP464
1University of Zagreb School of Medicine, Zagreb, Croatia;2University
Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.
Aims
Diabetic ketosis (DK) and diabetic ketoacidosis (DKA) are known complications
of type 1 diabetes mellitus (T1DM). However, DK and DKA have been described
EP465
in T2DM. Referred to as ketosis-prone T2DM, this subtype of T2DM has been
described in Hispanics and Afro-Americans of sub-Saharan Africa, but the
Carbohydrate metabolism disorders associated with different
incidence and pathogenesis remains unknown. We aimed to analyze charac-
glucocorticoid therapy schemes
Guzel Nurrulina, Farida Valeeva & Kamilya Khasanova
teristics of patients with diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in
Kazan Medical State University, Kazan, Russia.
Caucasian adults with T2DM.
Methods
Studied population included 261 749 adults. DK criteria included plasma glucose
Introduction
O13.9 mmol/l, and ketonuria O2; while in DKA bicarbonate !18 mEq/l or
Glucocorticoid therapy
(GCT) is one of the risk factors of carbohydrate
pH!7.30 was also required. Hyperglycemic crises without these criteria were
metabolism disorders (CMD) in patents with systemic inflammatory diseases.
defined as non-ketotic hyperglycemia (NKH).
CMD development is a concern not only with long-term therapy, but also during
Results
intensive short-term glucocorticoid
(GC) administration, which can lead to
During 5-year period, we observed 630 episodes of DK and 215 episodes of DKA.
different CMDs, including impaired glucose tolerance
(IGT) and diabetes
Only 8.6% of DK episodes and 34.4% of DKA were attributed to T1DM. Patients
mellitus (DM).
with T1DM were younger, leaner, majority had newly diagnosed disease, and
Aim
hyperglycemia was the main cause of admission. Stadardized incidence ratio for
To evaluate the prevalence of CMD after long-term and intensive GCT in patients
DK was 48.1 (95% CI 44.5-52.1) and 17.0 (95% CI 14.9-19.4) for DKA.
with systemic lupus erythematosus (SLE), systemic vasculitis (SV) and chronic
Incidence for both DK and DKA was increasing with age. Patients with T2DM
glomerulonephritis (CGN).
had a risk of 0.8% for developing DKA and 2.9% for DK over 5-year period.
Patients and methods
Conclusions
The study included 165 patients, among them with SLE - 53, SV - 35 and CGN -
Our study showed that DK and DKA are not uncommon in Caucasian adults and
67 patients. Ninety-eight patients received GC pulse-therapy (GCPT) (one series
the majority of episodes were contributed to T2DM. Further studies are needed to
of three sessions), and 67 - oral GCT (OGCT). All patients underwent standard
assess the impact of these clinical entities.
clinical and laboratory evaluation, oral glucose tolerance test (OGTT), evaluation
DOI: 10.1530/endoabs.49.EP463
of C-peptide, HOMA-IR and HOMA-islet indices.
Results
CMDs developed less often in patients receiving GCPT compared to long-term
OGCT (PZ0.035). In patients receiving OGCT the most prevalent CMDs were
IGT and DM - in 21 (31.1%) and 19 (28.4%) patients respectively, which was
significantly higher compared to patients in GCPT group (PZ0.038 and PZ
0.049). In both groups of patients with DM and IGT baseline C-peptide and
HOMA-IR before the treatment and OGTT was higher than in patients without
CMD or with IFG, which indicates the presence of insulin resistance in this
patient group. In DM patients a decrease of HOMA-islet index was observed in
the first group from 13.96 before OGTT to 11.8 after glucose load and in the
second group from 147 at baseline to 78.4 after the test.
EP464
Conclusion
HOMA-IR and HOMA-islet indices in the evaluation of different
GCT leads to IGT and DM in patients with increased insulin resistance both
carbohydrate metabolism disorders during glucocorticoid therapy
during GCPT and long-term OGCT. Long-term OGCT is associated with more
Guzel Nurrulina, Farida Valeeva & Kamilya Khasanova
CMDs compared to GCPT.
Kazan Medical State University, Kazan, Russia.
DOI: 10.1530/endoabs.49.EP465
Introduction
Diabetogenic effect limits the use of glucocorticoids (GC).
Aim
To evaluate the role of modified HOMA-IR and HOMA-islet indices in different
carbohydrate metabolism disorders (CMD) during oral (OGCT) and PULSE
(GCPT) glucocorticoid therapy (GCT).
EP466
Patients and methods
Type B insulin resistance syndrome in a patient with connective tissue
A study including 165 patients with systemic lupus erythematosus (nZ53),
disease
systemic vasculitis
(nZ45) and chronic glomerulonephritis
(nZ67) was
Agnieszka Lebkowska1, Anna Krentowska1, Agnieszka Adamska1,
performed. 98 patients received GCPT (course dose - 1800-3000 mg) and 67 -
Beata Piasecka1, Danuta Lipinska1, Otylia Kowal-Bielecka2,
OGCT 15-30 mg/day.
Robert Semple3, Maria Gorska1 & Irina Kowalska1
Results
1Department of Endocrinology, Diabetology and Internal Medicine,
GCPT was associated with less CMD compared to OGCT. Impaired fasting
Medical University of Bialystok, Bialystok, Poland;2Department of
glucose (IFG) was observed in 8 (8.2%) and 14 (20.9%), impaired glucose
Rheumatology and Internal Medicine, Medical University of Bialystok,
tolerance (IGT) - in 13 (13.3%) and 21 (31.3%) and diabetes mellitus (DM) - in
Bialystok, Poland;3The University of Cambridge Metabolic Research
12
(12.2%) and 19 (28.4%) patients receiving GCPT and OGCT, respectively.
Laboratories, Wellcome Trust-MRC Institute of Metabolic Science,
There was a significant decrease of HOMA-islet during glycemic peak in DM
Addenbrookes Treatment Centre, Cambridge, UK.
patients from 13.96 to 6.17 after GCPT (P!0.05), compared to insignificant
changes in other groups. After a course of GCPT HOMA-islet was significantly
lower in DM patients compared to patients with no CMD (11.8 vs. 15.4). No rapid
Introduction
decrease of b-cell function was observed in OGCT group, instead there was a
Type B insulin resistance syndrome is an autoimmune disorder characterized by
compensatory increase. Significant differences were observed in patients
the production of autoantibodies against the insulin receptor. It leads to glucose
receiving OGCT both at baseline and after OGTT on HOMA-IR (4.53 vs. 9.81
metabolism disorders, extreme insulin resistance, hyperandrogenism and is
in patients with IGT; 5.6 vs. 11.27 in patients with DM); no differences were
associated with other features of autoimmunity.
observed in patients without CMD (2.59 vs. 2.88) and with IFG (2.88 vs. 5.85). A
Case report
significant decrease of b-cell function was observed in DM patients, reflected by a
A 27-year-old man, with a 2-years history of psoriasis, was admitted to our
decrease of HOMA-islet after OGTT compared to baseline (147 vs. 78.4).
Department because of loss of weight (20 kg in 1 year) and fatigue. He also
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
reported Raynaud’s phenomenon. One year earlier the patient underwent careful
from the emergency department, during August 2017. Excluded patients who
haematological assessment because of peripheral lymphadenopathy and enlarged
were diabetic (phase 1). Non diabetic integrated a 3 phase study: phase 2 -
parotid glands, which showed changes characteristic for viral infection. Screening
Capillary glycemia evaluation 2 h after first meal; if O140 mg/dl, patient did
for cancer was negative. On admission, physical examination revealed
another evalution (fasting, 2 h after meal) (phase 3); if patient still hyperglicemic,
malnutrition
(BMI 16.4 kg/m2), acanthosis nigricans, sclerodactyly, psoriatic
the evaluated HbA1c and hemoglobine (phase 4).
lesions, enlarged parotid glands, palpable cervical and axillary lymph nodes,
Results
tachycardia. Laboratory analyses revealed anaemia, leucopaenia with lympho-
Evaluated 317 patients (121 diabetic, 196 non diabetics). Non diabetic group: 89
paenia, thrombocytopaenia, blood glucose concentration
-
361 mg/dl with
female, 107 male, age average 68.75G18.55 years, 75 patient from IM, 75 from
tendency to morning hypoglycaemia, HbA1c - 12.4% and glycosuria. Fasting
GS, 33 from OT and 13 from SU. 134 patients finished in phase 2, 47 in phase 3
C-peptide concentration was normal and increased adequately in glucagon
and 15 in phase 4. From patients that finished in phase 4, A1c average was 6.12G
stimulation test (00 2.87 ng/ml, 60 4.56 ng/ml). Fasting insulin concentration was
1.3% (four: A1c R6.5% and three: 5.7 !A1c ! 6.5%). In the previous group,
extremely high (O300 mIU/ml). In hyperinsulinaemic euglycaemic clamp insulin
only one patient had a hemoglobine
!12 g/dl and three were under
sensitivity index was decreased (M-2.1 mg/kg FFM/min). We confirmed the
corticosteroids. There was no statiscal signficance between glucose values and
presence of anti-insulin-receptor antibodies, indicating type B insulin resistance
the section of internament or days of hospital admission.
syndrome. Anti-GAD, IAA, IA2 antibodies were negative. Based on the clinical
Discussion
features, presence of antinuclear antibodies, anti-RNP/Sm antibodies, and
In the non diabetic group we calculated a 23.98% of ‘Stress Hyperglycemia’,
positive direct Coombs test diagnosis of mixed connective tissue disease/lupus
7.66% of the patients were at higher risk of developing diabetes, because they had
erythematosus was made. Tumour of blood cells was excluded. Firstly patient was
at least two hyperglycemic values and 2.04% were positive for Diabetes Mellitus
treated with insulin and metformin and then with metformin, prednisone and
(HbA1c R6.5%). The study identified a relevant percentage of people with a
chloroquine phosphate, which resulted in weight gain, normalization of blood
higher risk of developing diabetes, but a small percentage of people with diabetes;
glucose levels (HbA1c - 7.3%) and improvement of blood cell counts and skin
this might be explained by the efficiency of the national screening programmes.
lesions. Currently the patient is under metformin and hydroxychloroquine
DOI: 10.1530/endoabs.49.EP468
therapy.
Conclusion
We presented a case of severe type B insulin resistance syndrome, associated with
another autoimmune disease. Anti-insulin-receptor antibodies are crucial to
recognize the syndrome. The treatment is challenging and requires multi-
disciplinary approach.
DOI: 10.1530/endoabs.49.EP466
EP469
Evaluation of oral glucose tolerance test as a screening test detecting
glucose metabolism impairment in patients chronically treated with
glucocorticoids without previous history of diabetes
Karolina Nowak1, Katarzyna Romanowska-Prochnicka2,3,
EP467
Katarzyna Bornikowska1, Wojciech Zgliczynski1 & Lucyna Papierska1
Parvovirus B19 infection may have a role in the etiopathogennesis of
1Department of Endocrinology, Centre of Postgraduate Medical Education,
type 1 DM
Warsaw, Poland;2Department of General and Experimental Pathology,
Hasan Huseyin Gumuscu1, Kevser Onbasi1 & Nilgun Kasifoglu2
2nd Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland;
1Dumlupinar University, Kutahya, Turkey;2Eskisehir Osmangazi
3Department of Systemic Connective Tissue Diseases, Eleonora Reicher
University, Eskisehir, Turkey.
National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw,
Poland.
Parvovirus
(Erythrovirus) B19
(EVB19) infection may trigger autoimmune
diseases like SLE, RA, and vasculitis. Parvovirus B19 belongs to the parvoviridae
Introduction
family and to the erythrovirus genus. The etiopathogenesis of autoimmune
One of the most common side effects of glucocorticoid treatment is glucose
diabetes mellitus could not been explained yet. The aim of our study was to
intolerance and diabetes. Although glucocorticoids cause mainly postprandial
investigate whether EVB19 may have a role in the etiopathogenesis of type 1 DM.
hyperglycaemia the International Diabetes Federation, American Diabetes
Therefore have we examined whether EVB19 is more frequent among type 1
Association and The European League Against Rheumatism recommend to
diabetics. 32 patients with type 1 diabetes and 30 control patients were included in
screen patients chronically treated with glucocorticoids by regularly determining
the study. 25 of the 32 type 1 diabetic patients had parvovirus B19 IgG positive
fasting plasma glucose. Such an approach can lead to false negative results. Since
sera. The seroprevalence of IgG parvovirus B19 among controls were in 16 of 30
pre-diabetes and diabetes lead to life-threatening conditions such as chronic renal
persons. This was statistically significant (p level was 0,039). 25-OH vitamin D
failure and myocardial infarction it is important to correctly diagnose these
levels were lower among Parvovirus B19 IgG seropositive patients than higher
conditions.
patients. This may be related to the fact that the immune status is impaired in
Objectives
vitamin D insufficiency. In conclusion, parvovirus B19 infection may play a role
The aim of the study was to evaluate if oral glucose tolerance test (OGTT) is a
in triggering type 1 diabetes and low vitamin D levels may increase susceptibility
better screening tool than plasma fasting glucose levels in diagnostics of diabetes
to parvovirus B 19 infection.
in patients chronically treated with glucocorticoids without previously diagnosed
DOI: 10.1530/endoabs.49.EP467
pre-diabetes or diabetes. The second objective was to determine the risk factors of
developing steroid-induced glucose metabolism impairment.
Material and methods
In 50 patients on GCS treatment diagnosed with connective tissue diseases OGTT
was performed. All participants underwent clinical and biochemical evaluation
(age, sex, time of treatment, current and cumulative dose and type of steroid,
EP468
family history of diabetes, BMI, WHR, HbA1c, HOMA-IR).
Hyperinter study: evaluation of glycemic values in acute inpatients
Results
from medical and surgical units. population without diabetes
13 patients (28%) had impaired glucose tolerance (three of them had coincide
Helena Santos Gonçalves, Anusca Lopes Paixao, Cristina Lameirao,
impaired fasting glucose). One patient (2%) diagnosed with diabetes had normal
Ana Rafael, Marta Gomes, Rita Silva, Rita Queiros, Natália Lopes,
levels of plasma fasting glucose. 36 patients had normal glucose metabolism.
Ana Filipa Rebelo & Paula Vaz Marques
Apart from age the statistical analysis showed no significant difference between
Vila Real Hospital, Centro Hospitalar Trás os Montes e Alto Douro,
groups in the rest of analyzed parameters thus the prediction of risk factors was
Vila Real, Portugal.
impossible.
Conclusions
Introduction
Only by performing OGTT 22% of patients could be correctly diagnosed with
Although inpatients hyperglycemia is a current uneasiness among the medical
pre-diabetes and diabetes. The oral glucose tolerance test is the only standardized
community, its prevalence in Portugal in unknown. We aim to identify ‘Stress
tool that is able to effectively detect the steroid-induced impairment in glucose
hyperglycemia’ and ‘New onset diabetes’ cases in inpatients in a district hospital.
metabolism. It should be performed in every patients chronically treated with
Methods
GCS even without other risk factors of diabetes.
We evaluated inpatients from Internal Medicine (IM), General Surgery (GS),
DOI: 10.1530/endoabs.49.EP469
Orthopedics and Traumatology (OT) and Stoke Unit (SU) departments, admitted
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP470
stressors to maintain metabolic homeostasis). Thus, it is essential to identify key
modifiers of phenotypic plasticity that define individual susceptibility to develop
Impact of exercise training on insulin sensitivity estimated by HOMA
T2D. Particularly, there is emerging evidence that alternative mRNA splicing is
model in elite athletes: association with body composition
dysregulated under adverse metabolic-conditions, such as T2D, in several tissues.
Marina Djelic1, Sanja Mazic1, Mirjana Sumarac Dumanovic2,
Therefore, we hypothesized that, as gene expression pattern in PBMCs commonly
Rada Jeremic1, Ankica Vujovic1, Tijana Durmic1, Snezana Cvetkovic3 &
reflects disease-characteristic expression patterns, changes in spliceosome
Dragan Micic2
components of PBMCs may serve as early indicator of MetS/T2D development.
1Institute of Physiology, School of Medicine, University of Belgrade,
To explore this, the expression of selected components of the major (nZ13) and
Belgrade, Serbia;2Clinic for Endocrinology, Diabetes and Metabolic
minor spliceosome (nZ4), and associated splicing factors (SFs; nZ28) was
Diseases, School of Medicine, University of Belgrade, Belgrade, Serbia;
evaluated in PBMCs of individuals with high risk to develop T2D due to a
3Institute of Forensic Medicine, University of Belgrade, Belgrade, Serbia;
previously occurred cardiovascular event (CORDIOPREV study). Specifically,
4Clinics for Pulmology, Clinical Center of Serbia, Belgrade, Serbia.
87 patients that developed T2D during the first 3-year follow-up (43 during the
first, 23 during the second and 21 during the third year) and 87 non-T2D matched
It has been shown that low values of insulin sensitivity have been related to
controls were selected. PBMCs were isolated from basal and post-prandial blood
metabolic diseases. Exercise prescription is crucial to prevent low insulin
at the inclusion in the study. Results revealed that the basal expression of certain
sensitivity in general population, and athletes are good physiological model. If
splicing-machinery components was altered in PBMCs from patients who
this assumption is correct, examine insulin sensitivity in elite athletes should
developed T2D (e.g. SRSF5, U2AF1) compared to controls, especially on those
reflect the positive effect of exercise on insulin sensitivity. The aim of this study
patients that developed T2D in a short-term (first year of study). The most
was to investigate the effects of regular exercise on insulin sensitivity estimated
remarkable changes were observed during the post-prandial response wherein
by HOMA model in elite athletes, as well as the possible relationship the insulin
expression of several SFs (e. g. PTB, Tra2beta) was drastically induced in T2D-
sensitivity with body composition. Sixteen low fat athletes (LFAG, BF!12%),
developing individuals compared to controls, which might suggest that the
15 high fat athletes (HFAG, BFR12%) and 15 sedentary subjects participated in
alteration of these SFs precedes the development of T2D. Taken together, our
study. The subjects underwent to an assessment of body composition. All subjects
results reveal the existence of pre-T2D development-associated spliceosome
were exposed to one bout exercise test on treadmill in order to examine acute
alterations, which could be related to the loss of phenotypic flexibility, and could
changes of insulin response. Blood samples were obtained at rest, immediately
help to predict development of T2D in high-risk patients.
after the exercise test and 30 minutes after recovery. Separated serum were used
DOI: 10.1530/endoabs.49.EP472
for insulin ELISA analysis and glucose levels. Insulin resistance index (HOMA-
IR) was calculated. At rest, LFAG had significantly lower insulin compared to
control group (P!0.05). Also, there were no statistically differences in basal
level of glycaemia and HOMA index between groups. In all three study groups
insulin levels were higher immediately after an acute bout of exercise compared
to baseline values (P!0.05), and remained equal (LFAG, P!0.05 compared to
baseline) or even higher (P!0.05, HFAG, P!0.05, controls) in recovery. There
is no significant correlation between the parameters of body composition and
HOMA-IR in all groups. In conclusion, our findings show that insulin respond to
acute exercise depends on body composition. Acute exercise elicited higher
insulin response in HFAG and controls. Also, these results suggest that chronic
exercise dose not altered insulin sensitivity estimated by HOMA model in elite
athletes.
EP473
DOI: 10.1530/endoabs.49.EP470
Abstract withdrawn.
EP471
Abstract withdrawn.
EP474
Debut diabetes characteristics
María Rosa Alhambra Expósito, Inmaculada Prior Sánchez,
Paloma Moreno Moreno & María Ángeles Gálvez Moreno
Hospital Universitario Reina Sofía, Córdoba, Spain.
Background
The diabetes type 1 (DM1) is a chronic autoimmune disease, it tends to appear in
childhood, its incidence continues to rise and the complications arising from
improper care poses serious health problems for those who suffer. LADA diabetes
is autoimmune diabetes which appear in adults.
Objetive
EP472
To describe the characteristics of the new diabetes debut in our environment.
Material and methods
Dysregulation of the splicing machinery could represent an early,
We included all patients who attended the Diabetes Day Hospital of our hospital
predictive event in the development of type 2 diabetes
for unknown type 1 or MODY diabetes from October 2015 to September 2016.
Emilia Alors-Pérez1,2,3, Mercedes del Río-Moreno1,2,3,
Results
Sergio Pedraza-Arévalo1,2,3, Antonio Camargo4, Javier Delgado-Lista4,
A total of 43 patients were enrolled. With an average age of 36G13 years, 48.8%
José López-Miranda4, Manuel D Gahete1,2,3, Justo P Castan˜o1,2,3 &
were men. The 34.9% were LADA type diabetics and the rest DM1. At diagnosis
Raúl M Luque1,2,3
they had a mean BMI of 23G4 kg/m2, with an abdominal perimeter of 86G12 cm,
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC),
mean arterial tension 116G17/70G12 mmHg. An average glucose concentration
Cordoba, Spain;2Reina Sofia University Hospital (HURS), Cordoba, Spain;
of
238G106 mg/dl and an HbA1c of 11G3%, initial cholesterol of 173G
3Department of Cell Biology, Physiology and Immunology, University of
40 mg/dl, HDL 46G16 mg/dl, LDL 103G34 mg/Dl was noted. The level of
Cordoba (UCO); CIBER Physi, Cordoba, Spain;4Lipids and Athero-
peptide C at the diagnosis was 0.3G0.2 ng/dl (N up to 0.5 ng/dl). In DM-1, 72% of
sclerosis Unit, IMIBIC, HURS, UCO and CIBERobn, Cordoba, Spain.
patients had positive anti-GAD antibodies and 78% had anti-IA2 antibodies. In the
patients with diabetes type LADA 61% had positives only the Anti IA2, 24%
Metabolic syndrome (MetS) and type-2 diabetes (T2D) development is critically
antiGAD, the rest had positives both. Of the patients,
8% associated
affected by the loss of phenotypic flexibility (i.e. the difficulty to cope with
autoimmune thyroid disease. Without other autoimmune comorbidities.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
Results
The incidence of type 1 diabetes and MODY type diabetes is increasing in recent
The study concerned 16 type 2 diabetic patients. Females represent 66.7% and
years. In our setting, 78% of patients with DM-1 have positive antibodies. There
mean age was 55.8G14.73. The mean duration of diabetes was 5.06G4.02 years.
were few comorbidities al diagnosis.
The mean HbA1c was 7.52%. The means of Digit Span test were 5.26 before
DOI: 10.1530/endoabs.49.EP474
Ramadan, 5.80 during Ramadan, and 5.13 after Ramadan. The comparison by
repetitive measures did not show any difference between the three means.
Concerning the Cancellation task test, the comparison showed a significant
difference in the time response and the scores of the tests between the measures
during Ramadan (PZ0.029) and those after Ramadan (PZ0.015).
Discussion
These results show that fasting could impact the spatial recognition in type 2
diabetic patients. However, the evaluation of the short-term memory does not
show any difference between the three periods. We suggest that the difference in
the response time in our patients could be explained by the decrease in the
neuronal activity, secondary to the alteration of the carbohydrates intake cycle.
This suggests the importance of the regularity of the food intake in the
EP475
conservation of an appropriate cognitive functioning. However, this difference in
Effect of vitamin D supplementation on Glucose Tolerance, HOMA
results of the two tests shows the complexity of the neurocognitive processes.
indices and on the risk of GDM in pregnant women with vitamin D
Thus, they represent an interesting way to explore it.
deficiency - a prospective interventional study
Ramesh Jayanthy1 & Naga Satya Vani Mudiganti2
DOI: 10.1530/endoabs.49.EP476
1Sai’s Institute of Endocrinology, Hyderabad and Visakhapatnam, India;
2Osmania Medical College, Hyderabad, India.
Background
Vitamin D deficiency and GDM are highly prevalent with long term implications.
Prospective studies to analyse the effect of vitamin D supplementation on glucose
tolerance in pregnant women are limited.
Objectives
Objectives of the study are: 1) To determine the relation between vitamin D
deficiency and HOMA indices and glucose tolerance in the first trimester among
pregnant women. 2) To study the effect of vitamin D supplementation on HOMA
EP477
indices and on the occurrence of GDM in pregnant women with vitamin D deficiency.
Lack of postpartum reclassification test in gestational diabetes - factors
Methods
conditioning loss of follow-up
50 pregnant women in first trimester were enrolled. FPG, 2 hrPG, FPI, Plasma
Rita Bettencourt-Silva1,2, Pedro Souteiro1,2, Daniela Magalhães1,2,
25(OH)D were done and HOMA IR and HOMA B were calculated at baseline and
Sandra Belo1,3, Ana Oliveira1,4, Davide Carvalho1,2, Joana Queirós1,3 &
at 28 weeks of gestation. Vitamin D deficient women were prescribed 2000 IU of
Diabetes and Pregnancy Study Group Portuguese Society of Diabetology3
vitamin D per day as per ACOG recommendations.
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-
Results
talar São João, E.P.E., Porto, Portugal;2Faculty of Medicine, University of
There was no correlation between 25(OH)vitamin D and FPI, FPG, 2hrPG,
Porto, Porto, Portugal;3Diabetes and Pregnancy Study Group, Portuguese
HOMA IR and HOMA B in both vitamin D deficiency and sufficiency groups in
Society of Diabetology, Porto, Portugal;4Outpatient Clinic of Obstetrics and
the first trimester. At 28 weeks of gestation, in the vitamin D deficiency group,
Endocrinology, Centro Hospitalar São João, E.P.E., Porto, Portugal.
significant rise in FPG, 2hrPG, FPI and HOMA IR occurred despite correction of
vitamin D deficiency with supplementation. The risk of GDM was similar in both
Introduction
the groups.
Gestational diabetes mellitus
(GDM) is a risk factor for maternal-fetal
Conclusion
complications and development of diabetes or intermediate hyperglycemia after
There is no correlation between 25(OH)D and HOMA IR, HOMA B, FPG or
2hrPG in the first trimester of pregnancy. Vitamin D supplementation, in pregnant
pregnancy. The follow-up should be done by a multidisciplinary team. After
delivery, all women diagnosed with GDM should undergo an oral glucose
women with vitamin D deficiency, has no role in decreasing the risk of GDM at
tolerance test (OGTT) for reclassification
28 weeks follow up.
Aim
DOI: 10.1530/endoabs.49.EP475
To evaluate the non-adherence factors to reclassification OGTT after GDM.
Methods
A cohort of 5271 Portuguese women from the National Registry of GDM was
studied. Demographic, anthropometric and analytical data and maternal-fetal
outcomes were evaluated. The diagnosis of DGM was made according to WHO
criteria.
Results
In our sample, 1666 (31.5%) women with DGM did not undergo reclassification
OGTT. Of those who underwent OGTT, 92.2% had a normal test, 0.9% diabetes
EP476
and 6.9% intermediate hyperglycemia. The chance of follow-up loss was 46.5%
Rapid tests use in the evaluation of neurocognitive effects of Ramadan
higher in women below
30
year-old
(ORZ1.465, 95% CIZ1.294-1.660,
fasting in type 2 diabetic patients: Results of a pilot study
P!0.001) and 40.9% higher in those with R3
pregnancies
(ORZ1.409,
Ghizlane El Mghari, Loubna Oukit, Hanane Moata, Salwa Baki &
95%CIZ1.243-1.599, P!0.001). Women treated with insulin during pregnancy
Nawal El Ansari
had increased adherence to the reclassification test (ORZ1.377, 95% CIZ1.222-
Endocrinology Department, CHU Mohammed VI, Marrakesh, Morocco.
1.552, P!0.001), but those with worse glycemic control with HbA1cR5.7% in
Introduction
3rd trimester had 60% more chance of follow-up loss (ORZ1.608, 95% CIZ
Ramadan is the 9th month of the Muslim calendar, where people fast from the
1.318-1.962, P!0.001). The adherence to postpartum reclassification was also
sunrise to the sunset. Despite medical recommendations, 100 million Muslims in
significantly lower when there was fetal (ORZ5.085, 95% CIZ2.402-10.763,
the world with diabetes and 79% of patients with type 2 diabetes fast during
P!0.001) or neonatal (ORZ4.661, 95% CIZ1.365-16.055, PZ0.013) death.
Ramadan.
Age, number of pregnancies, HbA1c in the 3rd trimester and insulin treatment
The aim of our study is to determine the impact of fasting during Ramadan on the
remained statistically significant in the multivariate analysis.
cognitive performances for patients with type 2 diabetes using two fast tests.
Conclusion
Materials and methods
Younger women, with a higher number of pregnancies, worse glycemic control
Patients voluntarily accepted to participate to this study. The socio demographical
and fetal/neonatal mortality associated with pregnancy appear to be more likely to
and metabolical characteristics were collected. The evaluation of the neurocog-
lose the follow-up. Given the risk of diabetes after pregnancy, we should
nitive performances was obtained using two tests: Digit Span test which explores
emphasize the need for OGTT reclassification in the puerperium and define
the short-term memory and Cancellation test which explores the Visio spatial
strategies to promote their accomplishment.
component. Patients were explored before, during and after Ramadan. The results
DOI: 10.1530/endoabs.49.EP477
obtained were analyzed by ANOVA one factor.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP478
and gestation, among pregnant women with T1DM. Older than 26 years old
women has 7.4 times higher risk for negative birth outcome.
Gonarthrosis, Diabetes Mellitus (Type 1 or 2), Leptin, Nesfatin-1
Kadri Yildiz1 & Kenan Cadirci2
DOI: 10.1530/endoabs.49.EP479
1Erzurum Palandoken State Hospital, Erzurum, Turkey;2Erzurum Regional
and Educational Hospital, Erzurum, Turkey.
Gonarthrosis is a severe problem of movement system. It is a restrictive health
problem for modern human. And also; it is the other restrictive problem which
coexistence of diabetes mellitus
(DM) and gonarthrosis. Perhaps; an other
parameter that is deserved to research for this coexistence is metabolic syndrome.
Today, relationship between this clinical conditions are clear enough. And also
two lobotuary parameters as Leptin and Nesfatin-1 are an other headstone for
obesity and metabolic syndrome. Many studies established relationships between
obesity and Leptin, Nesfatin-1 separately. Leptin is a hormone that is made by
EP480
adipocytes and affects NeuroPeptid-Y levels. Its gene Ob is located in
The assessment of possible eating disorders among patients with type 2
Chromosome-7. Leptin regulates food intake and gain weight. Nesfatin-1 is a
diabetes mellitus using EAT-26 questionnaire
hormone that is released by hypothalamus. It regulates hungry and fat sorage. We
Veranika Labashova1, Alla Shepelkevich2 & Elena
aimed to evaluate the levels of these two hormones in diabetic patients that have
Brutskaya-Stempkovskaya2
gonarthrosis. 101 patients were measured clinically and laboratory by X-rays,
1Republic Centre of Medical Rehabilitation and Balneotherapy, Minsk,
levels of insulin, Leptin and Nesfatin-1 on 2014-2016. 46 patients have Type 1
Belarus;2Belarusian State Medical University, Minsk, Belarus.
DM and 55 patients have Type 2 DM. All patients have gonarthrosis clinically
and radiologically. 31 of all patients have overweight (25-29.9), 43 patients have
obese (30-34.9), 20 patients have severely obese (35-39.9) and seven patients
Controversial data exist regarding the prevalence of eating disorders in
have morbidly obese (40 and up) accoding to BMI. In the Leptin results; there
individuals with diabetes. EAT-26 questionnaire is as a validated widely used
were high levels of 81 patients with insulin resistance. And these patients have
self-reported tool recommended in general population for assessing eating
increasing BMI. In the Nesfatin-1 results; there were significant lower in diabetic
disorder risk. The study aimed to determine the prevalence of abnormal eating
patients except in 11 patients. And also there were correlation between Nesfatin-1
behavior in patients with type 2 diabetes mellitus and a matched sample of
lowerity and overweighty. It seem like Leptin levels is related with BMI directly.
nondiabetic control subjects.
High insulin levels may increase Leptin levels. But; Nesfatin-1 is lower almost all
Research design and methods
patients with insulin resistance. Leptin and Nesfatin-1 has severe regulation on
A total 63 participants were randomly selected: 29 patients with type 2 diabetes
body energy storage. And they deserve more studies about diabetic population
mellitus and 34 nondiabetic control subjects. No significant differences existed
with gonarthrosis.
between cases and controls for age or ethnicity. Responses of diabetic patients to
DOI: 10.1530/endoabs.49.EP478
the EAT-26 were compared with those of a nondiabetic control group. The score
of 20 or higher defined as positive cut off, the mean values of each question in
both groups were taking into account.
Results
A total of 14.7% (nZ5) of the control subjects and 34.4% (nZ10) of the diabetic
subjects scored above the predetermined screening cut off. The majority among
screen positive participants were women: 100% in control group and 60% in
diabetes group. However, the assessment of the mean values on each item
revealed the statistically significant differences registered on 16, 17 question
concerning ‘eating dieting foods’ and ‘avoiding food with sugar’ (P!0.001). The
higher average scores were in group of patients with DM
2.03
and 1.58
accordingly vs 0.53 and 0.38 in control group. We suggest that these items could
EP479
reflect the total scores and distort the data.
Conclusions
A right time for pregnant women with type 1 diabetes mellitus
Recent research indicates the higher prevalence of possible eating disorders
Diana Simoniene1,2, Rasa Mikalauskaite2 & Neli Jakuboniene1
among patients with type 2 diabetes mellitus on the total EAT-26, as compared to
1Hospital of Lithuanian University of Health Sciences Kauno klinikos,
the control subjects (34.4% vs 14.7%). Moreover, further work is needed to
Kaunas, Lithuania;2Lithuanian University of Health Sciences, Kaunas,
establish the diagnostic validity of EAT-26 across diabetic subgroup.
Lithuania.
DOI: 10.1530/endoabs.49.EP480
Objective
Pregnancy in women with type I diabetes mellitus (T1DM) is associated with an
increased risk of various obstetric complications. The purpose of this study was to
evaluate relation of HbA1c, delivery age and various diabetes aspects on
pregnancy outcome and gestation in women with T1DM.
Methods
This was a cross-sectional study. A total of 48 women hospitalized to the Hospital
of Lithuanian University of Health Sciences Kauno klinikos Endocrinology
Department were included. Diabetes control was assessed by HbA1C according
to An Endocrine Society Clinical Practice Guidelines.
Results
EP481
In the 48 women with T1DM, the mean age was 28.7 years old (G6.1). Based on
Mediterranean diet and glycaemic control in a Mediterranean
the area under Receiver operating characteristic (ROC) curve (59.6, P!0.05) the
population with type 1 diabetes: a pilot study
optimal age mean for pregnancy and successful delivery was 25 years old. It was
Alexis Kyriacou1,2, Josie M M Evans1 & Angelos Kyriacou2,3
found that only 27.1% of women in their first trimester of pregnancy with T1DM
1School of Health Sciences, University of Stirling, Stirling, UK;2CEDM
had good glycaemic control (HbA1c %6.5% (48 mmol/mmol)) and 72.9% had
Centre of Endocrinology, Diabetes & Metabolism, Limassol, Cyprus;
poor glycaemic control (HbA1c O6.6% (O49 mmol/mmol)). Moreover, it was a
3Endocrinology and Diabetes, Salford Royal NHS Foundation Trust,
significantly increase of premature deliveries in women with poor glycemic
Salford, UK.
control (PZ0.002). To further explore pregnancy outcomes, we fit a logistic
regression model to predict the risk of adverse birth outcomes. We found out that
Background
pregnant women with T1DM and older than 26 years old had 7.4 times higher risk
The Mediterranean diet (MD) is the traditional diet of the people living in the
for negative birth outcomes than younger women fitting the same criteria
Mediterranean basin and has been linked with positive health outcomes e.g.
(PZ0.034 (95% PI 1.16-47.19).
reduced incidence of cardiovascular and neoplastic disease. No study has
Conclusion
investigated the relationship between the MD and glycaemic control in a
This short study showed that glycemic control during pregnancy is insufficient in
Mediterranean population with type 1 diabetes mellitus (T1DM). Furthermore,
women with T1DM. We found out that poor glycemic control causes premature
it is unknown how well controlled are such patients and whether they follow
delivery (P!0.002) and age is an important risk factor for pregnancy outcome
the MD.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
EP483
Patients known with T1DM were randomly conducted through the registry of the
Bone mineral density in male patients with type 2 diabetes mellitus, with
Cyprus Diabetes Association. Ethics: Received from the University of Stirling
and without hypogonadism
and the Cyprus National Bioethics Committee.
Agathi Vasileiou1, Ioanna Karathanassi1, Parthena Navrozidou2,
Results
Marianna Vlychou2, Georgios Koukoulis1 & Alexandra Bargiota1
Twenty patients were conducted; eight patients fulfilled the inclusion criteria and
1Department of Endocrinology and Metabolic Diseases, University of
completed antropometrics and the questionnaires; six had biochemistry. Age was
Thessaly, Larissa, Greece;2Department of Radiology, Faculty of Medicine,
34.6G10.7 years. All patients were classified as having moderate adherence to
University of Thessaly, Larissa, Greece.
the MD using the MedDietScore scoring system (28.9G5.2; max score 55).
Lowest score was seen for potatoes and non-refined cereals (1.4G0.7 and 1.4G
0.9; max score 5) and the highest for use of vegetables and olive oil in cooking
Introduction
(4.1G1.5 and 4.8G0.7; max score 5). All six patients with biochemical testing
Type 2 diabetes mellitus (T2DM) affects bone metabolism, but its relation with
had undetectable levels of fasting blood c-peptide. HbA1c was
63.5G
bone mineral density (BMD) remains controversial. It is also known that T2DM is
5.8 mmol/mol and fasting glucose levels 227.7G64.8 mg/dl; none had optimal
associated with hypogonadism in males. Male hypogonadism can also affect
diabetes control i.e. HbA1c%53 mmol/mol. MD score was unrelated to HbA1c
BMD. Thus the aim of this study was to evaluate BMD in male patients with
(rZK0.65; PZ0.16) or fasting glucose (rZK0.66; PZ0.15). Mean BMI was
T2DM with and without hypogonadism.
27.0G5.5; 67% were overweight or obese; BMI was marginally related to HbA1c
Methods/design
(rZ0.8117; PZ0.0499).
Hypogonadism was defined as serum free Testosterone (fT) value !5 ng/dl or 5-
Discussion
9 ng/dl C1 major sign suggestive of androgen deficiency and eugonadism was
Our results show a no association between the MD and glycaemic control
defined as fT value O9 ng/dl. We studied
119 patients with T2DM and
although a type 2 statistical error is plausible. Adherence to the MD diet was
hypogonadism (Group H) (age: 61.2G8.2 years) and 45 patients with T2DM
moderate in-line with our previous research that showed a moderate and reducing
without hypogonadism (Group NH) (age: 58.4G10.3 years) matched for age,
adherence in the general population in Cyprus. Furthermore, our results are
duration of diabetes, BMI and HbA1c. In both groups, we measured, lumbar spine
worrying regarding glycaemic control. A larger study is underway to further
(LS) BMD and total Tscore by Dual-energy X-ray absorptiometry (DEXA).
investigate these relationships.
Results
DOI: 10.1530/endoabs.49.EP481
Mean BMI (kg/m2) was similar in both groups (H: 30.9G5.0 vs NH: 29.6G5.9,
PZ0.17). Mean duration of diabetes was 9.4G8.5 years in Group H and 8.6G7.8
years in Group NH (PZ0.54) and mean HbA1c was 7.8G1.9% in Group H and in
Group NH 7.61G1.5%(PZ0.47). BMD at LS (g/cm2) and total T-score measured
by DEXA were lower in Group H compared to Group NH (0.53G0.08 vs 0.81G
0.07, PZ0.041) (K0.12G1.0 vs 0.78G0.72, P!0.001).
Conclusion
Male patients with T2DM and hypogonadism are found to have lower BMD
compared to T2DM males without hypogonadism. Thus, in male patients with
T2DM, hypogonadism is a risk factor for low BMD.
DOI: 10.1530/endoabs.49.EP483
EP482
Analysis of zinc status in type 2 diabetic patients and its correlation with
glycemic control
Emna Elfaleh1, Mahdi Mrad2, Ibtissem Oueslati1, Afef Bahlous2,
Najla Bchir1, Imen Horchani1, Karima Khiari1 & Néjib Ben Abdallah1
1Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia;
2Biochemistry Laboratory, Pasteur Institute, Tunis, Tunisia.
EP484
Pregnancy outcome in relation to a disorder of glucose tolerance during
Introduction
pregnancy
Recent studies have highlighted zinc’s dynamic role as a cellular second
Violeta Mladenovic1,2, Jelena Nesic1,2, Marija Andjelkovic2,3,
messenger in the control of insulin signaling and glucose homeostasis. The aim of
Zoran Gluvic4,6, Aleksandar Djukic1,2 & Djuro Macut5,6
our study was to assess the concentration of serum and urinary zinc levels in type
1Center for Endocrinology, Diabetes and Metabolic Diseases, Clinical
2 diabetic patients and to investigate the correlation between this variable and
Center «Kragujevac», «Kragujevac», Serbia;2Faculty of Medical Sciences,
glycemic control.
Univeristy of «Kragujevac», «Kragujevac», Serbia;3Department of
Methods
Laboratory Diagnostics, Clinical Center «Kragujevac», «Kragujevac»,
Total 54 type 2 diabetic patients and 23 non diabetic healthy subjects (age
Serbia;4Division of Internal Medicine, Department of Endocrinology,
matched) were enrolled in a cross-sectional study. Patients with malabsorption
Zemun Clinical Hospital, Belgrade, Serbia;5Clinic for Endocrinology,
syndrome, chronic liver disease and chronic renal failure were excluded. Physical
Clinical Center Belgrade, Belgrade, Serbia;6School of Medicine,
examination and laboratory tests, including serum and urinary zinc measurements
University of Belgrade, Belgrade, Serbia.
were performed.
Results
The mean duration of diabetes was 4.32G7.95 years and mean HbA1c was 6.6G
Introduction
2.15%. Compared to control subjects, mean serum zinc level was significantly
Pregnancy as a state of insulin resistance can predict diabetes development in
lower in diabetic patients
(1.15G0.29
and
1.07G0.29 mg/l respectively,
some women, and is associated with increased risk for adverse outcome of
PZ0.02). However, urinary zinc level was significantly higher in diabetic
neonate and for mother.
patients than in control group
(1.04G1.06 mg/24 h and 0.57G0.4 mg/24 h,
Aim
respectively, PZ0.02). There were a negative correlation between serum zinc and
The aim of this study is to analyse pregnancy outcome in relation to a disorder of
HbA1c levels (rZ0.85, PZK0.01) and between serum zinc and fasting plasma
glucose tolerance during pregnancy.
glucose levels (rZ0.51, PZK0.01). However, a positive correlation between
Matherial and methods
urinary zinc and HbA1c levels (rZ0.23, PZ0.02) was observed.
The study included 77 healthy pregnant women in third trimester registered in
Conclusion
Center for endocrinology CC Kragujevac that were tested, according to conducted
In our study, patients with T2D had lower serum zinc concentration than non-
3 h OGTT with 100 g glucose (ADA criteria). As parameters of adverse outcomes
diabetic controls. This reduction could be associated with low zinc dietary intakes
we included: premature labor (before 37 gw., Low Apgar score (!8), neonatal
and increased urinary excretion relating to polyuria. Further studies were required
malformations, respiratory complications, hypoglycemia, birth body weight
to determine the role of zinc supplementation in improving glycemic control and
O4 000 g or !2 500 g, hyperbilirubinemia
preventing vascular complications in type 2 diabetic patients.
Results
DOI: 10.1530/endoabs.49.EP482
The mean age of patients was 30.8G4.7 years. The frequency of risk factors for
diabetes were: obesity (3.9%), hypertension (5.2%), previous gestational diabetes
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
mellitus (23.5%), smoking (23.4%), positive family history for diabetes (27.3%).
The first objective was to study the relationship between glucose, insulin and
From 77 patients, 18 was with GDM (23.3%). It has been shown that the number
C-peptide during a prolonged glucose load in two patients with active IAS. The
of risk factors significantly affect the outcome of pregnancy (P!0.005, c2 test),
second was to study the variation of these parameters between the active and the
and that the degree of disorder of glucose tolerance during pregnancy affect the
recovery disease states.
outcome of pregnancy (rZ0.164, c2 test). It has been shown that patients with
Methods
normal glucose tolerance usually have a favorable outcome of pregnancy, and a
Two patients with IAS and frequent hypoglycaemic episodes at the time of the
growing number of pregnancies with an adverse outcome.
first study underwent an extended oral glucose tolerance test with 75 g of glucose
Conclusion
(4 h). After apparent clinical and biochemical recovery, the procedure was
This study demonstrates that glucose intolerance during pregnancy predicts
repeated.
unfavorable adverse outcome
Results
Keywords: glicoregulation, pregnancy outcome
The data observed during the active and recovery states are shown in Table 1.
DOI: 10.1530/endoabs.49.EP484
Table 1
Hyperglycaemia phase
Hypoglycaemia phase
Glucose
Ins/c-pep
Glucose
Mean peak at
ratio
Mean peak at
State
1 h (mg/dl)
(uU/ng)
3-4 h (mg/dL)
(uU/ng)
Active
199
(range
7.0
52
(range
13.6
EP485
disease
187-210)
45-59)
Single standard labour tactic at 39-40 weeks in pregnancy with
Recovery
166
11.2
4.9
gestational diabetes - is it the best policy?
disease
Ofelia Bettikher & Irina Zazerskaya
Federal Almazov North-West Medical Research Centre, Saint Petersburg,
Russia.
Active disease state
The insulin/c-peptide ratio increased significantly from hyperglycaemia to
Objective
hypoglycaemia (PZ0.023) even after adjusting for the glucose levels (glycaemia
To assess labour outcomes in pregnancies with gestational diabetes
(GD)
to insulin/c-peptide ratio) (PZ0.027).
regarding different delivery tactics.
Recovery disease state
Design and methods
Patient showed a decrease in hyperglycaemia peak with a corresponding increase
The retro- and prospective study evaluating labour outcomes included 443 age
in the insulin/c-peptide ratio and a decreased insulin/c-peptide ratio during
matched patients with GD had given birth during 2014 (1st group - nZ251) and
hypoglycaemia phase.
2015
(2nd group - nZ192) according to the two clinical protocols, respectively.
Discussion
Expectant management in 2014 was supposed to use until 39-40 weeks of
During active disease, a lower insulin/c-peptide ratio during hyperglycaemia
gestation in the absence of any earlier delivery indications, in 2015 - until 40-41
and the paradoxical increase during hypoglycaemia seem to support the role of
weeks similarly. Statistical analysis was performed with SPSS 21.0 (SPSS Inc.)
insulin antibodies in the disease. During the recovery state, there is a reversal of
program. Statistical methods used: Student criteria for quantative analysis, c2
these ratios supporting an increase in bioavailable insulin with lower antibody
criteria for quality analysis; P!0.05.
titters.
Results
Labour induction rate was lower in the second group: 13.5% (26 of 192), than in
DOI: 10.1530/endoabs.49.EP486
the first: 17.1% (43 of 251), thus the rate of spontaneous labour raised (74.9%
(188 of 251) and 78.2% (150 of 192)). The rate of pre-arranged and urgent
caesarian section, macrosomia, diabetic embryopathy did not significantly differ
between groups, the same as dysthyroidism and fetal distress after induction
of labour: 7% (3 of 43) and 9.3% (4 of 43) - in the first, 7.7% (2 of 26) and 11.5%
(3 of 26) - in the second group, respectively. However, uterine inertia rate after
induction was twofold lower in the second group comparing to the first one: 7%
(3 of 43) and 15.4% (4 of 26), respectively.
Conclusion
Expectant management until 40-41 weeks in patients with GD in the absence of
earlier delivery indications has led to the labour complications rate fall and
spontaneous labour rate rise. Probably, single standard tactic for labour at 38-40
weeks in all patients with GD is not one of choice. Such management is preferable
EP487
for high risk antenatal fetal death pregnancies: fetal distress, macrosomia, diabetic
Lipoprotein particle size in women with type 1 diabetes mellitus and its
fetopathy or severe maternal conditions, first of all, preeclampsia.
relationship to carotid intima-media thickness
DOI: 10.1530/endoabs.49.EP485
Anjuli Gunness1, Mohamed Ahmed1, Agnieska Pazderska1, Niamh Phelan1,
Kevin Moore1, Gerard Boran2, Lucy-Ann Behan1, Mark Sherlock1 &
James Gibney1
1
Department of Endocrinology, Adelaide and Meath Hospital, Tallaght,
Dublin 24, Ireland;2Department of Clinical Chemistry, Adelaide and Meath
Hospital, Tallaght, Dublin 24, Ireland.
EP486
Although cardiovascular disease (CVD) is greatly increased in type 1 diabetes
mellitus (T1DM), patients typically have apparently healthy lipid profiles. Simple
Insulin autoimmune syndrome: the relationship between insulin,
measurement of plasma lipids however does not provide information regarding
c-peptide and glucose in active and recovering disease states
lipoprotein particle size which in the nondiabetic population is independently
Tiago Nunes da Silva1, Ana Gonçalves Ferreira1, Isabel Manita1,
predictive of CVD. Plasma lipids and lipoprotein subclasses (using polyacryl-
Ana Catarina Matos1, Isabel Carvalho2, Paula Font3, Susana Prazeres3
amide gel-tube electrophoresis) were studied in reproductive age women with
& Jorge Portugal1
T1DM and compared to a matched control group. Outcomes were correlated with
1Endocrinology Department Hospital Garcia de Orta, Almada, Portugal;
carotid intima-media thickeness (CIMT), a validated marker of atherosclerosis.
2Clinical Chemistry Department Hospital Garcia de Orta, Almada, Portugal;
Compared to nondiabetic women, T1DM women were younger (29 vs 34 years)
3Endocrinology Laboratory IPO Francisco Gentil, Lisboa, Portugal.
and of lower BMI (24.7 vs 31.3 kg/m2), with all data reported as median. Total
(TC) and LDL-cholesterol (LDL-C) did not differ between groups. Triglyceride
Insulin autoimmune syndrome (IAS) is a very rare cause of hypoglycaemia in
(TG) levels were lower (0.76 vs 0.91 mmol/l, PZ0.0331) and HDL-cholesterol
western countries. One proposed mechanism is anti-insulin antibody capture of
(HDL-C) greater (1.65 vs 1.49 mmol/l, PZ0.00331) in T1DM. T1DM women
prandial insulin followed by the dissociation of insulin from anti-insulin antibody.
had a greater proportion (46% vs 5%, P!0.0001) of small LDL-C particles,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
lower mean LDL particle size
(269
vs
272 A
˚, P!0.0001) and a greater
Methods
percentage of small-dense-LDL particles (%SDLDL; 3 vs 0%, P!0.0001).
A total of 65 patients (32 men and 33 women, mean age 51.6G5.2 years); 31-
CIMT correlated positively in T1DM with %SDLDL (r 0.2983, PZ0.0098) and
with type 2 diabetes and hypertension (group 1), 34 - with isolated arterial
negatively with LDL size (rK0.3118, PZ0.0068), but did not correlate with TC,
hypertension (group 2). Control group 20 healthy volunteers. We evaluated data
HDL-C, LDL-C or TG. Despite apparently healthy lipid profiles, women with
transthoracic echocardiography and ultrasound thickness of the intima-media
T1DM have a greater proportion than nondiabetic women of atherogenic small
complex of the common carotid artery (IMC CCA). Omentin level in blood serum
LDL particles. The likelihood that this is clinically relevant is strengthened by the
were determined by ELISA kit.
observed correlation of CIMT with particle size and lack of correlation with
Results
standard lipid profile. Further studies are needed to explore the mechanisms
Left ventricular hypertrophy (LVH) was diagnosed in 67.5% of patients in group
underlying these abnormalities.
1 and 34.2% of patients in group 2 (P!0.05). IMC CCA patients of group 1 was
DOI: 10.1530/endoabs.49.EP487
significantly higher than in the comparison group (P!0.001). Omentin level in
group 1 was reduced in comparison with the 2 - nd group and the control
(262.24G10.46, ng/ml versus 296.43G12.72, ng/ml and 379.46G6.22 ng/ml,
respectively, P!0.001). There was a negative correlation relationship between
the content omentin plasma and left ventricular hypertrophy
(rZK0.54;
P!0.05) and IMC CCA (rZK0.46, P!0.05).
Conclusions
It was found that patients with type 2 diabetes and hypertension observed the
progression of LVH and remodelling of the vascular wall, which are related to an
imbalance omentin serum. Thus omentin reduction level can be considered as a
EP488
biomarker of cardiovascular complications in these patients.
The upper limb infection in diabetic patients (about 32 cases)
DOI: 10.1530/endoabs.49.EP489
El Ansari Nawal, Habra Bahia & El Mghari Ghizlane
Service of Endocrinology Diabetology and Metabolic Diseases CHU
Mohammed VI, Faculty of Medicine and Pharmacy, Marrakech, Morocco.
Introduction
The diabetic patient is vulnerable to infection compared to the general population.
This is due to the deleterious effect of hyperglycemia on the basis of chemotaxis,
phagocytosis and bactericide neutrophils / What weakens the defenses of the
diabetic person to infections. Infections of the upper limb in diabetics are not
EP490
uncommon, and are often characterized by severity and often unfavorable
developments. The objective of this work: determine the prevalence, clinical and
Casuistic from Endocrinology Medical Consultation at
therapeutic characteristics of the infection of the upper limb in diabetics.
Clinica Girassol 2015
Matériels et méthodes
Domingos LIRA, Anselmo Castela, Gertrudes Béu & Francisca Silva
Study including
32
patients seen in the emergency. The parameters:
Clinica Girassol, Luanda, Angola.
epidemiological characteristics âge, sex, weight, size, marital status, housing
environment, origin, nature of the work, the pets, Characteristics of the diabetes:
Introduction
type, age of the beginning, evolution, treatment, glycemic balance, the follow-up.
There are few studies either hospital bases or population based in Africa and in
Characteristics of the lesions: type, Seat, the mechanisms, bacteriological sample.
Angola we also have the same situation regarding endocrinology data. With this
Deadline between the consultation and the appearance of the lesions. Manage-
paper, the Angolan Society of Endocrinology Diabetes and Metabolism
ment emergency: medical treatement, surgical care.
(SAEDM), wants to contribute to the systematic and continued study of
Discussion
endocrine pathology in Angola.
At our patients, the hurts were grave and spread, this can give some explanation
Objective
by the delay of the consultation been understandable by the educational lack and
Study of the casuistic of endocrine pathology in ambulatory setting regarding the
by the particularly vulnerable fragile ground to the infections seen the diabetes.
year 2015.
The diabetes was discovered on the occasion of the lesions of the upper limb in
Methods
18% of the cases, during the evolution, in spite of the institution of a local
Compilation of data obtained from medical notes files from the ambulatory
treatment and an antibiotic treatment, a locol extension regional and sometimes
appointments available in digital and physical support. Files with incomplete data
general of the infection drove to make an amputation in 25% of the cases for
or without prove or clinical-laboratory correlation have been discarded. We
saving of the patient.
designed the distribution of patients according to the pathology, or group of
DOI: 10.1530/endoabs.49.EP488
pathologies at the respective frequencies as per sex and age group. Diabetes
Mellitus and Obesity have been considered as specific pathologies. Thyroid
diseases have been included in the same entity considered as Thyroid Pathologies
and the others in a group classified as Other Endocrine Pathologies. Diabetes
Mellitus and Obesity (including overweight) were profiled according to the WHO
criteria; Disturbances of Thyroid have been established obeying to the
ultrasonography criteria or to functional anomalies.
Results
We worked with a pool of 1630 processes (files) related to patients that had
endocrine pathology. Ninety one (5.58%) were incomplete. Therefore were
EP489
excluded because had not confirmation data of endocrine disease. The validated
The peculiarities of structural and functional state of the myocardium
files (1539 files) could be distributed as follows: 1159 (75.3%) corresponding to
and blood vessels in patients with type 2 diabetes mellitus and arterial
Diabetes Mellitus, 156 (10.1%) corresponding to Pathologies of Thyroid, 85
hypertension depending on the dynamics of adipokines
(5.5%) corresponding to Obesity and 139 (9.0%) classified as Other Pathologies.
Olena Al-Trawneh, Oleksandr Bilovol & Lesya Bobronnikova
Distribution per sex: 794 (51.6%) were women and 745 (48.4%) men. The
Kharkiv National Medical University, Kharkiv, Ukraine.
distribution of pathologies per sex: Diabetes Mellitus: 533(45.9%) women and
626
(54.1%) men; for Obesity: 56 (65.9%) women and 29 (34.1%) men and for
Purpose
Pathology of Thyroid we found 132 (84.6%) women and 24(15.4%) men.
To study the features the structural and functional state of the myocardium and
DOI: 10.1530/endoabs.49.EP490
blood vessels in patients with diabetes mellitus and arterial hypertension
depending on omentin level.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP491
type
1 diabetes is more prevalent among women is in accordance to the
international data. It is important to highlight that significant number (63%) of the
Depression and quality of life in patients with type 2 diabetes mellitus
patients have been diagnosed in the status of diabetes ketoacidosis.
Andreja Maric, Dunja Molnar, Tea Premosa, Sonja Novak, Jurica Vidovic
& Maja Mikolaj Kiric
DOI: 10.1530/endoabs.49.EP492
County Hospital Cakovec, Cakovec, Croatia.
Introduction
Depression is the leading cause of disability worldwide, and is a major contributor
to the overall global burden of disease. People with DM have 2.4-4.3 times
greater risk of depression than people without DM as well as patients (pts) treated
EP493
with insulin. Women experience depression more often than men. Symptoms of
depression can make it more difficult to successfully manage diabetes and prevent
Bronze diabetes - a rare secondary cause of diabetes
diabetes-related complications.
Pedro Souteiro1,2, João Sérgio Neves1,2, Sofia Castro Oliveira1,2,
Materials and methods
Sandra Belo1,2, Celestino Neves1,2, Paula Freitas1,2 & Davide Carvalho1,2
1Department of Endocrinology, Diabetes and Metabolism, Centro
A total of 138 subjects (74 males, 64 females; aged 18-80 years) with T2DM
Hospitalar Sa˜o João, Porto, Portugal;2Faculty of Medicine of University
participated in cross-sectional study. Two questionnaires: BDI (Beck depression
of Porto, Porto, Portugal.
inventory) and SF-36 (Short-Form-36 Health Survey) were used. Using BDI the
severity of depression was detected; SF-36 was used for measuring self-reported
physical and mental health status.
Introduction
Results
Secondary causes of diabetes refer to a category in which diabetes is associated
The prevalence of depression was higher in females with diabetes (45.3%)
with other diseases. They are thought to constitute less than 2% of the total cases
compared to males (35.1%). Women with depression (29/64 of pts) were aged 39-
of diabetes.
76 yrs, BMI 22.3-44.6 kg/m2, HbA1c O7% was observed in 17/29 of depressive
Case report
women, duration of DM2 was 2-192 months. Men with depression (26/74 of pts):
A 56 year-old caucasian man, with no relevant medical history, presented to the
age 35-79, BMI 23.2-43.2 kg/m2, HbA1c O7% in 13/26 of depressive men,
Emergency Department with fatigue, polyuria, polydipsia, polyphagia and
duration of DM2 was 6-360 months. According to BDI questionnaire scores, mild
involuntary weight loss (6 kg in two weeks). He was hemodynamically stable
depression was reported in 17 male and 15 female pts, moderate depression was
and exhibited a glycaemia of 445 mg/dl without acidosis. Insulin perfusion was
found in 6 males and 9 females and severe depression in 3 male and 5 female pts.
initiated and the patient was hospitalized with the diagnosis of new-onset
Mean scores of SF-36 questionnaire were compared between diabetics with and
diabetes. Physical examination revealed a greyish skin tone, body mass index
without depression, and correlated to BDI scores. Depressive pts had statistically
of 19 kg/m2 and hepatomegaly. Blood analysis showed a haemoglobin A1c of
lower scores than non depressive (both sexes) in Physical functioning, Emotional
13.4%, negative anti-GAD and anti-insulin antibodies, transferrin saturation of
role functioning, Mental health, Bodily pain (just males) and General health
98% and high ferritin levels
(4533 ng/ml). This clinical picture raised the
perceptions.
suspicion of diabetes secondary to hemochromatosis. Abdominal ultrasound
Conclusion
showed an enlarged liver (19.5 cm) with bright echostructure and the hepatic
T2DM is associated with an increased risk of depression. In order to prevent
magnetic resonance imaging described signs of iron overload. Liver biopsy was
negative consequences of non recognized and untreated depression, evaluation of
then performed showing accentuated iron deposits in the hepatocytes, sinusoidal
psychological status in patients with T2DM is recommended.
lining cells and bile ducts epithelia. Genetic study identified a HFE gene mutation
DOI: 10.1530/endoabs.49.EP491
(C282Y homozygote). Due to possible iron accumulation in the pituitary gland
and the patient complaints of erectile dysfunction, pituitary function was
evaluated revealing hypogonadotropic hypogonadism
(total testosterone
0.59 ng/ml; FSH 3.40 mUI/ml; LH 2.78 mUI/ml) with no other axis affected.
Patient was discharged from hospital with a basal-bolus insulin regimen and a
250 mg testosterone monthly enanthate injection. He maintains follow-up with an
A1c of 7.3% and undergoing periodic phlebotomies.
EP492
Conclusions
In hemochromatosis iron accumulation in the skin and pancreas can lead to
Diabetes Mellitus type 1: characterization of patients at the endo-
hyperpigmentation and impair insulin production causing the so called ‘bronze
crinology ambulatory follow up during the year 2015
diabetes’. This case alerts clinicians not to overlook secondary causes of diabetes
Anselmo Castela, Gertrudes Béu, Francisca Silva & Domingos Lira
that can be precociously suspected based on a careful physical examination.
Clinica Girassol, Luanda, Angola.
DOI: 10.1530/endoabs.49.EP493
Introduction
Diabetes Mellitus is a chronic disease that has serious effects on the morbi-
mortality. Diabetes type 1 is less prevalent, representing 5-10% of the total cases.
Data collected in Africa are scarce, and prevalence and incidence at sub - Saharan
Africa are about 3-12/100,000 and 1.1-2.1/100,000 people, respectively. The
Angolan reality is not known.
EP494
Objective
To show the casuistic of diabetes type
1
obtained from the ambulatory
The epidemiology of type 2 diabetes mellitus and its complications in
consultation of Endocrinology for the year 2015.
South Korea
Methods
Ryungwoo Kang & Deborah Chee
We performed a retrospective study of the available clinical files in digital and
Korea National Enterprise For Clinical Trials, Seoul, Republic of Korea.
physical support. The diagnosis of type 1 diabetes was according to the diagnostic
criteria defined by the WHO. Parameters that have been studied: sex, age, A1c,
Background
clinical onset, duration of the disease.
The prevalence of diabetes in South Korea has drastically increased, and 8.6-
Results
11.0% of Korean adults aged R30 years were suffering for the disease in the early
In the year
2015, 1630 patients have been observed at the Endocrinology
2000s, according to the Korea National Health and Nutrition Examination
Ambulatory Service. Only 1539 process were considered for analysis. Among
Survey.
these patients, 1159 (75.3%) were diabetic, being 19 of them (1.63%) type 1
Objective
diabetics. The distribution by sex was: 9 (47.4%) men and 10 (52.6%) women.
The present study was performed to estimate the incidence and prevalence of type
The age spread from 4 to 40 years with a mean of 23 years. Diabetic ketoacidosis
2 diabetes mellitus (T2DM) and its complications in South Korea using the Health
(63.11%) was the clinic presentation found at the time of the diagnosis. The time
Insurance Review and Assessment (HIRA) database from 2010-2015, which
of evolution of the disease varied from 6 months to 15 years of age with an
covers 96.3% of the claim data of the Korean population.
average of 4.6 years. The average glycosylated hemoglobin (HA1c) was 8.86%.
Methods
Conclusion
T2DM, coronary artery disease (CAD), cerebrovascular disease (CVD), and
The epidemiology of diabetes is not known, and we cannot advance conclusions
peripheral artery disease
(PAD) were defined as underlying disease and its
from the data collected by our team. Most of the patients observed in
complications of T2DM. We used the Healthcare Common Procedure Coding
endocrinology (75.3%) had the diagnostic of Diabetes Mellitus. The fact that
System codes provided by HIRA to identify associated procedures or surgeries.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
A Poisson distribution was assumed when calculating 95% confidence intervals
sensitivity, patients are often misdiagnosed with type 1 or type 2 DM. Correct
for prevalence and incidence rates.
classification of this type of diabetes becomes essential for proper management of
Results
the disease. Our objective was to describe clinical features of patients with
After age standardization, the prevalence of T2DM in Korean adults aged more
MODY diagnosed at our institution.
than 30 years, was 6.3-7.5% and the annual incidence rates of T2DM ranged from
Methods
9.0-11.0/1,000 person-year during the six year. The incidence rates of T2DM in
We collected clinical data from patients with clinical characteristics and genetic
men and women aged more than 30 years significantly decreased from 2013 to
confirmation of MODY.
2015
(P%0.001). On the other hand, the incidence in women aged more than 65
Results
years significantly increased from 2013 to 2015 (P%0.001). The incidence rates
We included 30 patients (15 females). All patients but one had diagnosis of DM
of CAD and CVD with T2DM patients were 21.4 and 13.6/1,000 person-year.
(one female had gestational diabetes, but currently has no criteria for diabetes).
Conclusion
Mean age at diagnosis of DM and MODY was 27.5C/K10.8 and 46.3C/K13.2
This study estimated the incidences and prevalence of T2DM in most of Korean
years, respectively. Genetic testing was positive for mutation in the Glucokinase
population which is the great concern for public health. We also confirmed the
(GCK) gene in 3 patients, the ATP-binding cassette transporter sub-family C
relatively higher risk of as the complications with the T2DM patients compared to
member 8 (ABCC8) gene in 1 patient and the hepatocyte nuclear factor-1
the general population in Korea.
homeobox A (HNF1A) gene in 26 patients. Currently, 9 patients are exclusively
DOI: 10.1530/endoabs.49.EP494
treated with oral antidiabetic agents and 3 patients have no pharmacological
treatment. Last mean HbA1c was 7.5C/K 1.3%. Peripheral neuropathy was
diagnosed in 11 patients (36.7%), autonomic neuropathy in 5 patients (16.7%),
diabetic retinopathy in 16 patients (53.3%), diabetic kidney disease in 11 patients
(36.7%), ischemic cardiac disease in 2 patients (6.7%), vascular cerebral disease
in 3 patients (10%) and peripheral arterial disease in 4 patients (13.3%).
Conclusions
There is a relevant delay in MODY diagnosis and clinicians should be alert for
EP495
this type of diabetes. The most frequent mutation identified in our population was
Prevalence of obesity and diabetes among in a developing country
in the HNF1A gene. This study confirms the clinical heterogeneity of MODY
(Albania)
patients.
Dorina Ylli1, Tomi Thomo2, Violeta Hoxha1, Marjeta Kermaj1,
DOI: 10.1530/endoabs.49.EP496
Gerond Husi1, Thanas Fureraj1 & Agron Ylli1
1“Mother Teresa” Univeristy Hospital Center, Univerity of Medicine
Tirana, Faculty of Medicine, Tirana, Albania;2Ministry of Health, Tirana,
Albania.
It is well known nowadays the positive effect that early detection of prediabetes
has in preventing and postponing the diabetes onset. The aim of our study is to
EP497
explore the diabetes prevalence in Albania and to identify and stratify the
The relationship between Serum Vaspin and atherogenic risk factors in
population at risk for developing diabetes.
T2DM
Material and methods
Magda Shokry Mohamed, Manal Mohaned Abushady, Mona
A large scale multicentre screening was performed in Albania as part of a
Mohamed Abdelsalam, Maram Mohamed Maher, Lila Mahmoud Hendawy
National Campaign. 15744 patients were consecutively recluted. The following
& Rana Hashem Ibrahim
data were obtained: age, weight, height, BMI, waist circumference, glicemia, total
Ain Shams University, Cairo, Egypt.
cholesterol, LDL, Triglycerides, HDL. The subject were suddivided according
gender and age group.
Results
Introduction
In 15744 subjects, 62% females, 38% males, 49% was aged between 40-49 years
Increased visceral adiposity is usually associated with a clustering of atherogenic
old, 46% between 50-59 years old and 20% between 60-65 years old. 6.3% were
risk factors, such as insulin resistance, hypertension, dyslipidemia, alterations in
already diagnosed with diabetes mellitus (5.5% female and 7.4% male of the
coagulation and inflammatory cytokine profiles. Visceral adipose tissue derived
explored population). 15% of the patients who declared not having diabetes had a
serpin (Vaspin) is an adipokine with insulin sensitizing effect which is markedly
fasting glycaemia O 100 mg/dl. Of these 15%, 24% had a glycaemic value above
elevated in high body mass index (BMI) people.
126 mg/dl and 75.6% have glicemic value between 100-126 mg/dl (impaired
Aim
fasting glucose (IFG) or pre-diabetes. In the population with IFG 39.8% have a
To evaluate serum Vaspin level in relation to atherogenic risk factors such as
BMI between 25-30 and 44.8% kg/m2 a BMI O 30 kg/m2. 89.5% of females have
insulin resistance, dyslipidemia, hypertension, inflammation in obese subjects
a WC (Waist circumference) O 80 cm and 74% of males a WC O92 cm.
with T2DM and obese subjects without T2DM.
Conclusions
Method
Albania is a developing country who went trough important socio-economical
80 subjects participated, with BMI ranging from 27-39 selected from outpatient
changes in the last decade. We find a high diabetes mellitus prevalence which
clinic of Endocrinology of Ain Shams University Hospital. They were divided
could be higher because of the not yet diagnosed diabetes. An important role have
into 2 groups 40 obese subjects with T2DM (group I) and 40 obese subjects
the pre-diabetes population where a high prevalence of overweight and obesity is
without T2DM (group II). History, clinical examination, FBS, 2-PP, HBA1C,
observed. Campaign to rise diabetes and pre-diabetes awareness and encourage
Total cholesterol, Triglycerides, HDL and LDL, HOMA/IR, Serum Vaspin level
lifestyle modification are very important to prevent and postpone the diabetes
(by ELISA) and CRP were done.
onset in the prediabetes population.
Results
DOI: 10.1530/endoabs.49.EP495
Serum Vaspin was higher in group II than group I (P%0.01). HOMA-IR was
higher in group I than group II (esp. females) with P%0.01. Regarding hs-CRP
there was no significant difference. In Group I serum vaspin had a negative
correlation with age
(PZ0.010), diabetes duration
(PZ0.015), a positive
correlation with Waist/Hip ratio (PZ0.047), and LDL (PZ0.034). There were
no correlation with BMI, systolic blood pressure, diastolic blood pressure, HA1c,
fasting blood glucose, 2 HPP, total cholesterol, triglycerides, HDL, hs-CRP and
EP496
HOMA-IR (PO0.05). In group II, serum vaspin had no correlation with any of the
Maturity onset diabetes of the young - clinical characteristics of a
variants (P-valueO0.05). Vaspin level was found to be independently correlated
portuguese cohort
with male gender and younger age with (PZ0.031).
Ana Amado, Raquel Almeida, André Carvalho, Cláudia Amaral,
Conclusion
Cláudia Freitas, Conceiça˜o Bacelar, Joana Vilaverde, Maria
Obese subjects with T2DM have more atherogenic risk profile and lower Vaspin
Helena Cardoso, Sofia Teixeira & Fátima Borges
level than obese subjects without T2DM. It was inversely correlated with age and
Endocrinology Department, Centro Hospitalar e Universitário do Porto,
diabetes duration and positively correlated with Waist/Hip ratio, LDL. Male
Porto, Portugal.
gender and age are strong independent predictors of serum vaspin level. Vaspin
may be an important adepokine that may play an important protective role against
metabolic disturbance and cardiovascular risk in obese subjects with T2DM.
Introduction
DOI: 10.1530/endoabs.49.EP497
Maturity onset diabetes of the young (MODY) accounts for 1-2% of all forms of
diabetes mellitus (DM). As classic criteria that lead to its suspicion have low
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Diabetes Complications
EP500
EP498
Overweight and obesity in pregnant with diabetes mellitus type 1
Paloma Moreno-Moreno, Ángel Rebollo-Román, Rafael Palomares-Ortega,
Prevalence of diabetic neuropathy and nephropathy in different ethnic
Concepción Mun˜oz-Jimenez, María Rosa Alhambra-Expósito & María
minorities
Ángeles Gálvez-Moreno
Rajab Khan
Management Unit of Clinical Endocrinology and Nutrition, University
University of Manchester, Manchester, UK.
Hospital Reina Sofía, Córdoba, Andalucía, Spain.
Introduction
Objectives
The focus on diabetic complications has increased over the years yet it is only
Pregnant women who are overweight or obese have an increased risk of
recently that research has identified a link between ethnicity and the development
complications during pregnancy, as do pregnant women with type 1 diabetes
of diabetic complications.
mellitus (DM1). The objective of this study is to describe the prevalence of
Aims
overweight/obesity in pregnant women with DM1, and associated complications.
To establish the relationship between ethnic group and the prevalence of either
Patients and methods
diabetic nephropathy or neuropathy.
Retrospective descriptive study of pregnant women with DM1 (2004-2014).
Method
Variables analyzed: age, initial body mass index (BMI), HbA1c, abortions, type
A retrospective note review was undertaken for all diabetic patients who had a
of delivery and fetal malformations. Statistical analysis: comparing proportions
status of ‘current’ in the database. This returned 6608 patients, however, only
with the chi-squared and comparing means with Student’s test.
1838 patients met the inclusion criteria. The notes were reviewed, analysed and
Results
compared with the current literature on ethnicity and diabetic microvascular
156 pregnancies in women with DM1. Age 31.41G4.51 years. At the beginning
complications.
of pregnancy, 50.4% were normal weight, 36.2% were overweight (12.4% grade 1
Results
and 23.8% grade 2) and obesity was 10.5% (7.6% grade 1, 1.9% grade 2, 1%
Of the 1838 patients: 56.9% were Caucasian, 13.9% Afro-Caribbean, 23.0%
grade 3). 3% women had BMI !18.5 kg/m2. Normal weight vs overweight/-
South Asian and 6.3% Other. Afro-Caribbean’s had a higher mean systolic blood
obesity: unplanned pregnancies 70.4 vs 66.7% (PZ0.85); HbA1c (%) previous
pressure (139.03 mmHg) compared to other ethnicities with Caucasians having
gestation 7.4G1.4 vs 7.4G1.2 (PZ0.98), first trimester 7.4G1.7 vs 7.1G1.3
the lowest mean at 132.91 mmHg. Afro-Caribbean’s were found to have poorer
(PZ0.88), second trimester 6.3G0.8 vs 6.5G0.8 (PZ0.31), third trimester 6.5G
glycaemic control (69.5 mmol/mol) compared to the remaining ethnic groups.
0.8
vs
6.5G0.8 (PZ0.88); newborn weight 3516.1G735.22 vs 3617.07G
Nephropathy was found to be most common in Afro-Caribbean’s (14.3%)
693.10 g
(PZ0.42); newborn size
50.9G2.4
vs
50.8G2.5 cm
(PZ0.76).
followed by South Asians (13.1%). Caucasians and Other groups had lower rates
Maternal and neonatal complications (%) normal weight vs overweight/obesity:
at 7.8% and 8.6%, respectively. Neuropathy was most common in Caucasians
maternal hypoglycemia 3.7 vs 6.7 (PZ0.7); gestational hypertension 5.7 vs 12.2
(24.4%) and lowest in Afro-Caribbean’s (14.7%); the other two ethnic groups,
(PZ0.3); abortions 3.8 vs 9.5 (PZ0.33); induced childbirth 58 vs 61 (PZ0.92);
South Asians and Other, had similar levels at 17.4% and 16.4% respectively.
caesarean section
38 vs 55 (PZ0.12); macrosomia 29.4 vs 24 (PZ0.71);
Conclusion
congenital malformations 8 vs 7.1 (PZ0.78); newborn hypoglycemia 6 vs 5
The link between ethnicity and complications was found to be statistically
(PZ0.93).
significant (P!0.01). Future research and epidemiological studies must focus on
Conclusions
why these differences occur and if they are independent of socio-demographic,
In our series, the prevalence of overweight/obesity in pregnant women with DM1
anthropometric and clinical characteristics.
is high, occurring in almost half of pregnancies. There were no differences in
DOI: 10.1530/endoabs.49.EP498
glycemic control during gestation or in the occurrence of maternal or neonatal
complications associated with overweight/obesity.
DOI: 10.1530/endoabs.49.EP500
EP499
Correlation of homocysteine with macro and microvascular
complication in patients with diabetes mellitus type 2
Marija Krstevska1 & Ksenija Bogoeva Kostovska2
1Department of Medical and Experimental Biochemistry, School of
Medicine, University Ss. Cyril and Methodius, Skopje, Center, Macedonia,
EP501
2Doctor’s Practices Prof. Dr Bogoev, Skopje, Center, Macedonia.
Does empowerment from an ‘ABC approach’ and ‘Telemedicine’
improve outcomes in a nurse-led diabetes kidney clinic?
Susan Irwin & Parijat De
In recent years, plasma homocysteine (Hcy) level, has been reported to be
Sandwell & West Birmingham Hospital NHS Trust, Birmingham, UK.
associated with the vascular complications of diabetes mellitus type 2 (DM2). In
patients with DM2, elevated Hcy levels were associated with insulin resistance
and nephropathy. The aim of this study was to investigate the association of
Aims
hyperhomocysteinaemia with micro and macrovascular complications, increased
Implementation of a protocol-driven, nurse-led clinic to see influence on
levels of HbA1c and lipid parameters in patients with DM2 in a Macedonian
cardiovascular risk and renal disease progression using a simple ‘ABC’ approach
population. 80 DM2 patients were enrolled for the study and were classified into
- target HbA1c !7%, BP !125/75 mm Hg and Cholesterol !4 mmol.
two groups: 30 patients with no associated complications, control, and 50 patients
Method
with complications. Homocysteine levels and the other conventional parameters
Weekly Diabetes Specialist Nurse (DSN) clinic with emphasis on ABC approach
(HbA1c, lipid profile, and microalbuminuria) for identifying complications of
and guided FLORENCE Telehealth free texting technology for medication
DM2 were measured. The Hcy levels were significantly higher in DM2 patients
reminders and self-monitoring of BP (machines provided).
(16.05G6.12 vs 10.44G3.33 micromol/l) compared with control. Significantly
Results
elevated homocysteine levels were found in DM2 patients with CAD (P!0.001),
May 2008 - Apr 2009 (12 months) - Cohort A 41 patients. May 2010 - June 2014
neuropathy (P!0.000), retinopathy (P!0.05), high blood pressure (PZ0.02)
(24 months) - Cohort B 133 patients. Mean age 64 years, 78-90% patients
and microalbuminiria (P!0.000) as compared to control subjects. There was a
Asians/Afro Caribbean. Excellent patient satisfaction scores, significant
positive correlation between elevated HbA1c (rZ0.475) levels and serum LDL-
reductions in HbA1c in Cohort A and B by 0.7% (7.62 vs 8.32%) and 1.5%
cholesterol (rZ0.871) with Hcy concentration in DM2 patients with compli-
(9.1
vs 7.6%) respectively, SBP (12-16 mmHg) and DBP (3-6 mmHg) and
cation. The results of this study have shown that homocysteine levels were
Cholesterol in all cohorts were achieved. Urine ACR decreased significantly in
significantly higher in DM2
patients with developed micro-/macro-vascular
both cohorts
(by mean
17-39 mg/mmol). Number of BP medications
(3)
complications and highly positive correlated with HbA1c and serum LDL-
increased in all cohorts. 95 and 85% patients respectively in both cohorts were
cholesterol, also. Results have shown that hiperhomocysteinemia is risk factor in
prescribed ACE, ARB or both.
etiology of vascular complications in DM2 patients.
Conclusions
DOI: 10.1530/endoabs.49.EP499
Outcomes suggest that our nurse-led clinic is highly effective in DN patients. The
‘ABC approach’ and simple information sharing strategy
(Telehealth
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
FLORENCE) were effectively used to inform strategic decision making/intensi-
Additional investigations were performed: kidney ultrasound, which revealed
fication of therapy through patient empowerment, up-skilling of knowledge and
shrunken kidneys, Urea- 64.21 (N 15.0-45.0), Phosphorus-1.98 (N 0.48-2.19),
improved medication compliance - 3 key processes in any chronic disease
Parathyroid hormone-273.76
(N
9.0-79.5),Vitamin D-7
(N
30.0-100.0);
management.
Potassium-5.59 (N3, 5-5), pH-7.26 (N 7.32-7.72) Hemoglobin-10.2 (N 12-16).
DOI: 10.1530/endoabs.49.EP501
The patient had no diabetic specific complications. When DM was diagnosed the
patient has already got dipstick proteinuria 0.3 g/l and it was considered as the
result of diabetes. Therefore no further investigations were performed to find out
the cause of proteinuria. We have not performed renal biopsy to diagnose the real
cause of proteinuria, we just started to treat CKD.
Conclusion
Often proteinuria is revelaed when DM is diagnosed, that’s why, no further
investigations are performed to precise the real cause of it. Yes, hyperglycemia
EP502
can cause various damages of kidney, but not in all cases. So, we always have to
Causes of diabetic ketoacidosis: type 1 diabetes versus type 2 diabetes
remember that in diabetic patients the cause of proteinuria may be due to other
Marwa Omri, Rayene Ben Mohamed, Imen Rezgani, Sana Mhidhi,
reasons. We always have to pay attention to other diabetic specific complications
Aroua Temessek & Faika Ben Mami
and always ask about detail clinical history, for correct diagnosis, better
National Institute of Nutrition, Tunis, Tunisia.
management and prevention of progression of renal disease.
DOI: 10.1530/endoabs.49.EP504
Aim
The aim of our study was to compare the clinical profile of type 1 and type 2
diabetic patients who are hospitalized in our service for diabetic ketoacidosis.
Methodology
This was a descriptive study involving 121 diabetic patients hospitalized for
diabetic ketoacidosis in the C department of diabetology of the national institute
of nutrition of Tunis.
Results
EP505
Of the 121 subjects studied, 57.85% are type 2 diabetic patients and 42.15% are
A Review of the literature: What are the impacts of hypoglycaemia in
type1. Type 2 diabetic patients are older, have a higher glycated hemoglobin level
insulin-dependent diabetic adults?
and a higher BMI compared to the type 1 diabetic patients. For both type of
Charles O’Donovan1 & Olivia O’Donovan2
diabetes, the principal causes of ketoacidosis are infectious diseases represented
1University of Leeds, Leeds, UK;2Bradford Teaching Hospitals, Bradford,
mainly by urinary tract infection. For type
2 diabetic patients cessation of
UK.
treatement, inaugural diabetes, insulinopenia and lipodystrophy are observed
respectively in 22.7, 12.3, 11.9 and 10.1% of patients presenting ketoacidosis. For
type 1 diabetic patients cessation of treatment, inaugural diabetes, pregnancy and
Background
lipodistrophy are observed respectively in 18.4, 14.6, 8.9 and 7.1% of patients
The prevalence of diabetes has reached epidemic proportions and according to the
hospitalized for ketoacidosis.
World Health Organisation (WHO) more than 220 million people worldwide have
Conclusion
diabetes. The main complication in insulin-dependent diabetes mellitus (IDDM)
The main causes of diabetic ketoacidosis are infectious diseases and cessation of
patients is hypoglycaemia, with approximately 90% of all IDDM patients having
treatment, in type 2 diabetic patients as well as in type 1 diabetic patients. So that,
experienced a hypoglycaemic episode. Hypoglycaemia has a substantial clinical
education remains the best way to prepare diabetic patients to face situations of
impact in terms of mortality, morbidity and quality of life.
stress and to have a good therapeutic compliance.
Methods
DOI: 10.1530/endoabs.49.EP502
A systematic search of MEDINE and EMBASE was performed for all relevant
published articles. Reference lists of all included studies were also searched.
Studies were included assessing fear of hypoglycaemia, recognition of symptoms,
health-seeking behaviour and impact on overall wellbeing. One reviewer
screened abstracts of all identified citations, selected potentially eligible studies
and assessed their full-text versions using the STROBE
(Strengthening the
EP503
reporting of observational studies in epidemiology) checklist for cohort, case-
control and cross-sectional studies (combined.) Findings from the studies were
then narratively synthesized.
Abstract withdrawn.
Results
Eight studies were included in this review. After hypoglycaemia, IDDM patients
have significantly (o!0.01) raised fears of future hypoglycaemia, more fatigue,
reduced alertness and a negative impact on health-related quality of life (HRQL.)
Conclusion
Hypoglycaemia has a wide range of negative emotional, social and behavioural
consequences on IDDM patients. These impacts, hence are a major barrier to
IDDM patients achieving optimal glycaemic control. There remains a need for a
large multi-country study that incorporates mixed-methods data collection,
including a qualitative aspect to provide more in-depth views of the effects of
hypoglycaemia.
EP504
DOI: 10.1530/endoabs.49.EP505
Is proteinuria always associated with diabetes mellitus?! Do we always
make right diagnosis?!
Natia Katamadze & Anna Shamanadze
V.Iverieli Endocrinology, Metabology, Dietology Center ‘ENMEDIC’,
Tbilisi, Georgia.
EP506
Introduction
A protective effect of lobeglitazone on renal fibrosis in unilateral
Proteinuria is a condition in which urine contains an abnormal amount of protein.
ureteral obstruction mice model
Proteinuria is a sign of chronic kidney disease (CKD), which can result from
Hye-Soon Kim1, Kwi Hyun Bae1, Gwon Soo Jung1, Hye Jin Ham1,
diabetes, high blood pressure and other diseases that cause inflammation in the
Bo Yoon Park1, Yeon Kyung Choi1, hyun Ae Seo2, Jung Beom Seo1 &
kidneys. If CKD progresses, it can lead to end-stage renal disease, when the
Keun Gyu Park1
kidneys fail completely.
1Kyungpook National University Hospital, Dae Gu City, Republic of Korea;
Case presentation
2Fatima Hospital, Dae Gu City, Republic of Korea.
Sixty-three years old female patient attended our clinic as her glycaemia was poor
controlled. She is diagnosed with diabetes mellitus (DM) type 2 during 9 years.
Laboratory studies were performed: HbA1c- 9.4%, elevated plasma creatinine
Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly
176.32
(N53, 0-97.2) and proteinuria in urine with dipstick 1.01 g/l was observed.
all cause types of chronic kidney disease. Although classic peroxisome
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
proliferator-activated receptor-gamma (PPARg) agonists have a protective effect
Results
on diabetic nephropathy, much less is known about their direct effects in renal
A significant among-group difference was found in adiponectin (ApN) (DM1 vs
fibrosis. This study aimed to investigate possible beneficial effects of
DM2 vs DM3Z15.23G11.54 vs 7.93G5.75 vs 4.47G2.14; ANOVA: FZ11.56,
lobeglitazone, a novel PPARg agonist, on renal fibrosis in mice with unilateral
dfZ2, P!0.0001), C-reactive protein (CRP) (DM1 vs DM-OH vs DM-INS Z
ureteral obstruction (UUO). Through hematoxylin/eosin and Sirius red staining,
2.14G2.42 vs 4.15G5.13 vs 2.16G2.32; FZ7.27, dfZ2, PZ0.026), high
we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy
density lipoprotein (HDL) (DM1 vs DM-OH vs DM-INS Z1.71G0.21 vs 1.37G
and fibrosis. Immunohistochemical analysis in conjunction with quantitative
0.35 vs 1.52G0.31; FZ14.01, dfZ2, P!0.001), uric acid (UA) (DM1 vs
RT-PCR and western blot analysis revealed that lobeglitazone treatment inhibited
DM-OH vs DM-INS Z249.12G71.3 vs 351.4G88.1 vs 321.9G137.13; FZ
UUO-induced upregulation of renal Smad-3
phosphorylation, alpha-smooth
14.23, dfZ2, P!0.001) and body mass index (BMI) (DM1 vs DM-OH vs
muscle actin, plasminogen activator inhibitor-1, and type 1 collagen. In vitro
DM-INS Z24.35G4.01 vs 30.45G7.17 vs 28.51G5.17; FZ12.01, dfZ2,
experiments with rat mesangial cells and NRK-49F renal fibroblast cells
P!0.0001), between tested groups. Tukey post hoc test showed a significant
suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are
difference (P!0.05) in ApN between DM1 and DM-OH, DM1 and DM-INS, and
mediated by inhibition of the TGF-b/Smad signaling pathway. In conclusion, the
DM-OH and DM-INS, but not in BMI (PZ0.12), CRP (PZ0.21), UA (PZ0.41)
present study demonstrates that lobeglitazone has a protective effect on UUO-
and HDL (PZ0.89) between DM-OH and DM-INS. In DM-INS the best model
induced renal fibrosis, suggesting that its clinical applications could extend to the
(R2Z0.942) for ApN included HDL (R2Z0.66, PZ0.002) and UA (R2Z0.35,
treatment of non-diabetic origin renal disease.
PZ0.007). In DM-INS ApN correlated significantly (P!0.05) with HDL (rZ
DOI: 10.1530/endoabs.49.EP506
0.55), FPG (rZ0.42), CRP (rZ0.49), and fibrinogen (FIB) (rZ0.69). Duration of
insulin therapy did not correlate with ApN in DM-INS (PZ0.82).
Conclusions
ApN was decreased in DM-INS compared to DM-OH, which could be explained
with an effect of insulin on adipocytes and C-peptide, consequently on ApN level.
Decreased ApN suggests increased risk of vascular disease in insulin treated
patients. HDL was among the main predictors of ApN. In DM-INS HDL was not
decreased, while CRP was not increased, which could be beneficial in CVD
EP507
protection.
Using the plastic closure techniques of wound defecting treatment of
DOI: 10.1530/endoabs.49.EP508
patients with diabetic foot syndrome
Maksym Prystupiuk, Iuliia Onofriichuk, Liudmyla Naumova,
Lev Prystupiuk & Marianna Naumova
Bogomolets National Medical University, Kyiv, Ukraine.
Purpose
To improve methods of plastic closure of wound defects in patients with diabetic
foot syndrome using skin flaps on vascular pedicle of the perforating vessels.
Methods
EP509
The study involved patients with diabetes type 2 complicated with diabetic foot
syndrome neuroischemic form. The study included 31 patients, 15 people in the
Prayer marks in immigrants from Bangladesh with diabetes mellitus
study group and 16 people - the control group. Area wounds ranged from 3.8 to
who live in Greece
21 cm2. Cleansing the wounds was performed by ultrasonic cavitation. On the
Georgios Papadakis1, Thomas Zambelis2, Kostas Konstantopoulos3 &
wound bandage with sorption-based antimicrobial composition of nanosized
Stylianos Chatzipanagiotou4
silica. Thus, the wound was purified for 2-3 days. On the third day, the wound
1STEPS Stoffwechselzentrum, Biel/Bienne, Switzerland;2Department of
was applied vacuum-assisted closure with a standard negative pressure of
Neurology, Aeginition Hospital, Athens, Greece;3Department of Haema-
125 mm Hg. The device was applied for 3-6 days. The number of colony-forming
tology, Laikon University Hospital, Athens, Greece;4Department of
units for the success of the operation should be less than 10. Formed flap, which
Medical Biopathology, Aeginition Hospital, Athens, Greece.
corresponds to the size and configuration of the defect on the foot.
Results
Introduction
In the study group noted engraftment graft in 14 patients. Time of full engraftment
Prayer marks (PMs) have been reported in the literature among Muslim prayers.
and the healing of the wound defect in patients of the main group was 14G3 days
PMs are found most often on the forehead, knees, ankles and dorsa of the feet. The
in the control group healing ulcers - 51G10 days.
most common changes consist of thickening, lichenification and hyperpigmenta-
Conclusions
tion of the skin, the causative factors being repeated pressure and friction during
Improved techniques in the treatment of wound autodermoplastic defects in
pray.
patients from diabetic foot syndrome, which is preparation wounds using an
Objectives
ultrasonic cavitation, vacuum bandage hardware. Using a split skin flap can
Immigrant populations are disproportionately affected by diabetes and its
effectively cover the bandage wounds, supporting the ability to save limbs and
complications. Moreover, diabetic foot ulcer is a major complication of diabetes
improve the quality of life.
mellitus, and probably the major component of the diabetic foot. PMs are foot
DOI: 10.1530/endoabs.49.EP507
lesions that can ulcerate. In our study we focused on the frequency of PMs among
Bangladeshi immigrants who live in Athens, Greece and have diabetes.
Methods
A total of 166 immigrants from Bangladesh (150 men and 16 women) with
diabetes mellitus and 65 (58 males and eight females) normal subjects from
Bangladesh were recruited. Characteristic pictures of PMs are taken and
provided.
EP508
Results
Insulin therapy with an impact on inflammation can change the risk for
The mean duration of living in Greece was 10.34G6.2 years. The mean age was
cardiovascvular diseases in type 2 diabetes
44.05G8.1 years old and the reported duration of diabetes 4.86G4.5 years. The
Spomenka Ljubic1,2, Anamarija Jazbec2, Martina Tomic1, Ivana Antal1 &
mean A1C was 7.74G1.6% and the mean Glucose values 190.3G72 mg/dl. A
Lea Smircic-Duvnjak1,2
total of 28 patients with diabetes (16.9%) (one patient with type 1 DM, and 27
1Vuk Vrhovac University Clinic, Merkur University Hospital, 10000
patients with type 2 DM) and one subject in control group (1.5%) had PMs and all
Zagreb, Croatia;2University of Zagreb, 10000 Zagreb, Croatia.
of them where males. Diabetic patients with PMs and diabetic patients without
PMs had similar and not statistical significant BMI (23.67G2.89 vs 24.30G
3.42 kg/m2, PZ0.187), age
(44.04G7.3
vs
44.06G8.35
years, PZ0.488),
Introduction
disease duration (3.86G3.0 vs 5.07G4.74, PZ0.080), and A1C values (7.4G
Patients with diabetes (DM) are at increased risk for cardiovacular disease (CVD).
1.3 vs 7.8G1.6%, PZ0.408). None of the PMs had infection, ulceration or
Possible effects of insulin therapy on development of atherosclerosis and CVD
bleeding at the time of examination. The marks were not itchy or painful and they
were studied.
were observed on the dorsal aspect of the left foot.
Patients and methods
Conclusions
Relevant metabolic parameters were determined in 348 patients assigned into
PMs can often provide clinicians with helpful information for the patient’s
groups with DM2 on oral hypoglycemic drugs (DM2-OH) and insulin (DM2-INS),
cultural background. PMs could ulcerate and our study emphasizes the need for
and with DM1.
clinical awareness of PMs, especially for patients with diabetes. Moreover, people
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
come from different ethnic groups and ethnicity can have important effects on
Objective
health and on the management and treatment of diabetes.
A diabetic state is causally related to heart failure (HF) which is a leading cause of
DOI: 10.1530/endoabs.49.EP509
mortality. Early detection of high-risk individuals is imperative for primary
prevention. The aim of this study was to investigate the role of N-terminal pro-B-
type Natriuretic Peptide (NT-proBNP) in patients with diabetes type 2 (DT2).
Methods
We investigated 86 patients both sexes with DT2 aged 65.54G11.37 years (from
50 to 65 years) without clinical cardiovascular disease at baseline. Plasma levels
of NT-proBNP and other biochemical data were measured. Control group
included 34 healthy subjects the same age.
EP510
Results
Therapy of hormonal disorders in women with acne
NT-proBNP level increased with age in both the diabetic and control group but
Liudmyla Naumova, Lev Prystupiuk, Maksym Prystupiuk,
patients with DT2 had higher NT-proBNP levels (P!0.05). NT-proBNP was
Marianna Naumova & Iuliia Onofriichuk
significantly correlated with HbA1c
(rZ0.53, P!0.001), serum creatinine
Bogomolets National Medical University, Kyiv, Ukraine.
(rZ0.62, P!0.001), serum cystatin C (rZ0.48, P!0.001), and age (rZ0.31,
P!0.001). Multivariate linear regression analysis of the significant variables
Introduction and objectives
showed that age (PZ0.011), male gender (PZ0.012), triglyceride (P!0.001),
About 9% of world population suffer from acne, which occupies the 8th place
systolic blood pressure
(P!0.001), and cystatin C
(P!0.001) were the
among all human diseases, and the 3d place among dermatological disorders.
independent predictors of fasting serum log-NT-proBNP levels in diabetic
Acne is diagnosed in 54% of 18 year aged women. Acne manifests mostly in 12-
patients.
14 year age and regresses after 20 year age, even though more and more women
Conclusions
have recently addressed their doctors for acne problem developing after 20 year
We showed the role of risk factors to heart failure in patients with DT2. In these
age. Location of this dermatosis in open areas of skin leads to depression and
patients, the presence of dyslipidemia, hypertension, and renal impairments were
social disadaptation, which underlines the actuality of this problem. It is well
predictors of fasting serum log-NT-proBNP levels. Thus adjustments for the age,
known that a leading role in the development of adult acne is played by
sex and renal function are necessary for determining cardiac risk based on
hyperandrogenism, which is often caused by polycystic ovarien syndrome
NT-proBNP level.
(PCOS). Well known also is that combined oral contraceptives are used for the
DOI: 10.1530/endoabs.49.EP511
treatment of female acne caused by hyperandrogenism syndrome. However, not
all patients benefit from this kind of treatment. Therefore, the aim of our study
was to better investigate endocrine system status and establish disorders
stimulating the appearance and development of acne in adult women and then
prescribe the proper therapy.
Material and methods
Our study involved 126 women with acne, of 18-37 year age. It included the
EP512
performance of Sonography of thyroid gland and pelvic organs as well as the
Metabolic risk factors in adolescent girls with type 1 diabetes
determination of levels of the following hormones: Prolactin, TSH, FSH, LH,
Marta Isabel Pinheiro1, Juliana Oliveira1, Rita Santos Silva2,3,
17-Hydroxyprogesterone, DHEAS, Free testosterone, Oestradiol, Progesterone,
Cíntia Castro Correia2,3 & Manuel Fontoura2,3
Anti-Mullerian hormone.
1Department of Pediatrics. Hospital Pediátrico Integrado, Centro Hospitalar
Results
de Sa˜o João, Porto, Portugal;2Pediatric Endocrinology and Diabetology
The investigation confirmed high androgenic hormones level in 86.5% of women
Unit, Hospital Pediátrico Integrado, Centro Hospitalar de São João, Porto,
with acne, although clinical manifestations of hyperandrogenism syndrome were
Portugal;3Faculdade de Medicina da Universidade do Porto, Porto,
found only in 45% of these women. i) PCOS was found in 20.2% of women with
Portugal.
acne. ii) Hyperprolactinemia - in 34.9%. iii) Atypical (late) form of congenital
adrenal dysfunction - in 44.9%. So, it was established that, other than PCOS,
Hyperprolactinemia and Atypical (late) form of congenital adrenal dysfunction
Background
are also main causes of hyperandrogenism in women, which can lead to acne.
Adolescent girls with type
1 diabetes
(T1DM) have a higher incidence of
Depending on the endocrine pathology of patients, appropriate treatment was
metabolic risk factors like hypertension, dyslipidemia, non-alcoholic hepatic
prescribed: i) Oral contraceptives for PCOS. ii) Dopamine agonists for
steatosis (NASH), abdominal adiposity and polycystic ovarian syndrome (PCOS)
Hyperprolactinemia. iii) Synthetic glucocorticoids for Atypical (late) form of
when compared with their non-diabetic peers. Moreover, metabolic risk factors
congenital adrenal dysfunction. Also, regardless of the type of hormonal
seem to appear even in T1DM girls without overweight or obesity. We aimed to
disorders, all women received proper topical therapy in accordance with the
determine the prevalence of several metabolic risk factors in adolescent T1DM
severity of acne.
females, according to their nutritional status.
Conclusions
Methods
As a result, we got to the following conclusions: i) On the background of the
Girls older than 14 with T1DM for a period longer than 2 years were included.
proposed differentiated combined therapy within 6 months, positive effects were
They were divided into two groups according to their body mass index (BMI
achieved in 85% of women with significant reduction of the eruption and without
above or below the 85th percentile). The two groups were compared in what
its recurrent appearance. ii) The condition of skin and acne eruptions was clearly
regards the presence of abdominal adiposity, hypertension, lipid profile
dependent on hormone levels in the blood. iii) In order to achieve efficient
abnormalities, NASH and PCOS.
treatment of female acne, combined therapy should be based on the correction of
Results
hormonal disorders.
44 adolescents were included: 25 with normal weight and 16 (39%) with obesity
DOI: 10.1530/endoabs.49.EP510
or overweight. No difference was found between age (17G1.8 for girls with
normal weight vs 17G1.7 for obese and overweight girls; PZ0.49) or mean A1c
among groups (8.5G1.4 vs 8.5G1.1; PZ0.98). Girls with normal weight had a
longer duration of T1DM (9G4 vs 7G4; PZ0.03). In what regards overweight or
obese girls, 23% had abdominal adiposity, 14% hypertension, 21% lipid profile
abnormalities, 23% NASH, 23% PCOS and 20% metabolic syndrome. Among
normal weight diabetic girls, 6% had abdominal adiposity, 19% hypertension, 5%
lipid profile abnormalities, 6% NASH and 6% PCOS. No statistical significant
differences were found between the two groups.
Discussion
EP511
The prevalence of metabolic risk factors, including NASH and PCOS, was similar
N-Terminal pro-B-type natriuretic peptide level in type 2 diabetic
of that reported in the published data concerning diabetic young women, although
patients
there are few studies in the pediatric population. Even though metabolic
Volha Vasilkova1,3, Tatiana Mokhort2, Elena Naumenko3 &
syndrome and its components were more prevalent among overweight and obese
Margarita Zmailik3
T1DM girls, they were also present among normal weight diabetic individuals.
1Gomel State Medical University, Gomel, Belarus;2Belarusian State
DOI: 10.1530/endoabs.49.EP512
Medical University, Minsk, Belarus;3The Republican Research Center for
Radiation Medicine and Human Ecology, Gomel, Belarus.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP513
both increased NF-kB p65-Ser536 phosphorylation and decreased GSK3b-Ser9
phosphorylation in the aortas from high-fat fed mice were reversed by treating
Transcultural prevalence of depression in type 2 diabetic patients in
with telmisartan. Taken together, our findings demonstrate that telmisartan
Egypt and Yemen
ameliorates hyperglycemia-exacerbated vascular inflammation at least in part by
M. M. Aboshady1, M. R. Halawa1, A. A. Elewa1, G. El-Khouly2 &
increasing GSK3b-Ser9 phosphorylation, which mediates a decreased VCAM-1
A. S. Bin-Nabhan3
expression in a PPARg-independent manner. Telmisartan may be useful for the
1Endocrinology Unit and Internal Medicine Department, Faculty of
treatment of DM-associated vascular inflammation and cardiovascular diseases.
Medicine, Ain Shams University, Cairo, Egypt;2Neuropsychatry Depart-
ment Ain Shams University, Cairo, Egypt;3Endocrinology Unit and Internal
DOI: 10.1530/endoabs.49.EP514
Medicine Department, Hadhramout University, Sanaa, Yemen.
Background and aims
Depression is a common co-morbidity among people with diabetes that reduces
quality of life and is associated with morbidity, mortality, and health care costs.
We aimed to assess the prevalence of depression among patients with type 2
EP515
diabetes in two Arabic nations, Egypt and Yemen and to examine its relationship
Continuous glucose monitoring system in the value of diabetes mellitus
with socio-demographic data and diabetes complications.
type 1 control
Methods
Tatiana Mokhort2, Elena Makhlina1, Marina Kapliyeva1, Yana Navmenova3
We conducted a cross-sectional analysis on 200 subjects with type 2 diabetes,
& Irina Savosteeva
divided into two groups: 100 Egyptian and 100 Yemeni subjects. All selected
1Gomel State Medical University, Gomel, Belarus;2Minsk State Medical
subjects were subjected to full medical history and clinical examination.
University, Minsk, Belarus;3Republican Scientific and Practical Center for
Laboratory tests included fasting plasma glucose and HbA1C. MADRS scale
Radiation Medicine and Human Ecology, Gomel, Belarus.
was used for diagnosis of depression.
Results
Both groups were age and sex matched. The prevalence of depression was 39% in
Purpose
Egyptian and
34% of Yemeni patients, with no statistical significance. In
Estimation of the continuous glucose monitoring system (CGMS) in the value of
Egyptian diabetics, depression was significantly associated with female gender,
diabetes mellitus type 1 (DM1) control.
duration of diabetes, poor glycemic control, higher number of children, low and
Materials and methods
very low socioeconomic levels, high mean number of cigarette smoking, lower
162 DM1 patients have been divided on 2 groups: 1st group with adequate control
mean number of years of education and presence of diabetes complications.
DM1 - glycated hemoglobin (HbA1C) %7.5% (nZ38) and 2nd group with
However, in Yemeni diabetics, depression was significantly associated with
inadequate control - HbA1CO7.5% (nZ124). All patients carried out CGMS
female gender, birth order, poor glycemic control, Low and very low
with glycemia symmetrization scales and an estimation of probability of a
socioeconomic levels, lower mean number of years of education, diuretic usage
dysglycemia, hypo- and hyperglycemias risks with calculation of indexes of risk
for medical co-morbidities. The most important predictors of depression were
(InR). High risk of a hypoglycaemia at InR more than 4.5; low - less than 2.5.
female sex, higher number of children, divorce, Low and very low socioeconomic
The high risk of a hyperglycaemia at InR is more 9.0, low risk - less than 4.5.
levels and lower mean number of years of education.
InR dysglycemias - a difference of InR hyper- and hypoglycemias.
Conclusion
Results
High prevalence of depression among Egyptian and Yemeni type 2 diabetic
HbA1C level in the 1st group of patients was 6.75% (6.40; 7.25) - adequate
patients. Depression associated with poor glycemic control.
control DM1, and in 2nd - 9.40% (8.30; 11.10) - inadequate control. InR in group
Keywords: Diabetes mellitus; depression; Egyptian; Yamani.
1 was less (8.25 (4.80; 14.70)), than in the 2nd group - 16.24 (10.45; 20.60) (P!
DOI: 10.1530/endoabs.49.EP513
0.001). In the group with inadequate control of DM1 InR of a hyperglycaemia has
been raised at 85% of patients, in comparison to 48% of patients in the 1st group.
Low InR of a hyperglycaemia in 2nd group was at 2% vs 1st group - 23% (P!
0.001). InR hypoglycemias has made 5.60 (3.00; 10.50) in 1st group and 5.00
(1.60; 9.20) - in 2nd group. In the absence of differences between groups in InR
hypoglycemias, InR of a dysglycemia significantly differed: 2.40 (3.00; 8.20) vs
9.85
(2.80; 18.55), (P!0.001). Hypoglycaemia InR exceeded 4.5 independently
EP514
of adequacy of control DM1 (high risk of hypoglycemias) at 53% of patients of
1st group and at 62% of patients 2nd group. Low InR of a hypoglycaemia in 2nd
Telmisartan attenuates hyperglycemia-aggravated VCAM-1 expression
group was at 19% that is significantly less (P!0.001), than in 1st group - 31%.
and monocytes adhesion in TNFa-stimulated endothelial cells by
Conclusions
increasing GSK3b-Ser9 phosphorylation
Inadequate control of HbA1C level among the patients with DM1 was observed
Du-Hyong Cho1, Sun-Ju Bae1 & Kee-Ho Song2
three times more often than adequate. By results of CGMS the insulin therapy
1Eulji University School of Medicine, Daejeon, Republic of Korea;
scheme has been optimizated according to a daily nutrition that allowed to reach
2Konkuk University School of Medicine, Seoul, Republic of Korea.
improvements of control DM1.
DOI: 10.1530/endoabs.49.EP515
Uncontrolled hyperglycemia accelerates endothelial damage and vascular
inflammation caused by proinflammatory cytokines including tumor necrosis
factor a
(TNFa), which leads to arteriosclerotic cardiovascular diseases.
Glycogen synthase kinase 3b (GSK3b) is reported to mediate TNFa-stimulated
nuclear factor-kB
(NF-kB) activation and expression of vascular adhesion
molecules. Although a few clinical trials have suggested that telmisartan, an
angiotensin II type
1
receptor blocker
(ARB), decreases cardiovascular
EP516
complications in diabetic patients, the underlying molecular mechanisms for
the beneficial effects have not been fully elucidated. Here, we investigated a
Chronic kidney disease in elderly patients with type 2 diabetes: 6 years
of follow-up study
molecular mechanism mediating the telmisartan’s beneficial effects on vascular
Soo-Kyung Kim, Kyung-Soo Kim, Seok Won Park & Yong-Wook Cho
inflammation in hyperglycemia-treated endothelial cells. Telmisartan dose-
CHA Bundang Medical Center, CHA University, Seongnam,
dependently attenuated the hyperglycemia-aggravated vascular cell adhesion
Republic of Korea.
molecule-1
(VCAM-1) expression and THP-1
monocytes adhesion, which
accompanied an increased GSK3b-Ser9 phosphorylation and a decreased NF-
kB p65-Ser536 phosphorylation. Among ARBs, including losartan and fimasartan,
Objective
only telmisartan induced GSK3b-Ser9 phosphorylation and showed the inhibitory
To evaluate prevalence of chronic kidney disease (CKD) and risk factors for
effects on expression of VCAM-1 and phosphorylation of NF-kB p65-Ser536. The
decline of renal function in elderly patients with type 2 diabetes (T2DM) after
telmisartan’s beneficial effects were not changed by pretreatment with GW9662, a
6 years of follow-up.
specific and irreversible peroxisome proliferator-activated receptor g (PPARg)
Methods
antagonist, although GW9662
clearly inhibited rosiglitazone-induced CD36
A cohort of 208 elderly patients (65 years or older) with T2DM participated in an
expression. Ectopic expression of GSK3b-S9A, a constitutively active mutant of
examination during 2005, a 6-years follow-up examination during 2011. An
GSK3b, significantly restored the telmisartan-attenuated VCAM-1 expression,
estimated glomerular filtration rate (eGFR) was calculated using the modification
NF-kB p65-Ser536 phosphorylation, and THP-1 monocytes adhesion. Finally,
of diet in renal disease equation. CKD was defined as eGFR !60 ml/min per
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1.73 m2 and worsening nephropathy was defined as eGFR !45 ml/min per
calculated by Cockcroft-Gault formula. Anemia was defined according to World
1.73 m2.
Health Organization criteria
(2008). In addition to routine clinical tests we
Results
measured serum levels of EPO and TNF alpha using immunoassay. Correlations
Among the 208 elderly patients with T2DM, 95 patients (45.7%) had CKD at
were assessed by Spearmen’s correlation coefficient
(rs). We found EPO
baseline. Obesity, longer diabetes duration, and usage of ACEI or ARB were
deficiency in 46.3% and decreased serum ferritin levels in 11.6% patients. Serum
independent factors related to the presence of CKD. Mean follow-up duration was
level of TNF alpha correlated negatively with hemoglobin level (rsZK0.311,
54.9 months. On multivariate Cox analysis, elderly patients with diabetes duration
PZ0.003). It had no significant interrelations with age, serum creatinine, ferritin,
R10 years had a 2.85-fold increased risk for worsening nephropathy compared
cholesterol, glomerular filtration rate and urinary albumin excretion. In patients
with those with diabetes duration !5 years (95% CI 1.29-6.30; PZ0.010).
without EPO deficiency TNF alpha level correlated with mean cell hemoglobin
Compared with HbA1c !8.0%, HbA1c R9.0% had a 2.82-fold increased risk for
content (rsZK0.700, PZ0.003), serum EPO (rsZ0.375, PZ0.017) and urea
worsening nephropathy (95% CI 1.40-5.69; PZ0.004). Elderly patients with
concentrations (rsZ0.433, PZ0.011). In EPO-deficient patients it correlated with
obesity showed worse renal prognosis than those without obesity (HR 1.89; 95%
serum urea (rsZ0.393, PZ0.032) but not with mean cell hemoglobin content
CI 1.01-3.53; PZ0.045).
(PZ0.950) and EPO level (PZ0.247). The results of the study suggest that
Conclusions
anemia in patients with early DN is multifactorial. EPO-deficient and EPO-
Since CKD was commonly accompanied in elderly patients with T2DM, it is
sufficient anemic patients with DN are characterized by different clinical
important to monitor and manage renal function in those patients, especially who
correlates of serum TNF alpha level. Further larger studies are needed to elucidate
had diabetes duration R10 years or HbA1c R9.0% or obesity.
clinical implications of these findings.
DOI: 10.1530/endoabs.49.EP516
DOI: 10.1530/endoabs.49.EP518
EP517
EP519
Association of metabolic risk factors with hyperfiltration and urine
Non-alcoholic steatohepatitis and diabetes mellitus: a case report
albumin creation ratio in represent Korean population (Korea National
Sara Castelo Branco1, Miguel Vasques2, Lurdes G. Matos2, Edite Filipe2 &
Health and Nutrition Examination Survey 2011-2014) without chronic
Adelaide Milheiro2
kidney disease
1Santa Marta Hospital, Lisbon, Portugal;2Curry Cabral Hospital, Lisbon,
Eun-Gyoung Hong, Sangmo Hong & Yun Mi Choi
Portugal.
Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si
Gyeonggi-do, Republic of Korea.
Non-alcoholic steatohepatitis (NASH) is a clinical entity characterized by the
infiltration of fat into the liver associated with hepatic inflammation. The etiology
The development of glomerular hyperfiltration precede the diagnosis of diabetes,
is unknown, however its most frequently observed in patients with type 2 diabetes
but most study had undertaken with diabetes or obesity patients. In this study, we
mellitus (DM 2), obesity or insulin resistance. DM 2 is an independent risk factor
determine the association between glomerular hyperfiltration and other metabolic
for the progression of NASH. Usually there are no symptoms, so it is not possible
risk factors which associated diabetes in represent Korean population without
to estimate its prevalence. The treatment focuses on the control of associated
chronic kidney disease. We analyzed 19 244 subjects with a estimated glomerular
diseases such as DM 2 and obesity. A 65-year-old woman without alcohol or
filtration rate(eGFR) above 60 ml/min per 1.73 m2 and urine albumin creation
toxicophilic abuse, without obesity (BMI of 22.7) and with clinical history of
ratio (ACR) below 30 mg/g from the 5th (V-2,3, 2011-20012) and 6th (VI-1,2,
immune thrombocytopenic purpura, DM 2 (controlled under diet), hypertension
2013-2014) Korea National Health and Nutrition Examination Survey
and cystic lesion of the pancreas (5 years before biopsy compatible with mucinous
(KNHANES). The estimated glomerular filtration rate was calculated on the
lesion). Due to the increasing of the pancreatic lesion, with dilatation of the
basis of the CKD-EPI equation. Hyperfiltration was defined as eGFR above the
wirsung canal, the patient was submitted to body-caudal pancreatic resection.
age- and sex-specific 95th percentile for healthy subjects. According to glucose
During the intraoperative period, the liver presented with a cirrhotic pattern, and
tolerance, the prevalence of hyperfiltration were increased 4.7% in normal, 4.9%
liver biopsy was performed. Histology showed steatohepatitis, with fibrosis grade
in prediabetes, and 5.4% in diabetes (P for trend !0.001). After adjusting age,
5/6 and focal balloonization of hepatocytes. Additional study: ANA 1/160,
sex, body weight, hyperfiltration associated with higher body mass index
remaining autoimmunity (AMA, SMA, LKM and antibodies anti-liver antigens)
(P!0.001), waist circumference (P!0.001), systolic blood pressure (PZ0.003),
and viral serologies (HIV, hepatitis B and C) negative. After the surgery, insulin
HbA1c (PZ0.039), fasting plasma glucose (PZ0.005), triglyceride (PZ0.001),
therapy was initiated with good metabolic control. The patient did not present
energy intake
(PZ0.001), protein intake
(PZ0.034), and sodium intake
micro or macrovascular complications. The present case describes a diabetic
(PZ0.002). Hyperfiltration was independently associated with ACR
(BZ
patient with an incidental diagnosed cirrhotic liver caused by NASH. The
0.053, P!0.001) in multiple regression analysis with above mentioned factors.
association of NASH and DM2 is present in more than 75% of the diabetics and in
Higher waist circumference (P!0.001), systolic blood pressure (P!0.001),
this case other related conditions (as obesity, hyperlipidemia, insulin resistance,
HbA1c (P!0.001), fasting plasma glucose
(P!0.001), and triglyceride
and drugs) were excluded. The early intervention in DM 2 is crucial, in order to
(PZ0.001) were also independently associated with ACR. In Korean general
reduce related pathologies and their progression especially in this case with silent
population, both hyperfiltration and ACR were associated with similar metabolic
steatohepatitis and cirrhotic liver.
risk factor and each were independently associated. Longitudinal studies are
DOI: 10.1530/endoabs.49.EP519
needed to explore the risk for hyperfiltration and microalbuminuria.
DOI: 10.1530/endoabs.49.EP517
EP520
A novel lipid tetrad index as predictor of premature coronary artery
EP518
disease in diabetic patients
Clinical correlates of TNF alpha levels in anemic patients with early
Saswati Das & S. K. Gupta
diabetic nephropathy
Maulana Azad Medical College, Delhi, India.
Ivan Pchelin & Alexander Shishkin
Saint Petersburg State University, Saint Petersburg, Russia.
Background
The aim of this study was to explore if evaluation of lipid risk factors like
Anemia occurs early and predicts high risk of cardiovascular events and death in
Lipoprotein(a) (Lp(a)) and conventional lipid profile parameters can be a efficient
patients with diabetic nephropathy (DN). It results from various factors including
predictor of the cardiovascular risk in the patients of Diabetes.
erythropoietin (EPO) deficiency and inflammation. The aim of this study was to
Methods
evaluate clinical correlates of TNF alpha levels in anemic patients with early
Sixty individuals with angiographically proven premature CAD and 30 healthy
diabetic nephropathy. We investigated 95 anemic patients with type 2 diabetes
individuals matched for age and sex were studied a tertiary health care centre,
mellitus and chronic kidney disease (stages 1-3). Glomerular filtration rate was
New Delhi, India, over a period of 18 months. CAD patients were divided into
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
two groups based on presence (nZ30) (group I) and absence (nZ30) (group II) of
EP522
type 2 diabetes mellitus (DM). The serum levels of Lipoprotein (a) were measured
by ELISA and routine lipid profile (serum triglyceride, total cholesterol, HDL-C
and LDL-C) was measured by automated analyzer. Angiographic clinical vessel
Abstract withdrawn.
scoring was also done for all the patients.
Results
Lipoprotein (a) levels for Group I was 40.26G8.23 mg/dl, Group II was 40.81G
11.16 mg/dl respectively which was significantly (i.e. P!0.01) higher than the
levels in healthy controls (Lp(a)Z16.39G5.71 mg/dl). We found a significant
increase in mean levels of Total cholesterol (TC), Low Density Lipoprotein-
Cholesterol (LDL-C) and Triglyceride (TG) in cases than controls (P!0.01). In
contrast High Density Lipoprotein-Cholesterol (HDL-C) values decreased. Non
HDL-C was calculated using the equationZ(Total Cholesterol[TC]KLDL-C).
Lipid Tetrad Index (LTI) and Atherogenic Index were also calculated for all
patients. The Modified Lipid Tetrad Index that we propose was calculated using
the equation MLTIZ(non HDL-C!triglycerides!lipoprotein(a)/HDL-C). On
analyzing by cumulative probability plot the new modified Lipid Tetrad Index
defined by us is able to discriminate case and control populations more precisely
EP523
than the existing LTI and Atherogenic Index. The Modified Lipid Tetrad Index
The prevalence of common risk factors for depression development in
has a better sensitivity and specificity than the existing LTI and also has a better
diabetes mellitus of the type 1
correlation with the angiographic vessel score in all patients.
Yana Navmenova1, Eelena Mahlina1 & Tatyana Mohort1,2
Conclusion
1The Republican Research Center for Radiation Medicine and Human
The new proposed Modified Lipid Tetrad Index is a better marker and predictor of
Ecology, Gomel, Belarus;2Gomel State Medical University, Gomel,
severity of premature CAD diabetic patients from India, than the existing Lipid
Belarus;3Belarusian State Medical University, Minsk, Belarus.
Tetrad Index and Atherogenic Index.
DOI: 10.1530/endoabs.49.EP520
Objective
To evaluate the frequency of common risk factors for depression development in
patients with the diabetes mellitus of the type 1 (DM1).
Materials and methods
163 patients with DM1 at the age of 18-65 years old, period of DM is 11.18 (4.28;
22.33) years. The evaluation of the anxiety and depression level was carried out
with the use of the Hospital anxiety and depression scale (HADS); a questionnaire
was carried out with the use of specially developed form to reveal common risk
factors for depression development. A study group was divided into two
EP521
subgroups depending on the level of depression in accordance with the HADS:
Assessing the impact of ‘nephrogenic’ risk factors on the development
group 1 included patients with DM1 and depression (nZ46) and group 2 included
of cardiac pathology in patients with long duration diabetes type 1
patients with DM1 without depression (nZ117).
Margarita Arutyunova, Alexandra Glazunova, Inna Klephortova,
Results and conclusion
Sergey Martynov, Oxana Manchenko, Irina Ulianova, Alexandr Ilyin,
i) There are more patients that live alone (23.9% in comparison with 9.4%
Minara Shamkhalova & Marina Shestakova
consequently, rZ0.04) and person with disability status (69.6% in comparison
Endocrinology Research Centre, Moscow, Russia.
with 47.9% consequently, rZ0.03), among patients with DM1 and depression,
than among patients with DM1 without depression. ii) The disability status is
Aim
associated with the risk for depression development in DM1
(ORZ2.41;
The aim of study is to investigate the effects of renal pathology on the
PZ0.01; 95% CI 1.16-4.19).
cardiovascular system in patients with T1D, the detection of the most important
DOI: 10.1530/endoabs.49.EP523
cardiovascular risk factors associated with CKD.
Methods
The study includes 156 patients with a long duration of T1D (more than 20 years):
24 patients without CKD, 82 patients with 1-4 stages of CKD, 29 patients on
hemodialysis, 21 patients after kidney transplantation. In addition to the routine
methods of survey assessed indicators of phosphorus-calcium metabolism
(calcium, phosphorus, parathyroid hormone (PTH), vitamin D, fibroblast growth
factor 23 (FGF-23)), the markers of: cardiac disease - atrial natriuretic peptide
(NT-proBNP), endothelial dysfunction - asymmetric dimethylarginine (ADMA),
systemic inflammation (C-reactive protein, fibrinogen). All patients underwent
EP524
ambulatory blood pressure monitoring, echocardiography, had a multi spiral
Comorbilities and morbimortality of patients with hospital
computed tomography of heart with Agatston index definition.
hyperglycemia in the health area of Cuenca (Spain)
Results
José Pérez-Rodríguez, Dulce Calderón-Vicente, Santiago Aranda-Regules,
Decrease of glomerular filtration rate (GFR) was associated with: increased
Lidia Guerra-Navarro, Paula García-Notario, Mubarak Alramadan &
systolic blood pressure
(SBP) (rZK0.209762; P!0.05), mass index myo-
David Martín-Iglesias
cardium of left ventricular
(LVMI) (rZK0.221375; P!0.05), the level of
Virgen de la Luz Hospital, Cuenca, Spain.
NT-proBNP (rZK0.465808; P!0.05), ADMA (rZK0.355866; P!0.05),
C-reactive protein
(rZK0.204248; P!0.05), fibrinogen
(rZK0.224840;
Introduction and objectives
P!0.05), triglycerides (rZK0.287844; P!0.05), a decrease of HDL-C (rZ
Hyperglycemia (HG) is a common problem in hospitalized patients that increases
0.179257; P!0.05)/Albuminuria is positive correlated with hypertriglyceridemia
infections, mortality, costs and the hospital stay. The objective of this study is to
(rZ0.335853; P!0.05), SBP (rZ0.262411; P!0.05), NT-proBNP level (rZ
know the association of the HG with cardiovascular risk factors (CVRF), stress
0.218696; P!0.05). The mineral and bones disorders of CKD (CKD-MBD) such
factors, hospital stay and mortality.
as secondary hyperparathyroidism (SHPT), deficiency of vitamin D, calcification
Methods
of the coronary arteries was the most relevance factors among the nephrogenic
We designed a cross-sectional observational study. We included patients admitted
risk factors of cardiac disease.
in the hospital every three days in two months. We excluded patients younger than
Conclusion
15 years, stays less than three days and those of the pediatric, gynecological,
CKD and conditions accompanying it for, especially MBD-CKD, are powerful
emergency and intensive care services. We collected the data from these patients
predictors of cardiovascular disease. The reason of such a close relation is caused
the third day of admission and at discharge. We defined HG as two or more
not only by the negative impact of nephrogenic risk factors, but also by worsening
capillary glucose values greater than 140 mg/dl. We consider stress factors as
conditions such as dyslipidemia, systemic inflammation, endothelial dysfunction,
infection/sepsis, surgery and corticosteroids treatment.
as demonstrated in our study.
Results
DOI: 10.1530/endoabs.49.EP521
A total of 328 patients were included 109 of patients had HG. Regarding CVRF,
the hyperglycemic patients had hypertension in 67%, dyslipidemia in 45.9% and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
both disorders in 38.5%; compared to 42.9%, 24.7% and 17.8%, respectively in
Methods
non-hyperglycemic patients. The HG group had two stress factors in 33.7% vs
A comparative observational study of 60 patients, male and female (1:1) aged 60-
8.4% in non-HG group; and three stress factors in 10.6% vs 3.6% respectively.
85 years. Enrolment criteria - known diabetics, HbA1c 7-9 and DPN of 1-5
Hyperglycemic patients were treated with corticosteroids in 36.7% vs 15.6% in
years. Patients were randomized into 2 treatment groups G1 and G2. The study
non-hyperglycemic patients. The mean hospital stay was 9.17 days in HG group
period was 4 weeks (w) with results assessed at baseline and bi-weekly follow-ups
compared with 7.53 days in non-HG group (P!0.52). Longer stays were
using diabetic neuropathy symptom (DNS) score. G1: 30 patients with an
observed in HG group. Finally, the rate of mortality in hyperglucemic patients
established DPN were treated with PEMF therapy - frequency of 10 Hz, thru two
was of 3.7%, vs 0.5% of the non-hyperglycemic patients (P!0.044).
emitters of 20 mTesla and 6 mTesla, keeping north polarity was towards the body.
Conclusions
A total of 15 sitting of 20 (10C10) min - one per day. G2: 30 patients with an
Patients with hospital HG are more likely to have other CVRF associated. Stress
established DPN were continued on oral symptomatic treatment options like -
factors such as surgery, corticosteroids treatment and infection/sepsis increase the
amitriptyline, duloxetine, gabapentin, pregabalin and tramadol. Patients in both
risk of HG. Finally HG is associated with a longer hospital stay and higher
the groups were on Vitamin B 12C Alpha Liponic Acid which were continued.
mortality.
Results
DOI: 10.1530/endoabs.49.EP524
In G1 application of LF-PEMF therapy significantly facilitated the regression of
the main clinical symptoms of DPN. Patient scores were more differentiated on
DNS score. Complete relief in the symptoms of DPN was achieved in four
patients at 2 w which sustained at four patients at 4 w. DNS score of 1 was
achieved in ten patients. DNS score of 2 was achieved in 18 patients at 2 w which
was sustained at 4 w. Overall 32 patients had a relief of main clinical symptoms
on the DNS score. In G2 there was a mild regression of the main clinical
symptoms of DPN. Complete relief in the symptoms of DPN on DNS score was
achieved in 0 patients at 2 w and in one patient at 4 w. DNS score of 1 was
achieved in two patients at 2 w which increased to three patients at 4 w. DNS
EP525
score of 2 was achieved in seven patients at 2 w which was increased to 11
Diabetes and mental health disorders: not a good combination
patients at 4 w. Overall 14 patients had a relief of main clinical symptoms on the
Rahat Tauni1,2, Nida Ali2, Ravina Tanna2, Debbie Charles-Obi2,
DNS score.
Jyotsna Bhudia2 & Ritwik Banerjee2
Conclusion
1Cambridge University Hospitals, Cambridge, UK;2Luton and Dunstable
The present study provides convincing data regarding the effectiveness of
University Hospital, Luton, UK.
LF-PEMF therapy, on patients with DPN symptoms. The usage of oral
symptomatic drugs is limited due to the high frequency of adverse events, lack
of evidence of long term efficacy and concern about dependence. Considering the
A 49 year old lady presented to the hospital unconscious with severe
benefits and safety, in comparison to oral symptomatic drugs, LF-PEMF can be
hypoglycaemia. She had type 1 diabetes for 24 years and coeliac disease. She
used as an adjacent in the management of diabetic neuropathy cases. A bigger
was hypo-unaware and had multiple admissions with DKA and hypoglycaemia
study is warranted to determine whether DPN can be modulated with LF-PEMF
over the years. She did not engage in the self-management of diabetes, therefore,
and how it can influence nerve regeneration. Limitations of this study include
insulin was being injected by the carers in the community and by nurses in the
small sample size, short duration of treatment and non-availability of follow-up
hospital. Her erratic and unpredictable glycaemic control was attributed to non-
data.
compliance. She admitted to eating gluten diet, and recent upper GI endoscopy
Keywords: LF-PEMF - low frequency pulsed electro magnetic field, DPN -
showed mark villous atrophy. Her meal size and pattern were variable at home.
diabetic polyneuropathy, DNS - diabetic neuropathy symptom, w - weeks.
During admission, she was found to be self-injecting her own insulin without a
DOI: 10.1530/endoabs.49.EP526
clinical indication. She was assessed by a psychiatrist and was diagnosed to have
a personality disorder. She was deemed to have full mental capacity and insight
into her condition and the harm that can occur with her behaviour. She was seen
by a psychologist and admitted to self-injecting insulin without a clinical
indication. It transpired that this was due to an ongoing court battle with her
children, and the secondary gain was to get the attention of her children. Diabetes
can contribute to the pathogenesis of psychiatric disorders, and some psychiatric
disorders are significant risk factors for the development of diabetes. Up to 45%
of mental disorders and severe psychological distress goes undetected in people
being treated for diabetes. Psychiatric disorders co-existing with diabetes include
EP527
delirium, mood disorders, substance abuse, anxiety, eating disorders and
Correlation of NGAL and thyroid function in patients with type 1
psychosis. There could also be some overlap between physical features of
diabetes
diabetes especially hypoglycaemia and symptoms of psychiatric disorders.
Alena Sazonava1,2, Tatiana Mokhort1, Volha Shyshko1, Alena Mokhort1 &
Physicians and endocrinologists should actively seek these issues especially in
Natalia Karlovich1,2
people with ‘brittle’ diabetes as early recognition and treatment of psychiatric and
1Belarusian State Medical University, Minsk, Belarus;2City Endocrinolo-
behavioural problems may lead to satisfactory diabetes control and avoid hospital
gical Dispensary, Minsk, Belarus.
admissions.
DOI: 10.1530/endoabs.49.EP525
Neutrophil gelatinase-associated lipocalin (NGAL) was shown to be highly useful
in assessing kidney injury in patients with diabetic nephropathy. Taking into
account recent data that dysthyroidism may have reversible effects on GFR the
purpose of the study was to investigate potential relationship between serum
NGAL levels, thyroid status and ultrasound thyroid characteristics in patients
with type 1 diabetes (T1D) with CKD.
Materials and methods
We recruited 118 patients (43m; 75f; age 40.78G12.241 years; BMI 25.50G
4.956 kg/m2; duration of T1D 22.86G9.737 years) with CKD. Hypertension was
observed in 76 (64.41%) patients, 56 (47.46%) took ACE inhibitors. Lipid profile
EP526
changes were found in 87 (73.73%) patients, and only 30 (25.42%) of them
received statins. GFR was estimated by CKD-EPI formula. All patients were
Management of diabetic peripheral neuropathy (DPN) using low
divided into two groups: group 1 comprised 95 patients with GFRO45 ml/min,
frequency pulsed electro magnetic field (LF-PEMF)
group 2 - 23 patients with GFR!45 ml/min. Biochemical parameters, NGAL,
Satish Chander Wasoori1, Deepak G. Pande2, Chetan Bhardwaj1 &
thyroid hormones levels were measured. USG of thyroid gland was performed.
Manoj Naik1
Nonparametric statistical methods were used. A P-value !0.05 was considered
1Park Hospital, Gurgaon, Haryana, India;2G D Diabetes Center, Delhi,
significant.
India.
Results
Groups were matched by age, gender, HbA1c, TSH, fT4, ATPO levels, thyroid
Objective
gland volume (VolThG). Comparative analysis of patients in the subgroups
To evaluate the effectiveness of low frequency pulsed electro magnetic field (LF-
according to GFR revealed reliable differences in fT3 (PZ0.028) and NGAL
PEMF) in the management of diabetic peripheral neuropathy (DPN) symptoms.
levels (PZ0.0003). Low-fT3 was occurred significantly more often in group 2 -
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
34.78% vs 16.84% (c2Z4.5, PZ0.034). Mean NGAL levels in patients with
Aim and objective
GFR!45 ml/min (1.98 [0.91; 3.29]) were higher than those in group with GFRO
Mucormycosis is a rare life-threatening fungal infection. Immunocompromised
45 ml/min (0.88 [0.48; 1.30]). Presence of nodal pathology observed more
patients are often affected. We report a rare diabetic patient with pancreatic
frequently in group 2 - 39.13% vs 16.84% (c2Z5.5, PZ0.019), despite the fact
adenocarcinoma who was presented diabetic ketoacidosis and rhino-orbito-
that there were no differences in presence of hypoechoic nodes O1 cm.
cerebral mucormycosis.
Correlation of VolThG and NGAL (rZK0.288) and serum creatinine levels
Case presentation
was revealed (rZ0.222).
A 66 years old man with pancreatic adenocarcinoma and type 2 diabetes mellitus
Conclusion
was presented diabetic ketoacidosis and severe infection of the facial sinuses,
Decline of GFR leads to deviation from the normal structure of thyroid gland and
orbita, and soft palate in the right half of the face. It was learned that the infection
developing of local nodal pathology in group of patients with T1D and is
developed after tooth extraction. Diabetic ketoacidosis improved after fluid and
accompanied by an increase of NGAL levels and low-fT3.
electrolyte replacement and insulin treatment. Non-septate hyphae structures
DOI: 10.1530/endoabs.49.EP527
were shown in biopsy sample from affected tissues. Brain MRI showed that this
infection was extended to the brain. Amphotericin B therapy was started
immediately due to delay rapid progression and recommended surgical
debridement. Surgical debridement is the main therapy for mucormycosis but
patient and his relatives did not accept surgical treatment. Amphotericin B
therapy was continued but he dead within the following 2 months.
Conclusion
In diabetic patients with impaired immunity, procedures such as tooth extraction
can cause rare serious infections like mucormycosis.
DOI: 10.1530/endoabs.49.EP529
EP528
Impaired awareness of hypoglycemia in adults with type 1 diabetes is
not associated with peripheral neuropathy
Damianos Tsitlakidis, Milena Djordjevic, Nicolle Muller, Ulrich Muller &
Christof Kloos
University of Jena, Jena, Germany.
Objective
The impaired awareness of hypoglycemia (IAH) affects people with type 1
diabetes and is a risk factor for severe hypoglycemia. This study aims to evaluate
EP530
the association between the impaired awareness of Hypoglycemia by diabetes
Renal function preservation with Manidipine vs Amlodipine in type 2
type 1 and the peripheral neuropathy (PNP).
diabetic hypertensive patients with persistent microalbuminuria
Methods
Sara Quintana-Arroyo1, Carmen Acosta-Calero1, Claudia Arnás-León1,
276 adults with type 1 diabetes, 135 men and 141 women, were studied from Mai
Ana Delia Santana-Suárez1, Agnieszka Kuzior1, Margarita Sáiz-Sátjes2,
2015 to January 2016 to the outpatient department of University hospital of Jena.
Manuel Nivelo-Rivadeneira1 & Francisco Javier Martinez-Martin1
A cross sectional study was performed, using the Gold Score for assessing
1Servicio de Endocrinología y Nutrición, Hospital Dr. Negrín de Gran
hypoglycemia awareness and the peripheral neuropathy was evaluated with the
Canaria, Las Palmas de Gran Canaria, Spain;2CAP Rambla Terrassa,
Neuropathy Symptoms Score (NSS) and the Neuropathy disability Score (NDS)
HUMT, Barcelona, Spain.
from Young and Boulton.
Results
The median age of the group was 51G16 years with 23G13 years diabetes
Objectives
duration. The BMI score was 27G5 kg/m2 and the DDCT adjusted HbA1c was
The AMANDHA randomized study (PROBE design) showed that the addition of
7.27%G1.1. 85 patients had PNP and 80 had IAH. 27.6% of patients without PNP
Manidipine 20 mg vs Amlodipine 10 mg for 2 years in 91 hypertensive type 2
and 38.8% of patients with PNP had IAH (PZ0.067). The HbA1c did not show
diabetic patients with persistent microalbuminuria, uncontrolled with a renin-
any difference between the adults with and without IAH (7.1 vs 7.3%; PZ0.121).
angiotensin system inhibitor (given full-dose for at least the 6 previous months)
The duration of diabetes was longer for the adults with IAH (31.34 vs 26.95 years;
was more effective in reducing albuminuria in spite of similar blood pressure
PZ0.001). In the regression analysis, a significant association of the IAH to the
control. Patients with significant renal impairment (PlCr O1.4 mg/dl in women
diabetes duration (Exp(B)Z1.031; PZ0.007), but not to PNP (Exp(B)Z1.387;
and O1.5 in men) had been excluded. However, no data were published on the
PZ0.284) or HbA1c (Exp(B)Z0.801; PZ0.115), is shown.
progression of renal dysfunction, with only PlCr values reported, which were not
Conclusions
significantly different. We undertook to establish if there were differences in
This study revealed in adults with diabetes type 1 association between the
glomerular filtration rate (GFR) progression.
diabetes duration and the IAH but not with the presence of PNP.
Methods
DOI: 10.1530/endoabs.49.EP528
Post-hoc analysis of AMANDHA. GFR was estimated by the MDRD-4 equation
for each individual measurement. Point-to-point GFR were compared by unpaired
t-test and progression was compared by the Kruskal-Wallis test. (non-parametric
ANOVA). Values are given as mean (G standard error).
Results
Baseline GFR were
67.3
(G5.2) and
70.2
(G5.0) ml/min/1.73 m2
with
Manidipine and Amlodipine, respectively; at 6 months they were 68.6 (G5.6)
and 69.5 (G5.3), and at 2 years 66.9 (G4.7) and 65.5 (G5.0). During follow-up,
patients treated with Manidipine lost 0.4 (G3.9) ml/min/1.73 m2 of FGR vs 4.7
(G5.2) with Amlodipine. Point-to-point GFR were not significantly different
between the groups, but GFR loss after 2 years was lower with Manidipine
EP529
(PZ0.032).
A rare presentation of diabetic ketoacidosis: Rhino-orbito-cerebral
Conclusions
mucormycosis
The previously published data of AMANDHA showed a markedly greater
Askin Gungunes1, Senay Arikan Durmaz1, Selim Yalcin2, Aydin Cifci3,
albuminuria reduction (about 40% more) with Manidipine vs Amlodipine, which
Veysel Burulday4 & Ayse Carlioglu5
was attributed to efferential arteriole dilatation. The present post-hoc analysis also
1Department of Endocrinology and Metabolism, School of Medicine,
shows a better preservation of renal function with Manidipine. These results
Kirikkale University, Kirikkale, Turkey;2Department of Oncology, School
strengthens the case for combined treatment with Manidipine and a renin-
of Medicine, Kirikkale University, Kirikkale, Turkey,3Department of
angiotensin system blocker in hypertensive type 2 diabetic patients with persistent
Internal Medicine, School of Medicine, Kirikkale University, Kirikkale,
microalbuminuria.
Turkey;4Department of Radiology, School of Medicine, Kirikkale
DOI: 10.1530/endoabs.49.EP530
University, Kirikkale, Turkey;5Department of Internal Medicine, Erzurum
Regional Training and Research Hospital, Erzurum, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP531
control. Apart from the slow-down of neuropathic symptoms some patients from
the main group demonstrated growth of hair on legs
(12.5%) which was
Significance of hemorheological approach for screening diabetic
considered as a positive potentiating effect of phosphocreatine on the background
nephropathy in the type II diabetes mellitus
therapy of diabetic neuropathy.
Sangbae Lee, Kahui Park, Jung Hye Kim, Ji Hong You, Yusik Kim,
Conclusions
Ji sun Nam, Jong Suk Park & Chul Woo Ahn
1. The ITT-analysis in the primary end point after the combined therapy with
Gangnam Severance Hospital, Seoul, Republic of Korea.
application of phosphocreatine showed the decrease of NSS score by 42.1%, and
NDA score by 13.3%.
Objective
2. Use of phosphocreatine as a cytoprotective agent in the combined DN therapy
Hemorheologic alterations or changes in blood viscosity have been suggested to
is pathogenetically substantiated and allows to expand the opportunities of drug
play a role in the pathogenesis of diabetic microvascular complications. We
therapy for patients suffering from DN.
measured various hemorheologic parameters in type 2 diabetes patients and
3. Results of the conducted trials demonstrate a potential for further study of
assessed their possible role as a diagnostic tool for diabetic nephropathy.
administration of this medicine in a larger long-term randomized and controlled
Methods
trial.
Four hundred-seventy patients with type 2 diabetes were included in this study.
DOI: 10.1530/endoabs.49.EP532
Hemorheologic parameters, including erythrocyte deformability, elongation
index (EI), critical shear stress (CSS), and aggregation index (AI) were measured
using microfluidic hemorheometer. Various metabolic parameters were assessed
from fasting blood samples and urinary albumin to creatinine ratio was used to
assess diabetic nephropathy.
Results
There were significant differences in Elongation index at 3 Pascal (EI at 3Pa),
Fibrinogen/EI, and shear stress among patients in different stages of chronic
kidney disease
(all P!0.05), EI at
3 Pa, Fibrinogen/EI, and shear stress
significantly differed among the groups. Fibrinogen/EI differed between normal
or CKD 1 and CKD 2 patients. In multiple regression analysis, Fibrinogen/EI at
3Pa was an independent predictor of albumin to creatinine ratio independent of
EP533
age, ESR, hematocrit, HbA1c, and body mass index (ßZ0.101, P!0.05). Also,
The effect of different antihypertensive treatment protocoles on
critical time, critical stress, fibrinogen/EI at
3Pa, CSS/EI et
3Pa, ad
glycemic control and lipid profile in type 2 diabetic patients with
fibrinogen/CSS at 3Pa were significantly different among patients at different
microalbuminuria and stage 1 hypertension
stages of diabetic nephropathy (all P! 0.05). Among the variables, Fibrinogen/EI
Muge Erek1, Alparslan Ersoy1 & Canan Ersoy2
at 3Pa showed area under the ROC curve of 0.721, suggesting 860 mg/dl% as a
1Department of Nephrology, Uludag University Medical Faculty, Bursa,
cut off point for diabetic nephropathy with the sensitivity of 74% and specificity
Turkey;2Department of Endocrinology and Metabolism, Uludag University
of 62%.
Medical Faculty, Bursa, Turkey.
Conclusion
Fibrinogen/EI is a sensitive parameter measured via point-of-care testing for
screening diabetic nephropathy in patients with type 2 diabetes.
In hypertensive diabetic patients, renal angiotensin system blockers are first
DOI: 10.1530/endoabs.49.EP531
preferred due to their antihypertensive and antiproteinuric activities. Carvedilol, a
third generation beta blocker, may provide additional benefits in diabetic patients.
We aimed to compare the short-term efficacy of losartan treatment alone and in
combination with cilazapril or carvedilol on blood pressure, glycemic control and
lipid profile in microalbuminuric type 2 diabetic patients.
Methods
The study conducted in 30 consecutive patients with type 2 diabetes mellitus and
stage 1 hypertension. After 2 weeks follow-up period (Period 1), all patients
received losartan 50 mg/day as a single dose for 6 weeks (Period 2). Then,
patients were randomized into 3 groups at the end of 6th week. Losartan dose was
increased to
100 mg/day in the first group
(Group
1, n:10). Carvedilol
EP532
(25 mg/day) in the second group (Group 2, n:10) and cilazapril (5 mg/day) in
New features of pathogenetic treatment of diabetic neuropathy (DN)
the third group (Group 3, n:10) was added to losartan 50 mg/day treatment for
at on early stage
another 6 weeks (Period 3).
Kulshara Yerdesova & Aknur Myrzabaeva
Results
Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
In all three groups, effective blood pressure control was provided during losartan
50 mg administration and post-randomization treatment period. Body mass index
in Group 1 significantly decreased during the losartan dose-increasing period.
Goal of research
When the losartan dose was increased in Group 1, fasting glucose values were
To evaluate the clinical efficacy of phosphocreatine in the combined metabolic
significantly decreased, but not in other groups. There was no significant
therapy of diabetic neuropathy at an early stage.
difference in measurements of post-prandial glucose, and serum fasting insulin,
Materials and methods
fructose, lipid and apolipoprotein levels between the three groups. A1c values in
A pilot study was carried out with participation of 36 patients suffering from DM
the losartan group significantly decreased from baseline 8G1.2% to 7.8G1.0 at
2. Using the method of randomization the patients were divided into two groups.
6th week and 7.5G0.9% at 12th week. The reductions in A1c values of losartan
Apart from the standard therapy the main group (nZ24) received phosphocrea-
plus carvedilol and losartan plus cilazapril groups were not significant (PO0.05).
tine
(intravenous infusion dose
2 g per 100.0 of saline solution). DN was
Conclusion
evaluated using the Neuropathic Symptomatic Score (NSS) by means of filling in
As a result, the use of high-dose losartan in hypertensive microalbuminuric type 2
a questionnaire used for analysis of the presence and strength of neuropathic
diabetic patients provided short-term more effective glycemic control when
symptoms. As well as using the Neuropathic Dysfunctional Account (NDA), at
compared to carvedilol or cilazapril treatments with low-dose losartan.
that vibration, tactile, temperature, pain sensitivities of lower limbs. The main
Significant decreases in the high dose losartan group in terms of body mass
parameters of efficacy were NSS score after 6 weeks of treatment and NDA score
index, fasting blood glucose and A1c levels, it could explained by diet compliance
after 6 weeks of therapy.
and better weight control when compared with other groups.
Results, discussion
DOI: 10.1530/endoabs.49.EP533
A faster clinical effect was noted in the main group during analysis of the score,
relief of neuropathic symptoms occurred even without changes in the metabolic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP534
Conclusions
SMCG showed preprandial hyperglycemia, mainly before breakfast and dinner.
Impact of skin bundle implementation on hospital aquired pressure foot
Few hypoglycemias were detected but before lunch and night. Maternal and
ulcers and lenght of stay in inpatients with diabetes
neonatal outcomes were similar to other studies.
Khaled Ashawesh1, Asma Elyousfi2, Masoud Alam1, Lynda Bloomer1 &
Abdul Wajid Safi1
DOI: 10.1530/endoabs.49.EP535
1Dudley Group of Hospitals Foundation Trust, Dudley, UK;2University of
Leicester, Leicester, UK.
Objective
To assess the impact of launching SKIN (Surface, Keep moving, Incontinence,
Nutrition) bundle on development of pressure foot ulcers among in-patients with
EP536
diabetes.
Methods
The analysis of interrelation of filtrational ability of kidneys and
SKIN Bundle was launched at Dudley Group of Hospitals Foundation Trust in
indicators of the androgenic state at patients with diabetes
mellitus type 1
mid- February 2011. Data on pressure foot ulcers were collected among patients
Elena Vaschenko1 & Tatjana Mokhort2
with and without diabetes admitted during February 2010- February 2011 and
1The republican Research Centre for Radiation Medicine and Human
then from February 2011-March 2012, from pressure ulcer database.
Ecology, Gomel, Belarus;2Belarusian State Medical University, Minsk,
Results
Belarus.
Between 14/02/2010 and 13/02/2011, number of admissions to adults’ wards was
64,000. Of these, 5,452 had diabetes. Out of the latter, 72 patients were identified
to have foot ulcers, of them 23 patients developed the foot ulcers during their
Objective
hospital stay, giving rise a 0.42% rate of development of hospital acquired foot
To analyze correlation between the duration of diabetes mellitus (DM), renal
ulcers among in-patients with diabetes. During the thirteen and a half month
function and androgenic state indicators in patients with DM type 1.
period following SKIN bundle launch (14/02/2011 - 31/03/2012), there were 13
Material and methods
patients who developed hospital acquired foot ulcers out of 6,232 in-patients with
191 males with DM 1 type in the age of 18-55 years. The control group included
diabetes admitted during the same period, giving rise to a lower rate (0.21%) of
25 almost healthy males in the age 21-41 years. The compensation of DM was
development of foot ulcers in the hospital among patients with diabetes. The
estimated by the level of glycosylated hemoglobin. Also, the indicators of lipid
development of hospital acquired foot ulcers among patients with diabetes,
profile, glomerular filtration rate MDRD, total testosterone, luteinizing
therefore, dropped significantly by 51% P value of 0.04 (P!0.05) after the
hormone/follicle-stimulating hormone
(LH/FSH), prolactin, sex hormone-
launching SKIN bundle. The average length of hospital stay (LOS) among
binding globulin.
patients with diabetes who had foot ulcers was significantly shorter by an average
Results
of 3.55 days, P value of 0.044 (P!0.05), after this SKIN bundle implementation.
It was defined that diabetes duration significantly it is above at patients with GFR
Conclusion
!60 ml/min/1.73 m2. In the group with GFR
!60 ml/min/1.73 m2 in the
SKIN bundle resulted in more than 50% reduction in pressure foot ulcers, with
absence of compensation (Hb A1c O7.5%) more than LH, FSH, LH/FSH high
significant decrease in LOS among those who developed ulcers. SKIN Bundle can
levels and significantly lower levels of the general and free testosterone were
therefore be considered as a tool to reduce inpatient pressure Ulcers.
noted significantly. At patients with GFR MDRD O60 ml/min/1.73 m2
DOI: 10.1530/endoabs.49.EP534
significant distinctions on the level of testosterone and gonadotrophins at various
compensation of SD haven’t been revealed.
Conclusion
The revealed changes are important risk factors for development and progression
of vascular complications and require appropriate arrangements.
DOI: 10.1530/endoabs.49.EP536
EP535
Continuous glucose monitoring system in patients with gestational
diabetes mellitus: a prospective study
Rosa Marquez-Pardo, Isabel Torres-Barea, Mgloria Baena-Nieto,
Concepcion Cruzado-Begines, Manuel Cayon-Blanco, Rosario
EP537
Lopez-Velasco & Lourdes Garcia-Garcia-Doncel
PDE5i preserves renal function in models of Diabetic Nephropathy:
Jerez Hospital, Jerez de La Frontera, Cádiz, Spain.
from bench to bedside
Riccardo Pofi1, Daniela Fiore1, Tiziana Feola1, Elisa Giannetta1, Giulia
Le Grazie1, Carla Di Dato1, Daniele Gianfrilli1, Biagio Barbano2,
Introduction
Mary A. Venneri1, Andrea Lenzi1 & Andrea M. Isidori1
Gestational diabetes mellitus (GDM) is associated with an increase of maternal-
1Department of Experimental Medicine, Sapienza University of Rome,
fetal complications. Continuous glucose monitoring system (CGMS) detects
Rome, Italy;2Department of Clinical Medicine, Sapienza University of
postprandial hyperglycemia and hypoglycemia during 24 h.
Rome, Rome, Italy.
Methods
Women with GDM in gestational weeks 26-32 were allocated a CGMS (IproTM2)
after diagnosis in an observational prospective study. It was analysed:
One third of diabetic patients suffer from Diabetic Nephropathy (DN) that leads to
- CGMS: Mean glucose and standard deviation, area under the curve (AUC) with
end-stage renal disease
(ESRD). The molecular pathways involved remain
glucose O140 and !70. Percentage of glucose above or below the limit of
underexplored. We showed that chronic phosphodiesterase-5 inhibition (PDE5i)
normality before and after breakfast, lunch, dinner and night. (Target ranges:
improve vascular inflammation [1] and tissue remodelling, reducing proteinuria
before meals 70-95, after meal 70-140 and night 70-120 (expressed: mg/dl)).
[2] in murine diabetes. Our aim was to investigate the effect of PDE5i on animal
- Maternal and neonatal outcomes.
and human models of DN.
Results
Materials and methods
nZ32. Maternal age 33 years (O35 years Z43.8%), family history of diabetes
16 mice were randomly assigned to four groups: control (CTRL), sildenafil
47%, personal history of diabetes
34.4%, prepregnancy BMI
25.9 kg/m2
(SILD), streptozotocin (STZ), STZCSILD. Renal Doppler ultrasound (RDU)
(O30 kg/m2 Z21.8%), weigh gain 7.7 kg, HbA1c 4.9%, insulin treatment
was performed at baseline and after 6 weeks. Renal resistive index-RRI, GFR
28%. CGMS: Glucose before breakfast 90G7.5, after breakfast 120G20, before
(ml/min), mean Blood Pressure-MBP (mmHg) were recorded. FITC-dextran
lunch 86G9.9, after lunch 112G19.6, before dinner 93G12.3 and after dinner
(2 mg/kg) was used to assess permeability and integrity of renal endothelium. 30
110G17.8. AUC O140Z0.81 and !70Z0.59. Percentage of glucose above or
type 2 diabetic (T2DM) patients were randomly assigned to placebo (PLC) or
below targets: before breakfast O95Z33.6% and !70Z5.4%, after breakfast O
tadalafil (TAD) 20 mg/die. RDU was performed at baseline and after 5 months.
140Z24.6% and !70Z0.6%, before lunch O95Z20.8% and !70Z11.9%,
Results
after lunch O140Z14.5% and !70Z2.2%, before dinner O95Z37.6% and !
All STZ-treated animal developed diabetes. Compared to the STZ, STZCSILD
70Z6.3%, after dinner O140Z8.1% and !70Z2.9%, night O120Z8.4% and
preserved renal function. Specifically, SILD treatment prevented: (a) the ESRD-
!70Z8.9%. Maternal and neonatal outcomes: Caesarean 25%, gestational age
related hypertension
(MBP, mean change from baseline: STZ 28.72G3.76,
at delivery 39 week, macrosomia 12.5%, large for gestational age 25%, small for
STZCSILD K9.46G4.84, PZ0.002); (b) the fall in GFR (STZ K15.24G3.67,
gestational age 6.3%, neonatal hypoglycaemia 21.9%, need for supplemental
STZCSILD 17.79G3.67; PZ0.005); (c) the rise in RRI (STZ 0.10G0.03,
oxygen in the neonatal 6.3%.
STZCSILD K0.07G0.03; PZ0.026); (d) the reduction in FITC-perfuse vessels
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(microvascular density mean change STZ -2.45G0.48, STZCSILD 2.1G0.49,
Materials
PZ0.005); (e) pericytes detachment from endothelial cell coverage (STZ 10%,
Patients who had a diagnosis of DKA.
STZCSILD 60%, P!0.01). TAD treated T2DM patients: (a) improved renal
Methods
microcirculation (RRI: PLC 0.01G0.04, TAD K0.04G0.03; PZ0.014); (b)
Survey about the character of nutrition, alcohol drinking and other risk factors.
decreased diastolic pressure (PLC 0.71G9.00, TAD K6.00G9.11; PZ0.012).
Design
Conclusions
All patients were divided into two groups according to their age. The first group-
PDE5i treatment reversed ESRD in a hyperglycemic mouse model targeting renal
12 patients younger then 65 y.o.-Nutritional Risk Screening survey, the second
pericytes and restoring intrarenal haemodynamics. In humans, PDE5i improved
group - 3 patients (65-90 y.o)-Mini Nutritional Assessment survey. ‘Alcoholic
renal microcirculation slowing worsening of renal function in course of DN.
agnosia’ survey for identification of alcohol addiction.
PDE5i could disclose novel treatment strategies for DN.
Results
References
Fifteen patients - 11 men and 4 women. Average age - 36G0.93 y.o. According
1. Venneri MA Chronic inhibition of PDE5 limits pro-inflammatory monocyte-
to diabetes types: 11 patients of type 1, 4 patients of type 2. From 15 members of
macrophage polarization in streptozotocin-induced diabetic mice. Plos One 2015.
the nutrition
10
members (66.66%) had nutrition problems. Five patients
2. Sonneveld R Sildenafil prevents podocyte injury via PPAR-g-mediated TRPC6
(33.33%) were closed to the nutrition risk questions. According to ‘Alcohol
inhibition. J Am Soc Nephrol. 2016.
agnosia’ survey: five patients had alcohol problems(33.33%), three of them (60%)
DOI: 10.1530/endoabs.49.EP537
realized this problem, two (40%) were indifferent. Ten patients did not have
(66.66%) alcohol addiction. The risk factors DKA: inadequate insulin therapy - 7
patients (46.66%), 5 of them (71.42%) had alcohol problems, 2 of them (13.33%)
had sober life style. Two patients took drugs (13.33%) and alcohol problems.
Exacerbation of concomitant diseases - 6 patients (40%), 4 of them had problems
with alcohol (66.66%).
Conclusion
The most significant risk factors for DKA developing were inadequate insulin
EP538
therapy, exacerbation of concomitant diseases (40%), alcohol drinking (33.33%),
Relationship between microvascular complications of Diabetes Mellitus
taking drugs (13.33%). 66.66% had nutrition problems but this state is rather
and trace element levels
result then cause of DKA.
Zeliha Temurer Af¸ar, Yasemin Tutuncu, Berçem Ayçi
¸ek,
DOI: 10.1530/endoabs.49.EP539
Engin Sennarog˘ lu, Dilek Berker & Serdar Guler
Ankara Numune Training and Education Hospital, Ankara, Turkey.
Objective
To determine whether relationship between trace element levels and micro-
vascular complications of type 2 Diabetes Mellitus (T2DM).
EP540
Methods
One hundred eighteen patients with type 2 DM (mean age: 56G6.2 years) and 40
Somnological parameters for patients with type 1 diabetes and
control subjects (mean age: 40.0G8.8 years) were included in the study. Group 1
nocturnal hypoglycemia
(nZ40 patients) was composed of patients with no had microvascular
Ina Darashkevich1, Tatiana Mokhort2, Lola Nikanava1, Ludmila Smirnova1
complications and it divided into two subgroup, first subgroup (nZ20) included
& Serhej Tishkovsky1
patients with glysemic regulation, the second subgroup (nZ20) with not glysemic
1Grodno State Medical University, Grodno, Belarus,2Belarus State Medical
regulation. Group 2 included 38 patients with diabetic retinopathy (19 patients
University, Minsk, Belarus.
had proliferative retinopathy,
19 patients had nonproliferative retinopathy).
Group 3 included 40 patients with both diabetic retinopathy and nephropathy (20
Objective
patients had microalbuminuri, 20 patients had macroalbuminuri). Patients with
To determine the effects of hypoglycemia while sleeping on somnological
type 2 DM who had liver disease, renal disease, malabsorbtive disease and who
parameters for patients with type 1 DM.
had been taken any diuretic drugs were excluded. Trace elements including Crom
Materials and methods
(Cr)(mg/l), Copper (Cu)(mg/l), Zinc (Zn)(mg/l) were measured by Inductively
The study included 57 person with type 1 DM (Group 1 - patients with blood
Coupled Plasma-Mass spectrophotometry (ICP-MS). And, Iron (Fe)(mg/dl) was
glucose levels (BGL) during sleep !3.9 mmol/l; Group 2 - Patients with BGL -
measured by ELISA.
from 3.9 to 10.0 mmol/l. The examination included: daily monitoring of blood
Results
glucose by ‘CGMSGold’ (‘MedtronikMINIMED’ (USA)), polysomnography
Difference of age was only found between control subject and all patients with
«SOMNOlab2 (PSG) Polysomnography (R & K)», the definition of HbA1c.
DM (P!0.001). Mean age were found not difference between in Group 1,2,3
Results
(PZ0.24, PZ0.22, PZ0.26). Magnesium, Fe, Zn, Cr levels were lower in all
Table
diabetic patients than control healthy subjects (P!0.001, PZ0.039, PZ0.001,
P!0.001). Crom levels were found lower in patients with both only diabetic
retinopathy and only diabetic nephropathy than patients with not any
microvascular complications (P!0.01, for both). Also, Cr levels were found
Group 1 nZ14
Group 2 nZ43
lesser in patients with only diabetic nephropathy than in only with diabetic
Indicator
Me [25;75]
Me [25;75]
retinopathy (P!0.01).
BGL during sleeptime
2.35[2.00;3.10]*
6.10[4.10;7.50]
Conclusions
(mmol/l)0
The study indicated that an association between low Crom levels and existence of
Hypoglycemia «before
7.00[3.00;27.00]*
5.23[0.00;5.00]
microvascular complications of DM when trace element levels were measured by
sleep» (%)
ICP-MS.
HBA1c (%)
7.00[6.00;8.10]
7.67[6.40;9.00]
DOI: 10.1530/endoabs.49.EP538
Total sleep time (TST) (h)
6.24[5.40;7.10]*
5.30[4.51;6.20]
REM (%)
39.50[26.00;48.00]*
29.70[23.00;45.80]
N1(%)
14.11[10.60;23.00]*
8.80[4.70;14.30]
N2(%)
38.8[35.20;61.40]
48.20[34.00;53.30]
N3(%)
3.00[1.20;6.10]
3.44[2.30;6.30]
N4(%)
1.45[0.00;2.89]*
3.00[1.00;8.40]
EP539
*P!0.05.
The frequency of different risk factors for diabetic ketoacidosis in real
clinical practice in Russia
Discussion and conclusions
Irina Dzherieva, Natalia Volkova, Pavel Anchutin & Valerya Nechayeva
For patients of Group 2 marked shortening of TST - 5.30 [4.51; 6.20] hours vs 6.24
Rostov State Medical University, Rostov, Russia.
[5.40; 7.10] hours (PZ0.0219). Night hypoglycemia extend REM-sleep (39.50
[26.00; 48.00]% vs 29.70 [23.00; 45.80]% in the comparison group (PZ0.0479),
The purpose
N1 sleep stage (14.11 [10.60; 23.00]% vs8.80 [4.70; 14.30]% (PZ0.0110), as well
To estimate the frequency of appearance of different risk factors for the DKA
as reduce the N4 stage of sleep (1.45 [0.00; 2.89]% vs 23.00 [1.00; 8.40]%).
(diabetic ketoacidosis) developing in a real clinical practice in Rostov-on-Don.
The share of hypoglycemia ‘before sleep’ extends N1 (rZ0.5442); an increase
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
in the length of N1 leads to a reduction in the duration of the deep stages of slow-
The aim
wave sleep N3 (rZK0.6835), N4 (rZK0.5673); an increase in the duration of
Of the study was to determine the relationship between depression and anxiety
REM reduces N3 (rZK0.5887).
symptoms and chronic diabetes complications, disease duration, glycaemic
Conclusion
control in type 1 diabetic patients.
Hypoglycemia during sleep lengthens REM-sleep, REM sleep so reduces
Methods
glycemia, providing interactive effects relative to each other, helping to increase
18-54 year old 215 patients with T1DM were enrolled in the study. Participants
the N1 and reduction of deep sleep stage (N3 and N4).
filled questionnaires about DM, disease duration, complications and Beck’s
depression (DB) and anxiety (BA) inventory. All patients were evaluated for
DOI: 10.1530/endoabs.49.EP540
microvascular complications. Laboratory tests: HbA1c, creatinine, albumin in
24 h urine sample were performed.
Results
124 females (57.67%) and 91 males (42.33%) participated in the study. Cohort
consisted of 66 participants with DN (mean age 32.44G6.5 years) and 149
without DN (mean age 31.53G9.99). The group without DN consisted of 53
EP541
patients without any complications (mean age 29.49G9.25) and 96 patients with
The value of blood glucose levels for the parameters of nocturnal sleep
DP and/or DR (mean age 31.07G9.11). The emotional state of females was worse
for patients with type 1 diabetes
than males (BD: female 9.78G9.07; male 7.51G7.11; P!0.05; BN: female
Ina Darashkevich1, Tatiana Mochort2, Lola Niconova1 &
13.86G9.99; male 8.86G7.79; P!0.01). There was no statistically significant
Serhey Tishkovsky1
difference between BD among patients with or without complications (PO0.05).
1Grodno State Medical University, Grodno, Belarus;2Belarus State Medical
There was a statistically significant difference (PZ0.04) between BA scores
University, Minsk, Belarus.
among patients without any complications (NZ53, female 31/male 22) (BA
9.42G8.1) and those with DN (NZ66, female 36/male 30) (BA 12.05G8.84).
The emotional state of patients with longer disease duration (O30 years) (BD
Objective
13.59G11.49; BN 15.61G9.79) was worse than patients with shorter one (!10
To establish the differences in terms of sleep for patients with type 1 diabetes,
years)
(BD 8.14G8.55; BN 10.86G9.67)
(P!0.05). There was nofound
depending on the level of blood glucose levels (BGL) during the night.
statistically significant differencebetween the emotional state and glycaemic
Materials and methods
control in T1DM patients.
The study included 43 participants with type 1 diabetes (Group A - patients with
Conclusions
BGL during sleep from 3.9 to 7.4 mmol/l, Group B - 7.5-10.0 mmol/l. Patients
The emotional state of females’ with type 1 diabetes mellitus is worse than males’.
had daily monitoring of BGL ‘CGMSGold’ by ‘MedtronikMINIMED’ (USA),
Patients with chronic diabetes complications have more anxiety symptoms than
polysomnography
«SOMNOlab2 (PSG) Polysomnography (R & K)», the
those without any complications. Emotional state is worse in diabetics whose
definition of HbA1c.
disease duration is longer.
Results
DOI: 10.1530/endoabs.49.EP542
See Table.
Group A nZ25
Group B nZ18
Indicator
Me [25;75]
Me [25;75]
BGL during sleep time
4.50[4.00; 5.60] &
8.20[7.50; 9.50]
(mmol/l)
BGL “after sleep” (mmol/l)
7.90[7.40; 9.20]&
9.65[8.50;11.30]
HBA1c (%)
7.00[6.00;8.50]&
8.95[7.50; 9.30]
EP543
Total sleep time (TST) (h)
5.59 [4.80; 6.53]&
4.90[4.23; 5.39]
REM (%)
29.40[22.50;43.00]&
39.90[24.70;41.40]
The trigger off severe vomiting and hypertension during pregnancy in
N1 (%)
11.05[5.00; 18.30]
7.00[4.70;14.00]
type 1 diabetic patient: case report
N2 (%)
48.50[38.00;53.10]
41.29[25.70;53.90]
Egle Kreivaitiene1, Ruta Kriksciuniene1,2 & Evalda Danyte1,2
1
N3 (%)
4.00[2.70; 7.80]&
2.65[0.00; 5.25]
Department of Endocrinology, Hospital of Lithuanian University of Health
N4 (%)
3.50[1.90;13.50]&
1.30[0.00; 7.50]
Sciences (HLUHS), Kaunas, Lithuania;2Lithuanian University of Health
Sciences (LUHS), Institute of Endocrinology, Kaunas, Lithuania.
&P!0.05
TST is longer in the group with BGL 4.50 mmol/L. REM sleep 10.5%
increase in Group B. The shares represented a deep sleep are larger in
Diabetic mothers have an increased risk for pregnancy (early pregnancy
Group A. In Group A the increase of TST decreases BGL during sleep (rZ
loss, polyhydramnios, pre-eclampsia, premature labor) and progression of
0.4098) and N2 sleep stage (rZ0.4246). Decrease in N2 share decreases
diabetic complications. We present a case of the progression of diabetic-
BGL during sleep (rZ0.4997) and reduces N4 (rZ0.5182), and has a
related complications including autonomic neuropathy (AN) which caused
negative coefficient with a value of REM sleep (rZK0.4330). In group B,
severe vomiting during pregnancy. A 27-year-old type 1 diabetic woman
REM sleep phase is inversely correlated with BGL “after sleep” (rZK
with pregnancy of 8 weeks gestational age (GW) was admitted to our
0.5056), N3 (rZK0.8371), N4 (rZK0.7594).
hospital for glycemia and diabetic-related complications control. She has
had diabetes for 13 years. The control of diabetes was poor (HbA1c 9.13%).
She was already diagnosed with multiple diabetes-related complications
Conclusion
(nonproliferative diabetic retinopathy and maculopathy, polyneuropathy,
BGL 4.5 mmol/l during sleep increases the duration of sleep by increasing the N2,
nephropathy). An insulin-pump therapy was started to achieve a better
N4 and extending reduce REM sleep.
glycemia control during pregnancy. The minor progression of albuminuria
was noticed during first hospitalization. Around 11 GW she was hospitalized
DOI: 10.1530/endoabs.49.EP541
for the second time because of the sudden blood pressure (BP) elevation
(160/110 mmHg), nausea, vomiting, headache, glycemia variability. The
progression of diabetic nephropathy was observed, antihypertensive (AH)
drugs for the treatment of secondary hypertension were started. Despite the
better glycemia control which was achieved (HbA1c 6.1%) in few months,
the patient was hospitalized for the other nine times during the pregnancy.
EP542
The main complains were severe nausea, vomiting, BP elevation and
Emotional state association with microvascular complications, disease
ketonemia. The progression of all diabetes-related complications was
duration and glycaemic control in type 1 diabetic patients
observed. The maximum doses of AH drugs were required for management
Edita Prakapiene2, Karolis Zukas1, Lina Radzeviciene2,3 &
of BP. Albuminuria progressed to nephrotic level, hypoalbuminemia and
Rasa Verkauskiene2,3
hypoproteinemia occured. Diabetic retinopathy developed to proliferative.
1Lithuanian University of Health Sciences (LUHS), Faculty of Medicine,
Severe vomiting led to electrolytes dis-balance. Nausea and vomiting was
Kaunas, Lithuania;2Department of Endocrinology, Lithuanian University of
considered to be caused by the progression of AN, when other possible
Health Sciences (LUHS), Kaunas, Lithuania;3Lithuanian University of
causes were excluded. At 36 GW during planned C-section a healthy girl
Health Sciences (LUHS), Institute of Endocrinology, Kaunas, Lithuania.
was born (Abgar 8/8). Poor control of diabetes may lead to the severe
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
progression of the diabetes-related complications. The progression of
his mother, uncle, aunt and all six brothers were diagnosed as diabetes
diabetic autonomic neuropathy remains forgotten in many cases during
mellitus. His uncle, aunt and aunts children were using oral antidiabetics.
pregnancy.
His system query showed that he had pollakuria and nocturiafor the last 3
DOI: 10.1530/endoabs.49.EP543
months. His physical examination was normal except diminished skin turgor
tonus. His laboratory was normal except blood glucose of 564 mg/dl, HbA1c
8.2%, urea 50 mg/dl, creatinin od 1.34 mg/dl, urine ketone bodies were
CCC, urine glucose 500 mg/dl. He was treated with i.v. saline, and
insulin. On the follow up basal-bolus regimen was initiated. He had
hypoglycemias due to four units bolus insulin and 14 units basal insulin
glargine so bolus insulin was stopped and vildagliptine-metformin and
insulin glargine was added. He had hypoglycemias as well and insulin
glargine was stooped and gliclazide MR 60 mg was started and discharged.
After 2 weeks his HbA1c was 6.9%, fasting plasma glucose was 122 mg/dl
EP544
so vildagliptine-metformin was stopped and gliclazide was tapered to
Predictor factors of hypertension induced in pregnancy in patients with
30 mg/day. After 3 months his fasting blood glucose was 98 mg/dl and
gestacional diabetes mellitus
HA1c was 5.1%. His peripheral blood analysis was consistent with HNF1A
Begon˜a Sanchez-Lechuga1, Cristina Lopez-Tinoco1, Antonio
gene and diagnosed as MODY 3. Transcription factor defects are the most
Campos Caro2, Raquel De la Varga Martín2, Isabel Mateo Gavira1,
common reasons of the MODY. Insulin secretion is decreased up to 85% but
Francisco Javier Vilchez Lopez1 & Manuel Aguilar Diosdado1
is sensitive to sulfonylureas. Low dose sulfonylureas generally control
1Endocrinology and Nutrition Department, Puerta del Mar University
glycemia very well. But diabetic ketoasidosis is a very rare complication for
Hospital, Cadiz, Spain;2Investigation Unit Department, Puerta del Mar
MODY 3.
University Hospital, Cadiz, Spain.
DOI: 10.1530/endoabs.49.EP545
Gestational diabetes mellitus (GDM) is associated with an increased risk of
pregnancy-induced hypertension (PIH). Ambulatory blood pressure moni-
toring (ABPM) has been used to screen for PIH and preeclampsia. To date,
there are no data regarding ABPM in women with GDM. Currently, little is
known in GDM about the role of inflammatory biomarkers in PIH
development and their impact on perinatal morbility and the risk of future
complications. With this study we aim to identify, in women with GDM, at
an early stage inflammatory markers and BP profiles (detected by ABPM)
that could define a population at higher risk of developing PIH and
EP546
preeclampsia. We prospectively studied 113 normotensive women with
GDM consecutively recruited at 28-32 weeks of pregnancy. ABPM was
Screening for macrovascular complications in diabetic patients in
carried out for one 24-h period on each patient, using the SPACELABS
Korça, Albania
90207 ABP monitor. Serum biomarkers (PAI-1, IL-6, IL-8, leptin, IL1-b,
Ema Lumi1, Dorina Ylli2 & Agron Ylli2
TNF-a, adiponectin, resistin, NGF, HGF and MCP1) were determinated in
1Department of Internal Medicine, Regional Hospital, Korce, Albania;
61 patients by MILLIPLEX kit. Clinical and metabolic data, obstetric and
2Department of Endocrinology, UHC Mother Teresa, Tirana, Albania.
perinatal outcomes were analysed. The mean age was 34.4G4.2 years and
BMI was 27.5G5.3 kg/m2. Fifty-six percent of the patients had non-dipper
Background
pattern. In this group, BMI was significantly higher (P!0.05) and the levels
Diabetes mellitus (DM) is a common metabolic disorder and is associated with
of night-time systolic (105.3 vs 98.8 mmHg) and diastolic BP (63.1 vs
development of chronic macrovascular complications leading to significant
57.2 mmHg), and furthermore, higher levels of PAI-1 (296.99G161.3 vs
morbidity and mortality. The aim of the study was to evaluate the prevalence and
162.07G117.52 pg/ml) and resistin
(175.69G92.17
vs
101.74G
clinical profile of macrovascular complications in diabetic patients in Korca,
64.34 pg/ml) were observed. Seventy-eight women delivered to date, 3%
Albania.
had preeclampsia and 7% PIH. Higher levels of adiponectin (125 992.7G
Material and methods
94 472.4 vs 39 850G31 136 pg/ml) were observed in patients who not
A total of 456 cases with type 2 DM attending Department of Endocrine
develop PIH. We concluded that a higher rate of non-dippers pattern and
(outpatient/inpatient), from January 2012 to March 2016 (4 years), were recruited
night-time systolic/diastolic BP were observed. The non-dipper group had
in this study. Ages (15C) cases were screened for macrovascular complications.
higher BMI and levels of PAI-1 and resistin, which could be a useful
Demographic, clinical and laboratory parameters were included in analyses. A
predictor of PIH. Adiponectin was significantly lower in patients with PIH
thorough cardiovascular and cerebrovascular history as documented by previous
and then could point at a protective mechanism in PIH. Further studies will
medical records (including medical and hospital records) was collected for all of
be needed to determine the relationships between BP alterations and
the patients. Standardised electrocardiogram and a careful examination of the
inflammatory markers, and obstetrics and perinatal outcomes.
lower extremities was made for all patients.
DOI: 10.1530/endoabs.49.EP544
Results
During the 4 years study 456 patients were evaluated. The mean age of the study
population was 63.78G10.02 S.D., with female:male ratio 270/186; duration of
diabetes 7.32G7.0 S.D. Of those 82 cases (18%) were newly diagnosed with DM.
Mean HbA1c was 8.5G1.5 DS. Mean BMI was 28.06kg/m2 G4.37 DS (range
17.6-45.9). 47% of the patients were overweight and 27.5% were obese.77.4% of
the patients had hypertension.
13.4% of patients were tabacco users. The
prevalence of macrovascular diseases in total was 25.7%. The prevalence of
cardiovascular disease, cerebrovascular disease (stroke), diabetic foot wounds
and amputacion of an extremity were 16.9, 4.16, 4.37 and 0.21% respectively.
EP545
The prevalence of cardiovascular disease was three times more often in males
Patient first admitted as diabetic ketoacidosis and diagnosed as
than females. There was significant positive correlation
(P!0.05) between
MODY 3
macrovascular complication and the duration of diabetes, age of the patients, BMI
Ahmet Kaya, Mustafa Kulaksizoglu & Ilker Cordan
and hypertension respectively.
Necmettin Erbakan University, Meram Medical Faculty, Division of
Conclusion
Endocrinology and Metabolism, Konya, Turkey.
There was high prevalence of macrovascular disease, especially cardiovascular
disease in Korc¸a population with DM. Screening for chronic macrovascular
complications of diabetes is recommended in order to prevent and treat them,
reducing morbidity and mortality from diabetes.
A male patient aged 63 years old was admitted to the emergency department
Keywords: Type 2 Diabetes Mellitus;macrovascular diseases, cardiovascular
with the complaints of polydipsia, polyurea and dizziness. He had
disease, cerebrovascular disease, diabetic foot wounds, amputation.
hypertension which was on a calcium channel blocker and his hypertension
was in control. His plasma glucose was measured as
564 mg/dl and
DOI: 10.1530/endoabs.49.EP546
hospitalized due to his new onset diabetes. His family history showed that,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP547
decompensation factor (50%), followed by therapeutic failure (40%). Add
Osteoprotegerin as a cardiovascular risk marker in diabetic patients
that, 21% of patients required ventilatory support, 19% needed vasopressor
Anna Dabrowska1, Beata Wojtysiak-Duma2, Dariusz Duma3, Anna
support and only 2.3% of the patients were dialyzed. This review shows that
Torun-Jurkowska4, Anna Mieszkowska1, Beata Matyjaszek-Matuszek1 &
despite all the teachings and warnings about the disease and its severity,
Jerzy Tarach1
many patients maintain a poor understanding of it, and it continues to be
1Department of Endocrinology, Medical University of Lublin, Lublin,
necessary to develop strategies to improve adherence to therapy and to
Poland;2Department of Biochemical Diagnostics, Chair of Laboratory
achieve a better metabolic control.
Diagnostics, Medical University of Lublin, Lublin, Poland;3Department of
DOI: 10.1530/endoabs.49.EP548
Laboratory Diagnostics, Medical University of Lublin, Lublin, Poland;
4Department of Mathematics and Medical Biostatistics, Medical University
of Lublin, Lublin, Poland.
Introduction
It’s known that type 2 diabetes is an independent risk factor for cardiovascular
disease. Osteoprotegerin (OPG), a glycoprotein secreted mainly by osteoblasts, is
also produced by heart muscle and vessels. Its role in the pathogenesis of
atherosclerosis and future cardiovascular events is still discussed.
EP549
Material and methods
Prognostic factors and all-cause mortality in patients with type 2
The study was conducted in 113 patients (48 F, 65 M) with type 2 diabetes
diabetes presenting with diabetic ketoacidosis: a population based,
mellitus (DM2) and coronary heart disease (CHD), aged mean 68.22G9.56. The
case-control study
studied group was divided into subgroups: 61 subjects with acute coronary
Petra
´ a
´ić1, Miroslav
´
aći
´2, Ivan Kruljac2, Bo
ˇidar Peri
´2,
syndrome (ACS) and 52 subjects with stable angina (SA). Among patients with
Maja Filipović-Grčić2, Gorana Mirošević2 & Milan Vrkljan1,2
ACS two groups were separated: with myocardial infarction (MI) and with
1University of Zagreb School of medicine, Zagreb, Croatia;2Department of
unstable angina (UA). The control group was composed of 46 well-balanced
Endocrinology, Diabetes and Metabolic Diseases ‘Mladen Sekso’,
patients (33 F, 13 M) without DM2 and CHD. Determinations of serum OPG
University Hospital Center ‘Sestre Milosrdnice’, Zagreb, Croatia.
levels with the use of MicroVue OPG-EIA (an assay sensitivity of 0.4 pmol/l)
were performed. Statistica
10.0
StatSoft was used for data analysis. OPG
concentrations were shown as medians.
Introduction
Results
Little is known about diabetic ketoacidosis (DKA) in type 2 diabetes mellitus
Patients with DM2
and ACS as well as subjects with DM2 and SA had
(T2DM). Moreover, the clinical impact of diabetic ketosis (DK) in T2DM is
significantly higher OPG levels than patients in control group (6.5 pmol/l and
elusive. The aim of this study was to analyze characteristics and mortality of
5.64 pmol/l vs 3.48 pmol/l) (HZ62.258; PZ0.000) (P!0.001). The tendency of
patients with DKA and DK and to identify possible prognostic factors.
higher OPG concentrations in subjects with ACS compared to patients with SA
Methods
was observed (PO0.05). Higher OPG levels were noted in patients with MI
This was a population-based, cross-sectional study that included all patients with
(7.36 pmol/l) than in those with UA (4.72 pmol/l)
(P!0.05). Patients with
T2DM presenting to emergency department with DKA, over the 5-year period.
complications in the course of ACS such as: cardiac arrhythmias, pulmonary
We analyzed all first admissions of 137 patients with DKA and 137 age- and
oedema, cardiac tamponade had statistically significantly higher OPG concen-
gender-matched patients with non-ketotic hyperglycemia (NKH) and DK.
trations (8.40 pmol/l) compared to subjects with uncomplicated course of ACS
Results
(5.86 pmol/l) (P!0.05). Higher OPG levels were also found in patients with
During a median follow-up of 35.0 months, 55 (39.9%) patients in the NKH
transmural MI
- with Q-wave MI
(8.37 pmol/l) than in patients with
group, 32 (23.2%) patients in the DK group and 61 (44.2%) patients in the DKA
subendocardial MI - with non-Q wave MI (6.44 pmol/l) (P!0.05).
group died. Patients with DKA had significantly higher mortality rates when
Conclusions
compared with DK (HR 2.55, 95% CI 1.65-3.92, P!0.001) and NKH (HR 1.27,
OPG may be a marker of cardiovascular disease and ischemia’s severity in
95% CI 1.05-1.53, PZ0.012). In patients with DKA, age, serum urea and
diabetic patients.
sodium, the use of calcium channel antagonists, ASA and insulin therapy
correlated positively with mortality, while weight loss and increased body
DOI: 10.1530/endoabs.49.EP547
temperature prior to the DKA episode, smoking and alcohol consumption were
associated with decreased mortality. A nomogram derived from these variables
predicted mortality with a sensitivity of 69.7%, specificity of 90.0% (AUCZ
0.866).
Conclusion
DK and DKA represent two distinct subgroups of patients with T2DM. A
nomogram derived from independent prognostic factors may have important
clinical role in selecting high risk patients with DKA.
DOI: 10.1530/endoabs.49.EP549
EP548
Diabetic ketoacidosis in an intensive care unit - review
Joana Oliveira, Rodolfo Gomes, Bárbara Picado, Fernando Gonçalves &
José Araújo
Hospital Beatriz Ângelo, Lisboa, Portugal.
Diabetic ketoacidosis (DK) is one of the most serious complications of
diabetes mellitus
(DM). We performed a case review of DK patients
EP550
admitted to the intensive care unit (ICU) of our Hospital between 1 June
Can the most frequent DRB1* gene’s alleles be associated with
2012 and 30 June 2016. A demographic analysis was made, time of DM
cardiovascular autonomic neuropathy among patients with type 1
evolution, the therapy and the factors that led to its decompensation. Thus, a
diabetes mellitus? A case - control pilot study
total of 42 DK patients were admitted to the ICU in the referred period, mean
Dovile Razanskaite-Virbickiene1, Vilma Vezbaviciene1,
age was 45 years, a clear predominance of female patients (67%) and
Erika Skrodeniene2 & Rimantas Zalinkevicius3
Caucasian patients (76.7%). The majority of the patients were type 1
1Department of Endocrinology, Medical Academy, Lithuanian University of
diabetics (57%), 40% were diabetic type 2 and 3% had a diagnosis of
Health Sciences, Kaunas, Lithuania;2Department of Laboratory Medicine,
diabetes secondary to corticosteroids. The mean duration of the disease was
Medical Academy, Lithuanian University of Health Sciences, Kaunas,
12 years, and diabetes was previously unknown in 12% of the patients,
Lithuania;3Institute of Endocrinology, Medical Academy, Lithuanian
where appears as an inaugural diagnosis. The mean HbA1c value of these
University of Health Sciences, Kaunas, Lithuania.
patients was 12.6%. Regarding the treatment, 64% of the patients were
exclusively treated with insulin, 21% only with oral antidiabetics and 12%
did not do any type of therapy, considering that the disease was not known.
Background and aim
Half of the patients presented nausea and vomiting, and prostration was the
HLA alleles are associated with type 1 diabetes (T1D) and a spectrum of risk can
second most frequent presentation (33%). Infection was the most common
be from increased to neutral or to protective. We aimed to evaluate the association
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
of cardiovascular autonomic neuropathy (CAN) with DRB1* gene’s alleles
Table 1. Baseline Characteristics.
among T1D.
Methods
NDMCNCVD
NDMCCVD
The case - control pilot study included 70 patients with T1D at the age 18-54
years. 36 patients with CAN were assigned to the case group and 34 patients
N
20
20
without CAN - to the control group. The groups were homogeneous according to
Age, years
62.86G6.15
65.57G8.40
the duration of diabetes, mean age at diabetes presentation and gender. The
*BMI, kg/m2
24.05G1.52
26.53G3.36
diagnosis of CAN was confirmed when 2 or more pathological standartized
Sex (M/F)
3/10
3/10
cardiovascular tests were present. HLA alleles identification was determined for
Age at Diagnosis
41.5G6.52
44.6G8.55
all participants by using the polymerase chain reaction with sequence specific
Duration T2D
23
23
primers.
*Fasting glucose, mmol/l
8.65G3.73
10.12G2.71
Results
HbAlc, %
8.63G2.25
8.9G0.98
70 patients with T1D were included in the study: 26 males and 44 females.
Cholesterol, mmol/l
4.54G0.57
5.29G1.09
Patients mean age was 30.48G11.22 years, mean duration of diabetes - 17.52G
Triglyceride, mmol/l
1.17G0.45
1.21G0.89
6.96 years, mean HbA1c 9.26G1.74%. The frequency distribution of DRB1
gene‘s alleles among case group showed, that the most frequent alleles were: *04
Means G SD *: P!0.05
allele - 18 (25.00%), *03 - 12 (16.66%), *01 - 11 (15.27%), *07 - 8 (11.11%),
*08 - 6 (8.33%), and among control group - *04 allele - 22 (32.35%), *01 - 14
(20.58%), *03 - 8 (11.76%), *13 - 6 (8.82%). We confirmed the 3.20 (pZ0.018)
Conclusion
increased relative risk for CAN in T1D with DRB1 gene‘s *08 allele, also *11
Our results provide evidence that diabetic CVD is associated with methylation
(OR 1.67), *07 (OR 1.66) and *03 (OR 1.63) alleles were associated with
changes in metabolic pathway alterations in blood leukocyte DNA. These
increased risk. The highest probability was to find heterozygotes of *08/*X (OR
differences in methylation are worthy of further validation using larger cases of
3.20), *03/*04 (OR 3.20), *07/*X (OR 2.07), *03/*X (OR 1.79) genotypes among
diabetic patients with and without cardiovascular disease.
T1D with diagnosed CAN.
Conclusion
DOI: 10.1530/endoabs.49.EP551
DRB1 gene’s *08 allele and *08/*X, *03/*04, *07/*X, *03/*X genotypes are
associated with increased risk for CAN among patient with T1D.
DOI: 10.1530/endoabs.49.EP550
EP552
Prevalence of eye complications and its correlation with kidney
function: clinical practice data of diabetes patients
Kalpana Dash, Sunil Kumar Ch, Aftab Ahmed, Sambit Das,
EP551
Balaji Jaganmohan, Surekha Tippisetty, Vamsi Krishna Kolukula
Genome-wide DNA methylation analysis for type 2 diabetes mellitus
& Krishna G. Seshadri
and cardiovascular disease: from a 23-year follow-up in the Da Qing
Apollo Sugar Clinics, Hyderabad, India.
diabetes prevention study
Xiaonan Dong, Yanyan Chen & Guangwei Li
Department of Endocrinology, FuWai Hospital, National Center for
Background
Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking
Type 2 Diabetes Mellitus (T2D) patients are at very high risk to have eye
Union Medical College, Beijing, China.
complications. Purpose of the study was to determine the prevalence of diabetes
eye complications (DEC) and its correlation with glomerular filtration rate (GFR)
in diabetes population attending community clinics across India.
Background
Methods
Cardiovascular disease (CVD) is a serious complication of diabetes mellitus
A total of 1547 T2D patients (935 males and 612 females) EMR records were
(DM) and is associated with considerable morbidity and high mortality. There is
retrospectively analyzed. For DEC correlation with GFR, patients were grouped
increasing evidence to suggest that dysregulation of the epigenome is involved in
into GFR %60 and GFR O60 mg/ml/1.73m2. Statistical analysis was done using
diabetes and CVD.
SPSS version 20, with significance P %0.05.
Objective
Results
To assessed the alteration of DNA methylation in patients with/without diabetes
In 1547 T2D patients, 204(13.1%) had DEC, mean (SD) age 56.7(10.0) years;
but developed CVD in a cohort study of Chinese patients.
122(59.8%) males and 82(40.2%) females. Of these, GFR calculated for 443
Methods
patients had mean GFR of 91.2 mg/ml/1.73 m2; 388(87.5%) and 55(12.5%)
40 patients were randomizely selected from diabetics/nondiabetics with/without
patients had GFR O60 and %60, respectively. DEC was observed in 79(17.8%)
CVD after 23 years follow-up, including 20 DM without CVD, 20 DM with CVD.
patients, mean (SD) age 55.5(13.8) years; among them 49(62%) males and
Then a genome wide methylation analysis was conducted using the recently
30(38%) females. GFR was significantly lower in patients with DEC compared to
developed Illumina Infiniumw Methylation EPIC BeadChip, and focusing on
patients without DEC (79.4 vs. 93.8 mg/ml/1.73m2; PZ0.000). Prevalence of
individual cytosines at CpG loci throughout the promoter regions.
DEC in patients with GFR %60 was higher compared to patients with GFR O
Results
60(38% vs.
15%; PZ0.000). However, there was no specific gender
DNA methylation data was analyzed with RnBeads software, and we observed
preponderance.
CpG sites in promoter area of CPT1C, CREB5, ACACB, OLR1, CXCL11
Conclusion
showing higher methylation levels and HADHB showing lower methylation
Our study is one of the few studies from India that reports the prevalence of DEC
levels in DM with CVD patients after enrolling top 500 regions among combined
from a community based clinics based on fundus photographs and correlating
rank (combined P value !0.05, respectively). Singular Value Decomposition
with GFR, thus diabetes kidney disease (DKD). The correlation of DEC with low
(SVD) analysis indicated that significant bvalue of DNA methylation correlated
GFR can suggest presence of DKD in a community, thus, reiterating the
with patient BMI, fasting glucose, cholesterol, triglyceride. After adjusting for
significance of EC screening in community diabetes practices. Implementing
confounding factors, these CpG sites were correlated with fasting glucose. These
these findings into clinical decision pathways may improve the quality of health
genes were then clustered in Fatty acid degradation, Glucagon signaling pathway,
care delivery.
Adipocytokine signaling pathway and PPAR signaling pathway according to
DOI: 10.1530/endoabs.49.EP552
KEGG analysis, which play a role in the synthesis of key enzyme in lipid
metabolism.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP553
was no association between pancreatic steatosis and diabetic retinopathy observed
in the obese group.
Atherosclerotic cardiovascular risk assessment score in diabetes
Conclusion
patients: a retrospective analysis of clinical data
In this study, pancreatic steatosisis was strongly associated with diabetic
Sanjiv Shah, Jayaprakashsai Jana, Balaji Jaganmohan, Raja Selvarajan,
retinopathy in non-obese subjects with T2DM. This result suggests that pancreatic
SG Moazam, Vamsi Krishna Kolukula, Surekha Tippisetty &
steatosis might affect the prevalence of microvascular complication in patients
Shashank R Joshi
with T2DM. However, we still need more studies to define the relationship
Apollo Sugar Clinics, Hyderabad, India.
between pancreatic steatosis and microvascular complication of diabetes mellitus
in details.
Background
DOI: 10.1530/endoabs.49.EP554
The study aimed to minimize the risk causing factors and evaluate new
atherosclerotic cardiovascular disease (ASCVD) risk score using Million Heartsw
Longitudinal ASCVD risk assessment tool among type 2 diabetes mellitus (T2D)
patients.
Methods
A non-interventional retrospective analysis of electronic medical records of
Apollo Sugar Clinics, India. A total of 365 patient’s data was collected, and were
EP555
categorized into normotensive (!120-129/80, mmHg), prehypertensive (130-
Dyslipidaemia and diabetes: a real world clinical evidence in Indian
139/80-89, mmHg), and hypertensive (O140/90, mmHg) based on their blood
scenario
pressure (BP). ASCVD risk score of each patient was calculated using Million
Shantharam Duvvuru, Sambit Das, Moazam SG, N Rajendiran,
Heartsw Longitudinal ASCVD Risk Assessment Tool, as per ACC/AHA 2016
S Venkataraman, NK Narayanan, AV Bhanu Keerthi,
guidelines. Statistical analysis was done by using SPSS version
20, with
Vamsi Krishna Kolukula & Shashank Joshi
significance set at 2 tailed P %0.05.
Apollo Sugar Clinics, Hyderabad, India.
Results
Total 365 patients were analysed, their mean (SD) age was 52.6 (11.9) years,
63.6% were males and 36.4% were females. Of these patients 45.8%, 24.4%, and
Background
29.9% were normotensive, prehypertensive, and hypertensive, respectively. The
Dyslipidaemia, a major risk factor for cardiovascular disease
(CVD) is
indicators of ASCVD risk, age, BMI, and total cholesterol (each P!0.05) were
considerably increasing in patients with diabetes. The purpose of the study was
significantly different among three groups. Of the 365 patients only 161 patients
to evaluate the lipid profiles of diabetes patients attending Apollo Sugar Clinics
who met the ASCVD risk assessment criteria the score was calculated. The
across India.
10-year baseline risk score was 16.8% and expected risk would reduce to 12.5% if
Methods
statin therapy is initiated. A significant difference in risk score was observed
The current study was a retrospective analysis of electronic medical records of
among three groups at baseline (14.4%; 15.6%; 19.4%, PZ0.05), and expected
1487 type 2 diabetes (T2DM) patients who registered at (Dec 2014 to Oct 2016)
10-year risk (10.8%; 11.6%; 14.4%, PZ0.07) if statin therapy initiated.
Apollo Sugar Clinics, across India. Patients with diabetes were diagnosed as per
Conclusion
the ADA guidelines, and the data was collected from the patients after signing
Treatment of cholesterol level by moderate or high intensity statins should be an
informed consent. Statistical analysis was done by using SPSS version 20, and a
essential component of multifactorial intervention for primary prevention of CV
2-tailed P %0.05 was set to be significant.
disease in diabetes patients.
Results
DOI: 10.1530/endoabs.49.EP553
In total (NZ1487) T2DM patients, males and females were 64.9% and 35.1%,
respectively and had mean (SD) age 53.0 (10.6) years. Of these patients analysed,
54.8% had high low density lipoprotein (LDL; O100 mg/dl), 86.1% had low high
density lipoprotein
(HDL; !50 mg/dl),
40.7% had hypercholesterolemia
(O180 mg/dl) and 76.3% had hypertriglyceridemia (O100 mg/dl). In low HDL
group of 86.1%, 54.3% had high LDL and 79% had high TG. Further, mean
concentrations of LDL (111.1 vs 105.6; PZ0.01), HDL (43.3 vs 38.9; P!0.001),
and TC (177.9 vs 169.2; P!0.001) were significantly higher in females compared
EP554
to males (P %0.01). However, of these patients 45.2% and 59.3% are at LDL and
The association between pancreatic steatosis and diabetic retinopathy in
TC targets, respectively.
patients with non-obese type 2 diabetes mellitus
Conclusions
Jee Sun Jeong1, Mee Kyung Kim1, Kyung do Han2, Ki-Hyun Baek1,
The prevalence of dyslipidaemia was observed to be high in diabetes patients than
Ki-Ho Song1, Dong Jin Chung3 & Hyuk-Sang Kwon1
reported in normal population. The pattern of dyslipidaemia is different in India
1Department of Internal Medicine of The Catholic University of Korea,
which is termed as ‘atherogenic dyslipidaemia’ where, in addition to low HDL,
Seoul, Republic of Korea;2Department of Medical Statistics of The
there were elevated levels of both TG and LDL. This increases morbidity of non-
Catholic University of Korea, Seoul, Republic of Korea;3Department of
communicable disease and needs multifactorial intervention for primary
Radiology of The Catholic University of Korea, Seoul, Republic of Korea.
prevention of CVD in diabetes.
DOI: 10.1530/endoabs.49.EP555
Background
In the previous study, it was demonstrated that pancreatic steatosis was
significantly associated with subclinical atherosclerosis in patients with non-
obese T2DM. As the result, it was suggested that pancreatic steatosis might be
related to macrovascular complication of T2DM. However, the association of
pancreatic steatosis on microvascular complication of T2DM has been unknown.
Objective
EP556
This study aimed to investigate the relation between pancreatic steatosis and
Markers of nonalcoholic fatty liver disease in patients with diabetes
diabetic retinopathy in T2DM subjects.
Irina Savasteeva1, Maria Rusalenko1, Yulia Yarets1, Veronika Selkina1,
Method
Yana Navmenova1, Marina Kaplieva2, Alena Makhlina2,
Attenuations of pancreas and spleen of 168 patients with T2DM were measured
Tamara Yeudachkova1, Elena Vaschenko1 & Tamara Moskvicheva1
by using non-enhance computed tomography (CT) imaging. Then the difference
1Republican Scientific and Practical Center for Radiation Medicine and
of attenuation between pancreas and spleen
(P-S) and attenuation ratio of
Human Ecology, Gomel, Belarus;2Gomel State Medical University, Gomel,
pancreatic-to-spleen (P/S) values were calculated for evaluation of pancreatic
Belarus.
steatosis. Obesity was defined when subjects had BMI O25 k/m2 according to the
Asian-specific BMI cut-offs. The presence of diabetic retinopathy was assessed
by an expert ophthalmologist using dilated fundoscopy.
Given the significant correlation between the indices of lipid metabolism, liver
Results
dimensions, glycated hemoglobin and indicators cytolysis of hepatocytes
The attenuation values of P-S and P/S were significantly related to diabetic
identified a number of predictors that have had a significant influence on the
retinopathy in patients with non-obese T2DM. In the non-obese group, compared
formation of NAFLD. At a BMI above 26.5 kg/m2, the relative risk (RR) for BMI
with those without, P-S odds ratio (OR) of patients with pancreatic steatosis was
was 20.02 and was statistically significant (8.25O48.61). When VLDL level
0.192
(95% CI 0.051, 0.727) and P/S OR was 0.12 (95% CI 0.028, 0.515) for
above 0.6 mmol/l relative risk for NAFLD also was statistically significant
diabetic retinopathy, after adjusting for age, gender, and BMI. However, there
(RRZ28.50; 11.18O72.65). With increasing levels of triglycerides above
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1.43 mmol/l relative risk for NAFLD was 34.69 and was statistically significant
Results
(12.68O94.91). In the course of the factor analysis, we analyzed the contribution
82 patients were seen in total. 64 patients had full medicines management review
of isolated predictors in the development of NAFLD patients with diabetes. So
whilst the pharmacist individually reviewed 34 patients. Complete data for this
with type 2 diabetes have made the contribution to such predictors as a BMI
audit was available in in 48/82 patients. 30/48 (62%) were males. Ethnicity
(65.4%), and increase level of triglycerides (16.85%), while type 1 diabetes - BMI
distribution was - Asian 17, Afro-Caribbean 16, Caucasian 12, others 3. A mean
(65.4%) and the level of VLDL (81.0%). In type 2 diabetes the leading influence
reduction in HbA1c from 75 to 70 mmol/mol (PZ0.01) was achieved. Systolic
obesity and atherogenic focus lipogenesis. Patients with type 1 diabetes on the
blood pressure reduced from 136.8 to 137.2 mmHg (NS). No significant change in
development of obesity affects both NAFLD and associated levels of atherogenic
diastolic blood pressure was seen either
(71.5
to
71.0). Significant urinary
lipids, and the degree of compensation of carbohydrate metabolism and
albumin:creatinine ratio
(ACR) improvement was observed: 49 down to 40
associated level of glycation of proteins.
mg/mmol (P!0.01). 28/64 (43%) patients were not on an antiplatelet agent.
DOI: 10.1530/endoabs.49.EP556
60/64 (94%) were on a lipid-lowering agent. 47/64 (73%) patients received an
ACE inhibitor, ARB or both. 9/48 (19%) patients were either referred to renal
physicians or discussed in the renal-diabetes MDT. 11/48 (23%) patients used
Telemedicine and patient held records to improve self - management skills (FLO
Telemedicine-8, Patient Knows Best PKB-3).
Conclusion
These results suggests that the nurse-led clinic is effective in reducing HbA1c and
urine ACR levels in this high CV risk patients and should help improve
EP557
cardiovascular and renal outcomes in future. Pharmacist presence helps improve
Meal composition affects risk markers for kidney disease differently in
medication knowledge and adherence - most patients received lipid-lowering
type 2 diabetes and healthy subjects
agents and majority were on ACE/ARBs, whilst aspirin prescription remained
Camilla Olofsson1,2, Agneta Hilding1, Nicola Orsini1,
low. We hope to further improve results as the clinic progresses to its full
Inga-Lena Andersson2, Ole Torffvit3, Kerstin Brismar1,2 &
potential in future.
Neda Rajamand Ekberg1,2
DOI: 10.1530/endoabs.49.EP558
1Karolinska Institutet, Stockholm, Sweden;2Karolinska University
Hospital, Stockholm, Sweden;3Lund University Hospital, Lund, Sweden.
Background/aims
Oxidative stress and inflammation play a role in development of diabetic kidney
disease. Postprandial hyperglycemia and hyperlipidemia are speculated to be
associated with increased oxidative stress and inflammation. The aim was to
examine the effect of meal composition on post-prandial risk markers for kidney
disease among those with type 2 diabetes (T2D) and healthy subjects (HS).
Material/methods
EP559
On four occasions 21 patients with T2D and 21 HS ingested an isocaloric lunch
Inhibin B levels and bone health in male adult patients with Type 1
(600 kcal) with different compositions of carbohydrate (CH) (54%), CH & fibers
Diabetes Mellitus
(15 g), fat (50%) and protein (40%). Blood samples were taken and urine samples
Eleftheria Barmpa1, Spyros Karamagiolis2, Stelios Tigas3,
collected before and up to four hour after the meal. B-glucose, insulin,
Parthena Navrozidou4, Marianna Vlychou4, Ioannis Fezoulidis4,
triglycerides, CRP, IL-6, IL-18, and urine IgG2, IgG4 and ACR were analyzed.
Georgios N. Koukoulis1 & Alexandra Bargiota1
Statistical method: repeated measure ANOVA and area under the curve.
1Department of Endocrinology and Metabolic Diseases, University of
Results
Thessaly, Larissa, Greece;2General Hospital of Larissa, Larissa, Greece;
T2D had a mean age (GSD) of 63 (4) years while HS had a mean age of 52 (16),
3Department of Endocrinology, University of Ioannina, Ioannina, Greece;
PZ0.004, and T2D had higher BMI (29 vs 24 kg/m2, P!0.001). There were
4Department of Radiology, University of Thessaly, Larissa, Greece.
postprandial differences between the meals for glucose, insulin and triglycerides
for both groups, all P!0.05. High CH meals resulted in higher peaks of glucose
and insulin, while high fat meal gave higher peaks of triglycerides. Both groups
Introduction
had an overall increase in IL-6 for all meals. IL-18 decreased after CH meal only
Existing data suggest that Type 1 Diabetes Mellitus (T1DM) can affect both
in HS, PZ0.003. Urine IgG2 and IgG4 responses were different between the
hypothalamic-pituitary-testis axis and bone health. The mechanisms by which sex
groups after CH-meal (PZ0.02). CRP, urine ACR, urine IgG2 & IgG4 was not
steroids influence bone remodeling remain incompletely understood. Data linking
affected by meal composition within the groups.
gonadal function and bone turnover in male patients with T1DM are lacking. The
Conclusion
purpose of this study was to examine any possible association between sex
CH meal showed higher glucose and fat rich meal higher triglyceride levels
steroids levels and parameters of bone assessment in male adult patients with
suggesting risk for oxidative stress in T2D. However, CRP, IL-6, IL-18, urine
T1DM.
albumin excretion, IgG2 & IgG4 were not significantly modulated by meal
Methods/design
composition in this population.
We studied 53 male patients with T1DM (Group-D) and 42 healthy controls
DOI: 10.1530/endoabs.49.EP557
(Group-C) matched for age, sex and BMI. In both groups HbA1c, Inhibin B
(InhB), total testosterone (TT), SHBG, LH, FSH, b-crosslaps, type 1 procollagen
total N-terminal propeptide (TP1NP) and BMD at lumbar spine (LS), femoral
neck (FN) and total hip (TH) by dual energy X-ray absorptiometry (DXA) were
measured.
Results
Mean age (years) (D: 34.9C10.6 vs C: 34.1C9.9, PZ0.41) and BMI (kg/m2) (D:
23.7C8.1 vs C: 24.5C7.7, PZ0.38) were similar in both groups. In Group-D,
mean duration of DM was 14.4C8.5 years and mean HbA1c was 7.8C1.3%.
EP558
Higher levels of FSH (PZ0.043) and SHBG (PZ0.041), and a trend towards
Audit of a nurse-led and pharmacist assisted diabetes renal out-patient
lower InhB (PZ0.049) and TT (PZ0.051) concentrations, were observed in
clinic - does it help improve medicines management and clinical
Group-D compare to controls. LH was similar in both groups (PZ0.069). Total
outcomes?
BMD (tBMD, g/cm2) and z-scores were lower in Group-D at all three sites ((LS:
Susan Irwin, Gurpreet Kaur, Caroline Lacy & Parijat De
PZ0.031 and PZ0.036), (FN: PZ0.042 and PZ0.039), (TH: PZ0.046 and
Sandwell & West Birmingham NHS Trust, Birmingham, UK.
PZ0.044)). No significant difference in b-crosslaps (PZ0.080) and TP1NP
(PZ0.086) was found between the two groups. Regression analysis showed: a
negative association between InhB and HbA1c (PZ0.038), InhB and tBMD at LS
Aim
(PZ0.041) and a positive association between InhB and b-crosslaps (PZ0.044)
To audit clinical outcomes and adherence to prescription recommendations in a
and InhB and TP1NP (PZ0.047).
diabetes renal clinic.
Conclusion
Method
These data suggest that InhB might contribute to bone turnover changes observed
Baseline data was compared to the final clinic visit within a 12 month period,
in T1DM. Further studies are needed.
using information from clinic letters and electronic records of patients attending
our hospital diabetes renal clinic in 2016 (1st January - 31st December). Patients
DOI: 10.1530/endoabs.49.EP559
with at least 1 follow-up within a 12 month period were included.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP560
(88.7;142.2) compared with euglycemia
97.0
(83.2;107.0), PZ0.046
and
hyperglycemia 96.0 (79.2;110.2), PZ0.028. protein S level was significantly
Cardiovascular disease and risk factors in patients with type 1
increased during hypoglycemia 93.6 (79.2;103.4) compared with euglycemia 77.6
diabetes mellitus
(52.6;90.2), PZ0.046 and hyperglycemia 76.3 (61.0;84.5), PZ0.046. Protein C
Irina Tenu1, Cornelia Bala2, Silvia Iancu2, Gabriela Roman2 &
level, AT-III, vWf, IAT induced by arachidonic acid (PZ0.069) and adenosine-
Ioan Veresiu2
diphosphate (PZ0.058) did not differ between groups.
1Department of Endocrinology, Cluj County Clinic Emergency Hospital,
Conclusions
Cluj-Napoca, Romania;2Department of Diabetes, Nutrition and Metabolic
Acute insulin-induced hypoglycemia causes platelet hyperactivity, which may
Disease, Cluj County Clinic Emergency Hospital, Cluj-Napoca, Romania.
increase the risk of adverse cardiovascular and cerebrovascular events.
Hypoglycemia leads to increased free protein S level, which, is probably, due
Objective
to activation of the endothelium in patients with DM1 without microvascular
The occurrence of cardiovascular disease (CVD) in patients suffering from type 2
complications.
diabetes is a widely discussed issue, less so in those with type 1 (T1DM). The
DOI: 10.1530/endoabs.49.EP561
purpose of this study was to evaluate the frequency of these complications as well
as certain risk factors that they are associated with.
Material and methods
We conducted a retrospective observational study by analyzing data from the
observation charts of 106 patients evaluated in our clinic between January 2015
and December 2016. All patients had a history of T1DM of more than 20 years.
We assessed the occurrence of hypertension
(HT), stroke, acute coronary
EP562
syndrome (ACS) and peripheral artery disease (PAD), as well as certain risk
Biomarkers status and their relation with the presence of type 2
factors. One patient was excluded due to insufficient information.
diabetes with and without angiopathy
Results
Ana Valente1,2, Manuel Bicho3,4, Rui Duarte5, João Raposo5 &
We included 105 patients (46% women), with a mean age of 51.46G12.58 years,
Helena Soares Costa1,6
mean disease duration of 30.16G8.69 years and the mean age at diagnosis of
1Unidade de Investiga
¸a˜o e Desenvolvimento, Departamento de
21.31G11.82 years. The frequency of chronic diabetes complications was: 87%
Alimenta
¸a˜o e Nutrição, Instituto Nacional de Saúde Doutor Ricardo Jorge,
retinopathy, 89% neuropathy, 42% nephropathy and 12% amputations, and for
I.P., Lisboa, Portugal;2Atlântica University Higher Institution, Barcarena,
CVD: 60% HT, 10% ACS, PAD 19 and 5% stroke. There was a statistically
Portugal;3Laboratório de Genética, Instituto de Saúde Ambiental,
significant higher risk in patients diagnosed with CVD in regard to the mean age,
Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal;
mean duration of disease and mean age at diagnosis of T1DM. There was a
4Instituto de Investiga
¸a˜o Científica Bento da Rocha Cabral, Lisboa,
statistically significant correlation for the presence of peripheral neuropathy and
Portugal;5Associac¸ão Protectora dos Diabéticos de Portugal, Lisboa,
nephropathy in patients with HT (P-value 0.0205 and 0.0001 respectively).
Portugal;6REQUIMTE-LAQV/Faculdade de Farmácia da Universidade do
Patients suffering from PAD had a worse glycemic control (HbA1C 9.4 vs 8.80%,
Porto, Porto, Portugal.
P-valueZ0.033) and lower HDL-cholesterol levels
(54.04
vs
63.30 mg/dl,
P-valueZ0.040) than those without. Patients who had suffered a stroke had better
cholesterol and LDL-cholesterol levels
(158.8
vs
189.04 mg/dl, P-valueZ
Introduction
0.000196 and 81.8 vs 106.33 mg/dl, P-valueZ0.029 respectively).
A useful tool for disease clinical characterization and treatment of type 2 diabetes
Conclusion
is the knowledge on the status of several biomarkers. The aim of this study was to
More attention should be awarded in the screening for CVD in patients with a
evaluate the levels of cardiovascular, oxidative stress and nutritional biomarkers
long history of T1DM.
and their relationship with the presence of type 2 diabetes and angiopathy.
Methods
DOI: 10.1530/endoabs.49.EP560
A population-based case-control study in 150 Portuguese type 2 diabetic patients
was performed. Group I - 75 diabetics with angiopathy, group II - 75 diabetics
without angiopathy and group III - non-diabetic controls. Plasma levels of
homocysteine, cysteine, malondialdehyde (MAD), vitamins B6, C, A and E and
carotenoids were measured by HPLC methods. Vitamin B12 and folate serum
levels were achieved by an electrochemiluminescence method.
Results
EP561
The hyperhomocysteinemia prevalence was 20% (group I), 8.7% (group II) and
0.71% (group III). Group I showed the higher prevalence of hypercysteinemia
Platelet aggregation and physiological anticoagulants in acute
(17%). The MAD serum levels were above the reference value for all groups. The
insulin-induced hypoglycemia in patients with type 1 diabetes (DM1)
Karina Sarkisova1,2, Ivona Renata Jarek-Martynowa2, Marina Shestakova1,2
percentage of subjects with ascorbic acid low plasma levels were statistically
& Ekaterina Koksharova2
different in diabetic (I: 55%; II: 47%) compared to non-diabetic subjects (III:
1I.M. Sechenov First Moscow State Medical University, Moscow, Russia;
22%). The prevalence of hypovitaminosis B6 deficiency was at least 30% for all
2Endocrinology Research Centre, Moscow, Russia.
groups. In group I, the probability to have hyperhomocysteinemia was around
three times higher
(PZ0.04) in comparison with group II and
35
times
(PZ0.0006) with group III. The combined effect of type
2 diabetes and
Background and aims
angiopathy is associated with high MAD (OR: 5.33; PZ0.002) serum levels
Hypoglycemia can be a risk factor for adverse cardiovascular and cerebrovascular
compared to group III. Type 2 diabetes predisposes to hypovitaminosis C (OR:
events. However, changes in platelets and coagulation hemostasis during
3.10; PZ0.0002).
hypoglycemia have not been extensively studied. The aim of this study was to
Conclusion
assess the impact of insulin-induced hypoglycemia on the platelet activity,
The prevalence of hypovitaminosis C and B6 were relevant. The presence of type
endothelial dysfunction and the physiological anticoagulant level in patients with
2 diabetes increases the risk of hyperhomocysteinemia, oxidative stress and
DM1.
hypovitaminosis C. The isolated effect of angiopathy increases the probability to
Research design and methods
have hyperhomocysteinemia.
We studied seven patients with DM1 (four male and three female, age 26.5G5.8,
DOI: 10.1530/endoabs.49.EP562
A1C 8.4G1.8%) without microvascular complications during hyperinsulinemic
(1 mU/kg per min) hypoglycemic clamp protocol. Induced platelet aggregation
(IAT) in whole blood using thrombin receptor activating peptide 6 (tRaP-6),
collagen, arachidonic acid, adenosine-diphosphate was measured during
hypoglycemia (plasma glucose
2.3G0.1 mmol/l), normoglycemia (pg 4.4G
0.4 mmol/l), and hyperglycemia (pg R12 mmol/l) by multiple electrode platelet
EP563
aggregometry (Multiplate). Physiological anticoagulants (Protein S, Protein C,
Severe hypoglycaemias in patients with unnoticed hypoglycaemias:
AT-III), von Willebrand factor (vWf) was determined by ELISA. Statistical
a two-year follow up
analysis was performed with SPSS 22.0 for Windows, P!0.05.
Eyvee Arturo Cuellar Lloclla, Guillermo Martínez de Pinillos Gordillo,
Results
Carmen Carretero Marín, Fernando García Pérez, José Álvaro
Collagen-induced platelet aggregation was significantly increased during 20-min
Romero Porcel, Ignacio Fernández Pen˜ a, Juan Manuel García de
of hypoglycemia 34.0 (25.2;51.7) compared with euglycemia 26.5 (18.0;35.0),
Quirós Mun˜ oz, Ignacio Fernández López, Mariana Tomé Fernández-
PZ0.027 and hyperglycemia 23.5 (20.0;23.5), PZ0.028. Thrombin-induced
Ladreda & María Victoria Cózar León
platelet aggregation was significantly increased during hypoglycemia
104.0
Hospital de Valme, Sevilla, Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction and objectives
Conclusion
Having frequent hypoglycaemias can enable the appareance of severe and
In our sample, the prevalence of SGA was 3.5 times higher compared to LGA.
unnoticed hypoglycaemias, as well as favouring vascular damage in these
Women without previous GDM or macrosomia, with lower BMI before
patients. Our objective is to evaluate de incidende of severe hypoglycaemias (SH)
pregnancy, insufficient weight gain during pregnancy, lower HbA1c in 3rd
in patients with Diabetes Mellitus type
1 and the reduction of perceived
trimester and twin pregnancies had significantly more SGA. Monitoring fetal
hypoglycaemias.
intrauterine growth, assessing risk-benefits of therapeutic and an individualized
Material and methods
approach is required.
A prospective study was conducted. Patients attending to their Endocrinology
DOI: 10.1530/endoabs.49.EP564
appointments between September 2013 and January 2014 were surveyed to
evaluate their capacity to perceive hypoglycaemias (Clark’s test). Patients with a
test result compatible with a diminished capacity to sense hypoglycaemia were
tracked 2 years later. The data was analysed using a Chi-squared test (IC 95%)
with SPSS 21.0.
EP565
Results
104 patients were surveyed, out of which 41 had a diminished capacity to perceive
A case of pulmonary tuberculosis presented with recurrent diabetic
ketoacidosis
hypoglycaemia (mean age 36.6G11.6 years, 61% women, HbA1c, 26%G1.04%
Nalan Okuroglu, Sabiha Komoglu, Rojda Usta, Berrak Tas, Meltem Sertbas
and 58.5% had O20 years diabetes evolution). After 2 years, 43.9% referred
& Ali Ozdemir
having had severe hypoglycaemias, out of those 55.6% had had more than 3
Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.
episodes and 33.3% had had a loss of consciousness. 19.5% had an insulin pump
(21.4% in patients with severe hypoglycaemia). We found a statistically
significance between Clark’s test results and severe hypoglycaemias
(P!0.002).
People with diabetes are at increased risk for developing tuberculosis than
Conclusions
non-diabetics. We presented a patient with recurrent diabetic ketoacidosis
A pathological Clark’s test may be able to identify patients at risk for severe
who was later diagnosed with pulmonary tuberculosis.
hypoglycaemia, which makes it a useful tool to detect this group of patients. If a
Case
high incidence of severe hypoglycaemia is observed, measured should be taken to
A 22 year old male with type 1 diabetes for nine years was admitted to the
educate this patients to be able to recognize and interpret the symptoms of low
emergency service due to nausea and vomiting. Detecting high anion gap with
blood glucose as well as developing therapeutic strategies to avoid them, all of
metabolic acidosis in his blood gas), and ketones in urine analysis,the patient was
which would improve their quality of life.
hospitalized for diabetic ketoacidosis (DKA). Additional analysis of urine, liver,
DOI: 10.1530/endoabs.49.EP563
kidney tests, abdominal ultrasound, chest X-ray were within normal limits.
Lumbosacral MR imaging based on the low back pain did not reveal any
pathology. Serological tests of celiac disease was negative. After receiving
intravenous insulin, DKA resolved and he was discharged. 1 week later, the
patient admitted to our hospital because of high anion gap metabolic acidosis and
hyperglycemia. The cortisol and anterior hypophysis hormones made for the
etiology of DKA were within normal range. Recommending outpatient clinic
control the patient was discharged. For the third time, after another nausea,
vomiting and abdominal pain, the patient was referred to another health center
EP564
with diabetes ketaoacidosis; gastroscopy was performed and esophageal lineer
Small for gestational age and gestational diabetes - Should we be more
ulcers were detected. Pathology was compatible with non-specific inflammation.
permissive?
After being discharged, the patient was presented again to our emergency
Rita Bettencourt-Silva1,2, Pedro Souteiro1,2, Daniela Magalha˜es1,2,
department suffering from chest pain, retrosternal burning and weight loss. Again
Sandra Belo1,3, Ana Oliveira1,4, Davide Carvalho1,2, Joana Queirós1,3 &
ketoacidosis was detected and hospitalized. During his admission, chest X-ray
Diabetes and Pregnancy Study Group Portuguese Society of Diabetology3
revealed right upper lobe cavitary lung lesion. With positive sputum acid-fast
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-
bacilli(AFB) stains he was diagnosed and treated for pulmonary tuberculosis.
talar São João, E.P.E., Porto, Portugal;2Faculty of Medicine, University of
Discussion
Porto, Porto, Portugal;3Diabetes and Pregnancy Study Group, Portuguese
The tuberculosis incidence in diabetes is four times higher than general
Society of Diabetology, Portugal;4Outpatient Clinic of Obstetrics and
population. Especially in the developing countries like Turkey where the
Endocrinology, Centro Hospitalar Sa˜o João, E.P.E., Porto, Portugal.
prevalence of type 2 DM is increasing, tuberculosis is an important health
problem and patients with diabetes should be screened for tuberculosis.
Introduction
Gestational diabetes mellitus (GDM) is a risk factor for large for gestational age
(LGA) newborns. The optimization of glycemic control and weight gain
restriction during pregnancy according to BMI has contributed to decrease
LGA but may increase the risk of small for gestational age (SGA).
Aim
To evaluate the predictors of SGA in women with DGM.
Methods
A cohort of 5271 Portuguese women from the National Registry of GDM was
studied. Demographic, anthropometric and analytical data and maternal-fetal
outcomes were evaluated.
Results
Women presented a mean age of 33.14G5.4 years, mean BMI of 26.99G
5.81 kg/m2 and mean weight gain during pregnancy of 9.63G5.78 kg. The
newborn’s growth was evaluated according to Fenton curves in 4727 cases. We
identified 3898 (82.5%) newborns appropriate for gestational age (AGA), 180
(3.8%) LGA and 649 (13.7%) SGA. Women with SGA had a significant lower
DOI: 10.1530/endoabs.49.EP565
pre-pregnancy weight
(66.95G15.20 vs 71.01G16.04, P!0.001) and BMI
(26.07G5.75 vs 27.06G5.77; P!0.001). The prevalence of SGA was lower in
women with previous GDM (ORZ0.592, 95%CIZ0.466-0.805, P!0.001) or
macrosomia (ORZ0.274, 95%CIZ0.145-0.520, P!0.001) and greater number
of pregnancies
(ORZ0.798, 95%CIZ0.737-0.863, P!0.001) and two-fold
higher in twin pregnancies
(ORZ2.059, 95%CIZ1.313-3.229, PZ0.001).
Insufficient weight gain during pregnancy increased the possibility of SGA by
EP566
35% (ORZ1.346, 95%CIZ1.127-1.609, P!0.001). A lower value of HbA1c in
Which one is much more cause in osteoarthritis? Diabetes mellitus
3rd trimester was presented in pregnancies with SGA (5.18G0.38 vs 5.25G0.44,
Type 1 or 2?
ORZ0.662, 95%CIZ0.516-0.849, PZ0.001). No significant differences were
Kadri Yildiz1 & Kenan Cadirci2
found regarding age, week of diagnosis and treatment with insulin or oral
1Erzurum Palandoken State Hospital, Erzurum, Turkey;2Erzurum Regional
antidiabetic agents.
and Educational Hospital, Erzurum, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Osteoarthritis is a great public health problem indiscriminately; ie
Background and aims
goanrthritis, coxarthritis or dejenerative spine diseases. Osteoarthritis is
To evaluate the level of tubular and glomerular biomarkers of kidney injury as
focude sixth decades in elderly people, espicially in women. Many studies
potential nephroprorotective effects of GLP-1R agonist (liraglutide) addition in
assingned the efficiancy of Diabetes Mellitus in the etiology of
type 1 diabetic patients compared to standard insulin therapy.
Osteoarthritis. Correlations between bone-destructive characteristics and
Materials and methods
carbohydrate metabolism errors is now quite accused in this clinical views.
12 T1DM patients with normo-(AER !20 mg/l, nZ7) and microalbuminuria
A comparing between Diabetes Mellitus Type 1 and 2 is aimed in this study
(AER!199 mg/l, nZ5) with liraglutide 1.2 mg as add on to insulin for 6 month
which one cause in much more osteoarthritis. 167 (69 gonarthroisis, 57
and
12 patients with normo-(AER
!20 mg/l, nZ8) and microalbuminur-
coxarthritis and 41 dejenerative spine diseases) patients is joined to this
ia(AER!199 mg/l, nZ4) on standard insulin therapy. Biomarkers of kidney
trials for
4 years. All patients were evaluated by endocrinologists and
damage (collagen i.v., nephrin, podocin, cystatin C, kidney injury molecule-1
orthopaedists. According to results; there were more counts of Type 2
(KIM-1), neutrophil gelatinase-associated lipocalin
(NGAL), uromodulin,
patients in all groups (51 Type 2 and 18 Type 1 in gonarthrosis; 46 Type 2
osteopontin) were measured by enzyme-linked immunosorbent assay ELISA in
and 11 Type 1 in coxarthritis, 32 Type 2 and 9 Type 1 in dejenerative spine
the morning urine and fasting plasma; overnight AER by immunoturbidimetry
diseases). Statistical difference is significiant
(P!0.05). Many recently
assay; glomerular filtration rate (GFR) by CKD-EPI formula were measured
clincal and laboratory studies assigned a correlations between Diabetes
before and after 6-month treatment. Concomitant RAAS blockage-drugs given in
Mellitus and all rheumatoid diseas. Carbohydrate metabolism is a headstone
stable doses. Differences were examined for statistical significanse (P!0.05)
of all metabolic systems. All defects and errors in carbohydrate metabolism
using Wilcoxon Signed-Rank Test.
can affect other metabolic systems and bone-soft tissue systems by the
Results
metabolits, especially sorbitol. And also presdisposition of Type
2 to
Initially the groups were similar by average age, HbA1c, plazma glucose, BP,
Metabolic Syndrome can mark pathophyisology of Osteoarthritis as
lipids, uric acid, C-reactive protein, creatinine, eGFR. HbA1c before and after
difference proportions of these types.
6 month treatment. There were no significant differences in BP, albuminuria,
creatinine, eGFR, HbA1c in 6 month. BMI decreased from 29 (22;38) to 26.8
DOI: 10.1530/endoabs.49.EP566
(21;34.7) kg/m2, PZ0.01 in GLP1 group. Urinary levels of podocin, KIM-1 and
collagen did not changed before and after therapy. In GLP1 group observed
significant reduction in the urinary levels of NGAL/creatinine 1.48(0.81;2.29) vs
0.65(0.34;0.74) ng/mmol, PZ0.015; KIM-1/creatinine
115(35;328) vs
47(21;116) ng/mmol, PZ0.02; cystatin C
881(464;1579) vs
136(91;205)
EP567
ng/mmol, PZ0.01; nephrin 0.1(0.09;0.15) vs 0.004(0.01;0.1), uromodulicreati-
Prevalence of distal symmetric polyneuropathy in diabetic patients in
nine rised from 175(82;278) to 458 (235;754); and plazma levels of cystatin and
general medicine wards
osteopontin after treatment: 1264 (877;1472) vs 722 (672;848) ng/ml, PZ0.007;
Ana Lopes1, Helena Gonçalves2, Liliana Fonseca1, Catarina
126.8
(45;161) vs 65 (45;74), PZ0.02, respectively compared to the stable levels
Castelo Branco1, João Gonçalves1, Luisa Sousa1, Margarida Calejo1,
of markers in the standard insulin treatment group.
Sara Martins1, João Neves1 & Sofia Teixeira1
Conclusion
1Centro Hospitalar do Porto, Porto, Portugal;2Centro Hospitalar
The present data suggest that GLP-1R adding to standard insulin therapy might be
Trás-os-Montes e Alto-Douro, Vila Real, Portugal.
effective for the weight reduction and as potential nephroprotective strategy for
attenuating the chronic kidney injury in T1DM.
DOI: 10.1530/endoabs.49.EP568
Background
Distal symmetric polyneuropathy (DSPN) is one of the most prevalent chronic
complications of diabetes and the most common cause in the pathway to diabetic
foot ulceration. Screening for DSPN enables early intervention and prevention of
complications. The Semmes-Weinstein Monofilament Examination (SWME) is
currently the method of choice to screen DSPN, but ideally two neurologic tests
should be used. The Michigan Neuropathy Screening Instrument (MNSI), which
evaluates vibratory sensation and ankle reflex, has been proposed as a useful
screening test of DSPN. The objective of this study was to determine the
prevalence of DSPN in diabetic patients in general medicine wards.
Methods
EP569
Diabetic patients admitted within a 5 months period were evaluated with the
MNSI and the SWME after exclusion of other causes of polyneuropathy. A score
Diabetic choroidopathy and renal function
O2 in the clinical examination of MNSI and %7 positive answers in a total of 10
Antonio Manuel Garrido Hermosilla1,2, Mariola Méndez Muros3, Cristóbal
in SWME were considered positive.
Morales Portillo3, Tomás Martín Hernández3, Natividad González Rivera3,
Results
María Jesús Díaz Granda1,2, Enrique Rodríguez de la Rúa Franch1,2 &
Twenty-three patients were included (75.6G13.7 years; 56.5% male; 9.9G6.1
Estanislao Gutiérrez Sánchez1,2
years of disease duration). Only 2 (8.7%) had previously been diagnosed with
1Ophthalmology Department, Virgin Macarena University Hospital, Seville,
DSPN. The SWME was positive in only one of these patients while the MNSI was
Spain;2OftaRed - RETICS Ocular Pathology, Institute of Health Carlos III,
positive in both. In the remaining undiagnosed 21 patients, 12 patients (57.1%)
Madrid, Spain;3Endocrinology Department, Virgin Macarena University
were positive for the MNSI, while 14 (66.7%) were positive for the SWME. Both
Hospital, Seville, Spain.
MNSI and SWME were positive in 10 out of 23 patients (43.5%) and 19 out of 23
(82.6%) had at least one screening test positive.
Objectives
Conclusion
Examine the relationship between choroidal thickness (CT) and renal function
In this study, more than half of the diabetic patients without a previous diagnosis
tests.
were screened positive for either the MNSI or SWME test. Data indicates that
Methods
using both MNSI and SWME increases the detection of DSPN. This study
Cross-sectional study with 42 eyes of 21 ocular treatment-naïve diabetic patients.
confirms that DSPN is a prevalent complication of diabetes and that
Demographic and ocular data were analyzed as well as the following renal
hospitalization is an excellent opportunity to screen for DSPN.
function tests: microalbuminuria, microalbumin/creatinine ratio and glomerular
DOI: 10.1530/endoabs.49.EP567
filtration rate (CKD-EPI and MDRD-4). Choroidal thickness was measured by
swept-source ocular coherence tomography (SS OCT).
Results
The mean age was 49.76G17.61 years old (18-74), with a sex ratio of
approximately 1:1. 66.7% suffered from type 2 diabetes mellitus, with a mean
time of evolution of 12.14G10.08 years. 51.2% of patients didn’t present diabetic
EP568
retinopathy. Among renal function tests, only microalbuminuria positively
Tubular and glomerular biomarkers of kidney injury on glucagon-like
correlated with CT (P!0.05).
peptide-1 (GLP-1) therapy in type 1 diabetic patients
Conclusions
Zamira Zuraeva2, Olga Vikulova1,2, Olga Mikhaleva2,
The analysis of CT with SS OCT could be a prediction tool of renal function in
Marina Shestakova1,2, Aleksandr Ilyin1, Minara Shamkhalova1,2 &
diabetic patients.
Ivan Dedov1
1Endocrinology Research Center, Moscow, Russia;2I.M. Sechenov First
DOI: 10.1530/endoabs.49.EP569
Moscow State Medical University, Moscow, Russia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP570
Chronic kidney disease (CKD) is an important complication of diabetes and
Risk factors of diabetic foot complications
determinant of mortality. Albuminuria represents early diabetic nephropathy, and
Radhouane Gharbi, Melika Chihaoui, Ons Rejeb, Meriem Yazidi,
also indicates generalised vascular dysfunction. Understanding the epidemiology
Ibtissem Oueslati, Fatma Chaker & Hedia Slimane
of CKD and albuminuria helps inform health planning and identify opportunities
University of Tunis El Manar, Faculty of Medicine of Tunis, La Rabta
to prevent or delay progression of diabetic kidney disease. The last available
Hospital, Department of Endocrinology, Tunis, Tunisia.
serum creatinine and urine albumin/creatinine ratio (UACR) in patients with Type
1
(T1DM) or Type 2 (T2DM) diabetes recorded on the DIAMOND database were
used for analysis. Patients were divided into tertiles of age. CKD was defined
Introduction
as eGFR!90 ml/min; microalbuminuria as UACRO2.5 mg/mmol
(male),
Diabetic foot disease is a major health problem. The identification of its risk
O3.5 mg/mmol (female); macroalbuminuria as UACRO20 mg/mmol. NA-
factors should guide preventive measures. The aim of this study was to determine
normal albumin excretion; MA-microalbuminuria; A-macroalbuminuria;
the factors associated with diabetic foot complications.
ND-not done CKD was common and increased with age. Microalbuminuria
Patients and methods
also increased with age and was similar in patients with and without CKD.
It is a retrospective study including 47 patients admitted at the department of
Macroalbuminuria was uncommon. In summary, CKD is common in hospital-
Endocrinology in La Rabta hospital for diabetic foot complications during the
based diabetic patients. The low prevalence of macroalbuminuria indicates that
years 2015 and 2016. Clinical and para-clinical data were collected.
this mostly does not reflect classical diabetic nephropathy.
Results
The mean age was 51 years (27 to 78). There were 39 men (83%). It was a type 2
diabetes in 85% of patients. The mean duration of the disease was 13 years (0 to
30 years). Patients were illiterate or had a primary school level in
73%.
T2DM, No
Hypertension was present in
23% of the patients, smoking in
61% and
T1DM, CKD
T1DM, No CKD
T2DM, CKD
CKD
dyslipidemia in 29%. Diabetes was complicated with peripheral neuropathy in
Number/ %
Number/ %
Number/ %
Number/ %
81% of the patients, retinopathy in 54% and nephropathy in 53%. Coronary artery
(%NA/MA/A/ND)
(% NA/MA/A/ND)
(%NA/MA/A/ND)
(%NA/MA/ND)
disease was present in 15%, stroke in 6% and peripheral artery disease in 46%.
Age 18-58
271/ 27%
732/ 73%
721/ 42%
978/ 58%
Conclusions
(nZ2702)
(60/ 13/ 6/ 21)
(51/ 10/ 1/ 38)
(56/ 14/ 4/ 26)
(60/ 13/ 6/ 21)
Diabetes foot problems occur more often in men with a long duration of diabetes,
Age 58-71
106/ 75%
36/ 25%
1736/ 67%
826/ 33%
peripheral neuropathy and peripheral artery disease.
(nZ2704)
(56/ 19/ 5/ 20)
(45/ 23/ 6/ 26)
(50/ 17/ 5/ 28)
(50/ 17/ 5/ 28)
DOI: 10.1530/endoabs.49.EP570
Age 71-107
54/ 85%
9/ 15%
2244/ 84%
397/ 16%
(nZ2704)
(20/ 31/ 6/ 43)
(44/ 22/ 11/ 23)
(40/ 28/ 6/ 26)
(47/ 20/ 5/ 28)
DOI: 10.1530/endoabs.49.EP572
EP571
Diabetes mellitus as an important comorbidity in patient with sepsis
Entela Puca1, Edmond Puca2, Agron Ylli2 & Pellumb Pipero2
1American Hospital 2, Tirana, Albania;2UHC Mother Teresa, Tirana,
Albania.
Sepsis represents the host’s systemic inflammatory response to a severe infection.
It is a common condition in hospital settings and is associated with high rates of
EP573
morbidity and mortality. Since1992 the knowledge about sepsis epidemiology has
Two case reports of diabetic ketoacidosis: as lethal as avoidable
clearly improved. There are differences in epidemiologic data about sepsis
Rodolfo Gomes, Joana Oliveira, Bárbara Picado, Fernando Gonçalves &
identification in different countries. The aim of our study is to make a panoramic
José Araújo
view of sepsis at the service of Infectious Diseases, University Hospital Center,
Hospital Beatriz Ângelo, Loures, Portugal.
‘Mother Teresa’, Tirane, Albania during January 2009 to December 2013 and to
highlight its accompanying diseases.
Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes
Material and methods
mellitus (DM). We describe 2 cases of type-2 diabetic patients admitted by a
In our study we included patient over O14 years old, since we are a service for
surgical reason/trauma in which DM control was neglected. We present a
adult patients only. Our study was a retrospective one. A septic patient was
defined based on the 2001 sepsis conference definition. Study period was from
74-year-old patient with poor metabolic control (HbA1c 7,6%) treated with
January 2009 to December 2013.
metphormin, sitagliptin and glibenclamide, admitted for orthopaedic surgery.
Results
During hospitalization, there were noted several episodes of disorientation with
During our study time from 2009-2013 we had 707 patients with sepsis. The
hyperglycaemia about 300-350 mg/dl. At day 6, the patient was prostrated and
mean age was 50.3879 years old and SDEV resulted G19.59 years old. The most
with a glucose over 500 mg/dl and metabolic acidosis (pH 7,34; pCO2 29 mmHg;
affected age resulted 55-75 years old. Comorbidities in patients with sepsis were
pO2 89 mmHg; HCO3 15,6 mmol/l; lactate 8 mg/dl). Because of DKA, the patient
as below: Diabetes mellitus 5.2%, HIV/AIDS 4.5%, malignancies 1.6%, alcoholic
was transferred to an Intermediate Care Unit (IntCU), where it was begun fluids
cirrhosis 1.2%, autoimmune diseases 0.99%, post-transplant patients 0.84%, and
and insulin perfusion, with great response. Simultaneously, we present a case of a
homeopathies 0.7%.
70-year-old patient, already with diabetic retinopathy, treated with insulin,
Conclusions
metphormin and sitagliptin, that was admitted because of a pneumothorax and 3
In nowadays sepsis definition is modified. However its concept remains the same.
broken ribs after a fall. She was admitted in Pneumology ward, maintaining
hyperglycemias, nauseas and vomiting. At day 8, she was found prostrated,
The sepsis cases are increasing. The age and other comorbidities are risk factors
frankly dehydrated and with a hyperglycaemia over 500 mg/dl. After diagnosing
that play an important role in the increasing of morbidity and mortality. Diabetes
DKA with a serious metabolic acidosis
(pH
6,97; pCO2
8 mmHg; pO2
mellitus resulted as a major comorbidity in patient with sepsis.
106 mmHg; HCO3 3 mmol/l; lactates 31 mg/dl), she was transferred to IntCU,
DOI: 10.1530/endoabs.49.EP571
where she was treated with fluids and insulin, with good posterior metabolic
control. In both cases, the patients presented had the DM diagnosis, being treated
accordingly at home. Although, after being admitted for an unrelated reason, it
was neglected all DM control as well as the symptoms that came from its
decompensation, ending in an extremely serious state. This reinforces the need of
EP572
approaching each patient with all its conditions, reassuring the essential role of
The prevalence of chronic kidney disease and albuminuria in patients
Internal Medicine in management and orientation of these patients since their
with Type 1 and Type 2 diabetes attending a single centre
admission.
MS Majeed, G Boran, LA Behan, M Sherlock & J Gibney
DOI: 10.1530/endoabs.49.EP573
Departments of Endocrinology1, and Chemical Pathology 2, The Adelaide
and Meath Hospital, Incorporating the National Children’s Hospital,
Tallaght, Dublin 24, Dublin, Ireland.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP574
deplete and often have minimal symptoms. Cautious administration of fluid
boluses with monitoring is recommended in the presence of intravascular volume
Characteristics of patients with cystic fibrosis and hydrocarbon
depletion. Rarely, DKA can cause pulmonary oedema in these patients due to
alteration in an adult unit
interstitial hypertonicity from hyperglycaemia, which often responds to insulin
Elena Fernández González, Nerea Aguirre Moreno, Layla Diab Cáceres,
treatment alone. If there is inadequate response to maximal medical therapy,
Carmen Acosta Gutiérrez, Ana Ramos-Leví, Miguel Sampedro Nu
˜ ez,
earlier haemodialysis is warranted.
Isabel Huguet Moreno, Mónica Marazuela Azpiroz, Rosa María
Conclusion
Girón Moreno & Alfonso Arranz Martín
Aggressive intravenous fluid resuscitation is a key treatment for DKA. However,
Hospital Universitario La Princesa, Madrid, Spain.
cautious fluid administration should be considered in dialysis-dependent patients.
DOI: 10.1530/endoabs.49.EP575
Introduction
Hydrocarbon Alteration (HA) is considered as the most common complication in
Cystic Fibrosis (CF) and is related to a further deterioration of the lung function
and the nutritional status.
Objective
Analyze the prevalence of HA in patients with CF in an adult unit and its
relationship with pulmonary complications.
EP576
Material and methods
Severe diabetic gastroparesis - two cases of challenging treatment
We conducted a retrospective study with 71 patients of our CF unit (age 30C/K9
Pedro Souteiro1,2, Sofia Castro Oliveira1,2, Joa˜o Sérgio Neves1,2,
years, 50.5% women, BMI 22.2C/K3.8 kg/m2 and CF evolution 22C/K9 years).
João Santos-Antunes2, Rita Bettencourt-Silva1,2, Sandra Belo1,2,
Patients were classified, according to the glycaemic response to oral glucose
Celestino Neves1,2, Paula Freitas1,2, Joana Queirós1, César Esteves1,2 &
overload, in 3 categories: normal glucose tolerance (NGT, 31%), pre-diabetes
Davide Carvalho1,2
(preDM, 29.6%) and diabetes (CFRD, 39.4%). The analysis included the variables:
1Department of Endocrinology, Diabetes and Metabolism, Porto, Portugal;
age, sex, BMI, lung function, chronic bronchial infection, pulmonary exacer-
2Faculty of Medicine of University of Porto, Porto, Portugal.
bations and its degree of severity.
32.4% of the patients received some
hypoglycaemic treatment (78.6% of them were CFDR): 32% were under bolo-
basal insulin, 28% basal insulin, 16% oral drugs and 24% other treatments.
Introduction
Statistical analysis was performed with STATAv12.0.
Gastroparesis is defined by a delayed gastric emptying without mechanical
Results
obstruction. It can be a debilitating complication of diabetes that is poorly
Lower BMI was observed when comparing patients with CFRD (20.65C/K
understood and has limited therapeutic options.
0.6 kg/m2) and preDM (23.72C/K0.7 kg/m2) (PZ0.005); and a tendency was
Case reports
noticed between CFRD and NTG
(22.64C/K0.6 kg/m2)
(PZ0.1). CFRD
1st case - We report the case of a 34-year-old woman with type 1 diabetes mellitus
patients showed greater frequency of severe pulmonary exacerbations than
(T1DM) with diabetic nephropathy and gastroparesis, and a reasonable glycaemic
preDM (PZ0.016). Higher colonization prevalence by Staphylococcus aureus
control (haemoglobin A1c 6.9%) on insulin-pump regimen. Gastric emptying
meticilin-resistant
(MRSA) (NTG 4.54%, preDM 9.5%, CRFQ 17.86%) and
scan revealed 100% contrast retention 2 hours after its ingestion, confirming
Achromobacter xylosoxidans (NTG 4.54%, 19.05% preDM, DRFQ 21.43%) was
severe gastroparesis. Repeated vomiting, refractory to oral anti-emetics, led to her
observed. This trend was not noticed for Staphylococcus multisensible aureus,
hospitalization 8 times in one year in a total of 109 days. She also underwent a
Pseudomonas aeruginosa, and Haemophilus influenzae.
medical pregnancy interruption due to hyperemesis gravidarum. Due to difficult
Conclusions
management of vomits the patient underwent a gastric peroral endoscopic
HA is frequent among our CF patients. Lower BMI is associated with higher
pyloromyotomy (G-POEM). After the procedure she had pronounced sympto-
degree of HA. CFRD patients show more frequent severe pulmonary
matic improvement and reduced need of hospitalization (only 10 days in the
exacerbations and higher prevalence of infections by MRSA and Achromobacter
6 months of follow-up). The post-procedure scan showed a near-normal gastric
xylosoxidans. This reinforces the importance of adequate nutritional and
emptying (52% contrast retention at 2 hours).
endocrine control as well as the need to a multidisciplinary approach for the
2nd case - A 23-year-old woman with T1DM with diabetic gastroparesis with no
treatment of CF patients.
other end-organ damage. She presented a poor glycaemic control with a
DOI: 10.1530/endoabs.49.EP574
haemoglobin A1c of 10.3%. Gastric scan revealed severe retention with a half-
emptying time of 862.6 minutes (normal time of 80G20). She was severely
disabled by vomit episodes that required frequent and prolonged hospitalization
periods. She also underwent G-POEM with fair symptomatic improvement and
reduced need of hospitalization during her follow-up despite post-procedure
gastric scanning still showed a delayed gastric emptying (93% retention at
2 hours).
Conclusions
EP575
Diabetic gastroparesis presents a challenging treatment since medical therapy has
Management of diabetic ketoacidosis in haemodialysis patient
disappointing results in some patients. In those cases, endoscopic procedures can
Heidy Hendra, Hannah Stacey & Sumith Abeygunasekara
lead to symptomatic relief and enhanced quality of life obviating the need of more
Broomfield Hospital, Chelmsford, UK.
aggressive alternatives like gastrectomy.
DOI: 10.1530/endoabs.49.EP576
Introduction
Diabetes mellitus is the commonest cause of chronic kidney disease leading to
end-stage renal failure (ESRF). Fluid replacement is one of the cornerstone
treatments of DKA, however anuric dialysis patients are at risk of fluid overload.
Information for managing DKA in haemodialysis patients is relatively sparse.
Case report
A 76-year-old gentleman with type 1 diabetes was admitted with drowsiness. He
EP577
has twice weekly dialysis and on 700 ml/day fluid restriction. Due to recurrent
Predictors of in-hospital mortality in diabetic patients - analysis of
episodes of hypoglycaemia, his insulin dose was reduced. On examination he had
958305 hospitalizations
dry mucous membranes, cool peripheries and erythematous left below knee
Magdalena Walicka1, Monika Puzianowska-Kuznicka2,3, Marcin Chlebus4,
amputation stump. Blood pressure was 92/50 mmHg. Blood gas showed pH 7.17,
Andrzej Sliwczynski5, Melania Brzozowska5, Daniel Rutjowski5,
HCO- 13.2, glucose level 35 and ketones of 6 mmol/l. He was diagnosed with
Lidia Kania1,2, Marcin Czech6, Andrzej Jacyna5 & Edward Franek1,2
DKA precipitated by inadequate insulin administration and stump infection. He
1Department of Internal Diseases, Endocrinology and Diabetology, Central
was commenced on fixed rate insulin infusion (FRII) and antibiotics. In total he
Clinical Hospital of the Ministry of the Interior and Administration,
received 1 litre of fluid. He continued his scheduled haemodialysis sessions.
Warsaw, Poland;2Department of Human Epigenetics, Mossakowski
Discussion
Medical Research Centre, Warsaw, Poland;3Department of Geriatrics and
Currently there are no studies available which assess the treatment of DKA in
Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland;
dialysis-dependent patients. DKA is uncommon in these patients as ESRF leads to
4Department of Quantitative Finance, Faculty of Economic Sciences,
improved glycaemic control due to reduced kidney gluconeogenesis, less insulin
University of Warsaw, Warsaw, Poland;5National Health Found, Warsaw,
clearance and improved insulin sensitivity. Anuric dialysis patients do not have
Poland;6Warsaw University of Technology, Business School, Warsaw,
glycosuria and osmotic diuresis, therefore they are less likely to be volume
Poland.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
Diabetes Therapy
Diabetes mellitus is a lifelong chronic disease with higher risk of mortality and
EP579
morbidity
A modelling approach for cost-savings in the elderly ontarian
Objective
population with type 2 diabetes due to reduction in mild hypoglycemia
To study the risk factors of death in hospitalized diabetic patients
events for SGLT-2 inhibitor versus sulfonylurea (SU) initiation after
Methods
metformin
Data obtained from the database of the National Health Fund (NHF), a public
Pendar Farahani
organization financing medical procedures in Poland regarded
958305
McMaster University, Hamilton, Ontario, Canada.
hospitalizations of adult (R18 years old) patients with diabetes in 2014 year.
Logistic regression models were performed to identity independent predictors of
in-hospital mortality.
Background
Results
Mild hypoglycemia in elderly is associated with significant chronic consequences
There were 573719 hospitalizations in non-surgical wards and 384586 in surgical
leading to physical and cognitive dysfunction and eventually frailty and
wards. The mean in-hospital mortality rate was 3,20% (4,52% in non-surgical and
disability. Mild hypoglycemia appears to be under-recognized in real-world
1,23% in surgical wards). In non-surgical wards, odds ratio for in-hospital death
clinical settings in the elderly and can lead to significant costs for patients.
increased with patients age, being 52-fold higher in the R95 years old group
Objective
compared to the 18-24 years age group; male gender, emergency admission,
To calculate cost-savings due to mild hypoglycemia reduction for SGLT-2
admission on weekend or other non-working day, hospitalization in county/town,
inhibitor versus SU initiation after metformin for elderly Ontarians with type 2
private or regional hospital (vs teaching hospital), were factors associated with
diabetes.
greater mortality. In surgical wards odds ratio for in-hospital death started to
Methods
increase after 75th year of life, being 13-fold higher in the R95 years old group
An economic model was calculated incorporating data from RCTs on SGLT2I for
compared to the 18-24 years age group; female gender, emergency admission,
mild hypoglycemia. Data on prevalence of type 2 diabetes and SU utilization for
admission on weekend or other non-working day, hospitalization in county/town
elderly in Ontario were obtained from published data from Institute for Clinical
or regional hospital (vs teaching hospital), were factors associated with greater
Evaluative Sciences
(ICES). Costs per event for mild hypoglycemia were
mortality.
obtained from published studies.
Conclusions
Results
Predictors of in-hospital mortality in patients with diabetes are age, sex, type of
With assumption of only one mild hypoglycemia during the first year of SU
hospital admission, admission on non-working day and type of hospital.
versus SGLT2 inhibitor initiation as add-on to metformin for the elderly Ontarian
DOI: 10.1530/endoabs.49.EP577
population with type 2 diabetes, the total cost from the patients’ perspective
would lead to an annual cost-savings of CDN $2 066 224 due to less cost for mild
hypoglycemia episodes treatment. Sensitivity analysis resulted in a minimum
annual cost-savings of CDN $691 048 and a maximum annual cost-savings of
CDN $8 402 373 for SGLT-2 inhibitor versus SU initiation after metformin due
to mild hypoglycemia reduction for the Canadian population with type 2 diabetes.
Conclusion
This study illustrates that reduction in mild hypoglycemia episodes (which mostly
are not reported in real-world clinical settings) due to SGLT2I utilization instead
of SU in elderly Ontarian with type 2 diabetes can lead to a significant cost-
savings from patients’ perspective.
EP578
DOI: 10.1530/endoabs.49.EP579
Gestacional diabetes mellitus: 4 years study case at a tertiary level
maternity hospital
Francisco Evora, Marta Pinto & Céu Almeida
Bissaya Barreto Maternity - CHUC, Coimbra, Portugal.
Introduction
EP580
Gestational diabetes mellitus (GDM) is a carbohydrate intolerance with onset or
recognition during pregnancy. Timely screening and proper management of this
Do adding B vitamins and folate to metformin has beneficial effect on
condition is essencial to maximize pregnancy and neonatal outcomes.
renal function and lipids in type 2 diabetic patients
Methods
Marina Shargorodsky & Elena Omelchenko
Retrospective analysis of all cases of GDM, and the respective new-borns,
Wolfson Medical Center and Tel Aviv university, Holon, Israel.
followed in our obstetrics unit between 2012 and 2015. Clinical and workup
parameters were evaluated.
Introduction
Results
Metformin is effective in reducing cardiovascular mortality, however may
From a total of 644 cases of GDM, median age was 33, median BMI was 27
decrease vitamin B12 and folate levels, and increase levels of homocysteine.
(overweight/pre-obese) and the most common academic qualifications was a
Hyperhomocysteinemia is associated with adverse impact on lipid parameters and
licentiate degree (13 years of school). In terms of risk factors, 51% had a family
renal function. The present study was designed to determine the effect of
history of DM and a personal history of: GDM (11%), macrossomia (4%),
homocysteine lowering therapy by using group B vitamins and folate
hydramnios (3%), fetal malformations (5%) and fetal death (0.3%). With respect
supplementations on lipid metabolism especially HDL cholesterol as well as
to pregnancy and maternal complications we verified that 7% had hypertension
kidney function assessed by serum creatinine, urine microalbumin (MA), albumin
diagnosis during pregnancy, 4% had one or more urinary tract infection and 11%
creatinin ratio (MaCR) and GFR in diabetic patients treated with high doses of
had preterm birth. The labour was induced in 36% of the times, and we had a 37%
metformin.
caesarean rate, 20% of dystocic deliveries and an eutocic delivery in 43%.
Methods
Neonatal outcomes consisted of a morbidity rate of 22% and 0.5% mortality rate
In a randomized, placebo-controlled study, 60 diabetic patients treated with a high
(3 cases). Pharmacological management was necessary in 38% (35% insulin vs
dose of metformin were randomly assigned to receive daily oral supplementation
3% metformin).
with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10 mg) (Group 1) or
Conclusions
placebo (Group 2). Metabolic parameters were measured at baseline and after
There is no denying that GDM is increasing worldwide. From an obstetric
4 months folow-up.
perspective this is probably related with the increased mother weight (obesity
Results
epidemic) and the delayed age for the first pregnancy (social motives), which are
The two groups were similar at baseline in terms of metabolic parameters. After
represent at our casuistic. Not long ago, GDM management was a dichotomy that
4-months, HDL cholesterol was significantly greater in patients who received
consisted of lifestyle changes (diet and physical exercise) or insulin therapy.
vitamin supplementation than patients in the placebo group (P!0.0001). Post-
Nowadays, for selective cases we can also add to our therapeutic arsenal
treatment vitamin B12 and folic acid levels were greater in group 1 vs group 2
metformin, which was contraindicated in the past. At our maternity the metformin
(PZ0.007 and P!0.0001, respectively). Hcy level decreased significantly in the
therapy was implemented in 17 cases on 2014 and 2015, translating this new
treatment group from 10.0G4.4 to 7.6G2.5 mol/l, PZ0.002 and did not change
tendency.
in the placebo group
(PZ0.964). In GLM model, group was significant
DOI: 10.1530/endoabs.49.EP578
independent predictor of endpoint HDL choleserol
(PZ0.018), while post-
treatment LDL cholesterol did not differ by group after controlling for the other
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
variables in the model (PZ0.158). Posttreatment GFR was significantly greater in
EP583
patients who received vitamin supplementation than patients in the placebo group
Hypoglycemia, weight changes and health related quality of life
(P!0.003). Plasma creatinine, urine protein and urine microalbumin did not
(HRQoL) instruments for diabetes care
differ significantly by treatment group at baseline at the end of the study.
Carolyn Akladious1 & Pendar Farahani2
Nevertheless, within the vitamin -treated group, MaCR dcreased from baseline
1St. George’s University of London, London, UK;2McMaster Univerity,
(P!0.036) and did not change in the placebo group.
Hamilton, Ontario, Canada.
Conclusion
Adding B vitamins and folate supplementations to metformin was associated with
beneficial effects on HDL cholesterol and renal function in diabetic patients.
Background
DOI: 10.1530/endoabs.49.EP580
Diabetes is a chronic disease with significant negative impact on quality of life.
Hypoglycemia and weight gain are two important variables that can impact
HRQoL negatively in patients with diabetes under treatment with medication.
Objective
The objective of this study was to evaluate HRQoL tools and questionnaires and
to explore if the HRQoL instruments address issues related to hypoglycemia and
weight gain, which impact HRQoL along other domains.
Methods
EP581
A systematic review was conducted utilizing databases on PubMed, Google and
The role of sodium-glucose co-transporter 2 inhibitors as add-on
Google Scholar to find HRQoL tools that have been utilized in diabetes care. The
therapy in type 2 diabetes
tools in English language were selected. The construct of the HRQoL tools were
Maria Hayon Ponce1, David Blánquez Martínez2, Maria Jose
analysed by the domains.
Jiménez Jiménez1, Rossana Sofía Manzanares Cordova1, Maria del Carmen
Results
Serrano Laguna1, Miguel Quesada Charneco1 & Martin Lopez de la
In general, three types of HRQoL tools and questionnaires have been utilized in
Torre Casares1
diabetes care (total NZ84): diabetes specific (NZ27), domain specific (NZ33)
1UGG Endocrinología y Nutrición, Complejo Hospitalario Universitario de
and general HRQoL (NZ24). 9.5% (NZ8) and 2.5% (NZ2) of tools had domains
Granada, Granada, Spain;2Farmacia Hospitalaria, Complejo Hospitalario
for hypoglycemia or weight changes, respectively. None of the tools had both
Universitario de Granada, Granada, Spain.
domains, simultaneously. 88% (NZ74) of tools had no domain for hypoglycemia
or weight changes.
Objective
Conclusion
SGLT2 inhibitors, have been shown to improve glycaemic control, stabilize
This study illustrated that few HRQoL instruments incorporated domains related
insulin dosing and mitigate insulin-associated weight gain in patients whose type
to hypoglycemia and weight gain. This calls for developing more comprehensive
2 diabetes mellitus (T2DM) was inadequately controlled. The objective is to
HRQoL instruments to measure the impact of hypoglycemia and weight gain on
evaluate the real-world efficacy and safety of adding iSGLT-2
therapy in
quality of life of patient with diabetes on pharmacotherapy. Addressing such an
inadequately controlled patients with oral antidiabetic drugs and with or without
issue is very timely, in light of recent utilization of newer classes of medications
insulin therapy.
in diabetes care such as SGLT2I and GLP1A which have safer glycemic profile
and cause weight loss.
Materials and methods
This observational study assessed the efficacy and safety of SGLT-2 inhibitors
DOI: 10.1530/endoabs.49.EP583
used as add-on therapy in a group of 45 T2DM patients from a community
endocrinology practice from January 2015 to April 2016. Primary endpoint was
HbA1c mean change from baseline at 15 months. Secondary endpoints included
change in body weight,other glycaemic parameters,and percentage of patients
reporting adverse effects of therapy.
Results
A total of 45 patients met all the study criteria. 60% with oral antidiabetic drugs,
EP584
11.1% with oral antidiabetic drugs and basal insulin regimens, 11.11% with basal-
Use of an innovative Technology Enabled Care service (TECS)
bolus insulin therapy and 17.8% with oral antidiabetic drugs and basal-bolus
‘Florence’ to empower patients and enhance adherence to BP
insulin therapy.Baseline patient characteristics were as follows: average age,
treatments in diabetes
60.2G9.7 years; mean duration of T2DM, 11.3G8.3 years; 80% male; baseline
Susan Irwin & Parijat De
body mass index (BMI), 32.76G4.96 kg/m2; mean baseline HbA1c, 9.17G
Sandwell & West Birmingham NHS Trust, Birmingham, UK.
2.02%;systolic BP 143.67G15.46 mmHg and diastolic BP 80.44G10.16 mmHg.
Mean duration of SGLT2 inhibitors 7.42G4.22 months. HbA1c and weight were
significantly reduced by 1.36G1.79%, P ! 0.000 and 3.21G3.52 kg, P ! 0.000,
Background
respectively; systolic BP (12.91G10.57 mmHg, P !0.000), diastolic BP (6.39G
Social deprivation is high within our large ethnic and diabetes prevalent
7.34 mmHg P! 0.000) and triglycerides (45.58G115.65 mg/dl, P ! 0.011).
population. Compliance is a major stumbling block in the achievement of Blood
Genital- and urinary tract infections were reported by 6.7% patients.Any diabetic
Pressure (BP) targets. Given the above, we took the opportunity to enrol with
ketoacidosis case was reported.
West Midlands Academic Health Science Network (WMAHSN) Florence (Flo)
Conclusion
Exemplar project mobile phone texting service. Flo sends advice and collects
SGLT-2 Inhibitors added to other oral antidiabetic drugs or insulin in patients
patient information which clinicians can access through any device connected to
with uncontrolled T2DM significantly improved glycemic control, reduced
the internet.
weight, blood pressure and triglycerides,and was generally well tolerated.In
Aims
conclusion, SGLT-2
inhibitors,appears to be an important addition to the
Our aims were to improve adherence to BP treatment via engaging and motivating
therapeutic options for the management of type 2 diabetes, particularly when used
patients and determine the clinical and cost effectiveness of this simple
as add-on therapy.
Telemedicine model.
DOI: 10.1530/endoabs.49.EP581
Method and results
Of the 100 patients enrolled for BP management (April 2015-2016) from diabetes
renal clinics:
† BP medications adjusted in 27/100 (27%).
† 46/100 (46%) patients were discharged with good BP control following
medication adjustment.
Total outpatient attendances prevented: 107
EP582
† 45 (for those we continue to follow up)
† 62 (for those discharged)
This has saved £11 663 (national average £109 per OP attendance) simply from
Abstract withdrawn.
non-face to face BP management against a total cost of £2329 assuming 75% of
the 107 patients have used the WMAHSN Hypertension CKD/diabetes protocol
for the full 12 weeks (364 texts/patient, cost per patient £29.12 for the service).
Conclusion
Flo’s use continues to grow and 5 new teams are ready to join in our Trust. Thus,
this clinically and cost effective model of care delivery
(with high patient
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
satisfaction) utilises manpower resources and healthcare professional time
Aim
effectively to improve outcomes and can be easily replicated in any NHS Trust
To analyze the effects of inositol administration on parameters related to glucose
or CCG.
homeostasis.
DOI: 10.1530/endoabs.49.EP584
Material and methods
Systematic review and meta-analysis of articles published in Medline or Web of
Science Until February 1, 2016. We included studies that met the following
criteria: i) Randomized controlled clinical trials of inositol/inositol isomer
supplementation against placebo in parallel design, ii) performed in humans, iii)
with information about glycemic control parameters and iv) published as full
article. The following parameters were considered: Fasting plasma glucose (FPG),
blood glucose at 2 h after an oral glucose tolerance test (OGTT), impaired oral
glucose tolerance, need for insulin treatment, body mass index
(BMI),
insulinemia, HOMA-IR and HbA1c. For the meta-analysis, Revman 5.1 software
EP585
with a random effects model was used.
The decreased adiponectin level after the treatment with glibenclamide
Results
is associated with deterioration of left ventricular function
The search retrieved 476 publications, of which 22 articles were finally included,
Merita Emini1, Edmond Haliti2, Nikica Car3, Luljeta Begolli4,
with a total of 1533 individuals. Treatment time ranged from 28 days to 12
Artan Ahmeti2 & Gani Bajraktari2
months. Significant differences were observed in all parameters evaluated except
1Clinic of Endocrinology, University Clinical Center of Kosovo, Prishtina,
in BMI, HbA1c and % of patients who needed treatment with insulin. Treatment
Kosovo;2Clinic of Cardiology, University Clinical Center of Kosovo,
with inositol decreased FPG (mean difference K0.44 mmol/l (K0.65, K0.23)),
Prishtina, Kosovo;3University Clinic of Diabetes, Endocrinology and
glycemia at 2 h of OGTT (mean difference K0.69 mmol/l (K1.14, K0.23)), % of
Metabolism ‘Vuk Vrhovac’, University Hospital ‘Merkur’, Zagreb, Croatia;
patients with impaired glucose tolerance
(relative risk
0.28
(0.12,
0.66)),
4Institut of Biochemistry, University Clinical Center of Kosovo, Prishtina,
insulinemia (mean difference K38.49 pmol/l (K52.63, K24.36)) and HOMA-IR
Kosovo.
(mean difference K1.96 mIU/l!mmol/L (K2.62, 1.30)). No relevant side effects
were observed in patients treated with inositol.
Conclusions
Background and aim
Inositol treatment improves glucose tolerance and insulin resistance by a
Hyperglycemia is an important pathogenetic factor, which causes abnormalities at
mechanism independent of body mass index.
the cardiac myocyte level, leading to structural and functional abnormalities and
diabetic cardiomyopathy (DCM). It has been proposed that DCM could also occur
DOI: 10.1530/endoabs.49.EP586
as a consequence of other metabolic alterations. Adiponectin concentration is
negatively associated with obesity, insulin resistance (IR), oxidative stress and
endothelial dysfunction. It can be considered as a predictive biomarker of IR and
cardiovascular risk. Treatment of diabetic patients with conventional sulfonylurea
such as glibenclamide has been reported to be associated with adverse
cardiovascular effects and a higher incidence of cardiovascular death. The aim
of this study was to assess the effect of glibenclamide on adiponectine level and its
impact on left ventricular function in type 2 diabetic patients.
Methods
This single-blind, prospective, randomized controlled study consists of 32 weeks
EP587
screening period and a 24-weeks treatment period with glibenclamide. From the
A rare pediatric presentation of type 1 diabetes mellitus with duchenne
167 patients screened, most of whom were treated for hypertension or with
muscular dystrophy - what to expect in the future?
metformin, 40 type 2 diabetic patients, were divided in two groups (glimepiride vs
Pascu-Gabara Elena-Iuliana1, Arhire Amalia Ioana1, Ioacara Sorin1,2 &
glibenclamide) with a body mass index (BMI) O25 treated with glibenclamide
Fica Simona1,2
for more than
3
months before screening were included in the study.
1Elias University Emergency Hospital, Bucharest, Romania;2Carol Davila
Anthropometric, biochemical and echocardiographic measurements were
university of medicine and pharmacy, Bucharest, Romania.
performed before and at the end of treatment.
Results
In the glibenclamide group significant differences were observed in HbA1C
Introduction
which was decreased from 8.8%G1.4 to 8.3%G1.1% (P!0.001), and in the
Duchenne muscular dystrophy (DMD) is a genetic condition caused by mutations
other hand adiponectin was significanty decreased (from 34.3G22.6 to 20.3G
in the X-linked dystrophin-gene leading to muscle degeneration and early death in
11.3 ng/ml, PZ0.011). From echocardiographic measurements early diastolic
males.Since DMD is characterized by aggressive inflammation it is recommended
(e’) and systolic (s’) myocardial wall velocity of the septum (from 6.7G1.4 cm/s
the use of pharmacological treatment with corticosteroids (CS). Type-1 diabetes
to 5.6G1.5 cm/s, PZ0.04, and from 7.0G1.2 cm/s to 6.1G1.2 cm/s, PZ0.03,
mellitus (T1DM) is one of the most common chronic diseases in childhood and is
respectively); as well as right e’ and s’ (from 11.7G2.7 cm/s to 7.9G3.8 cm/s,
caused by insulin deficiency resulting from the autoimmune destruction of insulin
PZ0.01, and from 12.5G4.3 cm/s to 8.4G3.2 cm/s, PZ0.01, respectively) were
producing beta-cells of the pancreas.
decreased from baseline to the
24 weeks treatment. While DcT time was
Case presentation
significantly increased in the group of Glibenclamide, which can explain
We present the case of a 3-years-old male patient who was admitted in our clinic
worsening of diastolic dysfunction in diabetic patients treated with this drug.
for episodes of symptomatic hypoglycemia alternating with hyperglycemia. He
Conclusions
was diagnosed with T1DM and DMD 1-year prior his admission and had been on
The decreased adiponectine level after the treatment with glibenclamide is
Humulin-N and Humulin-R combination and Deflazacort 12mg/daily treatment
strongly associated with deterioration LV diastolic and systolic function, in type 2
ever since.His medical history includes upper respiratory tract infection remitted
diabetic patients. This finding highlights the need of further investigations of the
after bronchodilator and expectorant medication in the last month.Clinical
impact of metabolic disorders on cardiac function in diabetic patients, beyond
examination revealed short stature and overweight patient:heightZ90.9 cm
hyperglicemia.
(K2.71 SDS),
(5-th percentile); weightZ14 kg
(25-th percentile); BMIZ
DOI: 10.1530/endoabs.49.EP585
17.28 kg/m2, (88-th percentile); pubertal stage-1 according to Tanner; hypotonic
muscular system, hypokinetic, normal thyroid palpation, language deficiency.
Lab tests revealed glycemic control with HbA1cZ7.8% (in target for age),
hepatic cytolysis
(ASTZ244 IU/l, ALTZ583 IU/l), euthyroidism
(TSHZ
3.95 uIU/ml). Funduscopic examination and thyroid ultrasound were normal.
During admission the patient is switched from multiple-dose-injection therapy
(MDI) to cutaneous-insulin-infusion therapy (CSII) with aspart, well tolerated;
basal rates, the correction factor and carbohydrates-ratio are set, followed by
glycemic profile evolving favorably. Considering the risks of untreated DMD and
EP586
the metabolic pathology association, the patient continues treatment with
Effects of inositol on glucose homeostasis: systematic review and
Deflazacort 12 mg/daily under multidisciplinary surveillance. Parents received
meta-analysis of randomized controlled trials
nutritional counseling.
Inka Min˜ ambres1, Gemma Cuixart1, Ana Gonçalves2 & Rosa Corcoy1
Conclusion
1Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;2Centro Hospitalar
Possible endocrine complications of DMD with chronic CS treatment
Do Algarve, Algarve, Portugal.
consequences regarding growth failure, pubertal disorder due to hypogonadism,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
excessive weight gain, diabetes, especially in pediatric patients, and bone health
control by increasing the renal excretion of glucose. Vulvovaginal candidiasis
have not been explored in depth. Treating children can be challenging when
(VVC) is the infection of the vaginal vestibuler area. We present a case of VVC
having such rare presentation because there is a need for better comprehension of
accompanied by use of dapagliflozin.
metabolic and endocrine implications for DMD with the purpose of developing
Case
improved clinical treatments and/or quality of life.
A-48-year-old woman who had T2DM since 8 years was admitted to the
DOI: 10.1530/endoabs.49.EP587
endocrinology clinic. Her past medical history was remarkable for atopic
. She had been using metformin
dermatitis. Her body mass index was 33.7 kg/m2
and sulfonylurea. Her initial laboratory results were; fasting plasma glucose:
131 mg/dl, hemoglobin A1c: 7.8%. Dapagliflozin 10 mg daily therapy added to
her therapy. On the 12th day of dapagliflozin therapy she noted vulvovaginal
pruritus. Three days later she complained the severity of symptoms. Physical
examination revealed wide erythema on vulvar, vaginal and perineal regions of
genitourinary area. Positive vaginal culture for Candida albicans was detected.
She was diagnosed with VVC. The treatment of VVC was made through topical
clotrimazole. Three days later the clinical manifestations become worsened and
EP588
dapagliflozin was discontinued. Signs and symptoms of VV were regressed two
Significant effect of a group education program on glycemic control and
days later.
incidence of hypoglycemia in patients with diabetes mellitus type 1:
Summary
A case-controlled study
Vulvovaginitis is a frequently encountered acute and recurrent complication of
Zadalla Mouslech1, Maria Somali2, Sarantis Livadas5, Christos Daramilas2,
diabetes mellitus; tend to be worsened by poor glycemic control. Appropriate
Alexandra Chatzi3, Maria Papagianni3, George Mastorakos4,
diagnosis and management is essential to confirm optimal genital and metabolic
Christos Savopoulos1 & Apostolos I. Hatzitolios1
health. We consider that this case will be mostly useful among atopic patients who
11st Medical Propedeutic Department of Internal Medicine, AHEPA
have potential risk for VVC and drug withdrawal may be considered in such of
University Hospital, Aristotle University of Tessaloniki, Thessaloniki,
these patients.
Greece;2Endocrinology, Metabolism and Diabetes Unit, Euromedica
DOI: 10.1530/endoabs.49.EP589
General Clinic, Thessaloniki, Greece;3Endocrine Unit, 3rd Pediatric
Department, Aristotle University, Hippokration Hospital, Thessaloniki,
Greece;4Department of Endocrinology, Metabolism and Diabetes, Aretaeio
Hospital, School of Medicine, National and Kapodistrian University Athens,
Athens, Greece;5Endocrine Unit, Metropolitan Hospital, Athens, Greece.
DM1 constitutes a real challenge in everyday practice for both physicians
and patients. Due to the complexity of the disease and its unpredictable
nature, structured education and training programs are nowadays
EP590
implemented that ensure active patient involvement and self-care behaviors
to achieve adequate glycemic control, prevent diabetic complications and
Efficacy of body weight reduction on SGLT-2 inhibitor in people with
improve the quality of life of patients. These programs provide patients with
type 2 diabetes mellitus
the necessary knowledge and skills to self-monitor and self-manage the
Chong Hwa Kim1, Hyun A Cho1, Su Jin Jung1, Ki Young Lee2 &
disease and its associated metabolic conditions.
Sung Rae Kim3
Aims
1Sejong General Hospital, Bucheon, Kyunggido, Republic of Korea;
To evaluate the effect of a structured 12-month education program that motivated
2Gacheon University Gil Hospital, Incheon, Republic of Korea;3The
patients to follow a healthy Mediterranean diet and exercise regularly as well as to
Catholic University of Korea Bucheon St. Mary’s Hospital, Bucheon,
adjust carbohydrate intake and insulin dose according to their needs.
Kyunggido, Republic of Korea.
Methods
The education group (EG) was comprised of 62 patients (45 males) with type 1
Objective
DM, mean age 36G4.2 years and BMI: 24.2G3.1 kg/m2. An age- and BMI-
Dapagliflozin, sodium-glucose cotransporter-2
(SGLT-2) inhibitor, reduces
matched control group (CG, nZ25, mean age 41G6.4 years, BMI: 25.7G
hyperglycemia and body weight by inhibiting renal glucose reabsorption.
4.2 kg/m2) was composed of patients referred but not enrolled in the project.
However, only a few studies have shown the efficacy of dapagliflozin in type 2
Results
diabetic patients. We evaluated the efficacy and safety of body weight reduction
At the end of this program, HbA1C levels were significantly decreased (8.5G
of dapagliflozin in real practice with type 2 diabetes in Korea.
2.1%vs 7.08G0.79%, P!0.0001) as was also the incidence of hypoglycemic
Methods
episodes (P!0.05). Regarding daily glucose fluctuations, significant improve-
This is a retrospective, observational study, data from 61 patients with 12 months
ment (P!0.05) was observed, as reflected in low, high and daily median glucose
of dapagliflozin (10 mg once-daily) therapy were analyzed, visited medical center
values. On the other hand, the above parameters remained stable in the CG.
from January 2015 to July 2016. We had divided into three treatment groups: first
Conclusions
group taking combination of dapagliflozin and metformin (Group 1); second
These results strongly support the need for long-lasting structured education
group taking triple combination of dapagliflozin and metformin with sulfonylurea
group courses in adult diabetic patients keen to change their habits in order to
or dipeptidyl-peptidase IV (DPP-4) inhibitors (Group 2); third group taking
achieve self-management of the disease.
quadriple combination of dapagliflozin, metformin and sulfonylurea with DPP-4
DOI: 10.1530/endoabs.49.EP588
inhibitors (Group 3).
Results
After 12 months, mean change from baseline body weight was K3.4G2.6 kg
(P!0.001) for total, K3.4G3.1 kg (P!0.001) for group 1, K2.7G2.0 kg
(PZ0.008) for group 2, K4.0G2.3 kg (P!0.001) for group 3. In total, mean
change from baseline SBP and DBP were K6.0G14 mmHg (PZ0.001) and
K3.4G7.7 mmHg (PZ0.002) respectively. Patients who achieved body weight
reduction of R5% after 12 months were classified in the responder group and!
5% non-responder group. There were baseline fasting C-peptide level was higher
EP589
in responder group than non-responder group (3.25G1.07 ng/ml vs. 2.62G
Dapagliflozin induced vulvovaginitis in an atopic patient with type 2
1.02 ng/ml, PZ0.023). In total, reductions in HbA1c and PP2 glucose levels were
diabetes mellitus
K0.61G0.82% (P!0.001) and K35.4G62 mg/dl (P!0.001) respectively.
Narin Nasiroglu Imga, Merve Catak & Dilek Berker
There were no serious adverse event including hypoglycemia in dapagliflozin
Ankara Numune Education and Research Hospital Department of
group.
Endocrinology and Metabolism, Ankara, Turkey.
Conclusions
In patients with type 2 diabetes, SGLT-2 inhibitor improved glycemic control and
Introduction
reduced body weight reduction with safety of dapagliflozin.
Dapagliflozin is sodium-glucose co-transporter receptor 2 (SGLT2) inhibitor that
DOI: 10.1530/endoabs.49.EP590
is recently discovered an oral antidiabetic (OAD) agent that improves glycemic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP591
Results
107 of approximately 215 (49.7%) women completed the questionnaire. 83%
Modification of lifestyle and influence on leptin and insulin resistance to
were aware of risks related to DM in pregnancy. However, the majority of women
prevent type 2 diabetes mellitus
(74%) had not received preconception counselling. The main source of
Shishko Elena & Mokhort Elena
information regarding contraception was the general practitioner (70%). Most
Belarusian State Medical University, Minsk, Belarus.
women (78%) believed combined oral contraceptive pills (COCPs) were safe in
DM. 63% of women were uncertain of the safety of intra-uterine devices (IUDs)
The aim of the present study was to determine the change of fasting serum leptin
in DM and 44% were uncertain of contraceptive implant (CI) safety. The main
and insulin levels and insulin resistance in patients with risk factors of diabetes
forms of contraception ever used were condoms (87%) and COCPs (74%), with
mellitus of type 2 (DM 2) including impaired glucose tolerance/impaired fasting
34% using long-acting reversible contraception (LARC) of IUDs and CIs. 29% of
glucose (IGT/IFG), obese and first-degree relatives of patients with diabetes after
sexually active women were not using any contraception or planning pregnancy.
lifestyle modification.
Amongst 110 pregnancies in 47 women there were 78 (71%) live births, 4 (4%)
Material and methods
stillbirths,
16
(15%) miscarriages, 2 (2%) ectopic pregnancies and 10 (9%)
The study included 100 patients (32 men, 68 female) 25-65 years old at risk
terminations.
factors of DM 2. All patients received recommendations on a balanced diet and
Conclusion
physical activity. The average fasting plasma glucose (FPG), 2-h plasma glucose
Despite knowledge of pregnancy risks, preconception counselling is lacking and
concentrations (2-h PG) following a 75-g oral glucose tolerance test, HbA1c,
pregnancy outcomes poor. There was uncertainty regarding safety of LARC, the
index HOMA-IR. Fasting serum leptin and insulin levels were detected by
most reliable contraceptive methods and over a quarter of women used no
sensitive ELISA.
contraception. Better education of women with DM regarding contraception and
Results
preconception planning is needed.
During 18 months our study 56 patients carried out this recommendations
DOI: 10.1530/endoabs.49.EP592
(research group) and 44 patients did not (control group). Patients of the research
group demonstrated mean reduction of body mass index (K2.6G0.4 kg/m2) and
waist-to-hip ratio (K0.2G0.01) (P!0.01) and persons of the control group had
significant increase of these parameters (P!0.05). Among subjects with IGT/IFG
at baseline, glucose levels normalized in 56.0% of patients from the research
group and 4.5% in control group (P!0.001). Fasting serum insulin and HOMA-
IR in research group decreased from 11.9G4.3 to 9.6G4.5 mU/ml and from 3.6G
1.1 to 2.7G1.4 accordingly (P!0.05). In control group the specified parameters
had increased significantly (P!0.01). The main novel finding was that serum
leptin median in research group was decreased from 34.7 to 26.4 ng/ml (K23.9%,
P!0.001) and increased in control group from 37.9 to 44.7 ng/ml (C17.9%,
P!0.01). The risk reduction of DM 2 development among patients of the
EP593
research group was 48.0% compared to the control group.
Management and control of hospital hyperglycemia in the health area of
Conclusion
Thereby, lifestyle modification can prevent the development of type 2 diabetes in
cuenca (Spain)
subjects with risk factors by reduction leptin and insulin resistance.
José Pérez-Rodríguez, Paula García-Notario, David Martín-Iglesias,
Lidia Guerra-Navarro, Mubarak Alramadan, Santiago Aranda-Regules &
DOI: 10.1530/endoabs.49.EP591
Dulce Calderón-Vicente
Virgen de la Luz Hospital, Cuenca, Spain.
Introduction and objectives
Hyperglycemia is a common problem in hospitalized patients that increases
infections, mortality, costs and the hospital stay. The objective of this study is to
know the management and control of hyperglycemia in our hospital.
Methods
We designed a cross-sectional observational study. We included patients admitted
in the hospital every three days in two months. We excluded patients younger than
15 years, stays less than three days and those of the pediatric, gynecological,
EP592
emergency and intensive care services. We collected the data from these patients
Australian women with diabetes survey of contraceptive use and beliefs
the third day of admission and at discharge. We defined hyperglycemia as two or
about safety of contraceptive options
more capillary glucose values greater than 140 mg/dl.
Santhi Chalasani1, Pinar Kozan4,5, Rickie Myszka2, Kirsten Black1,3,
Results
Kris Park2 & Emily Hibbert1,2
A total of 328 patients were included. 109 patients had hyperglycemia and 85
1University of Sydney- Sydney Medical School Nepean and Central,
were known diabetics. Diabetic patients had the next previous treatments: only
Sydney, Australia;2Nepean Hospital, Kingswood, Australia;3Royal Prince
oral antidiabetic agents (55.3%), insulin (38.8%), and without treatment (5.9%).
Alfred Hospital, Sydney, Australia;4Garvan Institute of Medical Research,
During admission 48.5% were treated with insulin sliding scales, 19.2% with
Sydney, Australia;5University of New South Wales- St Vincent’s Clinical
insulin bolus-basal regimen, 12.1% with basal insulin, 7.1% with premixed
School, Sydney, Australia.
insulin,
2% with only antidiabetic agents and 11.1% without treatment. The
glycemic control during admission was considered good in 25% (mean glycemia
!140 mg/dl), regular in 45% (140-200 mg/dl) and bad in 29% (O200 mg/dl).
Introduction
Hypoglycemia was diagnosed in 12.5% (2.1% severe). Only 23% patients had a
Women with diabetes mellitus (DM) are at increased risk of adverse maternal and
recent HbA1c, with a mean HbA1c of 7.37G1.4%. When the patients discharge
foetal outcomes. Preconception planning is required to minimize risks, including
from hospital, the antidiabetic treatment for home was not adequately adjusted in
good understanding of contraceptive options.
47.4%.
Objectives
Conclusions
To determine in Australian women with DM beliefs regarding safety of various
A high percentage of diabetic patients are still treated with insulin sliding scales
contraceptive methods in DM, information sources regarding contraception,
during hospitalization. Few patients have a good glycemic control. Most of
recent and previous contraceptive use, knowledge of pregnancy risks, access to
patients hadn’t a recent HbA1c. Finally, treatment is not adequately adjusted at
preconception planning and pregnancy history.
discharge in almost half of patients. That’s why, we believe it’s necessary to
Methods
create a multidisciplinary protocol to improve the management of the hospital
We conducted a cross-sectional 22 item structured questionnaire-based study of
hyperglycemia.
Australian women with DM (Type 1 or 2) aged 16-49 years attending Nepean
Hospital, a tertiary referral centre. Women were recruited via mail, at scheduled
DOI: 10.1530/endoabs.49.EP593
appointments or hospital admission.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP594
combined AG and AA genotype) of the COMT Val108/158Met achieved
significantly better HbA1c values compared to patients carrying GG genotype.
Impact of the insulin pump therapy on quality of life children and
Conclusions
adolescents with diabetes mellitus type 1
Our results showed that the presence of one or two A allele of the COMT
Nataliia Nikolaeva
Val108/158Met was associated with improved glycemic response, and with a
Saratov Medical Univesity, Saratov, Russia.
better response to insulin detemir therapy in T2DM patients.
DOI: 10.1530/endoabs.49.EP595
Objectives
To investigate the changes parameters of quality of life (QoL) in children and
adolescents with diabetes mellitus type 1 (T1DM), using different regimes insulin
therapy.
Research design and methods
Thirty patients with diabetes mellitus type 1, aged 5-18 years (mean 13.3G3.04
yr), with disease duration from 1 to 10 years (mean 5.4G3.4 yr) took part in
EP596
paired study. QoL was assessed with the PedsQL (Generic Core Scales and
A dramatic improvement in metabolic parameters and cutaneous
Diabetes Module, Russian version) at two time points: 1st - during multiple daily
manifestations of insulin-resistance in a type 2 diabetic patient with
insulin injection (MDI); 2d - after initiation continuous subcutaneous insulin
Congenital Generalized Lipodystrophy (Berardinelli-Seip Syndrome)
infusion (CSII). Data were analyzed in subgroups aged 5-7 yr, 8-12 yr, 13-18 yr.
treated with pioglitazone
Results
Carolina Chaves, Catarina Moniz, Bernardo Dias Pereira, Isabel Sousa,
Nevertheless, analysis demonstrated positive dynamic of QoL in patients after
João Anselmo & Rui César
initiation CSII. Treatment barriers decreased due to reduction of a number of
Hospital do Divino Espírito Santo, Ponta Delgada, Portugal.
injections (75.3 vs. 90.0 P!0.05) in preschool-age children. Patients at the age of
8-12 evaluated higher physical function (74.2 vs. 94.0, P!0.05) after initiation
CSII. In adolescent’s group social activity indicates improved (85.0 vs. 95.0,
Background
P!0.05). Further, they were less worried about long-term complications
Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a autosomal recessive
(70.0 vs. 85.0, P!0.05).
disorder with only up to 500 reported cases. It is characterized by generalized
Conclusions
absence of fat since birth and severe metabolic derangements such as insulin
Using of insulin pump therapy in children with T1DM allows to improve of
resistance, hyperglycemia and dyslipidemia. Diabetes mellitus generally
quality of life. Preschoolers get used to the necessary of insulin therapy easier,
develops during the second or third decade of life. This is a rare clinical
schoolchildren and adolescents have opportunity to increase the level of their
condition, with worldwide prevalence of 1 in 10 million people and incidence of
physical and social activity.
1:500.000 newborns/year in Portugal.
DOI: 10.1530/endoabs.49.EP594
Patient and methods
11-year-old caucasian boy was referred to the Pediatric Endocrinology
consultation because of fasting hyperglycemia detected during routine blood
tests. There was no history of polyuria, thirst or weight loss. He was medicated
with antihypertensive medication since
6-years-old. Physical examination
revealed a thin patient with acromegaloid features and severe acanthosis
nigricans involving the posterior cervical region, axillary and periumbilical
areas. Subcutaneous tissue atrophy was notoriously evident in the face, trunk and
EP595
limbs. Secondary sexual characteristics were compatible with stage V of
Efficacy of insulin detemir treatment in type 2 diabetes mellitus is
TANNER scale. Blood tests revealed hyperglycemia with hyperinsulinemia,
associated with a allele od the catechol o-methyltransferase
dyslipidemia, low leptin, HOMAIR index indicating insulin resistance, alterations
polymorphism
in hepatic function suggesting fatty liver and all autoantibodies searched were
Tomislav Bozek1, Antonela Blazekovic2, Matea Nikolac Perkovic3,
negatives. Thyroid function, IGF-1 and Growth Hormone (GH) were within the
Kristina Gotovac2, Lea Smircic-Duvnjak1, Nela Pivac3 & Fran Borovecki3
normal range for age and sex. Abdominal ultrasounds revealed a hepatospleno-
1Vuk Vrhovac University Clinic, Merkur University Hospital, Zagreb,
megaly.
Croatia;2Department for Functional Genomics, Center for Translational and
Results
Clinical Research, University of Zagreb School of Medicine, Zagreb,
The presumptive diagnosis of BSCL was admitted and the patient was started on
Croatia;3Division of Molecular Medicine, Rudjer Boskovic Institute,
metformin 1000 mg twice daily. Pioglitazone, 30 mg/day in two divided doses
Zagreb, Croatia.
was added three months later. After
18 months of treatment, glucose and
triglycerides levels were near normal, hepatic enzymes, liver echographic
features and cutaneous manifestation of insulin-resistance were improved. Leptin
Introduction
remained undetectable.
Growing evidence suggests that nutrients and hormonal signals converge and
Conclusion
directly act on brain centers, leading to changes in energy metabolism and stable
Early introduction of pioglitazone in diabetic patients with BSCL may
body weight over time. Catechol O-methyltransferase (COMT) is one of the
dramatically improve insulin resistance without relevant side effects.
major enzymes involved in catecholamine and estrogen degradation. There is a
Keywords: Lypodystrophty, Berardinelli-Seip Syndrome, Insulin-resistance
well-established association between the COMT Val108/158Met polymorphism
DOI: 10.1530/endoabs.49.EP596
and abdominal obesity, blood pressure increase and T2DM. Basal insulin detemir
besides a low pharmacodynamic coefficient of variability, exhibits anorexigenic
features, probably through a complex interplay of its effects on the CNS and on
the finely tuned efferent and afferent signals between muscle, brain, liver, renal
and adipose tissues.
Aims
To investigate the association of COMT Val108/158Met polymorphisms with
EP597
effectiveness of insulin detemir in achieving glucose control and body weight
Comparison of neonatal outcome in women with gestational diabetes on
control.
different pharmacoglogical agents dilevered at term
Methods
Tarik Elhadd1, Sindu Jacob2, Vincent Boama2,3, Khaled Ashawesh1,
Observational study included 185 T2DM patients inadequately controled with
Khaled Dukhan1, Stephen Beer1 & Hiba Satti2
premix insulin analogues, which were replaced with three doses of insulin aspart
1Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar;
at mealtime and insulin detemir at bedtime that were followed for 52 weeks. After
2Department of Obstetrics, Alwakra Hospital, Hamad Medical Corporation,
DNA isolation from blood samples, genotyping of COMT Val108/158Met
Doha, Qatar;3Sidra Hospital and Research Centre, Doha, Qatar.
polymorphism (rs4680) was performed.
Results
The mean age of participants was 67.1G8.01 years, with a mean duration of
Objective
diabetes 16.1G5.9 years. HbA1c and fasting plasma glucose were significantly
Though many studies have looked at the neonatal outcomes in patients with
decreased after
52
weeks
(8.58% vs
7.78%,
11.7 mmol/l vs
8.7 mmol/l,
gestational diabetes on different medications, there is no consensus on the
respectively, P! 0.001). At the end of the follow up period, 28.1% of patients
preferred drug for initiation of therapy. We aim to compare the neonatal outcome
achieved HbA1c!7.0%. Insulin detemir had a significant weight sparing effect in
in a cohort of patients attending our service, to determine if one modality is
overweight patients. The most prominent finding was that A carriers
(the
superior to the other.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
Conclusion
This study is a prospective observational study from 1-07-2015 to 31-04-2016.
A 20 mg/day and its combination with Eslidine showed a good hypolipidemic
The data of all gestational diabetic patients referred to the Joint Diabetic Clinic, in
efficacy and tolerability in hyperlipidemic pts with CVD and type 2 DM. Addition
a local secondary Hospital, who required pharmacological intervention were
of Eslidine to statin therapy resulted in a more reduction in LDL-Ch and TG levels
entered into an excel spreadsheet. This included their antenatal, intrapartum and
and noticeably improved hepatic functional activity.
postnatal details. P values calculated with Student’s t-test. Statistical significance
DOI: 10.1530/endoabs.49.EP598
if P! 0.05.
Results
The total number of patients studied was 107. There were 58 patients (54%) who
were treated with Metformin only, their BMI at booking was 30 kg/m2, average
HbA1c 5.69%. The average birth weight of the neonates of this group was
3287.78 g and there were 9 (15.51%) Neonatal ICU admissions. 17 patients were
commenced on insulin, thier HbA1c was 5.78% and their booking BMI was 32.
EP599
The average birth weight in this subgroup was 3409.24 g with 2 (11.76%) NICU
admissions. 32 (29.90%) of our patients required Metformin and insulin. Their
Pancreas transplantation: experience in a central hospital
Ana Cláudia Martins1, Miguel Vasques1, Paula Bogalho1, Inês Aires2,
average weight at booking was 35, and thier HbA1c was 5.8%. In this subgroup,
Aníbal Ferreira2, Francisco Remédio2, Jorge Paulino3, Fernando Nolasco2,
the average birth weight was
3494.56 g with
5(15.62%) requiring NICU
Américo Martins3 & Ana Agapito1
admission. The least birth weight was observed in the subgroup with Metformin
1Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,
alone (54% of our patients), P!0.4. The subgroups with insulin showed a higher
Portugal;2Department of Nephrology, Centro Hospitalar Lisboa Central,
neonatal birth weight. The least NICU admissions were in the insulin only group.
Lisbon, Portugal;3Department of Surgery, Centro Hospitalar Lisboa
Discussion
Central, Lisbon, Portugal.
The least birth weight was observed in the subgroup with Metformin alone (54%
of our patients), with the subgroups with insulin showed a higher neonatal birth
weight. However, the least NICU admissions were seen in the insulin only group.
Introduction
Conclusion
Pancreas transplantation is an established treatment for selected patients with type
Whether the increase in birth weight seen in patients on insulin, is indicative of
1 diabetes mellitus (T1DM) and severe chronic kidney disease (CKD), reducing
uncontrolled blood sugars or due to the direct effect of insulin as shown in some
mortality and morbidity.
studies, requires further evaluation. Further analysis of the ongoing cohort is
Methods
needed before we can recommend any one mode of treatment as the preferred
We retrospectively reviewed the cases of pancreas transplantation performed at
choice in our setting.
our centre from 1-January-2011 to 30-June-2016.
DOI: 10.1530/endoabs.49.EP597
Results
In this period, 53 transplants were performed: 48 simultaneous pancreas-kidney
transplants and 5 pancreas after kidney. Age at time of transplantation was 38G7
years; 34 were male (64.2%). Patients had T1DM for an average of 26G8 years
(age at diagnosis:
12G5 years). All patients had severe CKD,
78.4% on
hemodialysis and 15.7% on peritoneal dialysis. Major postoperative compli-
cations occurred in 23 cases (43.4%): 8 infectious, 8 haemorrhagic, 7 thrombotic.
Pancreas graft survival was 86.7% at 1 year (39/45) and 83.3% after 2 years
(30/36). Kidney graft survival was 92.7% at 1 year (38/41) and 90.6% after
EP598
2 years (29/32). Graft failure ensued in 6 pancreatic grafts and 3 transplanted
The hypolipidemic and hepatoprotective efficacies of a fixed-dose
kidneys. There were 12 acute organ rejections (22.6%). Three patients died
combination of essential phospholipids with methionine (EPLCM)
(5.9%), 2 from infection, one from haemorrhagic shock. Patients had, on average,
during atorvastatin (A) therapy in hyperlipidemic patients with
2 hospital readmissions, mainly due to infection. Among those with preserved
cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM)
pancreatic grafts, 93.2% are insulin-free. Over the last 2 years, compared to the
(OLYMP trial)
first
2
years, there were more transplants performed
(23
vs
13), fewer
M G Bubnova, D M Aronov, Marina Bubnoa & David Aronov
postoperative complications (30.4% vs 61.5%) and higher 1-year pancreas graft
State Research Center of Preventive Medicine, Ministry of Health of the
survival rate (93.8% vs 69.2%). Young age at diagnosis of T1DM was negatively
Russian Federation, Moscow, Russia.
related to pancreas and kidney graft survival (P!0.05). Duration of dialysis and
coronary disease were negatively related to renal graft survival (P!0.05).
Conclusions
Objective
Patient and graft survival rates were similar to those described in literature. Better
Objective to study the hypolipidemic efficacy, hepatoprotective activity, and
outcomes observed in recent years reflect the experience acquired. Young age of
tolerance of the fixed-dose combination of essential phospholipids with
onset of T1DM, duration of dialysis and coronary disease may represent poor
methionine (EPLCM) - Eslidine in the combination therapy with A in patients
prognostic factors concerning graft function.
(pts) with cardiovascular diseases
(CVD) and type 2 DM who suffer from
hyperlipidemia (HL) in order to optimize their treatment in daily clinical practice.
DOI: 10.1530/endoabs.49.EP599
Subjects and methods
The trial enrolled 60 pts (mean age 58.1G4.5 years) with type 2 DM. All the pts
had essential hypertension, 84.8% were obese; 80% had increased echogenicity in
the liver and its enlargement, as evidenced by ultrasound study. The patients
received standard therapy appropriate for this disease, other than agents affecting
blood cholesterol (Ch) levels. After adherence to a hypolipidemic diet for 2
weeks, the pts were randomized to two groups: i) 30 pts received A in a dose of
EP600
20 mg/day; 2) 30 pts had the drug in the same dose in combination with Eslidine
Correlates of health-related quality of life in Bulgarian patients with
(EPLCM). The therapy duration was 12 weeks. The impact of therapy on lipid,
type 2 diabetes mellitus
lipoproteins, hepatic enzymes.
Georgi Levterov1, Boryana Levterova2 & Maria Orbetzova2,3
Results
1UMHAT Kaspela Ltd, Plovdiv, Bulgaria;2Medical University - Plovdiv,
After 12 weeks, the group of pts receiving A showed a significant reduction in the
Plovdiv, Bulgaria;3UMHAT St Georgi, Plovdiv, Bulgaria.
levels of total Ch by 42.4%, LDL-Ch by 44.9%, and TG by 45.4%; in the AC
Eslidine group, these indicators decreased by 37.8, 47.9, and 26.4%, respectively.
By the end of a course of therapy, the number of pts with LDL-Ch goals was 26.9
Background
and
36.4% in Groups
1
and
2, respectively. In the pts with significant
Diabetes mellitus (DM) is one of the greatest threats to global health and
hypercholesterolemia (LDL-Ch R4.2 mmol/l), the LDL-Ch decline was 46.9
development of the 21th Century worldwide. In Bulgaria, it affects 9.6% of
and 54.6% in those on A and ACEslidine, respectively (P!0.05); in the pts with
residents between ages 18-69 and has a profound impact on healthcare, economy
elevated TG levels
(1.7 mmol/l or higher), the fall was
36.2
and 47.2%,
and individuals. Diabetes and its complications are major causes of early death in
respectively (P!0.05). A caused a 47% increase in ALT activity (P!0.05),
our country - each year 4 125 women and 4 000 men die of diabetes-related
without exceeding the upper normal range. In the pts on therapy AC Eslidine, the
complication. Diabetes not only reduces patient’s physical wellbeing but also
activity of ALT was, on the contrary, unchanged, there was a significant decrease
compromises other aspects of Health-Related Quality of Life (HRQoL). The aim
in total bilirubin concentrations, glutamyl transpeptidase activity, and bile acid
of this study was to investigate the impact of demographic factors and glycaemic
levels.
control on quality of life in patients with type 2 diabetes.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Material and methods
hypoglycemia and improve glycemic control in clinical trials. However, in real
A cross-sectional survey was conducted in a sample of 540 adult patients under
practice we have few data in real practice.
secondary care. Respondents were recruited from nine randomly selected
Objective
outpatient endocrinology practices, 25% of all practices with contract to the
To compare the two ultralente insulin analogues in real practice. To analyze if
Regional Health Insurance Fund Plovdiv-second largest district in Bulgaria. The
they are cost effective.
survey was administered with disease-specific instrument ADDQoL -19.
Material and methods
Results
Observational study including patients with type 2 diabetes, referred to Diabetes
A total of 411 diabetic patients with average age of 59.9C11.6 years old
Day Hospital (DDH) to management diabetes in which we changed the basal
participated in this study. ‘Freedom to eat’ was the Audit of Diabetes-dependent
insulin regimen to Tresibaw o Toujeow. We revised them 3-6 months from change.
Quality of Life domain with the greatest negative average weighted impact
Results
(K4.0, on a scale of K9 to 3). In univariate analyses, older age, female sex, low
123 patients were included (68.3% Toujeow vs 41.7% Tresibaw). Mean age:
socioeconomic status, cardiovascular disease, microvascular complications,
52.60G19.67 years; _-58.5%. Most patients (83.7%) were with glargina basal
insulin use correlated with decreased quality of life.
insulin regimen. After 3 to 6 months from change in the insulin treatment, basal
Conclusion
blood glucose reduced significantly in both groups ((to average of 233.04G
Patients with type 2 diabetes have a substantially decreased HRQoL in association
87.80 mg/dl down from 132.39G66.03 mg/dl in Toujeow; P!0.001) and (to
with symptomatic complications. The data suggest that prevention of
238.44G86.28 mg/dl low from 143.11G66.90 mg/dl, in Tresibaw; P!0.001)).
complications have the greatest potential to improve health-related quality of
We also observed a significant reduction in HbA1c levels ((average reduction in
life in type 2 diabetes.
Toujeow of 2.03G2.28%, P!0.001) and (average decrease of 1.19G1.46%, in
Keywords: Diabetes mellitus, Health-Related Quality of Life, ADDQoL-19,
Tresibaw; P!0.001)). However, comparatively no differences in efficacy were
Bulgaria
found between groups (0.49G0.32%; PZ0.185). At the end of follow-up,
DOI: 10.1530/endoabs.49.EP600
the number of units of Toujeow increased an average of C5.08G18.55 UI
decreased an average of
(PZ0.014) while insulin requirements in Tresibaw
K4.20 28G7.36 UI (P 0.001). With regard to the cost, an average cost of
436.84G252.57 V per person (Toujeow group) vs 601.82G419.61 V per person
(Tresibaw group), (mean difference: 164.98 V, PZ0.027).
Conclusion
EP601
Both basal insulin analogues are effective in reducing basal glycemia and HbA1c.
Although there is an increase in insulin requirements when switching to Toujeow.
Effects of sitagliptin monotherapy on insulin resistance and immune
Potential economic savings are realized by using Toujeow instead of Tresibaw.
functions in type 2 diabetic patients
Serdar Almacioglu1, Ozen Oz Gul2, Soner Cander2 & Canan Ersoy2
DOI: 10.1530/endoabs.49.EP602
1Department of Internal Medicine, Diyarbakir Gazi Yasargil Education and
Research Hospital, Bursa, Turkey;2Department of Endocrinology and
Metabolism, Uludag University Medical School, Bursa, Turkey.
Background
Sitagliptin, unlike the some major antihyperglycemic drugs, is not associated with
weight gain and has neutral effects on body weight. It is unclear whether
EP603
sitagliptin treatment alters immune functions and insulin resistance in people with
type 2 diabetes. The aim of the present study was to assess the effect of sitagliptin
Glycemic control and weight evolution in DM2 patients with
on insulin resistance and immune functions in patients with type 2 diabetes
canaglifozina
mellitus.
Lidia Urbón López de Linares, Cristina Crespo Soto, Concepción Terroba,
Methods
Sara Garrote, Marta Ventosa, Tomás Marín & Luis Cuellar
Twenty type 2 diabetic subjects were randomly assigned to receive sitagliptin
Hospital Rio Hortega, Valladolid, Spain.
(100 mg/day; nZ10) or medical nutrition therapy (MNT) (nZ10) for 12 weeks.
Changes in anthropometric variables, glycemic control, insulin resistance, lipid
In the late years ISGLT2 have became an usual choice to treat diabetes. The
parameters and immune functions were evaluated at baseline and following
inhibition of the sodium-glucose co transporters
(SLGT2) inhibits also the
12 weeks of treatment. T lymphocyte subgroups like as CD3, CD4, CD8 and
glucose reabsorption in the proximale tubule and increases the glucose excreted in
TGF-b1, IL-12 were analyzed to evaluate immune functions.
the urine. Therefore hyperglycemia decreases and so does weight. This is a very
Results
convenient side effect since type 2 DM is highly associated with overweight/-
Significant decreases in body weight and body mass index were observed over the
obesity. We show the results of HbA1c and weight evolution after starting
entire study period in MNT treatment group but not in sitagliptin group. HbA1c
canaglifozina 100 (added to the previous treatment) in 60 patients. Six of them
and postprandial plasma glucose (PPG) levels were decreased in the sitagliptin
(four women) had to stop the drug (three because of genital pruritus, one
group compared with baseline values but not statistically significant while they
deterioration of renal function and one non related metastatic cancer). We also
were unchanged in the MNT group. There was a significant decrease c-peptide
show the results of canaglifozina 300 in 17 patients. Women represented the 33%
and insulin resistance (HOMA-IR) in sitagliptin group compared with baseline
and the medium age was 62G7years. We show data after 6 and 12 months on
values but not in MNT group at the end of the 12 weeks. Compared to the MNT
canaglifozina100. We have studied separately people older than 65 years old: 15
group we found a decrease in CD4 lymphocyte count by extension CD4/CD8 ratio
patients with medium age of 71G4 years, 10 of them women. This group showed
in the sitagliptin group though statistically insignificant.
no side effects and no treatment interrumptions. In 30 people we studied uric acid
Conclusion
levels, showing a difference of -0.9 mf/dl after 6 months on canaglifozina.
In this study of patients with type 2 diabetes, treatment with sitagliptin was
Seventeen patients progress to canaglifozina 300, the medium age was 63.2
associated with a significant decrease in insulin resistance. The decrease in CD4
(G5,6) years. After 6 months they got an additional weight loss of 1.8 kg (G0.5)
lymphocyte count was thought be possibly related to the upper airway tract
and decrease on HbA1c of K0.3% (G0.1). There were 18 patients on insuline
infection-like side effect described in the literature.
therapy with an average of 32(G26) daily units one year later the average was 21
DOI: 10.1530/endoabs.49.EP601
(G30) daily units of insulin. 2 patients stopped insulin therapy. Three patients
stopped sunfonilurea previously to canaglifoniza 100. Initially HbA1c increased
0.3% (G0.1) and weight decreased 3.3 (G1.7) kg, patients referred decrease or
disappearance of hypoglycemia. After one year on canaglifozina HbA1c
decreased 0.2 (G0.1)% and weight decreased 4.8 (G2.2) kg. The 96% were
satisfied with the new treatment for cana 100 and 100% for cana 300 (Table 1).
EP602
Real practice experience: Degludec vs Glargina U300
María Rosa Alhambra Expósito, Inmaculada Prior Sánchez, Paloma
Table 1
Moreno Moreno & M Ángeles Gálvez Moreno
Hospital Universitario Reina Sofía, Córdoba, Spain.
A1c6
A1c 1
Weight 6
Weight 1
A1c
months
year
Weight
months
year
Uric
Uric 1 year
Background
All
7.5G1.2
7G0.9
6.9G1.2
89G11
82.8G12
79.5G15
6G1.1
5G1.2
In last year, different analogues of very long duration basal insulin have appeared,
O65
8.1G1.7
7.7G1.4
7.8G1.4
86.8G11
83.2G12
80.8G8
6.6G1.6
5.7G0.8
cana300
73G0.8
xxxxx
7.0G0.2
81.7G16
xxxxxx
79.9G17
xxxxx
xxxxxx
which favors the flexibility in its use. Both ensure a decrease in the rate of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
EP605
Canaglifozina 100 added to the previous treatment for DM2 improved glycaemic
Efficacy and safety of evoglipitin monotherapy in patients with
control and produced weight loss. Canaglifozina 300 improved even more this
type 2 diabetes
results. A decrease in uric acid levels was showed. The results were the same in
Doo-Man Kim1, Sungwoo Park2, Mookyu Lee2 & Kunho Yoon3
the elderly group without increase of side effects. Patients on insulin decrease the
1Hallym University College of Medicine, Seoul, Republic of Korea;
dose with an improvement in the glycemic control. Stopping sulfonylurea
2Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
produced a transient increase in glycaemia with less hypoglycemia. The mail side
3Catholic University, Seoul, Republic of Korea.
effect was non complicated urinary infection.
DOI: 10.1530/endoabs.49.EP603
Background and aims
To evaluate the efficacy and safety of the newly developed dipeptidyl peptidase-4
(DPP-4) inhibitor evogliptin in drug-naïve patients with inadequately controlled
type 2 diabetes.
Materials and methods
In randomized, double-blind, placebo-controlled, parallel-group, multicenter,
phase III study, 160 patients with type 2 diabetes were randomized to evogliptin
5 mg or placebo for 24 weeks. The primary efficacy outcome measure was mean
changes from baseline to endpoint in hemoglobin A1c (HbA1c).
Results
The mean baseline HbA1c levels of the evoglipitin group and the placebo group
EP604
were 7.2G0.56% and 7.2G0.63%, respectively (PO0.05). Although the baseline
Intralesional epidermal growth factor treatment on diabetic foot ulcers
HbA1c was very lower when compared with other phase III clinical trials using
Aydin Cifci1, Birhan Oktas2, Senay Arikan Durmaz3, Askin Gungunes3,
DPP-4 inhibitors, evogliptin provided significant placebo-corrected reductions in
Irfan Karahan4 & Taner Sarak5
HbA1c from baseline of K0.23% (P!0.0001) at 24 weeks. Also, the response
1Department of Internal Medicine, School of Medicine, Kirikkale
rate achieving HbA1c !6.5% was significantly higher in the evoglipitin group
University, Kirikkale, Turkey;2Department of Orthopedics and Trauma-
than placebo group
(PZ0.008). Overall, incidences of adverse event and
tology, School of Medicine, Kirikkale University, Kirikkale, Turkey;
hypoglycemia were similar between the two groups.
3Department of Endocrinology and Metabolism, School of Medicine,
Conclusion
Kirikkale University, Kirikkale, Turkey;4Department of Internal Medicine,
In this
24-weeks study, once-daily evoglipitin monotherapy significantly
Yenimahalle Traning and Research Hospital, Ankara, Turkey;5Department
improved glycemic control and was well tolerated in patients with type 2 diabetes.
of Cardiology, School of Medicine, Kirikkale University, Kirikkale, Turkey.
DOI: 10.1530/endoabs.49.EP605
Objective
Treatment of diabetic foot ulcer is complex and difficult. Blood glucose
regulation, debridment and surgical revascularization are used in management of
diabetic foot ulcer. Intralesional Epidermal Growth Factor
(EGF) is a new
treatment approach for diabetic foot ulcer. We report our experience with eight
EP606
patients with diabetic foot ulcer who were treated by intralesional EGF.
Rabson mendenhall syndrome-a dilemma to treat in a resource
Patients and methods
poor country
A total of eight patients whose diabetic foot ulcers did not fully recover with other
Shehla Tabassum & Qamar Masood
treatments were included our study (Table 1).
Aga Khan University, Karachi, Pakistan.
Results
Complete healing was observed all diabetic foot ulcers after the intralesional EGF
treatment.
Background
Conclusion
Rabson Mendenhall Syndrome (RMS) is a rare genetic syndrome that is caused by
Our diabetic foot ulcers improved with intralesional EGF. Although our results
the mutation in the insulin receptor gene. Such mutation consequently results in
are quite impressive, this treatment is very expensive and caused of some allergic
severe insulin resistance. Patients suffering from RMS develop constant
reactions. Relation with malignancies is not known for long-term. In our opinion,
hyperglycemia from a progressive decline of endogenous insulin secretion.
intralesional EGF treatment should be used on wounds that did not heal with the
Drug therapy for RMS includes metformin, pioglitazones, large doses of insulin
other treatments.
alongwith recombinant human methionyl leptin or IGF-1. Here we describe a case
Table 1
of RMS who management poses a big dilemma due to unavailabity of these
treatment options in a low income country like Pakistan.
Numbers
Case presentation
Duration
Wagner
of EGF
A young Pakistani girl of 16 years of age presented in our Endocrine clinic with
No.
Age year Sex
of dm
Lesion place Grade
Prior treatment doses
uncontrolled blood glucose levels. She was diagnosed as case of type i diabetes
1
74
Male
20
Right 5.
4
Amputation
12
mellitus (DM) at the age of 4 years due to the complaints of polyuria, polydipsia
Phalanx
from left
and weight loss. She was being treated with insulin since then. Initially she
4.metatars
level
attained a good diabetic control but later on, her diabetes worsened. She was
2
65
Male
15
Left foot 5th
3
DebridmentC
9
never admitted to a hospital as a case of Diabetic Ketoacidosis (DKA). At the time
Metatars
Negative-
of her visit to our clinic, she was taking 70 units of Humulin-70/30 twice a day.
pressure
wound
Her fasting insulin level was 589 mU/ml, HbA1C was 16.8% with self-monitoring
therapy
of blood glucose levels being always recorded as ‘High’ at home. Examination
3
60
Male
22
Right foot
4
AmputationC
5
showed her body mass index of 17, short stature (less than 5th centile), severe
First
debridment
Phalanx
acanthosis nigricans, coarse facial features, broad nose, thick lips, dental
4
66
Male
16
Left foot First
3
AmputationC
12
dysplasia, prognathism, hirsutism, small hands with thick fingersnails and
Phalanx
debridment
abdominal distension. As genetic testing for RMS is not available in Pakistan, so
5
56
Male
33
Left heel, 2th
3
AmputationC
12
and 3th
debridment
she was diagnosed as a case of RMS with severe insulin resistance on clinical
Phalanx
grounds only. Her insulin dosage was increased gradually to 520 units/day &
6
57
Female
35
Left First
3
Debridment
9
MetforminCPioglitazone were added (as insulin sensitizers) to the regimen, but
Phalanx
and heel
still her blood glucose levels were uncontrolled. At last, she was admitted to
7
40
Female
25
Right 3th
3
Debridment
9
hospital for diabetic control. There she received MetforminCPioglitazoneC20
and 4th
units/day of insulin
(regularCNPH) along with continuous insulin infusion
Metatars
8
64
Male
20
Left- Foot
3
Debridment
5
@30 units/h bur still her blood glucose levels ranged between 400 and 600 mg/dl.
sole
As the 500 U/ml insulin is not available in a resource poor country like Pakistan
along with the unavailability of latest treatment options like recombinant leptin or
IGF-1, so it becomes a big dilemma for Endocrinologists about how to treat such
patient with RMS. Currently the patient is having poorly controlled DM and has
DOI: 10.1530/endoabs.49.EP604
started developing multiple bullous, ulcerated lesions all over the body due to
poor diabetic control.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
patients. In our study, it’s aimed to evaluate the effects of exenatide and
Several challenges are encountered by healthcare professionals while treating
laparoscopic sleeve gastrectomy (LSG) in obese diabetic patients on the clinical
patients of RMS in resource poor countries of the world. Concentrated insulin (U-
and laboratory parameters.
500) is not available everywhere to ease the pain of several daily insulin injections
Subjects and methods
and to improve compliance. We hope that future will hold promising horizon for
Twenty-five patients who had undergone bariatric surgery and 25 patients who
such patients and the global equal access to its available treatment options will
started exenatide treatment and followed up in our outpatients clinic were
result in their better quality of life.
included in the study.
DOI: 10.1530/endoabs.49.EP606
Results
At the end of the six month follow-up, weight loss was approximately 35.4 kg in
the surgery group and 11.5 kg in the exenatide group. Although postprandial
glisemi (PPG) and HbA1c were significantly decreased in both groups, the
decrease was significantly higher in LSG group compared to the exenatide group.
Although there was no significant change in fasting blood glucose (FBG) in the
exenatide group, there was a significant decrease in FBG in LSG group.
Discussion
EP607
LSG is a method that should be performed upon indication and much more radical
Does tolerance develop toward GLP-1 receptor agonists’
compared to exenatide administration but appears to be a more efficient
glucose-lowering effect?
application that corrects diabetes and obesity related metabolic parameters
Tuuli Sedman1,2, Maarja Krass1, Kertu Runkorg1, Eero Vasar1 &
compared to exenatide treatment in diabetic obese patients. Both treatment
Vallo Volke1,2
options must be evaluated for each patient regarding the advantages and
1Department of Physiology, Institute of Biomedicine and Translational
disadvantages and appropriate treatment option for each patient should be decided
Medicine, University of Tartu, Tartu, Estonia;2Tartu University Hospital,
according to patient’s characteristics.
Tartu, Estonia.
DOI: 10.1530/endoabs.49.EP608
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become a popular
tool for the treatment of type 2 diabetes. Unlike many other antidiabetic drug
classes, distinct GLP-1 RAs have different therapeutic profiles, mostly due to their
different pharmacokinetic properties. Animal experiments and human data
indicate that tolerance develops toward at least some of their effects, e.g., gastric
EP609
motility. Whether tolerance develops toward the glucose-lowering effect of GLP-
Increase in time in target when using a basal-bolus algorithm for insulin
1 receptor agonists has never been formally tested. We have conducted a series of
dosing with insulin glargine U300 during hospital stay
experiments in mice and a pilot clinical trial in healthy volunteers to address the
Julia K Mader1, Klaus Donsa2, Felix Aberer1, Katharina Lichtenegger1,
hypothesis of tolerance development.
Christian Lanz1, Edin Smajic1, Bernhard Holl2, Peter Beck3,
Methods
Thomas R Pieber1,2 & Johannes Plank
Male C57Bl/6J mice were used. Liraglutide (600 mg/kg once a day s.c.) or
1Medical University of Graz, Graz, Austria;2Joanneum Research GmbH,
exenatide (10 mg/kg twice a day s.c.) were given for 11 days (subchronic group)
Graz, Austria;3Decide Clinical Software GmbH, Graz, Austria.
or 18 days (chronic group). Treatment effects on nonfasting glucose level and
during the glucose tolerance test (GTT) were evaluated. Ten healthy volunteers
were treated with 0.6 mg liraglutide s.c. once daily for 21 days. The drug’s effect
Background and aims
was quantified by serial graded glucose infusion tests, with glucose and c-peptide
Insulin therapy and the use of clinical decision support systems to achieve
measured every 20 min and insulin secretion rate calculated.
glycaemic control in hospitalized patients with hyperglycaemia are recommended
Results (Mice)
by clinical guidelines. The aim of this evaluation was to assess time in target by
The effect of liraglutide on nonfasting glucose was clearly weaker after chronic
continuous glucose monitoring
(CGM) achieved by a basal-bolus insulin
administration, compared to acute administration (P!0.01 Duncan’s post hoc
algorithm using insulin glargine U300 during hospital stay in patients with type
test) while exenatide remained equally effective. During the GTT both liraglutide
2 diabetes (T2D).
and exenatide, decreased AUC for glucose significantly more after acute
Material and methods
administration compared to the chronic groups (P!0.05). Moreover, in the
30 patients with T2D (12 female, age 67G11 years, HbA1c 79G2 6 mmol/mol,
experiment with liraglutide the change in insulin-to-glucose ratio was
BMI 32G6 kg/m2, diabetes duration 14G11 years) were treated with GlucoTab,
significantly blunted after subchronic
(P!0.05) and chronic treatment
a mobile system providing automated workflow support and suggestions for
(P!0.01) compared to acute effect. Humans: (will be revealed during the
insulin dosing to health care professionals, during hospital stay. Insulins glargine
presentation).
U300 and glulisine were used for basal-bolus therapy. Additionally to blood
Conclusions
glucose measurements, blinded CGM
(iPro2, Medtronic) was performed
Prolonged treatment with exenatide and liraglutide induced tolerance in mice.
throughout the study.
DOI: 10.1530/endoabs.49.EP607
Results
Mean total daily insulin dose was 63.8G39.8 U. A total of 49,846 CGM values
were collected. Mean daily sensor glucose was 8.4G1.2 mmol/l. Percentage of
CGM values in the ranges was as follows: 5.6-7.8 mmol/l
(42.0%),
3.9-
10 mmol/l (80.2%), O10 mmol/l (19.0%), O16.7 mmol/l (1.5%). Percentage in
the hypoglycaemic range were low: !3.9 mmol/l (0.77%), !3.3 mmol/l (0.35%)
and !2.8 mmol/l (0.15%), respectively. When comparing the first vs last full
24-h period, time in target 3.9-10 mmol/l (61.8% vs 85.2%) increased, whereas
EP608
time in hyperglycaemia O10 mmol/l (37.1% vs 14.2%) and hypoglycaemia !
Comparative evaluation the effects of bariatric surgery and exenatide
3.9 mmol/l (1.2% vs 0.6%) decreased.
treatment on the clinical and laboratory parameters in obese type 2
Conclusions
diabetic patients
Basal-bolus insulin therapy using insulin glargine U300
safely establishes
Onur Elbasan1, Pinar Sisman2, Hande Peynirci3, Ozen Oz Gul4,
glycaemic control as assessed by CGM. Over time percentage of values in target
Soner Cander4, Erdinc Erturk4 & Canan Ersoy4
increases without increasing the risk of hypoglycaemia.
1Department of Internal Medicine, Uludag University Medical School,
DOI: 10.1530/endoabs.49.EP609
Bursa, Turkey;2Endokrinology and Metabolism Clinic, Harakani State
Hospital, Kars, Turkey;3Endocrinology and Metabolism Clinic, Munif
Islamoglu State Hospital, Kastamonu, Turkey;4Department of
Endocrinology and Metabolism, Uludag University Medical School,
Bursa, Turkey.
EP610
Background
Intensity of dapagliflozin induced glycosuria correlates with previous
Obesity and diabetes are major causes of morbidity and mortality that are
glycemic control but not with body weight or duration of type 2 diabetes
increasing all over the world. As obesity is a major risk factor for type 2 diabetic
Manuel Cayón-Blanco & Carolina García-Figueras Mateos
patients, weight loss has an important place in the treatment of type 2 diabetic
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
Introduction
Inhibitors of sodium-dependent glucose co-transporter
2
(SGLT2i) reduce
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a newly developed
circulating glucose concentrations via a renal mechanism. Its metabolic effects
class of oral anti-diabetic drugs with a unique mechanism of action and its use is
have not been fully described and there is a discrepancy on some clinical results
becoming more widespread. Given that dapagliflozin was the first drug of this
found in studies on SGLT2i. Our aims were to detect if there are some predictor
class used in Spain, available since December 2013, 3 years after its inception, we
factors to identify what patients will have higher response to dapagliflozin, a
aimed to investigate whether there have been differences in prescription patterns
SGLT2i, and second, to explore whether intensity of glycosuria is correlated to
of SGLT2i (using dapagliflozin as reference) in a Sanitary district from Spain
the intensity of metabolic and anthropometric changes.
over time.
Methods/design
Methods/design
23 participants with type 2 diabetes (T2D) (age: 53.1G7.6 years; 56.5% males,
Using electronic medical records, data of patients with type 2 diabetes who were
T2D duration 12.1G6 years) received dapagliflozin (10 mg/day) for 18 weeks in
prescribed dapagliflozin
10 mg/day, were collected at two periods of time:
conditions of normal medical practice. Parameters related to glucose metabolism,
i) between January to June 2013 (consecutive first prescriptions of dapagliflozin
renal function and anthropometric variables were measured at baseline and at
in our area) and ii) between June to December
2016
(last prescriptions).
week 18. Glycosuria was quantitatively measured at baseline and at the end of the
Epidemiologic, clinical and metabolic data as well as antidiabetic drugs received
follow-up.
were compared between the two periods.
Results
Results
At week 18, glycosuria increased from 6.4G2.2 to 68.9G50.4 g/24 (P!0.001).
A total of 36 prescriptions of dapagliflozin made in the first period were compared
Significant reductions in body mass index (BMI), HbA1c, fasting plasma glucose
to
32 prescriptions in the second period. Patients in the second period had
(FPG) were observed (P!0.01). Quantitative glucose urine levels at week 18
significantly (P!0.05) higher duration of diabetes (13.6G7.4 vs 10G9 years),
positively correlated with the following variables at baseline: FPG (rZ0.631;
lower A1C (%; 8.6%G1.3% vs 9.1%G1.1%) and a lower rate of microvascular
PZ0.001), HbA1c (rZ0.399; PZ0.03), glycosuria (rZ0.397; PZ0.034) and
(37.5% vs 78%) and macrovascular complications (18.7% vs 33.3%). Also, there
inversely correlated with albumin/creatinine ratio (rZK0.409; PZ0.037) but not
has been an increased used as second line treatment (21.9% vs 5.5%; P!0.001)
with age, T2D duration, eGFR or BMI. Intensity of glycosuria correlated with
as well as combined to basal insulin (62.5% vs 12.5%; P!0.001).
diuresis increase (rZK0.602; PZ0.002) but didn’t with and HbA1c or BMI
Conclusions
falls.
Patterns of prescriptions of SGLT2i have changed over the last 3 years in our area.
Conclusions
Its use as a second line treatment and combined with basal insulin has increased.
Glycosuric effect of dapagliflozin is correlated with glycemic control at baseline
Also, patients who are prescribed this class of antidiabetic drug have a better
independently of time of T2D evolution as result of a higher expression of SGLT2
diabetes profile and a lower rate of complications although a higher duration of
receptors in poorly controlled diabetic patients. The magnitude of glycosuria did
diabetes.
not provide higher weight loss or higher falls in HbA1c.
DOI: 10.1530/endoabs.49.EP612
DOI: 10.1530/endoabs.49.EP610
EP611
EP613
How can dapagliflozin affect blood pressure response in a real-life
cohort of people with type 2 diabetes and hypertension?
The insulin delivery system and its impact on quality of life and on
Manuel Cayón-Blanco & Carolina García-Figueras Mateos
psychopathological symptomatology
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
Miguel Pereira1, Celestino Neves1,2, César Esteves1, Sofia Oliveira1,
Cristina Arteiro1, Rui Coelho1,2 & Davide Carvalho1,2
1S. Joa˜o Hospital Center, Porto, Portugal;2Faculty of medicine, University
Introduction
of Porto, Porto, Portugal.
In clinical trials, dapagliflozin has been shown to lower blood glucose, reduce
weight and blood pressure in people with type 2 diabetes (T2D). However, there
are limited published data on quantitative changes on blood pressure of this drug
Introduction
in routine clinical practice. Our aim was to examine the clinical efficacy of
In chronic diseases a good psychological and behavioral adaptation is essential.
dapagliflozin in patients with T2D and hypertension in a real-life cohort.
Concerning diabetes the Insulin Delivery System (IDS) adopted tend to be an
Methods/design
important factor of adaptation, global satisfaction and, above all, quality of life
Prospective study including patients with poorly controlled T2D and hypertension
(QoL).
who were added dapagiflozin in conditions of routine medical practice. Metabolic
Objectives
profile, renal parameters and hemodynamic parameters were measured prior to
To analyze the QoL and IDS satisfaction and its relationship with psychopatho-
dapagliflozin intensification and at week 24.
logical symptomatology in patients on continuous subcutaneous insulin infusion
Results
(CSII) therapy.
16 patients were evaluated. At week 24, urine volume increased from 1761G
Patients and methods
693.6 ml/day to 2570.83G758.6 ml/day; P!0.001 as well as natriuresis (from
We gather a convenience sample of 42 type 1 (DM1) patients, with a mean age of
211.6G73.7 mEq/day at baseline to
252.8G94.5 mEq/day; pZ0.009). No
28.4G11.5 years, 61.9% female and with a mean IDS time of usage of 5.6G2
significant differences were observed in eGFR and albumin/creatinine ratio.
years. We applied the following questionnaires: the Audit of Diabetes Dependent
Systolic blood pressure significantly decreased from baseline (148.9G20.8 vs
Quality of Life (ADDQoL), o Insulin Delivery System Rating Questionnaire
141.5G17.9; PZ0.02) as well as diastolic blood pressure (84.3G11.9 vs 78.8G
(IDSRQ) e o Brief Symptom Inventory (BSI).
8.9: PZ0.001). In five patients, variability of blood pressure was measured
Results
showing a significant reduction (15.2G1.9 vs 10.4G2.1; PZ0.02).
Relatively to QoL, in this sample, the mean values were K1.68G1.37 (results go
Conclusions
from K9 to 9). We did not find any relevant psychopathological symptomatology
Our results show a higher decrease in blood pressure that observed in clinical
in general in the BSI questionnaire (GSI Z0.10G0.09). Regarding blood glucose
trials. Dapagliflozin might potentially improve not only the average blood
monitoring (BGM), 55.3% of patients perform 4-6 blood checks daily and 39.5%
pressure, but also reduces its variability. We included a little number of patients.
more than six times daily. 30% of patients carry out BMG a little more than they
Further investigations are needed to verify our observation and determine its
would like and 22.5% a lot more than they would like. We noticed a significant
potential role on cardiovascular outcomes.
statistical correlation between QoL and the level of satisfaction with BGM needed
(rZK0.50; PZ0.001) and also with psychopathological symptomatology
DOI: 10.1530/endoabs.49.EP611
(rZK0.53; PZ0.001).
Conclusions
Results in this study shows that the chosen IDS has a vital impact in
psychopathological symptomatology and in the levels of QoL that patients
reveal. This data allow us to conclude that the minor constraints that this IDS has
EP612
due to its utilization does not contribute negatively to CSII perception, moreover
Trends in prescription of Sodium-glucose co-transporter-2 inhibitors
when it is compared with multiple daily dosage.
(SGLT2i) over the last three years in a specialized setting
DOI: 10.1530/endoabs.49.EP613
Carolina García-Figueras Mateos & Manuel Cayón-Blanco
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP614
significantly improved glucose (area under the curve: 26603 vs. 31947, P!0.001)
and insulin (area under the curve: 6981 vs 8968, P!0.001) tolerance, insulin
New long-acting insulins in type 1 diabetes: implications for real clinical
resistance, insulin sensitivity, lipid profile, and decreased fasting glucose (8%)
practice
and insulin (11%), but had no effect on GSIS and islet insulin content. In diabetic
Miguel Damas-Fuentes, Cristina Díaz-Perdigones, Araceli Mun˜ oz-Garach,
rats, nitrate significantly increased tissue levels of GLUT4 by 17% and 22% in
María Molina-Vega, Carmen Hernández-García, Isabel Cornejo-Pareja,
soleus muscle and epididymal adipose tissue, respectively. Nitrate also decreased
Isabel Mancha-Doblas & Francisco J Tinahones-Madue
˜o
elevated serum IL-1b in diabetic rats (4.7G0.5 vs. 3.2G0.6 pg/ml, PZ0.02).
Endocrinology and Nutrition Department, Virgen de la Victoria
Conclusion
Universitary Hospital, Málaga, Andalucía, Spain.
Nitrate administration had favourable effects on glucose tolerance, insulin
resistance, insulin sensitivity, inflammation, and dyslipidemia in type 2 diabetic
The emergence of a new generation of long-acting insulin analogues (insulin
rats.
degludec -ID- and insulin glargine 300 U/ml -IG300-) has increased treatment
Keywords: Glucose tolerance; Insulin resistance; Insulin sensitivity; Inflam-
options in type 1 diabetes (T1D), demonstrating in clinical trials better metabolic
mation; Sodium nitrate; Type 2 diabetes.
control with lower hypoglycemia rates.
DOI: 10.1530/endoabs.49.EP615
Objectives
To assess characteristics of T1D patients who were given ID and IG300 in clinical
practice and to evaluate their effect on metabolic control, weight, insulin dose and
hypoglycemia, comparing results obtained.
Methods
Observational, retrospective study. We studied T1D patients whose habitual
treatment had been modified. We analyzed anthropometric data (weight, BMI),
EP616
biochemical parameters (fasting glycemia, HbA1c, lipid profile), insulin dose and
Impact of a universal educational animation movie in an hour workshop
number of hypoglycemic events per month (!5; 5-10; O10, initially and after
on the knowledge of patients with gestational diabetes
6 months.
Chaïnèse Cheikh, Emilie Lacquement, Régis Cohen & Ghada Hatem
Results
Hôpital Delafontaine, Saint Denis, France.
38 patients:
50% women, age 38G12.7 years, BMI 25.8G3.9 kg/m2, T1D
evolution time 14.9G8.6 years and HbA1c 7.4G0.8%. 57.9% initiated ID and
42.1% IG300. They presented: 7.9% hypertension, 13.2% retinopathy, 2.6%
history of ischemic heart disease, 2.6% nephropathy and 0% neuropathy. Initially,
This study assessed the dietary and medical knowledge before and after a
there were no differences between the two groups, except for higher blood glucose
group workshop viewing a 5-min animation film in patients with gestational
in ID group (189.2G12.1 vs 144.3G22.4 mg/dl, P 0.003). There was a significant
decrease in insulin dose with ID (29.05G9.25 vs 24.82G20.8 IU, P 0.010). There
animation movie (without speech) explains the course of the patients
was a weight loss of 1.9G4.4 kg in patients with IG300, but not statistically
suffering from GD by emphasizing the stakes, the diet and the medical
significant. We observed a significant decrease in the number of hypoglycemia
measures.
events in general (75% with O10 decreased to !5; PZ0.009). When stratified by
Patients and methods
comparison groups, the significance is maintained with ID but not with IG300.
This is a prospective self-assessment study of 10 questions in 100 consecutive
Conclusions
pregnant women.
1) ID group significantly decreased basal insulin dose. 2) We observed weight
Results
loss, not statistically significant, in IG300
patients.
3) There was significant
Seventy-four out of 100 subjects were included with their clinical data. Diagnosis
reduction of hypoglycemia rates with both basal insulin analogues. 4) Further
was based on the mean blood glucose after a 75 g load charge test: T0 0.92 g/l
studies are needed to distinguish which type of patient benefits more from each
(nZ47) T1 1.75 g/l (nZ46), T2 1.53 g/l (nZ46). Patients were characterized by a
insulin analogue.
mean age of 32 years, 6% with type 1 or 2 diabetes, G3P1, 91% of foreign origin,
DOI: 10.1530/endoabs.49.EP614
predominantly from the Maghreb (59%), mainly unemployed with an average
pre-pregnancy BMI of 28 kg/m2, a mean weight gain of 8 kg during pregnancy,
a 42% history of diabetes in the family, a 12% history of personal DG, a 11%
history of macrosomia and 24% insulin use. For 71/74, we collected information
on delivery accounting for
7% of macrosomia. The analysis of the
100
questionnaires revealed an average correct score of 6.3/10 before and 8.6/10
after the workshop. Before the workshop (99/100), patients were unaware of the
presence of sugar in bread, the number of dairy products to be consumed daily, the
EP615
importance of physical activity, and the possibility of using insulin if blood
Effect of oral nitrate administration on glucose metabolism and
glucose was too high. After the workshop (98/100), the score improvement was
inflammation in obese type 2 diabetic rats
mainly relevant for these four topics.
Asghar Ghasemi1 & Sevda Gheibi1,2
Conclusion
1Endocrine Physiology Research Center, Research Institute for Endocrine
Our animation film is a simple pedagogical tool that allows us to improve the state
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
of knowledge in an efficient manner.
2Neurophysiology Research Center and Department of Physiology, Faculty
DOI: 10.1530/endoabs.49.EP616
of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Introduction
Type 2 diabetes is associated with impaired nitric oxide (NO) bioavailability;
nitrate administration might act as a potential therapeutic agent in diabetes
through nitrate/nitrite/NO pathway. The aim of this study was to determine the
EP617
effects of sodium nitrate on glucose tolerance, insulin sensitivity, inflammation,
Insulin requirements in pregnant women with DM 1 with different
glucose-stimulated insulin secretion (GSIS), and islet insulin content in obese
duration of the disease
type 2 diabetic male rats.
Juliya Sharipova1, Leila Gaysina2, Gulnaz Gazizova1, Farida Valeeva1 &
Methods
Kamilya Khasanova1
Male Wistar rats were divided into four groups: Control, controlCnitrate,
1Kazan State Medical University, Kazan/Republic of Tatarstan, Russia;
diabetes, and diabetesCnitrate. Diabetes was induced using high-fat diet and low-
2Kazan Federal University, Kazan/Republic of Tatarstan, Russia.
dose of streptozotocin. Sodium nitrate
(100 mg/l in drinking water) was
administered for 2 months. Serum levels of fasting glucose, insulin, and lipid
profile were measured and the insulin resistance/sensitivity indices were
Background and aims
calculated every 2-weeks. At the end of the study, tissue levels of glucose
To study the need for insulin during pregnancy, depending on the duration of the
transporter
4
(GLUT4) protein and serum interleukin-1
beta
(IL-1b) were
disease.
measured as well as glucose and insulin tolerance test were done. GSIS from
Methods
isolated pancreatic islets and islet insulin content were also determined.
We studied 108 pregnant women with DM 1 receiving insulin with insulin pumps.
Results
Patients were divided into three groups: in the 1st group diabetes duration was less
Compared to the control group, diabetic rats had glucose intolerance,
than 5 years, in the 2nd - 5 to 15 years, 3rd - more than 15 years. We evaluated the
dyslipidemia, and higher serum glucose and insulin. In diabetic rats, nitrate
daily need for insulin on 12, 22-25, 30-32 weeks of gestation.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Methods
In the 1st group the daily insulin requirement (IU/kg) in the 1st trimester was 0.51,
Retrospective study of type 2 diabetic patients with newly diagnosed of pancreatic
in the 2nd 0.54, in the 3rd 0.79. Significant increase of insulin requirements was
or biliary tract cancer attended consecutively in a tertiary hospital between the
identified from the second to the third trimester (PZ0.34 between 1 and 2
years 2012 and 2015.
trimester, PZ0.005 between the 2 and 3 trimester, P!0.01 between 1 and 3
Results
trimester). By the third trimester the increase of the daily dose of insulin was on
A total of 37 patients were included. The prevalence of use for DPP-4 inhibitors in
56% (36; 87). In the 2nd group the insulin requirement was 0.6; 0.73; to
our cohort was 37.8% (sitagliptin, linagliptin and vildagliptin). No one patient
0.87 IU/kg, respectively, dose increased from trimester to trimester (P!0.01). By
was under treatment with GLP-1 receptor agonists. Subjects’ characteristics are
the third trimester, daily dose of insulin increased on 42% (28; 63). Insulin
shown in Table 1. Men developed cancer earlier than women (68.4 vs 75.5 years,
requirements in the 3rd group increased from the first (0.59 IU/kg) to second
PZ0.038). Smoking prevalence and time of diabetes evolution was higher for
(0.65 IU/kg) trimester, but in third trimester dose stabilized on
0.74 IU /kg
males. Subjects who were taking DPP4-i exhibited stages more advanced at
(P!0.01 between 1 and 2 trimester, PZ0.17 between the 2 and 3 trimester,
diagnosis (Table 2). However, this result did not reach statistically significant
P!0.01 between 1 and 3 trimester). However, the daily dose of insulin in this
differences (70 vs 50%, PZ0.250). Metformin use was not associated with
group increased only on 22% (11.5; 32.5).
different tumor staging (PZ0.169).
Conclusions
In pregnant women with DM 1 with disease duration more than 15 years we may
not see a significant rise in insulin requirements on the third trimester. This group
needs monitoring.
DOI: 10.1530/endoabs.49.EP617
EP618
Liraglutide restores the hyperglycemia-induced endothelial oxidative
stress in vitro
Sofia Gougoura, Alexandra Bargiota & Georgios N Koukoulis
Department of Endocrinology and Metabolic Diseases, University Hospital
of Thessaly, Larissa, Greece.
Introduction
Diabetes is characterised by increased oxidative stress and an insufficient
antioxidant response, which are crucial for the initiation and progression of
atherosclerosis. GLP-1 agonists, used for the treatment of diabetes, are considered
as cardioprotective agents but under that concept, there are limited data on their
ability to influence the endothelial antioxidant response.
Methods
In order to answer this question we studied the influence of liraglutide, a known
long-lasting GLP-1 agonist, on the antioxidant response markers (superoxide
dismutase (SOD), catalase, glutathione (GSH) system, endothelial nitric oxide
synthase (eNOS), intracellular reactive oxygen species (ROS) and extracellular
nitric oxide
(NOx)) of Eahy926
macroendothelial cells pre-treated in
hyperglycemic (25 mM) environment for 2 h.
Results
Hyperglycemia significantly increased the endothelial intracellular ROS content
(P!0.001) and decreased eNOS
(P!0.05), SOD (P!0.05) and catalase
(P!0.001) activity, GSH recycling rate (P!0.001) and Nox levels (P!0.05).
Conclusions
Liraglutide (40 nM) restored the increased intracellular ROS to levels comparable
This study supports DPP4-i safety from the point of view of tumorigenesis in humans.
to normal glucose treated cells (control). The elimination of intracellular ROS
However, the small sample size due to the low incidence of this lethal disease makes
was accomplished by the activation of SOD (P!0.05) and catalase (P!0.001)
us to be cautious in the conclusions. Further research is needed in order to ensure that
enzymatic antioxidant response and the increase (P!0.001) of intracellular GSH
incretin-based therapies are safe from the oncological point of view.
recycling rate. Moreover, liraglutide restored also eNOS activity and NOx release
DOI: 10.1530/endoabs.49.EP619
(P!0.05).
Conclusions
Our results indicate that liraglutide is involved in the redox balance of endothelial
cells. Its ability to counterbalance the increased endothelial free radicals induced
by hyperglycemia seems to work as a protective mechanism restoring cell
EP620
function and ameliorating the progression of atherosclerosis process.
Palpable purpura in an uncontrolled diabetic patient: an uncommon
DOI: 10.1530/endoabs.49.EP618
possible side effect of linagliptin
Omercan Topaloglu, Bahri Evren, Mahmut Kara, Seyfullah Yucel &
Ibrahim Sahin
Department of Endocrinology, Inonu University Medical Faculty, Malatya,
Turkey.
EP619
Introduction
Incretin-based therapies and pancreatic/biliary tract cancer
Incretin based therapeutics have commonly been used in the last years for the
Diana Boj-Carceller1, Sara Cay-Melero1, Isabel Azcona-Monreal1,
management of patients with type 2 diabetes mellitus (DM). Linagliptin is a
Leticia Pérez-Fernández1, Pilar Calmarza-Calmarza2 &
member of “dipeptidyl peptidase 4” (DPP-4) inhibitors and often preferred owing
Alejandro Sanz-París1
to some advantages over the others. We present a diabetic case developing skin
1Endocrinology and Nutrition Unit, Hospital Miguel Servet, Zaragoza,
findings after the initiation of linagliptin.
Spain;2Laboratory of Clinical Biochemistry, Hospital Miguel Servet,
Case
Zaragoza, Spain.
66 year-old woman with a history of type 2 DM for 10 years was admitted to our
clinics with the complaints of dry mouth, polydipsia and polyuria. She had also
Objective
history of coronary heart disease confirmed by coronary angiography. She had
To study the relation between incretin-based therapies, DPP-4 inhibitors and
been taking metformin, acetylsalicylic acid, and oral nitrate for 10 years. On
GLP-1 receptor agonists, and tumor stage at the time of diagnosis of pancreatic
physical examination; vital signs and examinations of cardiovascular, pulmonary
and biliary tract cancer.
and gastrointestinal systems were normal. She had no skin rash or lesions. Blood
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
glucose was 319 mg/dl, urine ketone negative, creatinine 0.78 mg/dl; and liver
Background
tests and arterial blood gas analysis were in normal limits. Firstly, we initiated
One of the most significant complications of type 2 diabetes (T2D) is non-
intensive insulin regimen together with tight glucose monitoring, to improve
alcoholic fatty liver disease (NAFLD). The search for new effective approaches to
uncontrolled hyperglycemia. We increased the dosage of rapid acting insulins
the treatment of patients with comorbid chronic condition such as type 2 diabetes
gradually to achieve optimal glucose control. Metformin was continued and
and NAFLD is relevant.
linagliptin was added to treatment. Lesions like palpable purpura arised on lower
Methods
legs and upper arms of the patient on the second day of linagliptin therapy. No
We have observed 118 patients, including 64 patients with T2D and NAFLD, 26
other drugs, chemicals or herbal preparations were given at this time. After
patients with T2D and 28 patients with NAFLD. The control group consisted of
cessation of linagliptin, palpable purpura lesions both on lower and upper
25 healthy individuals. Recommended treatment included individualized diet
extremities regressed gradually.
therapy with energy value of daily ration 1800-2300 kcal/day, a hepatoprotective
Conclusion
salt of arginine and glutamic acid at 0.75 mg 3 times a day and alive multistrain
Due to impact of DPP-4 inhibitors on the other DPP enzymes to some degree,
probiotic at 10 mg twice a day. Clinical manifestations, echography semiotics,
musculoskeletal and dermatological adverse reactions may occur during the
protein, lipid, enzyme and carbohydrate metabolism, the degree of IR,
treatment with these agents. To our knowledge, palpable purpura lesions were
subpopulations of lymphocytes and interleukins, IgG antibodies to LPS, the
detected with linagliptin therapy in our patient for a first time in the literature.
range of average weight molecules, circulating immune complexes
(CIC),
DOI: 10.1530/endoabs.49.EP620
dysbiotic disorders of the intestine in patients with T2D and NAFLD were
studied.
Results
The application of the developed medical complex that included individualized
diet, the salt of arginine and glutamic acid and a multiprobiotic contributed to the
normalization of lipid, enzyme, carbohydrate metabolism, improvement of
EP621
cellular and humoral links of the immune system, reducing levels of CIC 58.3%,
Dulaglutide added on Empagliflozin improves blood pressure, body
reduction of endogenous intoxication (level MCM254 - 30.5%, MCM280 - by
weight, glycemic control and albuminuria in obese diabetic patients
32.4% and the level of IgG antibodies to LPS in 1,6 times), improvement of
Carmen Acosta-Calero1, Claudia Arnas-Leon1, Ana Delia Santana-Suarez1,
intestinal microbiocenosis in 84.4% of patients with T2D with NAFLD and
Manuel Nivelo-Rivadeneira1, Agnieszka Kuzior1, Sara Quintana-Arroyo1,
normalization of pathological clinical manifestations in 68.8% of patients.
Nery Sablon-Gonzalez2 & Francisco Javier Martinez-Martin3
Conclusions
1Endocrinology Department, Hospital Universitario de Gran Canaria Dr.
This study revealed the effects of proposed treatment complex on the major
Negrin, Las Palmas de Gran Canaria, Spain;2Nephrology Department,
lymphocyte subpopulations and cytokine status, reduction of endotoxemia,
Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran
promotion of the positive dynamics of lipid and carbohydrate metabolism
Canaria, Spain;3Outpatient Hypertension Clinic, Hospital Universitario de
indicators and intestinal microbiocenosis of patients with T2D and NAFLD.
Gran Canaria Dr. Negrin, as Palmas de Gran Canaria, Spain.
DOI: 10.1530/endoabs.49.EP622
Objective
GLP-1 receptor agonists and SGLT2 inhibitors improve glycemic control, body
weight, blood pressure and albuminuria by different pathways. However, their
combination is not endorsed by ADA-EASD guidelines, and available data are
scarce. Our objective in this open observational study was to elucidate the effect
of added Dulaglutide in obese type 2 diabetic patients previously treated with
Empagliflozin but insufficiently controlled.
Methods
EP623
Dulaglutide 1.5 mg/week was added to the treatment of 20 type 2 diabetic patients
The role of diabetic educational programs in glycemic control in
with BMI O30 kg/m2 previously treated with Empagliflozin 10 mg/day for at
patients attending to our day hospital
least 3 months but having HbA1C O7%. They were re-evaluated after 3-6 months
Mariana Tome1, Guillermo Martínez de Pinillos2, Fernando García2, Eyvée
without additional medication changes, except for insulin dosage adjustments and
Arturo Cuéllar2, Ignacio Fernández2 & Juan Manuel Garcia de Quirós2
iDPP4 discontinuation. Besides clinical routine, 24 h. ABPM were performed
1Punta de Europa Hospital, Algeciras, Spain;2Valme Hospital, Sevilla,
before and after. Stats were performed by two-tailed paired t-test, *meaning
Spain.
P!0.05. Values are given as meanGS.D.
Results
Age was 49G11 and diabetes duration 8G3 years. 53% were women. Baseline
Objective
BMI was 34.9G2.5 kg/m2; ABPM: Awake, BP 131G8/85G8 mmHg, HR 74G
To assess improvement in glycemic control in those diabetic patients who have
10 bpm; Sleep,
127G8/78G10 mmHg, 69G10 lpm. Fasting glycemia was
received structured education in diabetes in our Day Hospital.
167G46 mg/dl, HbA1C 8.0G0.6%, urate 6.9G1.4 mg/dl, Cr 0.91G0.17 mg/dl,
Methods
GFR (CKD-EPI estimation) 87.1G16.8 ml/min/1.73 m2, Albuminuria 291G
A retrospective observational study was carried out in which 42 diabetic patients
268 mg/gr Cr; median 232, IQR 23-460. At follow-up there were no withdrawals
who had attended to educational courses in 1 year were included, determining the
due to side effects, one patient was lost to follow-up and 16% reported mild
age of the patient, type of Diabetes, score obtained in the questionnaires at the
nausea and/or diarrhoea. Body weight change was K4.0G2.6* kg, BMI
beginning and end of the course, as well as HbA1c before, at 6 months and at
K1.37G0.83* kg/m2. ABPM: Awake SBP K4G4*, DBP K1G3 mmHg, HR
12 months after the courses.
1G4 bpm; Sleep, SBP K6G5*, DBP K4G6* mmHg, HR C2G7 bpm. Fasting
Results
glycemia change K41G23* mg/dl; HbA1C K1.1G0.6* %, urate K0.12G
Of the 42 patients, 25 were diabetic type 1 and 17 diabetic type 2. Mean age
0.24* mg/dl; Cr K0.04G0.11 mg/dl, GFR C1.9G7.3 ml/min/1.73 m2, albumi-
43.64G14.36 years (Type 1 diabetes mellitus (DM1): 36.8G12.17 years; Type 2
nuria K71G105* mg/gr Cr (K29G31%).
diabetes mellitus (DM2): 53.7G11.2 years). Mean HbA1c before the course was
Conclusions
9.14G2% (DM1: 8.99G1.74%, DM2: 9.36G2.38%). Mean of HbA1c at
Dulaglutide added on Empagliflozin in obese type 2 diabetic patients was well
6 months of the course was 8.06G1.51%. (DM1: 8.09G1.45%, DM2: 8.03G
tolerated and effective for glycemic control, body weight, blood pressure
1.64%). A reduction of HbA1c of 1.08G1.87% (P !0.0001) was obtained. In the
(particularly nocturnal) and albuminuria.
DM1 group the mean reduction of HbA1c was 0.9G1.79% (PZ0.014) whereas
in the DM2 group it was 1.34G2% (PZ0.008). Of the 42 diabetic patients in the
DOI: 10.1530/endoabs.49.EP621
sample, HbA1c values were determined at 12 months in 27 of them (17 DM1 and
10 DM2). HbA1c at baseline in this group was 9.17G2.29%; At 6 months 8.13G
1.58% (PZ0.007) and at a year 8.05G1.25% (PZ0.007). In DM1 at the
beginning 8.64G1.47%, at 6 months 7.93G1.48% and at 12 months 8.06G1.1%.
In DM2 at baseline, 10.07G2.72%, at 6 months 8.48G1.75 (PZ0.019), at
EP622
12 months 8.02G1.78% (PZ0.009).
Modern treatment approaches of patients with type 2 diabetes and
Conclusions
non-alcoholic fatty liver disease
Attending courses in Diabetes Education significantly improved glycemic control
Kateryna Kondratiuk1, Nazarii Kobyliak1, Petro Bodnar1,
in all our patients. The type 2 diabetic group showed the greatest improvement in
Mykola Lysianyi3, Liudmyla Belska3 & Valentyna Kondratiuk2
glycemic control, obtaining even greater reduction of HbA1c at one year of the
1Bogomolets National Medical University, Kyiv, Ukraine;2State Institution
Education course. This is probably because it is the group that most benefits from
“Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine”,
lifestyle modification.
Kyiv, Ukraine;3State Institution “Institute of neurosurgery named after
DOI: 10.1530/endoabs.49.EP623
academician AP Romodanov of NAMS of Ukraine”, Kyiv, Ukraine.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP624
Introduction
Real-time detection of hazardous changes in blood glucose at the first
Gestational Diabetes Mellitus
(GDM) is a pregnancy complication that has
trimester of pregnancy in women with type 1 diabetes: a pilot study
experienced a worldwide growth. The use of insulin has to be considered as it may
Orit Barenholz-Goultschin1,2 & Michal Shauly-Aharonov1
be beneficial for both the mother and the new-born.
1Shaare Zedek Medical Center, Jerusalem, Israel;2Hebrew University,
Methods
Jerusalem, Israel.
Retrospective analysis of all cases of GDM, and the respective new-borns (NB),
followed in our obstetrics unit between 2012 and 2015. Clinical and workup
parameters were evaluated in 2 groups: GDM with no insulin therapy (GDMNIT)
Introduction
and GDM with insulin therapy (GDMIT). Data analysed using SPSSv23.0.
Type 1 diabetes (T1D) in pregnancy is known to be associated with increased
Results
risks of birth defects and miscarriages. Despite the technological improvement
We studied 644 GDM and 35% of them were treated with insulin. The BMI was
and availability of continuous glucose monitoring (CGM), women with T1D who
significantly higher in GDMIT (P!0.001). Induced labour occurred in 36% of
are adequately controlled according to CGM average and HBA1C still face these
GDMNIT and in 40% of GDMIT, with statistically significant difference
complications. Glucose variability was suggested as an explanatory factor of the
(PZ0.027). The number of C-sections was superior in GDMIT (41 vs 36%), but
difference between actual obstetric outcome and the expected outcome according
without significant difference. The need for hospitalization of the NB in the
to currently available monitoring tools.
Neonatal Intensive Care Unit (NICU) was significantly higher in GDMNIT. The
Aim
NB weigh (Fenton) was also significantly different between both group
To present an algorithm and to verify that it has a practical potential to notify early
(PZ0.019), with “large for gestacional age” being higher in GDMIT (7 vs 3%).
enough of increased risk of miscarriage or birth defect.
Postpartum positive screening for Diabetes Mellitus was 0% in GDMNIT and 2%
Methods
in GDMIT.
Change-point detection methods were applied on CGM data of eight pregnant
Conclusions
women with T1D during the entire first trimester of pregnancy.
One of the indications for induced labour is GDMIT because of the higher risk of
Results
fetal complications, which was verified in this study. As the literature states,
Seven pregnancies ended with good outcome and one pregnancy ended at a late
GDMIT is associated with a difficult blood sugar control during pregnancy. This
miscarriage (patient H). The average first trimester HbA1C of the pregnancies
means that an unsuccessful maintenance of euglycemia may be associated to
with good outcome was 6.58G1.2 (range 5.1-8.8), which is similar to the HbA1C
heavier NB and eventual peripartum complications. However, GDMNIT was
of the pregnancy that ended with a late miscarriage (6.6). The daily averages of
associated with more hospitalizations in NICU, and the main causes were
CGM data were not higher for patient H. Nevertheless, the statistical method
prematurity, hyperbilirubinemia and acute respiratory distress syndrome. The
(aimed at detection of an increase in the hourly StDev of glucose levels) did detect
results of postpartum screening are in accordance with the literature.
an exceptional elevation of glucose variability of patient H, at 8 weeks of
pregnancy, which was 7 weeks before the actual miscarriage. Namely, we could
DOI: 10.1530/endoabs.49.EP626
have predicted this poor outcome early enough to lessen glucose variability.
Conclusions
Analysis of eight first-trimester follow-ups (of more than 1600 hours z 20,000
measurements for each patient) showed the change-point detection method to fully
discriminate between proper pregnancies and pregnancies with adverse outcome.
This approach might serve as an additional tool to detect pregnancies at risk in real-
EP627
time and to plan better glucose control in order to improve pregnancy outcome.
Evaluation and descriptive analysis of our type 1 diabetes population
DOI: 10.1530/endoabs.49.EP624
and their insulin therapy
Cristina Díaz Perdigones, Araceli Mun˜ oz Garach, María Molina Vega,
Carmen Hernández García, Miguel Damas Fuentes &
Francisco J. Tinahones Madue
˜o
EP625
Endocrinology, Malaga, Spain.
Sense of coherence and glycaemic control among a sample of newly
diagnosed type II diabetics in rural Crete
Objectives
Dimitrios Anyfantakis1,2, Anastasios Anyfantakis4, Michaela Foukaki3
To evaluate the different insulin regimens and types of insulin used in our
& Serafim Kastanakis2
population of type 1 diabetes (DM1) patients in the last revision in our clinic.
1Primary Health Care Centre of Kissamos, Chania, Crete, Greece;2Saint
Method
George General Hospital of Chania, Chania, Crete, Greece;3Day-Care
A descriptive study was carried out in our population of 535 DM1 patients. They
Center for Elderly, Gortyna’s Municipality, Heraklion, Crete, Greece;
had their initial diagnosis between 1967 and 2014.
4Endocrinology Department, Veneizeleio Hospital, Heraklion, Crete,
Results
Greece.
In our population, 47.3% were women and 52.3% were men. The mean age of our
patients was 33.8 years (S.D. G12.31 years) and the mean age of diagnosis was
Aim
16.67
(S.D. 11G years). 17.39% of our population was taking antiplatelet therapy.
Currently there is much discussion on the protective effects of the sense of coherence
17.4% had hypertension, and 36% cdyslipidemia. There were 22.9% smokers and
(SOC) on health. Our aim was to examine possible associations between SOC and
10.3%. who had given up. The glycated hemoglobin value was 7.8 (S.D. G1.28%)
glycemic control among 60 newly diagnosed adults with type 2 diabetes.
and the body mass index 27.18 (S.D. 4G kg/m2). 91% had previously received
Methods and results
diabetic education assistance, and 32.1% completed the program. Total insulin
Thirty males and 30 females diagnosed 3 months before with type 2 diabetes
dose was 40.52 units (S.D. G29.9 IU) with 0.68 (S.D. G0.33 U/kg). Insulin
mellitus were included in the study. SOC was measured with the Greek translated
regimes used were: basal-bolus 91.3%, basal alone 1.5%, prandial plus mix 2.7%
and validated version of Antonovsky’s
29
item sense of coherence scale.
and mix combination 4.5%. In those using basal-bolus regimen, 42.67 (S.D. G
Biochemical tests and blood pressure measurements were also performed in all
25.8%) of total insulin dose (TID) was prandial insulin and basal insulin 54.05
participants. SPSSv 20 was used for the statistical analysis. Blood pressure has been
(S.D. G17.2%):
associated with low sense of coherence levels (P!0.001). Remarkably albuminuria
- Prandial insulins used were: lispro 41%, aspart 46.5%, glulisin 7.7% and regular
presence has been associated with poor SOC (P!0,001) while good glycemic
4.9%.
control presented a statistic significant positive association with SOC (P!0.001).
- Basal insulin used were: glargine 85.4%, detemir 13.5%, lispro protamine 0.2%,
Conclusion
NPH 0.8%.Time of injection was breakfast in 17.9%, lunch 15.8%, dinner 17.6%,
Further future investigations are required in order to address the effect of SOC on
before bedtime 34.2%; 14.5% in split doses. In 86%, the split dose regimen was
diabetic patients
given breakfast and dinner and 14% breakfast and before bedtime. We observed a
DOI: 10.1530/endoabs.49.EP625
higher dose of insulin among patients with two daily doses of basal insulin: 35.9
(S.D. G20) vs 25.54 (S.D. G12.2) IU (P !0.05).
Conclusions
Basal-bolus therapy is the most used regimen in our DM1 population. Those
patients using two basal doses per day needed higher TID. The majority of our
EP626
patients had educational support but less than a half complete the educational
Gestacional diabetes mellitus with and without insulin therapy: a case
program. It is important to aware our patients to finish these activities to better self
study
control of their disease.
Francisco Evora, Marta Pinto & Céu Almeida
DOI: 10.1530/endoabs.49.EP627
Bissaya Barreto Maternity - CHUC, Coimbra, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP628
EP630
Effects of dapagliflozin in treatment of gastroparesis considering the
Determinants of patient’s adherence and its relation to therapeutic
state of carbohydrate metabolism in patients with type 2 diabetes
success after hospital admission for decompensated diabetes
mellitus
Daniela Magalhães1,2, Ana Saavedra1,2, Pedro Souteiro1,2, Rita Bettencourt-
Iryna Kostitska
Silva1,2, Maria Manuel Costa1,2, José Luís Castedo1,2, Paula Freitas1,2,
Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine.
Cláudia Nogueira3, Joana Queirós1,2 & Davide Carvalho1,2
Diabetic gastroparesis (DG) is associated with high morbidity and is the most
1Department of Endocrinology, Diabetes and Metabolism of Centro
common precipitating factor to decompensation of carbohydrate metabolism.
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,
SGLT2 inhibitors are becoming a common and useful drug to treat type 2
Portugal;3Department of Endocrinology of Centro Hospitalar de
diabetes. Principle treatment of gastroparesis considering the state of
Trás-os-Montes e Alto Douro, Vila Real, Portugal.
carbohydrate metabolism in patients with type 2 diabetes mellitus are very
limited. The aim of this study was to compare the effects of dapagliflozin for
Introduction
management patients with DG. 16 patients with type 2 DM were randomly
Diabetes mellitus (DM) is a chronic disease that requires continuous medical care. Health
allocated into 2 groups: a first group (nZ8 (3M/5F), mean age was 41.4G6.7
care providers should adopt approaches that improve patient outcomes and adherence.
years old, DM during 12.2G5.4 years, body mass index (BMI) was 33.7G
Aims
1.4 kg/m2) with gastroparesis, and a second (control) group (nZ8 (4M/4F), mean
To evaluate the adherence to Endocrinology ambulatory follow-up after elective hospital
age - 45.3G3.9 years old, DM - 13.2G6.2 years, BMI - 32.9G2.5 kg/m2) to take
admission for decompensated DM and to determine the relationship between adherence
dapagliflozin (daily doses -10 mg) for 3 months. Gastric emptying rate (GER)
and therapeutic success after discharge.
measurement with the help13C-octanoic breath test (13C-OBT), prandial and
Methods
postprandial glucose levels and glycated haemoglobin (HbA1C) were performed
Retrospective study of 86 patients admitted at Endocrinology department in 2014-
at entry and at end of treatment period as well. Low gastric motility has been
2015. Two types of assessment were available after discharge: consultation and
diagnosed in all patients first group with help of13C-OBT: T1
2
-
98.84G
blood analysis. Adequate adherence was defined by the compliance to R80% of the
4.22 min, in the second group that result is T12 - 69.82G9.23 min. After the end
evaluations. We considered therapeutic success as A1c reduction R1.5% after
of 3 months therapy in the first group significantly improved T12
-83.11G
discharge and persistence of success as no increase of A1c after success achievement.
2.31 min (P!0.05). In the result after treatment we show that glycemic control to
Results
be significantly higher
(prandial glycemic-7.81G0.6 mmol/l, postprandial
-
After discharge, 79 patients maintained ambulatory follow-up, 62 with adequate
8.57G0.88 mmol/l, P ! 0.05) in the patients of the first group than subjects of the
adherence. Noncompliant patients were younger (52(IQR 39-60) years) than
second group (prandial glycemic- 8.44G0.34 mmol/l, postprandial - 9.28G
compliant patients (60(IQR 51-67) years) (PZ0.041). For each year of increase in
0.13 mmol/l, PO0.05). After treatment level of HbA1C significantly decrease in
patient’s age at admission we observed a 4% increase in adherence (ORZ1.04,
both groups (P!0.05).Dapagliflozin is an useful drug for treating type 2 diabetes
95%CI 1.00-1.08, PZ0.035). Hypertensive(HBP) patients showed
88.5%
with and without of gastroparesis. Patients with DG get normalization of gastric
compliance (P!0.05). Patients with HBP, compared to those without HBP,
emptying rate. It appears that this effect may be due to non-specific mechanisms.
showed an adherence of 9.6:1 (ORZ9.60, 95%CI 2.85-32.61, P!0.001). Previous
DOI: 10.1530/endoabs.49.EP628
treatment with metformin, DPP4i and statins was associated with a 3.9-fold (ORZ
3.90, 95%CI, 1.16-13, 46, PZ0.028), 4.7-fold (ORZ4.70, 95%CI 1.22-17.87,
PZ0.025) and
3.5-fold
(ORZ3.50, 95%CI,
1.15-10.6, PZ0.027) higher
adherence, respectively. The degree of adherence to follow-up didn’t influence
the therapeutic success at 6 (PZ0.547) nor 12 months(M) (PZ0.611). Of the
compliant patients, 55.4% achieved therapeutic success at 6M, however only 26.9%
of these maintained success at 12M. On the other hand, of compliant patients who
did not achieve therapeutic success at 6M, only 20.8% achieved it at 12M.
Conclusions
Approximately 80% of our sample showed adequate adherence. Advanced age,
HBP and previous therapy with metformin, DPP4i or statin were associated with
greater adherence. Therapeutic success was not related to follow-up adherence.
EP629
DOI: 10.1530/endoabs.49.EP630
Self-monitoring of blood glucose: how are glycemic readers used in
practice?
Meriem Haddad, Samir Aouiche & Aissa Boudiba
Department of Diabetes Research CHU Mustapha Bacha, Algiers, Algeria.
Endocrine Disruptors
Introduction
EP631
In recent years, the technique of ASG has gained much in simplicity, speed and
Study of metabolic and some hormonal aspects among pubertal type 1
acceptability, using readers more and more reliable. Despite this, some patients do
diabetic girls
not acquire the skills needed to achieve it. The aim of this study is to evaluate the
Fatma Hamad & Mohsen Khalid
technical gestures of use of blood glucose readers in current practice.
National Institute of Diabetes and Endocrinology, Cairo, Egypt.
Material and method
This is a prospective descriptive study including 369 diabetics for over a year,
followed in diabetic consultation in Algiers. A questionnaire was drawn up using
Background
the following items: frequency of capillary blood glucose checks, blood glucose
The onset of type 1 diabetes before menarche was a risk factor for the subsequent
readers
(choice, number of years of use, rhythm of change), modalities of
development of hyperandrogenic disorders. It has been also suggested that the use
capillary sampling,, The possible impact on daily life.
of exogenous insulin to treat type 1 diabetes mellitus in those patients may
Results
contribute to the development of PCOS. Abnormal lipid levels were also reported
Of the 369 diabetics we found 17% type 1 and 83% type 2, sex ratio at 1, the
in children with type 1 diabetes mellitus during pubertal years.
average age is 52.6G15.5 years, with a duration of diabetes of 10.3G8 years.
Aim of work
More than half are treated with insulin. Their average HbA1c is 8.25G1.8%.
This study was designed to investigate metabolic and some hormonal changes in
Patients have more than two readers in 33.9% of cases, the latter are changed with
relation to puberty among type 1 diabetic girls.
an average rhythm of 4G2.9 years, 22.36% of patients do not systematically wash
Subjects and methods
their hands before capillary blood glucose, and use of alcohol or other antiseptics
The study was carried out on 60 girls, 40 of them were type 1 diabetic patients (the
is observed in 32.5% of patients, 59.2% use recommended sites for stitching,
diabetic group), subdivided into two groups (according to age and Tanner breast staging),
alternative stitch sites are never used, the regular change of the lancets is observed
and 20 of them were normal healthy girls (the control group), also subdivided into two
in 2/3 of the cases and the elimination of the lancets is done with the household
groups (according to age and Tanner breast staging). All girls were subjected to full
waste In 86% of cases.
history taking, thorough clinical examination, estimation of fasting blood glucose and
Conclusion
HbA1c (as an estimation for glycemic control), lipid profile, hormonal profile (FSH, LH
Learning from the GSM must be included in a therapeutic patient education
and free testosterone) in addition to pelvic ultrasound.
program, as the Haute Autorité de Santé1 has highlighted, practical workshops
Results
will help them to master the GSM and easy use of the blood glucose meters.
There is an increased frequency of dyslipidemia in the form of hypercholesterolemia
DOI: 10.1530/endoabs.49.EP629
and increased levels of LDL among type 1 diabetic girls, and pubertal type 1 diabetic
girls show higher BMI and cholesterol levels compared to controls, and also show
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
higher levels of LDL compared to prepubertal type 1 diabetic children. Age at
Observations
menarche is delayed in pubertal type 1 diabetic girls having PCOS, while not delayed in
We report the case of a patient, aged 32 years with a personal history of total
those without PCOS but positively correlated to the longer duration of diabetes and
gastrectomy for gastric adenocarcinoma, regularly followed surgery consultation,
with the level of HbA1c. Both the frequency of PCOS and the level of free testosterone
a family history of diabetes and hypertension. The onset of the disorders dates
are higher in pubertal type 1 diabetic girls compared to their normal controls.
back to a postoperative month marked by the appearance of signs of adrenergic
DOI: 10.1530/endoabs.49.EP631
hypoglycemia without glycogenic signs in late postprandial periods i.e. 2-3 h
after a meal. Capillary glucose levels were made with regard to clinical
symptomatology Have returned to
!0.50 g/l. Patient in average general
condition with a normal BMI of 19 kg/m2. Remainder of the review is without
peculiarities. On the biological level, GAJ: 0.79,. GR 3.6, Hb 10.3, VGM 91,
CCMH 31%, GB 5360, Correct renal count: MDRD at 107. Hepatic balance
without abnormalities. Malabsorption balance: Normal calcium an 2.28 mmol/l,
Phosphoremia:
1.46 mmol/l, Serum iron:
9.65 mmol/l. ECG and Telthorax
EP632
without abnormality. Glycemic variability is high in our patient, with
Bone-to-muscle endocrine axis modulating adaptation to exercise in
hypoglycemia and abnormalities in the glycemic Holter
(CGMS) or even
athletes of mountain cycling in a Portuguese Marathon
recording.The symptoms disappeared following a dietary treatment with
Isanete Alves de Alonso1, Andreia Matos1,2, Ângela Gil1,2, Carlos Cardoso3,
improvement of the quality of life of the patient, without any medicinal
Luis Bettencourt Sardinha4 & Manuel Bicho1,2
intervention.
1Genetics Laboratory and Environmental Health Institute of Faculdade de
Discussions
Medicina da Universidade de Lisboa, Lisbon, Portugal;2Instituto de
Hypoglycemia of the syndrome is hyperinsulinic, by histological abnormalities of
Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal;
the pancreas (neisidioblastosis), and/or by stimulation of insulin secretion by
3Laboratório de Análises Clínicas, Grupo Dr Joaquim Chaves, Lisbon,
incretin, including glucagon-like peptide-1 (GLP-1). The absorption of glucose is
Portugal;4Exercise and Health Laboratory, CIPER, Faculty of Human
both accelerated and exaggerated due to direct communication between the
Kinetics, Universidade de Lisboa, Lisbon, Portugal.
stomach and duodenum. It is an exaggeration after the surgery of a phenomenon
of adaptation which exists in the non-operated ones to whom the glucose is
Introduction
infused directly in the duodenum. Patient semiology is not always accompanied
Besides the benefits of low-to-high intensity physical activity
(PA) on
by biological abnormalities. However, if hypoglycaemia is severe and
metabolism, it is currently emerging that excessive PA can be deleterious with
neuroglucopenic symptoms, hyperinsulinemia is constant. For the other cases,
serious implications not only in muscle but also, bone remodeling. Despite recent
the possibility that stress and physical exercise increase the semiology. The
findings remains still unclear and controversial, we hypothesize that exercise of
treatment consists of dietary measures: split the diet into 5 or 6 meals, slow down
impact, like mountain cycling, beyond influencing the metabolic and skeletal
gastric emptying, reduce glycemic load and glycemic index of food, avoid stress
profile, represents an important model of profoundly changes in bone metabolism.
at mealtime. Acarbose is also effective; other treatments (insulin, glucagon,
calcium channel blockers, hyperglycaemic sulfamides, somatostatin analogs,
Methods
GLP-1 analogues) have not been validated on a sufficient number of subjects to be
55 participants
(mean age 44.8G7.1 years old) of mountain cycling race
recommended.
(TransPortugal) were evaluated at the beginning/basal (M0) and 9-days post-race
Conclusion
(M9). Anthropometric/body composition parameters, haematological and liver
It is necessary to educate the patients operated on for gastric surgery, after the
function were evaluated by conventional methods. Serum Irisin and plasma
resumption of the oral feeding, so that he learns how to manage his functional
osteocalcin and IL-6 measurements were evaluated with ELISA (R&D systems
disorders, that he understands the interest of a supplementation, of fat soluble
and Phoenix Pharmaceuticals-Irisin). Statistical analyses included departure from
vitamins and Calcium and accepts the idea of regular clinical, biological and
normality and adequate parametric or non-parametric test to compare the means
ideally osteodensitometric monitoring, unlimited in time.
and the medians. The results were significant for P!0.05.
Results
DOI: 10.1530/endoabs.49.EP633
In the metabolic point of view, we found that this strenuous exercise induced a
significant decrease of fasting insulin, triglycerides, total-cholesterol, non-HDL
cholesterol, LDL and an increase of glucose, creatinine, uric acid, HDL, HOMA-
B (P!0.05). These results reflected the important modifications in muscle, being
the myokine/adipokine, irisin, significantly decreased post-race (PZ0.002). In
EP634
terms of bone remodelling, although not statistically significant, osteocalcin was
decreased post-race (PZ0.154), yet the plasma IL-6, a cytokine involved in
A case report of insulinoma in a patient with chronic headache
Enalda Demaj & Marjeta Kermaj
osteoclastic proliferation, was significantly increased post-race (P!0.0001).
1Regional Hospital of Berat, Berat, Albania;2University Hospital Center
Conclusions
‘Mother Theresa’, Tirana, Albania.
Our preliminary results, revealed a possible regulation of osteocalcin in glucose
and insulin metabolism, being the slowdown in bone formation observed, a
prompt metabolic response of bone to the increased energy demands of the
Introduction
muscle.
Pancreatic endocrine tumors are rare lesions, with an incidence of 4 cases per 1
DOI: 10.1530/endoabs.49.EP632
million pts-yr. Of these lesions,insulinomas are the most common. The
nonspecific symptoms and small sizes of these tumors led to difficulties of
diagnosis and localization.
Case report
A 60 year female pts, had history of episodic and repetitive symptoms of strong
headaches for the last 5 years; which were relieved with eating or taking glucose
Endocrine tumours and neoplasia
water orally. She noticed increased appetite over the past few years. No
medications at the time of evaluation. She was obese. Normal visual field exam.
EP633
On admission serum glucose level 55 mg/dl, insulin, c-peptide in normal range.
Dumping syndrome post total gastrectomy
Prolonged supervised fasting test was applied and produced symptomatic
Samir Ait Abderrahmane, Soumia Abdelkrim, Fadoua Boucelma,
hypoglycemia (33 mg/dl), with slightly elevated insulinemia
26 mU/l(4-23),
Lila Brakni & Brahim Oudjit
normal levels of C-peptide, cortisolemia and chromogranina A; interrupted on the
HCA, Kouba, Algeria.
first day after 5hours.Abdominal RMN with contrast demonstrated a well-defined
hypervascular lesion involving head-body of pancreas measuring about 1.6 cm.
Introduction
Postoperatively the patient was discharged in good health with normal glucose
Dumping syndrome, also known as rapid gastric emptying, is a relatively rare
level.
disorder. It is conventionally due to the brutal flooding of the small bowel by a
Conclusion
hyperosmolar food bolus and to the release of various digestive hormones whose
Insulinoma remains a diagnostic challenge to practitioners. This case illustrated
real responsibility in the syndrome remains poorly known. It is usually a
the importance of carefully questioning and examining patient for subtle
complication of the gastrectomy (10 to 40% of the cases). Hypoglycemia after
symptoms and signs of hypoglycemia. A chronic headache may hide an
surgery for digestive cancer is sometimes severe, but rare, and revealed by the
insulinoma.
monitoring of blood glucose, and then more frequent. The variability of the
Keywords: insulinoma, headache
definitions in the studies supports a single definition, Whipple, with a blood
DOI: 10.1530/endoabs.49.EP634
glucose level below 0.55 g/l.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Female Reproduction
signaling, suggesting a change in the type of oxidative metabolism in the muscle
tissue and increase in adipogenesis.
EP635
DOI: 10.1530/endoabs.49.EP636
Real-time continuous glucose monitoring during pregnancy in women
with type 1 diabetes: glycemic control and key obstertric outcomes
Harold de Valk1, Judith van Niel2, Bianca Silvius1 &
Nel Geelhoed-Duijvestijn2
1University Medical Center, Utrecht, The Netherlands;2Medisch Centrum
Haaglanden, den Haag, The Netherlands.
EP637
Introduction
The evaluation of sexual function of women with type 1 diabetes mellitus
Real time continuous glucose monitoring (RTCGM) has been shown to improve
Edita Prakapiene2, Kornelija Bagdonaite1, Lina Radzeviciene2,3 &
glycemic control. Limited data are available on the effects of RTCGM during
Birute Zilaitiene2,3
pregnancy. The current study assesses glycemic control and obstetric outcomes in
1Faculty of Medicine, Lithuanian University of Health Sciences (LUHS),
women with type 1 diabetes, comparing RTCGM with usual self measurement of
Kaunas, Lithuania;2Department of Endocrinology, Lithuanian University of
blood glucose (SMBG).
Health Sciences (LUHS), Kaunas, Lithuania;3Institute of Endocrinology,
Patients and methods
Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania.
Patients were recruited from two hospitals. All patients were eligible. Glycemic
control was assessed by preconception HbA1c and HbA1c during pregnancy.
Obstetric outcomes reported are premature delivery (PD, !37 weeks), and
Aim
macrosomia (Large for Gestational Age (LGA; birth weight R90th percentile;
The aim of this study was to evaluate the influence of age, disease duration,
Very Large for Gestational Age (VLGA; birth weight R97.7th percentile).
glycaemic control and diabetic nephropathy for the sexual function of women
Results
with type 1 diabetes mellitus (T1D).
67 women were included; 53 (79%) used RTCGM PD occurred in 22% of the
Methods
pregnancies, 19.6% with RTCGM, 31% on SMBG (PZ0.5). LGA occurred in
Study subjects - 18-52 year old women with type 1 diabetes. Participants filled
58% of pregnancies, VLGA in 31%. LGA with RTCGM 61%, with SMBG 46%
the Female Sexual Function Index (FSFI) and questionnaires about T1D, disease
(PZ0.4). VLGA with RTCGM 37.5%, SMG 50%, PZ0.9). Mean HbA1c was
duration, glycaemic control and complications. Laboratory tests including
significantly lower before pregnancy
(52.1G6.1
vs
67.8G18.4 mmol/mol,
glycated hemoglobin (HbA1C), creatinine, testosterone, Sex hormone-binding
P!0.001) and during the first trimester
(6
weeks:
47.9G5.4
vs
58.9G
globulin
(SHBG), estradiol levels and albumin in
24h urine sample were
18.1 mmol/mol, PZ0.002) and
12
weeks
(43.9G7.0 mmol/mol vs
53.6G
performed. Postmenopausal women were excluded from the study. Female sexual
12.8 mmol/mol, P!0.05), but not later in pregnancy.
dysfunction (FSD) was diagnosed based on FSFI total score lower than 26.55.
Conclusion
Results
RTCGM was associated with better early HbA1c. Premature delivery occurred
113 women (mean age 34.82G8.34) with T1D were included to the study.
less frequently with RTCGM, macrosomia more frequent. Future analysis with
Diabetic nephropathy (DN) was diagnosed to 43.4% (mean age 35.24G9.50),
this expanding group will assess whether these differences persist; at this moment,
56.6% had no DN (mean age 34.50G7.50). FSD was diagnosed to 42.6% (NZ40)
better early control is not readily associated with less macrosomia.
of participants. Neither age nor disease duration had influence to FSD. Worse
DOI: 10.1530/endoabs.49.EP635
glycaemic control had a statistically significant impact to the prevalence of FSD
(PZ0.028). Negative correlations between participant age and FSFI subscales of
desire and arousal were observed (P!0.001). Lubrication (PZ0.015) and orgasm
(PZ0.027) subscales were negatively affected by age only in the group of DN.
Statistically significant negative impact was found between glycaemic control
and lubrication in group without DN (PZ0.009). There was no statistically
significant difference between FSFI scores or sex hormones and disease duration
EP636
or DN. Free androgen index had impact neither to the FSFI subscale scores nor to
total score. Negative SHGB and high glycaemic level correlation was observed
Differential pattern of insulin signaling in adipose tissue and skeletal
only in DN group (PZ0.031).
muscle in adult female sheep exposed prenatally to testosterone
Conclusion
Daniel Sandoval1, Mónica P Recabarren1, Albert Carrasco1,
Female sexual function is often diagnosed in women with type 1 diabetes
Teresa Sir-Petermann2 & Sergio E Recabarren1
mellitus. Sexual function correlates with glycaemic control and age. Worse
1Laboratory of Animal Physiology and Endocrinology, Faculty of
glycaemic control has negative impact to SHBG levels.
Veterinary Medicine, University of Concepcion, Chillan, Region BioBio,
Chile;2Laboratory of Endocrinology and Metabolism, Western School of
DOI: 10.1530/endoabs.49.EP637
Medicine, Universidad de Chile, Santiago, Chile.
Insulin resistance is defined as the incapacity of insulin to increase glucose uptake
by peripheral tissues
(skeletal muscle and adipose tissue principally). This
phenomenon is present in different animal models for PCOS by prenatal exposure
to androgens. In the PCOS condition, the metabolic pathway of insulin activity is
Growth hormone IGF axis - basic
defective in skeletal muscle and adipocyte whereas the activation of
steroidogenesis is maintained. The decreased insulin stimulated glucose uptake
EP638
is due to impaired signaling and multiple downstream intracellular defects
GH is related to hepatic mitochondrial activity in humans
including impaired glucose transport and glucose metabolism. Previous results
Peter Wolf, Sabina Smajis, Martin Gajdosiik, Lorenz Pfleger,
from our laboratory have demonstrated that female sheep born to mothers
Yvonne Winhofer, Christian-Heinz Anderwald, Siegfried Trattnig,
receiving testosterone during part of their pregnancy exhibit features from early
Anton Luger, Martin Krssak & Michael Krebs
postnatal life until adulthood resembling those of PCOS women. In the present
Medical University of Vienna, Vienna, Austria.
work, the programming effect of prenatal testosterone on the insulin signaling was
explored in adult females born to testosterone treated mothers (testosterone-
females), and born to untreated mothers (C-females). Our aim was to define if
Background
prenatal exposure to testosterone affects insulin signaling in adipose tissue and
Altered hepatic mitochondrial activity plays a key role in the development of
skeletal muscle. Adults females (38 weeks of age) were sacrificed and samples of
non-alcoholic fatty liver disease (NAFLD). GH has been shown to stimulate
skeletal muscle
(Gluteus superficialis) and adipose tissue
(visceral) were
mitochondrial function in skeletal muscle. Therefore we hypothesize that the time
collected. The qPCR assays were performed to analyze gene expression of IR,
course of serum GH concentrations during an oral glucose tolerance test might be
IRS-1, IRS-2, PI3K, Akt, PKC, GLUT4 and b-actin. Expression pattern of insulin
related to hepatic mitochondrial energy metabolism in vivo in humans.
signaling were similar between groups with the exception that in skeletal muscle,
Methods
IRS-2
showed higher expression in testosterone-females
(P%0.05) than
15
volunteers
(male/female:
7/8;
55G8 years; BMI 25G4 kg/m2) were
C-females while on the contrary, the GLUT4 RNAm was lower in testosterone-
investigated on two study days; i) oral glucose tolerance tests were performed
females compared to C-females (P%0.05). In the visceral adipose tissue, AKT
to assess dynamics of glucose, insulin, C-peptide and GH concentrations and ii)
transcript expression was higher in testosterone-females
(P%0.05) than
hepatic lipid content was measured by 1H/31P magnetic resonance spectroscopy
C-females. Results show that prenatal exposure to testosterone affects the insulin
(MRS). Saturation transfer technique was applied to assess ATP synthesis rate (k).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Intervention
Basal GH concentrations and GH dynamics strongly correlated with hepatic
In terms of methodology, we studied: a family history of diabetes, hypertension
mitochondrial activity
(GHbaseline&kliver:rZ0.783; P!0.001; GHAUC& kliver:
and dyslipidemia; Girth, body mass index (BMI), hypertension, diabetes mellitus
rZ0.676; PZ0.008). There was no association between HCL and GH, as well as
or impaired glucose tolerance and dyslipidemia in these patients.
between HCL and kliver. Six subjects fulfilled criteria for NAFLD (HCLR5.5%).
Main outcome measure
They presented significantly higher glucose levels and insulin resistance. The
Glucose intolerance and diabetes with insulin resistance are commonly
strong relationship between GH and kliver did not differ between patients with and
encountered complications acromegaly. Some studies have shown a direct
without NAFLD.
correlation between the rate of GH and the degree of glucose intolerance. The
Discussion
hyperinsulinemia and insulin resistance may play an important role in the
Our data indicate that basal as well as postprandial (oGTT) GH concentrations are
cardiovascular risk of these patients. The role of insulin resistance, but also of
directly related to hepatic energy metabolism in insulin sensitive and insulin
pancreatic b dysfunction has been invoked in the pathogenesis of carbohydrate
resistant humans.
metabolism disturbances secondary to chronic excess GH.
DOI: 10.1530/endoabs.49.EP638
Result
The average age was 43 years (20-63) with a sex ratio (M/F) Z0.33. The duration
of the disease at diagnosis was on average 7 years (3-14). Family history were
13.3% diabetes mellitus and heart disease. Pathological BMI was objectified in
52% of cases; 46.6% of these patients had pre-diabetes, 40% diabetic (a total of
84.6% of carbohydrate anomalies) and 46.7% had dyslipidemia. Moreover 26.6%
of our patients where hypertensive.
EP639
Conclusion
Modulation of the 22 kD/20 kD growth hormone (GH) ratio by exercise,
Approximately 84.6% in our series of cases had carbohydrate abnormalities.
fasting and glucose load in premenopausal women
Diagnostic and therapeutic delay can worsen or even cause the patient’s death.
Michael Haenelt, Katharina Schilbach, Christina Gar, Andreas Lechner,
After surgical recovery, the evolution of diabetes and/or glucose intolerance is
Rita Schwaiger & Martin Bidlingmaier
usually favorable.
Medizinische Klinik und Poliklinik IV, Klinikum der Universitat Munchen,
DOI: 10.1530/endoabs.49.EP640
Munchen, Germany.
We previously have shown in a cohort of 236 non-fasted women that before and
after a short high intensity exercise protocol
(HIP) till exhaustion serum
concentrations of 20 and 22 kD growth hormone (hGH) are highly correlated
(P!0.0001). Although the GH response to exercise exhibited huge inter-
individual differences, the 20 kD/22 kD-GH-ratio remained unchanged (9.6% vs
Neuroendocrinology
11.1%, PZ0.313). A subgroup of the women was also studied under fasted
EP641
conditions in a moderate intensity protocol, applying an exercise (70% VO2 peak)
over a longer time (mean duration 45 min). In contrast to the HIP under non-
Comparison of GHRH C arginine vs glucagon test for the evaluation of
fasted conditions, baseline and post exercise
20 kD/22 kD GH ratio were
growth hormone secretion status in a cohort of adults with Prader-Willi
significantly higher in the fasted protocol
(mean 15.33% vs. mean 10.85%,
syndrome (PWS)
PZ0.0021). To further investigate the impact of fasting and glucose intake on the
Laia Casamitjana, Giménez-Palop Olga, Corripio Raquel, Pareja Rocío,
20 kD/22 kD-GH-ratio, we analyzed GH isoform secretion before and after an
Hurtado Marta, Gabau Elisabet, Cobo Jesús, Berlanga Eugenio,
oral glucose tolerance test (OGTT, 75 g glucose) in a subset of the cohort (nZ60;
Cano Albert, Albert Lara, Rigla Mercedes & Caixàs Assumpta
mean age 36 years (yr), range 20-44yr; BMI: mean 23, 2 kg/m2). GH isoforms
Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc
were measured using the IDS-iSYS GH CLIA specific for 22 kD GH and an
Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Barcelona,
in-house IFMA for 20kD GH (LoQ 0.025 ng/ml), respectively. 20 kD GH was O
Spain.
LoQ of the assay in all subjects at baseline and in 86% 60 minutes after glucose
ingestion. At baseline, fasting 20 kD/22 kD ratio in the subset was 12.9%. Ratio
Background
was not changed 60 min after glucose intake (12.3%; PO0.05). Due to the
Prader-Willi syndrome (PWS) is a rare genetic disorder evolving morbid obesity
expected suppression of GH following glucose intake, after
120 min the
and growth hormone deficiency (GHD). Testing GH-IGF1 axis is required before
20 kD/22 kD-ratio could only be measured in 18.3% of the subjects, but no
treatment with rhGH in adults with PWS (1). The most common used tests in
significant change in the abundance of 20 kD GH was observed (mean ratio
these patients are GHRHCarginine (GHRHCa) and insulin tolerance test. There
12.1%; PO0.05). In conclusion, the 20kD/22kD-GH ratio is lower in the non-
are no prospective data for glucagon test (GT) in comparison to GHRHCa in
fasted compared to the fasted state, both at baseline and following exercise.
adults with PWS. Mechanism by which GT causes GH release remains unclear,
However, short-term oral glucose intake per se does not significantly influence the
glucagon-induced GH release via noradrenaline secretion has been postulated.
20 kD/22 kD-GH ratio.
Objectives
DOI: 10.1530/endoabs.49.EP639
To compare two diagnostic tests to evaluate GH secretion status in a cohort of
adults with PWS.
Methods
Twenty-one SPW (8M and 13F, aged 29(17-51), BMI 36.2C/K10.2 kg/m2)
participated in the study. After an 8-10 h fast, all patients underwent the two
different provocative tests in separate days: GHRH (1 mg/kg, max 100 mg) C
arginine (5 g/kg, max. 30 g) and GT (1 mg). We considered GHD according to
BMI-specific cut-offs in GHRHCa (2) and when GH peak was !3 ng/ml in GT.
EP640
Results
Insulin resistance and acromegaly: about 15 cases
With the GHRHCa test, 14 of 21(660 7%) met diagnostic criteria for GHD and 19
El Ansari Nawal & Sara Askaoui
of 21 (90%) with GT. Only two patients did not meet criteria for GHD with both
Service of Endocrinology Diabetes and metabolic diseases, Cadi Ayad
tests. Most patients achieved GH peak at minute 45: 3.31 ng/ml (1.6-9.6), median
University, CHU Mohamed VI., Marrakech, Morocco.
(interquartile range) with GHRHCa test, whereas GH response was blunted with
GT. After the glucagon injection, an increment in plasma glucose levels was
Contexte
observed at 30 min with a peak at 60 min. One patient suffered an asymptomatic
Acromegaly is a rare disease, usually caused by hypersecretion of growth
hypoglycemia during the test.
hormone (GH) by a pituitary adenoma and very rarely by ectopic secretion of
Conclusions
GHRH. It remains a serious disease reduces life expectancy because of its
Glucagon seems to fail to stimulate GH in adults with PWS. Further studies are
cardiovascular and metabolic impact.
necessary to elucidate if the underlying autonomic dysfunction described in PWS
Objective
could be involved.
The objective of this study is to report the glycemic profile in patients followed for
References
acromegaly in the endocrinologic center of CHU Med VI of Marrakech.
1. J Clin Endocrinol Metab, 2013,98:E1072-E1087.
Patient - Intervention
2. Ther Clin Risk Manag 2016, 12;873-81.
We performed a retrospective study over a period of 2 years. Fifteen cases were
DOI: 10.1530/endoabs.49.EP641
identified.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Nuclear Receptors and Signal Transduction
drinking, exercise habit, medication and sleep condition were assessed by
multiple regression analysis. Having a short lunch time, preferring salty taste,
EP642
snacking after dinner and dinner within
2 h before sleep were positively
Dietary intake of linoleic, linolenic, oleic, and arachidonic acid PPAR-
associated with BMI, WC and WHO-5 score after adjusting for all confounders.
gamma gene expression in visceral and subcutaneous adipose tissue
Although eating vegetable and fruits were not independent of BMI, both are
among healthy subjects
positively associated with WHO-5 score. The present data demonstrate that
Emad Yuzbashian1,2, Maryam Zarkesh3, Golaleh Asghari1,
adjusting meal intake behavior could be helpful in preventing psychological
Azita Zadeh-Vakili3, Behnaz Mahmoodi1, Afsoon Daneshafrooz3,
distress as well as obesity.
Mehdi Hedayati3 & Parvin Mirmiran1
DOI: 10.1530/endoabs.49.EP643
1Nutrition and Endocrine Research Center, Research Institute for Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
2Student Research Committee, Biochemistry of Nutrition Research Center,
School of Medicine, Mashhad University of Medical Sciences, Mashhad,
Iran;3Cellular and Molecular Endocrine Research Center, Research
Institute for Endocrine Sciences, Shahid Beheshti University of Medical
Sciences, Tehran, Iran.
Objective
To investigate whether peroxisome proliferator-activated receptor gamma
EP644
(PPAR-gamma) gene expression in visceral and subcutaneous adipose tissue
A comparison of the metabolic parameters of obese and non-obese nafld
was related to intake of several fatty acid intakes.
patients with insulin resistance
Methods
Pinar Karakaya1, Bahar Pehlivan2, Meral Mert1, Hamide Karagoz1 &
For the current study 97 subjects (41 non-obese, 18 obese, and 38 morbid obese)
Yildiz Okuturlar2
were selected. All of the subjects were free of diabetes and cancers and without
1Department of Endocrinology, Bakirkoy Sadi Konuk Training and
using anti-lipid medication. Visceral and subcutaneous adipose tissues were
Research Hospital, Bakirkoy, Turkey;2Department of Internal Medicine,
obtained during an abdominal open surgery with minimal impact on dietary
Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Bakirkoy,
intake. The PPAR-gamma gene expression was assessed by Real-Time PCR.
Turkey.
Usual dietary intake was measured using a validated semi-quantitative food
frequency questionnaire. For calculation linoleic (18:2), linolenic (18:3), oleic
Introduction-aim
(18:1), and arachidonic acid (20:4) intakes, the USDA Food Composition Table
Non-alcoholic fatty liver disease (NAFLD) is a clinical condition of uncertain
was used.
etiology, in whose pathogenesis several mechanisms are involved and which is
Results
defined by fat vacuoles in more than 5% of hepatic histiocytes in the absence of
The PPAR-gamma expression in visceral adipose tissue among non-obese
serious alcohol consumption. It is frequently comorbid with obesity and insulin
subjects was correlated with oleic acid (rZK0.417, PZ0.007) and linoleic acid
resistance. However, NAFLD is also seen in non-obese individuals. The purpose
(rZK0.401, PZ0.009). Were seen significant correlations between subcu-
of this study was to compare insulin resistance and metabolic parameters in obese
taneous adipose tissue PPAR-gamma expression and linoleic acid (rZK0.310,
and non-obese NAFLD patients.
PZ0.049) among non-obese subjects. PPAR-gamma expression among obese
Materials-method
subjects in visceral adipose tissue was correlated with oleic acid (rZK0.686,
50 obese (BMI OZ30) and 50 non-obese (BMI !30) presenting to the Bakırkoy
PZ0.002) and linolenic acid (rZK0.699, PZ0.031) and also in subcutaneous
Dr. Sadi Konuk Education and Research Hospital Endocrinology, Diabetes and
adipose tissue was correlated with oleic acid
(rZK0.453, PZ0.048).
Obesity Clinic with hepatic steatosis determined at ultrasonography (USG) and
Furthermore, among morbid-obese subjects PPAR-gamma expression in visceral
with no causes such as alcohol use, viral diseases or drug use to account for fat
adipose tissue was correlated with linoleic acid (rZK0.336, PZ0.039) and in
deposition and consenting to participate were included in the study. Patients’
subcutaneous adipose tissue was correlated with linoleic acid
(rZK0.326,
demographic characteristics, biochemical tests and insulin levels were
PZ0.046) and oleic acid (rZK0.352, PZ0.030). Were seen no significant
investigated. Insulin resistance was determined using homeostasis model
association of dietary intakes of arachidonic acid with PPAR-gamma gene
assessment (HOMA-IR), a mathematical technique, with the formula fasting
expression.
insulin (U/ml) ! fasting glucose (md/dl)/405. Insulin resistance was defined as
Conclusions
HOMA-IR O2.5.
PPAR-gamma gene expression was negatively correlated with linoleic and oleic
Results
acids among non-obese and obese subjects.
One hundred patients with NAFLD, 63.3% female, were enrolled in this study.
Conflict of Interest
Fifty were obese and 50 were non-obese. Mean age was 44.1G11.1 years.
None of the authors has any personal or financial conflict of interest.
Hepatomegaly accompanied steatosis in 55% of patients. Mean BMI was 37.3G
Funding
5.63 in the obese group and 28.2G1.35 in the non-obese group. Mean blood sugar
Not applicable.
values were 99.3G9.78 in the obese group and 103.40G8.3 in the non-obese
DOI: 10.1530/endoabs.49.EP642
group, and the difference was not statistically significant (P:0.08). Insulin levels
were 10.1G3.3 in the obese subjects and 13.85G12.3 in the non-obese subjects,
while HOMA-IR values were 3.48G3.38 in the obese subjects and 2.57G.91 in
the non-obese subjects, and the difference was not statistically significant
(PO0.05). Insulin resistance was determined in 60% of obese patients and 50% of
non-obese patients (in 55% of the entire group). The difference was not significant
(P:0.3). When the general characteristics and metabolic parameters of the groups
Obesity
with and without insulin resistance were compared
(Table
1), significant
differences were observed in terms of BMI, waist circumference, insulin level,
EP643
HOMA-IR, GGT and indirect bilirubin levels, but none between the other
Association between meal intake behavior and body
parameters.
composition/psychological well-being in Japanese adults
Toshihiro Takao, Yoshiyuki Yamanaka, Sohachi Fujimoto &
Tomoari Kamada
Table 1
Kawasaki Medical School, Kurashiki, Japan.
Parameter
With IR
Without IR
P value
The study aims to evaluate the association between body composition/psycho-
logical well-being with meal intake behavior such as eating fast, snacking after
Age
46.48G11.77
41.3G9.78
0.072
dinner, dinner within
2 h before sleep. This cross-sectional study includes
Sex
F: 52.6%
F: 47.4%
0.098
nZ3066 participants aged 19-89 who had participated in an annual health
BMI (kg/m2)
34.48G6.84
30.71G4.5
0.017
checkup in 2015. BMI, Waist circumference
(WC) and the World Health
Waist
103.67G10.72
97.07G10.79
0.022
Organization (WHO)-5 Well-Being Index were assessed to determine. The meal
circumference (cm)
intake behavior were assessed with a modified questionnaire based on focused on
FBS (mg/dl)
103.88G8.63
98.26G9.17
0.01
metabolic syndrome in Japan. In addition, the relation with BMI/WC/psycholo-
Insulin (IU/dl)
15.62G10.99
7.55G1.88
0.000
gical well-being and meal intake behavior by controlling age, smoking, alcohol
HOMA-IR
4.03G3.01
1.79G0.42
0.000
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
authentic metabolic syndrome including obesity is very rare, though possible,
We compared metabolic parameters of obese and non-obese patients with
with a mixed clinical picture. The goal of our study is to evaluate the association
NAFLD and insulin resistance. Insulin resistance was present in 55% of the total
of type 1 diabetes with the metabolic syndrome.
group. We observed significant differences between insulin levels, HOMA-IR,
Material and methods
GGT and indirect bilirubin levels in subjects with insulin resistance. In
This is a retrospective cross-sectional study based on the observation of patients
conclusion, we think that fatty liver disease is by itself a risk factor for insulin
admitted for diabetes with insulin deficiency. The positivity of anti-pancreas
resistance independent of obesity, and that GGT and indirect bilirubin levels in
antibodies testified to the auto-immune characteristic; anti glutamic acid
particular can show insulin resistance in patients with hepatic steatosis.
decarboxylase GAD and/or anti tyrosine phosphatase IA2. The goal of the
Key words: Non-alcoholic fatty liver disease, insulin resistance, GGT
study is to determine the patients’ clinical and biological aspects as well as their
metabolic profile.
DOI: 10.1530/endoabs.49.EP644
Results
Our series was conducted with 359 patients: 209 men and 150 women, aged
between 10 and 69 years with an average of 28.75 years. Metabolic heredity was
found in 26 patients (7.2%), Diabetes heredity in 216 patients (60.1%); 147
(40.9%) of whom with type 2 history and 69 (19.2%) with type 1 history. Vascular
heredity was found in 27 patients (7.5%). 117 patients (32.6%) were smokers and
alcohol consumption was found in 85 of them (23.7%). The clinical picture was
ketotic in the majority of cases: 336 (93.6%), with inaugural ketosis in 313 cases
EP645
(87.2%). Insulin deficiency varied between one week an 36 months, with an
Associations between dietary food patterns and metabolic syndrome
average of 3.75 months and a standard deviation of 6.8 months, exceeding 6
risk in Albanian adolescents
months achieving a slow form and a previous oral treatment in 24% of cases.
Alba Themeli & Edmond Pistja
Regarding weight, the average BMI was 22 (extremes: 15 and 39), over 30 in
Medical Training Center Santa Maria, Lezhe, Albania.
22 patients. Overweight was more significant in patients over 20 years old, with
6% in the younger population, 14% between the ages of 20 and 40, and 34% in the
Background
patients over 40 years of age. Regarding waist size in women, a size over 80 cm
Adolescence is a period of rapid body growth and cognitive development,
was more significant in patients over 40 (38%) against 4% in women younger than
requiring balanced and sufficient nutrient intake. Since dietary habits are usually
20. Men’s waist size over 94 cm was more significant in patients over 40 (19%),
acquired in this period and could affect dietary practice in later life. It is crucial for
against 4% in the ones younger than 20. An obesity previous to the discovery of
adolescents to acquire healthy dietary behaviors for long-term health. However,
Diabetes was found in 80 patients (22%). Hypertension was found in 14 patients
the prevalence of diet-related metabolic syndrome risks such as obesity, glucose
(4%). Upon admission, average blood sugar levels were 16.40 mmol/l with an
average glycosylated hemoglobin HbA1C of 12.32%. Average LDL levels were
intolerance, elevated blood pressure, and dyslipidemia is increasing worldwide
of 0.912 g/l with a minimum of 0.2 g/l and a maximum of 3.18 g/l.
due to unbalanced nutrient intake among adolescents.
Conclusion
Objectives
Even though obesity is often associated with type 2 Diabetes, some type 1
The main objective of this study is to assess the association between habitual
Diabetics present with a metabolic syndrome that could mislead the diagnosis and
dietary patterns and the MetS risks after adjustments for biological and lifestyle
delay the appropriate management. Obesity in type 1 Diabetes is more correlated
variables in 112 adolescents aged 14-19 in Albania.
with advanced age and metabolic heredity.
Methods
A validated food frequency questionnaire was used to assess dietary patterns, in
DOI: 10.1530/endoabs.49.EP646
which three dietary patterns were identified and labeled as ‘ western -based’,
‘healthy based’ and ‘typical food’ patterns, whereas MetS risks was determined
using multiple indicators such as waist circumference (WC), systolic and diastolic
blood pressure (BP), and fasting glucose, triglycerides and HDL cholesterol
levels. The outcome variables were statistically normalized and expressed as
z-scores. A MetS risk score was computed as the means of these z scores.
Results
Multivariate analyses show that higher intake of western-based diet was
significantly associated with the MetS risk scores
(PZ0.003) and WC
(P!0.0001) and BP compared to those at lower intakes of western-based diet,
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after adjusting for age, gender,ethnicity, pubertal growth status, total physical
Intima media thickness of carotid arteries and cognitive function in
activity and sedentary screen-based levels. Similar pattern was found in typical-
Georgian nondiabetic obese and overweight hypertensive subjects
based diet, whereby adolescents who had higher intake of typical-based diet was
Ketevan Chagunava1 & German Lomtatidze2
significantly associated with higher levels of BP (PZ0.001) and MetS risk score
1New Hospitals, Tbilisi, Georgia;2Chaphidze Heart Centre, Tbilisi,
(PZ0.002) compared to those at lower intake group. In contrast, high intake of
Georgia.
‘healthy’ diet pattern was significantly associated with lower WC (P!0.0001),
BP (PZ0.022) and MetS risk scores (P!0.001) than those at lower health diet
Purpose
pattern.
Obesity is a serious health problem that has reached very high proportions in our
Conclusion
country; prevalence of obesity and overweight together is
56%. Obesity is
These findings suggest that high intake of ‘healthy’ diet that is high in dairy foods,
strongly associated with risk factors for cardio and cerebrovascular disease, AH,
legumes, fruits and vegetables and low-intake of western-based diet and typical
type 2 diabetes and cognitive disorders. The aim of our study was to analyze the
based diet were significantly associated with lower risks of abdominal obesity and
impact of AH and weight change on carotid artery intima-media thickness (IMT)
MetS among adolescents. Hence, effective dietary intervention strategies should
and cognitive function in Georgian nondiabetic obese and overweight
emphasize the promotion of healthy dietary practices among adolescents during
hypertensive individuals.
these critical years of growth in order to prevent the risk of excessive weight gain
Materials and methods
and metabolic-related disorders.
We studied 131 patients with mild to moderate AH (89 males/42 females, mean
DOI: 10.1530/endoabs.49.EP645
age 53.4G3,1 years, BMI 29.8G3.4 kg/m2, duration of AH 5.5G2.3 years).
Examination included: color triplex carotid artery scanning; 24-h BP monitoring,
mini-mental state examination test.
60
overweight patients
(25!BMI!
29.9 kg/m2) were assigned to group 1 and 71 obese patients (BMIO30 kg/m2)
to group 2.
EP646
Results
The groups were comparable by the age, duration of AH, daily mean BP values.
Type 1 diabetes and metabolic syndrome
Mean values of IMT (gr1:1,04G0.04 mm;gr2: 1.09G0.05 mm) were certainly
Ach Taieb, Hasni Yosra, Maaroufi Amel, Kacem Maha, Chaieb Molka &
increased in obese patients compared with overweight ones
(P!0.001).
Ach Koussay
Prevalence of carotid atherosclerosis was higher in gr2 (78% vs 65%). Occurrence
CHU Farhat Hached Sousse, Sousse, Tunisia.
of cognitive disorders was significantly higher in gr 2 (38vs26%)(P!0,05). BMI
positively correlated with IMT (rZ0.25, P!0.02).
Introduction
Conclusion
Contrary to type 2 diabetes, type 1 often occurs in young people, without obesity
Thus, in Georgian obese nondiabetic hypertensive subjects we detected more
or cardiovascular or metabolic diseases. The association of type 1 diabetes with an
pronounced and frequent carotid artery affection and cognitive dysfunction
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
comparing with overweight ones. Data of our study demonstrate importance of
Subjects and methods
more profound examination of cardiovascular system and neurological status in
The study was carried out on 140 subjects; 70 controls and 70 obese subjects (38
obese hypertensive patients to ensure further more aggressive blood pressure and
with metabolic syndrome and
32 without metabolic syndrome). All were
weight reduction.
subjected to full history taking, thorough clinical examination, fasting and post
DOI: 10.1530/endoabs.49.EP647
prandial blood glucose, HbA1c, lipid profile, fractalkine level and hs-CRP.
Results
Serum fractalkine level was significantly raised in obese subjects compared to
lean controls (being higher in those with metabolic syndrome). There was a
significant positive correlation between serum fractalkine level and BMI, WC,
WHR, fasting and post prandial blood glucose, HBA1c, total cholesterol,
triglycerides and LDL and it was inversely correlated with HDL while there was
no significant correlation between serum fractalkine level and hs-CRP.
EP648
Conclusions
CGI-58 gene expression profile in individuals with different body mass
Fractalkine, like otherknown adipocyte-derived chemokines was increased in
index
obese individuals and associated mainlywith metabolic syndrome. This is a step
Daisy Crispim1,2, Jakeline Rheinheimer1,2, Milene Moehlecke1,
in the way to understand and explain the exact pathogenesis of metabolic
Bianca de Souza1,2 & Cristiane Leitao1,2
syndrome as well as obesity linked complications.
1Endocrine Division, Hospital de Clinicas de Porto Alegre, Porto Alegre,
DOI: 10.1530/endoabs.49.EP649
Rio Grande do Sul, Brazil;2Post-graduation Program in Medical Sciences:
Endocrinology, Faculdade de Medicina, Universidade Federal do Rio
Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Background and aim
Although chronic low-grade inflammation is observed in obese subjects, the
underlying mechanisms modulating this process are still unclear. The
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Comparative Gene Identification-58 (CGI-58) is a lipid droplet-associated protein
The case of 36 years old obese male patient with high degree of
that has an important role in mediating intracellular fat hydrolysis by acting as a
proteinuria and a loosing weight as the major strategy of treatment
coactivator of the adipose Triglyceride Lipase (ATGL). Recent evidence suggests
Natia Katamadze, Natalia Chochishvili & Anna Shamanadze
that CGI-58 also has a role in chronic inflammation and insulin resistance (IR).
V.Iverieli Endocrinology, Metabology, Dietology center ‘ENMEDIC’,
Accordingly, macrophage specific Cgi-58 knockout aggravated high fat diet-
Tbilisi, Georgia.
induced inflammation and IR in mice through activation of the NLRP3
inflammasome. However, to date, only few studies have evaluated CGI-58
expression in obese patients, with inconclusive results. Therefore, the aim of this
Introduction
study was to evaluate CGI-58 expression in subcutaneous adipose tissue (SAT)
Obesity-related glomerulopathy(ORG) is a secondary form of focal segmental
from subjects with different BMI. Methods: SAT was obtained from
67
glomerulosclerosis
(FSGS) occurring in obese patients with a body mass
individuals who undergone bariatric surgery or elective abdominal surgery.
index(BMI) higher than 30 kg/m2.ORG is typically manifested by nephrotic-
Twenty-six patients were classified as having morbid-obesity (BMI R40 kg/m2),
range proteinuria without full nephrotic syndrome, and progressive renal
27 as having moderate-obesity (BMI: 30.0 - 39.9 kg/m2), and 14 as non-obese
insufficiency.
subjects (BMI !25 kg/m2). CGI-58 expression was quantified using RT-qPCR
Case presentation
technique. Basal metabolic rate (BMR) was measured by indirect calorimetry and
Thirty-six years old male patient (BMI 59.2 kg/m2) visited endocrinologist with
body composition variables by dual-energy X-ray absorptiometry. All subjects
complains of weight gain, hypertension, swollen lower extremities, dyspnea.
underwent complete physical and laboratory evaluations. Results: CGI-58
Laboratory studies revealed: dyslipidemia, primary hypothyroidism and nodular
expression was decreased in morbid-obese and moderate-obese patients
goiter. Liver function- normal. Fasting glucose, postprandial glucose and A1C
compared with the non-obese group (median 0.59 (minimum 0.18 - maximum
was normal-diabetes mellitus was excluded. In urine with dipstick proteinuria was
1.39) vs 0.83 (0.28 - 2.15) vs. 1.70 (0.73 - 3.63) n-fold change; P !0.001). CGI-
found O3.0 g/l. The patient was sent to nephrologist. The level of Creatinine-
58 expression was also negatively correlated with BMI (rZK0.432, P !0.001),
normal, Urea- normal, 24 hour protein urine test: 18872 mg/24 h (N!150) and
fat mass (rZK0.380, PZ0.003), free fat mass (rZK0.488, P !0.001), and
kidney biopsy was recommended. The patient was given low calorie diet
BMR (rZK0.373, PZ0.002). Regarding lipid profile, CGI-58
expression
(1600 kkal), L-Thyroxine 50 mkg., Simvastatin 20 mg. Because of Heart failure
negatively correlated with triglycerides (rZK0.585, P !0.001) and cholesterol
II
(NYHA), arterial hypertension III (ESC) AR blockers and diuretics were
levels (rZK0.305, PZ0.015) while positively correlated with HDL levels (rZ
advised. Despite of strict diet and high doses of diuretics he gained 6 kg in 7 days.
0.250, PZ0.046). Negative correlations were also found between CGI-58
Laboratory tests-slightly decreased albumin. Because of no effect of diuretics
expression and HbA1c (rZK0.421, P !0.001), insulin levels (rZK0.332,
Albumin transfusion was performed. For 4 days he lost 9 kg. Only moderate
PZ0.009) and IR (rZK0.317, PZ0.013). Conclusions: CGI-58 gene expression
edema of lower extremities rested, with AR blockers T/A was within normal
is decreased in obese patients compared to non-obese subjects and is inversely
range. After month proteinuria decreased till-2641 mg/24 h. He lost nearly 20 kg.
correlated with a worse metabolic profile.
He disappeared for 10 months, started to gain weight and whole clinical picture
DOI: 10.1530/endoabs.49.EP648
restored. Proteinuria was 4250 mg/24 h. Kidney biopsy was performed-secondary
form of FSGS was diagnosed. Treatment strategy remain the same. We concluded
that the main reason for proteinuria in this case was obesity.
Conclusion
ORG is in correlation with BMI. With the weight gain the level of proteinuria
increases.In the early stage of kidney disease process can be reversible. Loosing
weight is one of the most effective strategy of treatment.
EP649
DOI: 10.1530/endoabs.49.EP650
Fractalkinea as an inflammatory marker in obese subjects
Fatma Hamad, Mohsen Khalid, Asmaa Ibrahim & Ayat Ghanem
National Institute of Diabetes and Endocrinology, Cairo, Egypt.
Background
EP651
Fractalkine (CX3CL1) is known to convey its signals through a single G-protein
Mobile and wireless technology to combat obesity. Using on-line
coupled receptor
(CX3CR1). It is characterized as a structurally unique
program of good nutrition and wright diet: prevention and part of the
chemokine with both membrane-bound and soluble forms. Fractalkine expression
treatment of diabetes mellitus
has been detected in activated or stressed endothelial, smooth muscle, skeletal
Vadim Krylov
muscle, macrophages, neurons, hepatocytes and adipocytes. Inflammation up
First Moscow State Medical University, Moscow, Russia.
regulates Fractalkine particularly in adipose tissue of obese individuals.
Aim of Work
This study was designed to assess fractalkine level in obese subjects and its
Introduction
relation with some clinical and laboratory findings. It compares basal plasma
It is too much easier and cheaper to combat obesity, than in the future to treat
fractalkine and hs-CRP in obese patients (with and without metabolic syndrome)
diabetes mellitus and its complications.
and lean healthy controls.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
decreased in GB (PZ0.008). Mean WC increased in GA (PZ0.027). Percentage
We used an online system for patient education based on the video lessons, full of
of subjects with high diastolic BP (DBP) in GB decreased significantly from 36%
humor, pictures, and cartoons to convey the necessary information on good
to 9% (PZ0.031), and percentage of subjects with metabolic syndrome decreased
nutrition, necessary to do exercises and the need for exposure to the sun to our
significantly from 27% to 5% (PZ0.039) by the end of the study.
patients.
Conclusion
Results
Oligonol supplement succeeded in reversing MS in obese Saudi females by
Watching the short movies, the patients formed the habits of good nutrition during
controlling abdominal obesity, and DBP, and decreasing hypertriglyceridemia,
the first month already, which includes a diet with restriction of fat, digestible
thus decreasing cardiometabolic risk without dietary restriction or lifestyle
carbohydrates and daily consumption of low-fat dairy products, slow
modification.
carbohydrates, protein and fiber. Were also presented recommendations for
DOI: 10.1530/endoabs.49.EP652
compliance with the physical activity, as well as vitamin D consumption. A
patient was in touch with a doctor-endocrinologist, if he has any additional
questions. We examined data from a survey of 500 patients registered in the
online system and
100 patients control group who were given the same
recommendations on the appointment. Surprisingly, persistent decrease in body
weight by an average of 6.5 kg over 6 months was demonstrated in all patients of
the main group, the consumption of milk and dairy products increased by 2.6
times, compared with patients in the control group. The exposure to the sun was
observed 15 to 30 minutes daily, compared with the control group 5-10 minutes.
Regular physical activity were the main group of 260 minutes per week, in control
group 80 minutes per week.
EP653
Discussions
Metabolic and bone effects of high fat diet on adult zebrafish
Mobile and wireless technology helps physicians to combat obesity and be a part
Marta Carnovali1, Livio Luzi2,3, Giuseppe Banfi4,5 & Massimo Mariotti3,5
of the treatment of Diabetes Mellitus and we need to improve the quality of
1Gruppo Ospedaliero San Donato Foundation, Milan, Italy;2IRCCS
information material, including using online technologies to improve the quality
Policlinico San Donato, San Donato Milanese, Milan, Italy;3University of
and duration of life of our patients.
Milan, Milan, Italy;4Vita-Salute San Raffaele University, Milan, Italy;
DOI: 10.1530/endoabs.49.EP651
5IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
Obesity and type II diabetes have been linked to several health issues, including
an increased risk of bone fractures. It is well known that an increase of visceral fat
affects bone health causing fragility, mechanical strength reduction and increased
propensity of fractures because of impaired bone matrix microstructure and
aberrant bone cells function. Adult Danio rerio (zebrafish) represents a powerful
model to study fat and bone metabolism. Then, the aim of this study was to
evaluate bone and metabolic effects of high fat diet in adult zebrafish. Fish blood
glucose levels have been monitored in time course experiments and glycaemia
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curve was found altered in fat fish compared to non-fat ones (Figure 1). The adult
bone remodeling has been evaluated in fish using the scales as read-out system.
Oligonol supplementation decreases abdominal obesity and the
The scales of high-fat diet fish shown bone resorption lacunae associated with an
prevalence of metabolic syndrome in a sample of overweight and obese
intense osteoclast activity. In addition, high-fat fish scales shown a significant
Saudi females without dietary restriction or lifestyle modification
decrease of alkaline phosphatase (ALP) activity and increase of tartrate-resistant
Suhad Bahijri1,2, Ghada Ajabnoor1,2, Zuheir Awan1,2, Anwar Borai2,3 &
acid phosphatase (TRAP) activity. These data suggests that an imbalance in fat
Altaf Abdulkhaliq2,4
metabolism leads to an alteration of glucose metabolism and an osteoporotic-like
1Department Clinical Biochemistry, Faculty of Medicine, King Abdulaziz
phenotype in adult zebrafish. The zebrafish model of obesity can contribute to
University (KAU), Jeddah, Saudi Arabia;2Saudi Diabetes Research Group -
elucidate in vivo the molecular mechanisms of metabolic changes derived from a
KAU, Jeddah, Saudi Arabia;3Pathology Department, King Abdullah
high fat diet, which influence the bone tissues regulation and insulin signaling in
International Medical Research Center, King Saud bin Abdulaziz University
for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia;
human obese patients.
4Department Clinical Biochemistry, Faculty of Medicine, Umm Al-qura
University, Makkah, Saudi Arabia.
Background
Obesity, and metabolic syndrome (MS) are highly prevalent in Saudi Arabia,
increasing the risk for type 2 diabetes (T2DM), and cardiovascular disease (CVD).
Oligonol produced from lychee fruit polyphenols (LFP) has been reported to
reduce visceral obesity, and ameliorate MS in Japanese subject.
Aim
To investigate the effect of oligonol supplementation on MS risk factors in
overweight and obese Saudi females.
Subjects and methods
Sixty obese and overweight healthy Saudi females were recruited. Blood pressure
(BP), height, weight, waist circumference (WC) were measured, and glucose,
triglycerides, and HDL cholesterol were assayed in fasting serum samples.
Dietary intake, and lifestyle habits were recorded by questionnaire. Subjects were
divided into two groups with equal mean body mass index (BMI), in a double-
blind /Case-Control study design. Group A (GA) was given placebo, and group B
(GB) was given oligonol, and were followed for three months, with all
measurements being repeated at the end.
Figure 1
Results
Some subjects were excluded for various reasons, leaving 25 in GA, and 22 in
GB. Therefore, the two groups differed significantly in recalculated mean BMI at
zero time (29.30G3.97 for GA, and 31.63G4.16 for GB, PZ0.046). No side
effects or significant differences in diet or lifestyle were found at the end of the
DOI: 10.1530/endoabs.49.EP653
study. Mean triglycerides was significantly increased in GA (PZ0.011), and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP654
PF and increased in L. Among the studied cytokines, fractalkine and TNF-a were
decreased in the L group, with no changes in PF rats.
Growth hormone signaling and action in obese versus lean human
Conclusion
subjects: evidence of increased hepatic GH sensitivity in obesity
Central leptin infusion could preserve UCP-1 expression in brown adipose tissue
Morten Høgild Pedersen1, Ann Mosegaard Bak1, Steen Bønløkke Pedersen1,
through activation of insulin-related signaling.
Niels Jessen2, Niels Møller1 & Jens O.L. Jørgensen1
1Department of Endocrinology and Internal Medicine, Aarhus University
DOI: 10.1530/endoabs.49.EP655
Hospital, Aarhus, Denmark;2Department of Clinical Pharmacology, Aarhus
University Hospital, Aarhus, Denmark.
Context
Obesity is accompanied by blunted GH secretion but relatively normal serum
IGF-I levels, which suggests increased GH sensitivity. This, however, remains to
EP656
be tested at the level of GH signaling in human subjects.
Objective
Can night eating syndrome increase basal metabolic rate?
Senay Topsakal, Guzin Fidan Yaylalı & Semin Melahat Fenkçi
To compare the effects of an acute intravenous GH bolus in obese vs normal
Endocrinology Department, Pamukkale University Medical Faculty Denizli,
weight subjects on GH signaling pathways in adipose and muscle tissue, substrate
Turkey.
metabolism and insulin sensitivity.
Subjects and methods
Nine obese (BMI 35.7G0.9) and nine lean (BMI 21.5G0.4) young men were
Introduction
studied twice in a randomized crossover design: (1) After an overnight fast (12 h)
Night eating syndrome (NES) is an eating disorder associated with obesity,
(‘Control’) and
(2) After an overnight fast with an intravenous GH bolus
characterized by a delayed pattern of food intake in which recurrent episodes of
(0.005 mg/kg) (‘GH bolus’). Each study day consisted of a 4-h basal period (tZ0
nocturnal eating and/or excessive food consump-tion occur after the evening
- tZ240 min) followed by a 2-h hyperinsulinemic, euglycemic clamp (HEC). GH
meal.
(1) Studies showed significant weight gain among patients with
was injected at tZ0 and biopsies from muscle and fat were drawn. Muscle and fat
NES.However, the underlying reason is still controversial.The aim of this study
biopsies were taken at tZ60 min.
is to investigate the body composition and energy metabolism in patients with
Results
NES.
Spontaneous serum GH levels were lower in obese subjects, whereas the PK of
Methods
the GH bolus was comparable. The GH bolus was associated with a BMI-
Obese patients were divided into two groups according to the diagnostic criteria.
independent increase in STAT5b phosphorylation and CISH mRNA transcription
Diagnostic crite-ria for NES include: (1) recurrent episodes of night eating, as
in muscle and adipose tissue. The GH bolus, however, produced a larger relative
manifested by eating after awakening from sleep or by excessive food
increase in serum IGF-I levels in obese subjects
(P ! 0.01). GH acutely
consumption following the evening meal, (2) awareness of those eating episodes,
stimulated lipolysis (DFFA in serum, serum palmitate levels and fluxes) to the
and (3) significant distress or impairment caused by the disorder. Patients meeting
same extent in both groups. GH significantly reduced glucose uptake during the
these three criteria were considered NES(C) (2). 281 women and 46 men, (101
HEC in both groups (PZ0.23), but GH only antagonized insulin-induced
NES(C), 226 NES(K)) were included to study. Body mass index (BMI) and
suppression of endogenous glucose production (EGP) in the obese (PZ0.01).
waist to hip ratio (WHR) were measured. Biochemical tests were performed.
Conclusions
Total fat mass (FM), fat-free mass (FFM), Body Water (BW), basal metabolic rate
(1) Acute GH exposure induces pSTAT5b and CISH mRNA and transcription in
(BMR)were measured by Bioelectrical Impedance Analysis (BIA).
fat and muscle, and lipolysis to the same extent in obese and lean subjects, (2) A
Results
GH-induced relative increase in serum IGF-I levels and suppression of EGP was
BMI and WHR were similar in both groups. There were no significant differences
only recorded in the obese, (3) Our data thus suggest increased hepatic sensitivity
in total cholesterol, triglyceride, LDL, HDL, ALT, GGT, fasting glucose, insulin
to GH in obesity, which in turn may contribute to the blunted endogenous GH
levels, postprandial glucose and insulin levels. There were significant increase in
secretion.
BMR in patients with NES, and not significant differences in FM, FFM, BW.
DOI: 10.1530/endoabs.49.EP654
Conclusion
BMR is the least amount of energy necessary for life. It accounts for 60-70% of
the total energy expenditure in sedentary man and hence forms the basis for
human energy requirements. In this study, BMR was found high in patients with
NES. Fat distrubution was similar in both groups. There is no study that examines
the effects of this syndrome on energy metabolism. There was a need for further
EP655
work in this regard.
Insulin signaling is involved in the regulation of UCP-1 expression in
DOI: 10.1530/endoabs.49.EP656
brown adipose tissue after chronic central leptin infusion
Vicente Barrios1, Laura M. Frago1, Sandra Canelles1,
Emma Burgos-Ramos2, Julie A. Chowen1 & Jesús Argente1
1Department of Endocrinology, Hospital Infantil Universitario Nin˜o Jesús,
Instituto de Investigación La Princesa and CIBERobn, Instituto de Salud
Carlos III, Madrid, Spain;2Facultad de Ciencias Ambientales y Bioquímica,
Universidad Castilla-la Mancha, Toledo, Spain.
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Association between cardiometabolic risk indicators and FGF 19 in
Background
healthy Saudi individuals of different BMI grades
Brown adipose tissue (BAT) plays a pivotal role in the regulation of energy
Ghada Ajabnoor1,2, Yomna Hajjar2,3, Suhad Bahijri1,2 & Anwar Borai2,4
homeostasis and thermogenesis. This tissue responds to insulin, favoring the
1Department of Clinical Biochemistry, Faculty of Medicine, King
expression of uncoupling protein-1 (UCP-1), that in turn is inhibited by insulin-
Abdulaziz University, Jeddah, Saudi Arabia;2Saudi Diabetes Study
desensitizing cytokines. Leptin may abolish some of the effects of fasting on these
Research Group, King Fahd Medical Research Center, King Abdulaziz
parameters through its cross-talk with insulin-related signaling targets.
University, Jeddah, Saudi Arabia;3Postgraduate Student, Department of
Objectives
Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University,
We hypothesized that leptin infusion prevents UCP-1 depletion induced by food
Jeddah, Saudi Arabia;4King Abdullah International Medical Research
restriction through activation of insulin signaling in brown adipose tissue.
Center (KAIMRC), College of Medicine, King Saud Bin Abdulaziz
Methods
University for Health Sciences (KSAU-HS), Jeddah, Saudi Arabia.
We studied 18 male Wistar rats divided into three groups: rats receiving saline icv
(controls, C), those treated icv for 14 days with a daily dose of 12 mg of leptin (L)
and a pair-fed group (PF) that received the same food amount consumed by L. We
Background
analyzed relative mRNA levels of UCP-1 and glucose transporter 4 (GLUT4) by
Fibroblast growth factor 19 (FGF19) is an enterokine derived from the ileum, and
real time-PCR and changes in the cytokine levels and activation of insulin-related
synthesized in response to release of bile acids following food ingestion. It was
signaling targets by multiplexed bead immunoassay.
proposed to be an important regulator of the postprandial adaptive metabolic
Results
response. by stimulating glycogen and protein synthesis in the liver, and down
Relative UCP-1 mRNA levels were reduced in PF and unchanged in the L group.
regulating glucose production after a meal. There is limited research investigating
The mRNA levels of GLUT4 were increased in L rats, as well phosphorylation of
the association between FG-19 and metabolic dysregulation in overweight and
insulin receptor substrate 1. Akt phosphorylation on threonine 308 was reduced in
obese Saudi subjects.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Aim
Introduction
To study association of circulating FGF 19 in healthy individuals of different BMI
Obesity and diabetes mellitus type 2 (T2DM) are considered as one of the major
grades, with some cardiometabolic risk indicators.
risk factor for coronary heart disease (CHD) development, but the mechanisms
Subjects and methods
beyond this relationship still need to be clarified. miRNAs are supposed to be
Healthy adults aged
19-36 years were recruited. Height, and weight were
involved in regulatory mechanisms in this relationship.
measured to calculate body mass index (BMI). Sixty males and 60 females were
Aim
included in the study, divided equally between BMI categories (underweight,
To determine miRNAs expression in patients with obesity and T2DM.
normal, overweight and obese). Waist, hip, and neck circumference (WC, HC,
Methods
NC) were measured. Glucose, total cholesterol, triglycerides, high-density
MiRNAs were detected in peripheral blood of 43 patients, aged 48-65 years with
lipoprotein cholesterol (HDL-C), insulin, FGF19 and highly sensitive CRP (hs-
obesity and T2DM. Patients were divided in two groups: 1st group - 21 patients
CRP) were estimated in fasting serum samples, and low-density lipoprotein
with CHD, 2nd group - 22 patients with excluded CHD after Tredmil-Test. All
cholesterol (LDL-C), Atherogenic index of plasma (AIP), and homeostatic model
patients from the 1st group underwent coronary angiography (CAG).
assessment-insulin resistance (HOMA-IR) were calculated.
Results
Results
Nine CHD-related mRNAs were selected as candidates for the investigation:
No significant correlation (PZ0.457), or difference in means of FGF19 was noted
miRNA-1, miRNA-21, miRNA-26a, miRNA-27a, miRNA-33a, miRNA-33b,
between different BMI categories (PZ0.905). A negative significant correlation
miRNA-133a, miRNA-133b and miRNA-208. Expressions of these miRNAs
was found between FGF19 and WC, NC, and LDL-C: HDL-C ratio (rZK0.203,
were compared in studied groups. Expression of miRNA-21 (3.44 vs. 0.37;
PZ0.027, rZK0.297, PZ0.002, rZK0.187, PZ0.041 respectively).
PZ0.007) and miRNA-27a (0.86 vs.0.31; PZ0.013) in patients with CHD were
Conclusions
higher than that in 2nd group, while expression of miRNA-26a (1.06 vs. 2.14;
Serum FGF19 levels do not appear to be related to general obesity expressed as
PZ0.022) was lower in patients with CHD. Spearman correlation analyses
BMI. However, it was found to be associated negatively with indicators of
showed that miRNA26a was positively associated with cholesterol level (rZ
abdominal, and upper torso obesity, reported to be associated with increased
0.316, PZ0.042). MiRNA-21 and miRNA-27a were negatively correlated with
cardiometabolic risk, indicating the relationship of FGF19 with this risk. The
HbA1c in both groups
(rZK0.363, PZ0.042 and rZK0.420, PZ0.036,
strong correlation between FGF19 and serum LDL-C:HDL-C;a well established
respectively). MiRNA-208 was positively correlated with hypertrophy of the
indicator of cardiometabolic risk; validate the link further.
interventricular septum (rZ0.61, PZ0.027) and number of significantly affected
DOI: 10.1530/endoabs.49.EP657
coronary vessels according to CAG (rZ0.65, PZ0.034), negatively - with left
ventricular diastolic dimension (rZK0.52, PZ0.029).
Conclusion
1) Expression of miRNA-21 was increased by 9 times, miRNA-27a in 2.5 times in
patients with CHD, while miRNA26a compared with patients with type 2 diabetes
and obesity was lower in 2 times.
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2) We revealed correlations of miRNA-208,
27a,
21
with pathological
The role of pioglitazone and vitamin E for the treatment of NASH with
angiogenesis, and heart remodeling processes in patients with obesity and T2DM.
or without metabolic syndrome
3) Increased expression of miRNA-208
can determine the severity of
Nino Khabeishvili, Gocha Barbakadze, Ketevan Mikadze & Koba Burnadze
cardiovascular disease in patients with obesity and T2DM.
Clinic “Enmedic”, Tbilisi, Georgia.
DOI: 10.1530/endoabs.49.EP659
Introduction
Obesity is a global public health problem and is associated with metabolic
syndrome and dyslipidemia as well as very often with non-alcoholic
steatohepatitis (NASH).
Aim & methods
The aim of the present study was to evaluate the preventive and curable role of
EP660
vitamin E and pioglitazone (thiazolidinedione-type) in NASH patients with or
The surgical approach to obesity in numbers
without metabolic syndrome. 51 patients with NASH were divided into two
Nuno Cordeiro Raposo, Andreia Sousa Ferreira, Sónia Pratas &
groups: 26 patients with insulin-resistance (IR) plus obesity and 24 patients
Cristina Valadas
without IR. 12 patients from 1-st group (another 14 patients from this group
Hospital Beatriz Ângelo, Loures, Portugal.
served as a control subgroup) and 12 patients from 2-nd group were treated at
least during 3 months with vitamin E (500-1000 mg daily) plus pioglitazone 15-
30 mg/d (another 13 patients - control subgroup) as well as put on the low-fat
The prevalence of obesity has greatly increased worldwide in the last decades,
diet. Gender distribution of the patients was equal in each subgroup (26 male,
particularly in Europe and Portugal. It is associated with many health problems,
25-female). Mean age was 46.6G6.4 years. Mean BMI (body mass index) -
including cardiovascular diseases, cancer and diabetes.
34.6G4.1 kg/m2. HOMA-IR of patients from 1-st group was 2.7G0.8.
Methods
Results
Revision of the clinical records of all 61 patients who underwent bariatric surgery
The concentration of the serum aspartate aminotransferase
(AST), alanine
between 2013 and 2015. Analysis of their metabolic profile prior to surgery and
aminotransferase (ALT) levels (P!0.01) as well as cholesterol and triglycerides
its evolution after the operation.
(P!0.05) were found to be higher in the both subgroups without pointed
Results
treatment. HDL level, however, was comparable in both groups (PO0.05).
61 patients were reviewed, namely 90.2% females and 9.8% males. The mean age
Results also indicated that this therapy reduced BMI (P!0.05) and HOMA-index
was 43.6 years. All patients had class II or III obesity according to their BMI, with
(P!0.05) in both subgroups.
an average score of
46.4 kg/m2. The associated cardiovascular risk factors
Conclusions
include: hypertension (47.5%), total cholesterol O200 mg/dl (35.8%) and type 2
Insulin resistance appears to be the underlying pathophysiological defect leading
diabetes mellitus (10.6%). 60% had an apnea-hypopnea index great than 5/h.
to NASH. The data from this study demonstrate the possible mechanism by which
Most patients underwent gastric sleeve surgery (93.4%) and only 6.6% received a
pioglitazone and vitamin E mediate their beneficial clinical and metabolic effects
bypass surgery. Six patients were treated with an endoscopic intragastric balloon
in patients with NASH. To prevent this condition is to maintain a healthy diet and
prior to surgery. Weight was evaluated at 3 months’ intervals in the first 1.5 years,
rigorous exercise regimen.
and then every 6 months. 13.6 months was the mean follow-up time after the
DOI: 10.1530/endoabs.49.EP658
procedure. The average weight loss prior to surgery was 9.6% of the initial body
weight. After the operation, weight loss was more pronounced between the first
and third months (7.4% of the initial body weight). The trend of weight loss
remained until 9 months, stabilizing afterwards. The mean BMI reduction was
27.1% at the end of the follow-up time. Both HbA1c and triglycerides were
reduced by 11% and 15%, respectively, after surgery. HDL increased by 16%.
EP659
Conclusions
MicroRNAs, associated with coronary heart disease in patients with
The majority of patients eligible for bariatric surgery were young females with
obesity and diabetes mellitus type 2
class II or III obesity. Many had other cardiovascular risk factors, particularly
Teona Shvangiradze1, Irina Bondarenko1, Ekaterina Troshina1 &
hypertension and dyslipidemia. Gastric sleeve was the preferred technical
Marina Shestakova1,2
procedure and only a few patients received an endoscopic intragastric balloon to
1Endocrinology Research Centre, Moscow, Russia;2I.M. Sechenov’s First
aid weight loss prior to surgery. Weight loss was more pronounced in the first
Moscow State Medical University, Moscow, Russia.
3 months after surgery, but that tendency was mitigated after only 9 months.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Nevertheless, body mass index was reduced by a quarter at the end of follow-up.
Introduction
These results show the importance of the multidisciplinary approach to obesity
Peroxisome proliferator activated receptor-g
(PPAR-g) is a distinguished
and the potential benefits with bariatric surgery. However, we emphasize the short
transcription factor abundantly expressed in the adipose tissues and plays a key
follow-up time and the need to maintain evaluation of these patients in the future.
role in the regulation of adipocyte differentiation and development of obesity. In
DOI: 10.1530/endoabs.49.EP660
the current study, we aimed to investigate the association of PPAR-g mRNA
expression in omental and subcutaneous adipose tissues with anthropometric
indices and blood pressure (BP) among healthy adults.
Methods
97 subjects (41 non-obese, 18 obese, and 38 morbid obese) were eligible for the
study. Omental and subcutaneous adipose tissues were obtained during open
abdominal surgery. The PPAR-g mRNA level was evaluated in omental and
subcutaneous adipose tissues using Real-Time PCR assay. Height, weight, BMI,
waist, hip, and neck circumferences, and BP were determined according to
standard protocols.
EP661
Results
Decreased HDL cholesterol efflux capacity in morbidly obese
The mean of BMI was 24.8, 34.9, and 46.8 kg/m2 in morbid obese, obese and non-
individuals as a surrogate marker for increased cardiovascular risk
obese subjects, respectively. PPAR-g gene expression was not significantly
Idit Dotan1,2, Anouar Hafiane2, Isabelle Ruel2, Rajesh Aggarwal1,
different between omental and subcutaneous adipose tissues in each group.
Amin Andalib1, Jacques Genest1,2 & Mark Sherman1,2
However, PPAR-g mRNA expression was down-regulated in omental adipose
1McGill University Health Center, Montreal, Québec, Canada;2Research
tissues of non-obese subjects compared to obese subjects and up-regulated
Institute of the McGill University Health Center, Montreal, Québec,
compared to morbid obese ones (P!0.05). Among morbid obese subjects,
Canada.
diastolic and systolic blood pressures were positively correlated with omental
PPAR-g expression (rZ0.409, PZ0.020 and rZ0.371, PZ0.037, respectively);
waist and neck circumferences were positively correlated with both adipose
Background
tissues (P!0.05). Among obese subjects, PPAR-g expression in both tissues had
Obesity has become a worldwide epidemic and carries excess cardiovascular
significant positive correlation with waist circumference (P!0.05).
morbidity and mortality. HDL efflux capacity (HEC) was shown to be inversely
Conclusion
correlated with cardiovascular risk (CVR), both in the acute and the chronic
Our study suggested that several obesity-related indices have a positive
phases. Our aim was to understand if decreased HEC can serve as a surrogate
correlation with PPAR-g expression in omental and subcutaneous adipose tissues.
marker for the increased CVR in this population.
DOI: 10.1530/endoabs.49.EP662
Methods
Forty patients: 10 obese diabetic (OD), 10 obese non-diabetic (OND), 10 with
stable Coronary Artery Disease (sCAD) and 10 healthy controls were blindly
selected from another cohort and their HECs were studied using radioactive cell-
based assays.
Results
The mean age of the cohort was 50G12 years, with 72.5% men. Mean BMI for
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the obese groups was 46.8G7.03 kg/m2, for the sCAD group 27.7G3.3 kg/m2
Results of computer-assisted intravital microscopy in overweight
and for the controls 24.2G2.26 kg/m2. Mean HEC (adjusted to ApoA1 mass) was
and obesity
14.18G0.95% for the OD group, 14.73G3.18% for the OND group, 19.11G
Volha Shyshko1, Tatjana Mokhort1, Elena Konstantinova2 &
1.6% for the sCAD group and 16.01G1.6% for the controls. A linear regression
Natalia Tsapaeva1
model adjusted for age, sex, BMI and TG has found that both OD and OND have
1Belarussian State Medical University, Minsk, Belarus;2Institute of Heat
significantly lower HEC in comparison to controls (P!0.05 for both), whereas
and Mass Transver, National Academy of Science, Minsk, Belarus.
the sCAD did not.
Discussion
In the current study, we found that morbidly obese individuals have significantly
Rationale
lower HEC in comparison to controls. Given that HEC has an inverse correlation
Obesity, prediabetes and diabetes are strongly associated with microcirculation
with CVR, these finding may explain, at least in part, the increased CVR in
(MC) abnormalities. It is known that pathological changes in microvessels
morbidly obese patients. It is unclear if bariatric surgery improves HEC, but it is
predispose to CHD, CKD and retinopathy. Also it is widely recognized that
reasonable to speculate it does, given the other metabolic effects the surgery
biochemical and immunological changes accompanied with obesity and
exerts.
overweight lead to MC damage.
Conclusion
Objective
HDL function is compromised in morbidly obese individuals and contributes to
Of the study was to assess changes in MC in patients with overweight and obesity.
progressive atherosclerosis and increased CVR in this population. If HEC does
Materials and methods
improve post-metabolic surgery, decreased HEC might serve as another
Computer-assisted intravital microscopy (CAIM) was used to assess intra- (six
indication for bariatric surgery.
scores), extra-
(three scores) and vascular
(11
scores) changes of bulbar
DOI: 10.1530/endoabs.49.EP661
conjunctiva and vascular indexes were calculated. We included 91 patients
with overweight
(group
1),
103 patients with obesity
(group
2) both with
concomitant prediabetes and diabetes and 58 almost healthy person (group 3).
Results
Overweight and obesity are characterized by progressive changes in MC. A
significant difference was observed in perivascular edema in patients with
overweight (0.5 (0.0;1.0) as well as in patients with obesity (1.5 (0.5;1.0) (P1-3Z
0.025, P2-3Z0.012) compared to group
3. There were no any significant
intravascular changes between groups. Vascular changes included inequality in
Z
vessels size (1.0 (1.0;1.0) in groups 1 and 2 vs 1.0 (0.0;1.0) in group 3) P1-3
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0.012, P2-3Z0.010), meandrous tortuosity of venules (1.0 (0.0;1.0) in groups 1
The association of anthropometric measurements and PPAR-g gene
and 2 vs 0.0 (0.0;1.0) in group 3) P1-3Z0.002, P2-3Z0.001) and meandrous
expression among healthy adult subjects
tortuosity of capillaries (0.0 (0.0;1.0) in groups 1 and 2 vs 0.0 (0.0;0.0) in group 3)
Maryam Zarkesh1, Emad Yuzbashian2, Azita Zadeh-Vakili1,
P1-3Z0.001, P2-3Z0.004). Calculating of partial vascular indexes and total
Kimia Tabaei3, Afsoon Daneshafrooz1, Golaleh Asghari2,
vascular index optimizes results of CAIM. Vascular index was significant higher
Parvin Mirmiran2, Mehdi Hedayati1 & Alireza Khalaj4
in patients with overweight (10.0 (8.0;11.0) compared to patients with obesity
1Cellular and Molecular Endocrine Research Center, Research Institute for
(10.0
(9.0;11.0) (P1-3Z0.001, P2-3Z0.001).
Endocrine Sciences, Shahid Beheshti University of Medical Sciences,
Conclusion
Tehran, Iran;2Nutrition and Endocrine Research Center, Research Institute
Overweight and obesity are associated with MC abnormalities and mostly
for Endocrine Sciences, Shahid Beheshti University of Medical Sciences,
expressed in extra and vascular changes. Use of partial and total vascular indexes
Tehran, Iran;3School of Advanced Sciences in Medicine, Tehran Medical
optimizes evaluation of MC changes.
Sciences Branch, Islamic Azad University, Tehran, Iran;4Tehran Obesity
DOI: 10.1530/endoabs.49.EP663
Treatment Center, Department of Surgery, Shahed University, Tehran, Iran.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP664
Table 1 BMI, handgrip and biochemical measurements before and after
Assessment of adipose tissue distribution in youg women with polycystic
surgery in obese patients
ovary syndrome
A Savchanka & Tatjana Mokhort
Before
3rd mo. After
6th mo.fter
Belarussian State Medical University, Minsk, Belarus.
surgery
surgery
surgery
P
BMI (kg/m2)
48.3G8.9
40.4G7.9
38.1G11
0.0001
PCOS is characterized by abdominal obesity along with conventional diagnostic
Handgrip (kg)
28.1G9.2
21.6G7.5
21.3G6.4
0.001
features.
25OHD (ng/dl)
14.4G20
25.6G15.7
31.9G49
0.0001
Objective
Vitamin B12
284G154
339G219
326G208
0.004
To assess body composition in women with PCOS and normal body weight.
(ng/dl)
Materials and methods
Albumine (mg/dl)
4.42G0.2
4.30G0.3
4.07G0.9
0.0001
35 women (24G1.1 years old) with confirmed diagnosis of PCOS according to
Rotterdam criteria, 27 almost healthy women (25G1.2 years old), both groups
wotn normal weight. Whole Body Dual-energy X-ray Absorptiometry (DEXA
Total Body) scans were carried out using ‘Prodigy Lunar’ machine (USA).
shown in Table 1. Serum ferritin and, creatinine levels were in reference range
Results
and not change during the follow-up. In a multivariate regression model showed
Registered differences included increase of total fat accumulation, fat
that
25OH D and creatinine levels were independent risk factor for muscle
accumulation in android compartments as well as android-gynoid fat ratio
strength
(r2:16.2, P!0.0001). Serum albumin and handgrip measurements
index. Basic antropometric measurements and DEXA of patients with POCS and
showed a positive correlation (r:0.23, P!0.001).
control group. 29 (82.86%) patients in study group demonstrated significantly
Conclusion
higher waist circumference (77.1G11.2 cm) and higher percentage of adipose
Although appropriate vitamin and protein supplementation bariatric surgery
tissue in android area (37.9G3.0%) correspondingly compared to control group
patients are at risk of decreased muscle strength related complications.
(R - 0.846176 at P !0.05).
Conclusion
DOI: 10.1530/endoabs.49.EP665
Abdominal fat accumulation is attributable to patients with PCOS. Lack of
significant differences between BMI and total fat accumulation is apparently
explained by age, dietary habits, patient’s disease awareness as well as reasonable
life style modification and physical exercises modification.
Table 1
Study group,
Control group,
Measurements
nZ35
nZ27
Total fat content, g
34.257G5.763
17.737G2.393
EP666
Total fat content by
37.3G6.7. P!0.05
29.2G4.9
Comparison between mathematical indexes and histopathological
DEXA, %
findings in the diagnosis of nonalcoholic fatty liver disease in mexican
Trunk fat accumulation, g
11.315G3.400
6.326G1.592
population
Trunk fat accumulation, %
31.2G4.7
29.3G2.7
Karen-Ivette Gutierrez-Aguirre1, Maria-Luisa Lazo-de-la-Vega-Monroy1,
Fat accumulation in android
37.9G3.0, P!0.05
30.9G3.1
Yeniley Ruiz-Noa1, Lorena-del-Rocio Ibarra-Reynoso1,
compartments, %
Juana-Rosalba Garcia-Ramirez2, Benjamin Jordan-Perez2,
Fat accumulation in gynoid
40.5G4.3
39.3G2.8
Serafin Garnelo-Caban˜ as2 & Monica-del-Carmen Preciado-Puga1
1
compartments, %
University of Guanajuato, Leon, Guanajuato, Mexico;2Hospital General
Android-gynoid fat ratio index
0.91G0.1, P!0.05
0.76G0.1
Leon, Leon, Guanajuato, Mexico.
(A/G)
Introduction
Non-alcoholic fatty liver disease (NAFLD) is an emerging disease in Mexico,
DOI: 10.1530/endoabs.49.EP664
comprising a spectrum of histopathological findings ranging from simple steatosis
to steatohepatitis and cirrhosis. The gold standard continues to be the liver biopsy,
but several mathematical indices have been proposed, such as non-invasive
techniques, however there are very few studies in our population.
Objetive
This study aims to compare mathematical indexes and histopathological findings
for the detection of NAFLD in Mexican population.
Methods
A cross-sectional study was performed at the ‘Hospital General León’ between
EP665
November 2016 and January 2017. Patients aged
18 years or above that
Decreased muscle strength is associated with vitamin D and albumin
underwent laparoscopic cholecystectomy were recruited. No history of alcohol
levels after bariatric surgery
consumption habit or hepatic diseases characterized the patients. The fatty liver
Dilek Gogas Yavuz & Meliha Melin Uygur
index
(FLI) and the lipid accumulation product
(LAP) were calculated.
Marmara University School of Medicine Section of Endocrinology and
Demographics, blood samples, and a liver biopsy were obtained. Results between
Metabolism, Istanbul, Turkey.
FLI, LAP and livery biopsy were compared.
Results
Bariatric surgery patients are at risk of decreasing in muscle mass, vitamin and
A total of 59 patients were included (80.1% women and 19.1% men). The mean
protein deficiency. The aim of this study is to asses muscle strength, serum protein
age was 39.6G14.8 years, BMI 29.7G10.11 kg/m2. The FLI identified 31
and vitamin levels after bariatric surgery.
patients with NAFLD of which 11 were corroborated with biopsy, whereas the
Methods
LAP identified 26 patients of which 17 were corroborated with biopsy. From the
264 patients underwent bariatric surgery who completed 6 th month policlinic
patients with negative FLI index (nZ26), a total of 11 (42%) were diagnosed with
visits were included in the study. Patients were followed appropriately
steatosis by histopathology. For LAP, 31 patients (54.3%) were negative, four of
supplemented protein and vitamins as suggested; all study parameters were
which (7.01%) presented positive for NAFLD by histopathological diagnosis.
assessed before and after 3rd. mo. and 6th mo. of bariatric surgery. Handgrip
Conclusion
dynamometry was used to measure static muscle strength. Serum Albumin, 25OH
According to our results, at least in our population these two mathematical indices
vitamin D (25OHD), Vitamin B12, ferritin and creatinine levels were measured
are not useful for the diagnosis of NAFLD, so liver biopsy remains to be the gold
by immune- chemiluminecanse method.
standard for the detection of NAFLD. Future studies should be performed in order
Results
to continue looking for other non-invasive markers for NAFLD.
Postoperatively, all patients showed a significant decrease in the BMI in 3 mo and
DOI: 10.1530/endoabs.49.EP666
6 mo compared to preoperative levels (P:0.0001). Biochemical measurements are
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP667
EP669
Obesity and infertility among Tunisian women of reproductive age:
Menopause is a major determinant of endocannabinoid
about 40 cases
2-arachidonoylglycerol plasma level and of its relevance as biomarker
Faten Hadjkacem1, Mariem Rebai2, Dalila Saidane2, Dorra Ghorbel1 &
of dyslipidemia and insulin resistance in lean women
Mohamed Abid1
Flaminia Fanelli, Marco Mezzullo, Margherita Baccini, Elena Casadio,
1Department of Endocrinology and Diabetology of Hedi Chaker Hospital,
Daniela Ibarra Gasparini, Valentina Vicennati, Renato Pasquali &
Sfax, Tunisia;2Faculté de Pharmacie, Monastir, Tunisia.
Uberto Pagotto
Endocrinology Unit and Center for Applied Biomedical Research
Department of Clinical and Surgical Science, University of Bologna,
Obesity is on the increase worldwide and mainly in women of reproductive age.
S.Orsola-Malpighi Hospital, Bologna, Italy.
In turn, it is associated with various reproductive complications. To assess the
detrimental effect of obesity on reproductive health and the means of its
management, this retrospective cohort study of 40 obese and infertile women has
Context
been conducted in the department of endocrinology and diabetology of Hedi
The endocannabinoid system
(ECS) hypertonicity contributes to obesity
Chaker hospital in Sfax-Tunisia from 2009 to 2014. These patients have a mean
development and maintenance. Excess circulating levels of ECS mediator
age of 34 years and a mean BMI of 37.29 kg/m2. They were to suffer from
2-arachidonoylglycerol
(2AG) were reported in obese humans, however,
infertility for a mean period of 5,7 years. The polycystic ovary syndrome was the
unstandardized experimental settings (i.e. analytical conditions, sample size,
most common cause of infertility diagnosed in 52.5%. Classic morbidities of
concurrent diseases/medications, statistics, gender, body mass index (BMI) and
obesity were dominated by metabolic
(52.5%) and cardiovascular
(37.5%)
age), clouded its role in dysmetabolism and its usefulness as biomarker. The study
complications. Ovulation disorders were identified in 77.5% of cases and serious
aimed at describing
2AG associations with visceral obesity, dyslipidaemia,
complications during pregnancy were observed. These complications affect the
insulin resistance and hypertension in females according to BMI and menopausal
obese mother as well as the child: abortions (52.5%), delivery by caesarean
status.
section (35%), gestational diabetes (20%), foetal malformation (12.5%), neonatal
Methods
death (7.5). Though the management of the combination of obesity and infertility
Adult, unmedicated, disease-free premenopausal (preMP, nZ103) and meno-
was quite difficult, a weight loss of 5-8% has resolved 61.2% of menstrual
pausal (MP, nZ81) females were stratified in normal weight (NW, BMI:18.5-
irregularities and improves the chances of pregnancy in 20% of cases. Insulin
24.9kg/m2), overweight
(OW; BMI: 25.0-29.9kg/m2) and obese
(BMI
resistance and hyperleptinemia are the main mechanisms linking obesity to
R30.0kg/m2) classes. Plasma 2AG, anthropometric and metabolic parameters
infertility. Thus the establishment of a healthy lifestyle since a young age is the
were assessed.
best therapeutic solution for obesity-induced infertility. Obese women have a
Results
higher prevalence of infertility, maternal morbidity, mortality and foetal
Menopause (P!0.001) and BMI (PZ0.001) independently increased 2AG
anomalies. For these reasons it’s necessary to raise the public awareness on the
levels. NW (PZ0.001) and OW (P!0.001), but not OB, MP women, displayed
detrimental effects of obesity on reproductive health.
higher
2AG than preMP counterparts. 2AG increased with BMI in preMP
DOI: 10.1530/endoabs.49.EP667
(P!0.001), but not in MP cohort. 2AG displayed BMI-independent relationships
with triglycerides in both preMP (PZ0.006) and MP (PZ0.005) and with glucose
in MP (PZ0.036). When analyzed within preMP BMI classes, only in OB class
2AG significantly associated with total cholesterol
(TC, PZ0.040) and
triglycerides (PZ0.020). In MP cohort, 2AG associated with TC (PZ0.006),
glucose (P!0.001), HOMA-IR (PZ0.035) and triglycerides (PZ0.001) within
NW, with triglycerides in OW (PZ0.034) and with none of the parameters in OB
class. Moreover, increasing BMI significantly reduced 2AG associations with TC
(PZ0.037) and glucose (PZ0.002) in MP cohort, while 2AG associations with
TC, glucose and HOMA-IR significantly distinguished NW MP from NW preMP
women (PZ0.036, PZ0.005 and PZ0.027, respectively). No 2AG associations
EP668
were found with waist circumference and blood pressures.
Conclusions
Mindfulness-oriented weight management course in a tier 3/tier 4
Plasma
2AG is a valuable biomarker of clustering insulin resistance and
obesity service
dyslipidemia in lean menopausal women, and may play a causative role in
Petra Hanson, Louise Halder & Thomas Barber
menopause-related metabolic worsening.
University Hospital of Coventry and Warwickshire, Coventry, UK.
DOI: 10.1530/endoabs.49.EP669
Overeating contributes to obesity epidemic and has many causes. Evidence shows
that problematic eating behaviours can be modified with mindfulness. In the UK
the use of mindfulness in management of obesity has been studied only once
before. We aimed to pilot a new weight management course that would improve
patients’ skills and confidence in ability to lose weight, and reduce patient waiting
time. The course covered mindful eating, compassion and self-esteem, managing
EP670
relapses and weight loss orientated marketing. Four interactive sessions were
Genetical predictors of neuroendocrine disturbances in children with
delivered by dietitians and psychologists over 8 weeks, resulting in frequent
severe obesity
contact with participants. Patients were invited to participate in this course
Anzhalika Solntsava1, Olga Zagrebaeva1, Elena Aksyonova2,
following their first appointment, and received normal follow-up regardless of
Tatsiana Shatarnova2 & Tatsiana Yemelyantsava3
their participation. Ten patients were included in the final analysis. Anonymized
1Belarusian State Medical University, Minsk, Belarus;2Institute of Genetics
feedback and eating style questionnaires were collected before and after the
and Cytology of NAS of Belarus, Minsk, Belarus;3Republican Research and
course. The average weight and age were 120 kg and 45 respectively, and eight
Practice Center for Mental Health, Minsk, Belarus.
were women. 90% of patients lost weight (0.4-5 kg). Average weight loss was
1.54 kg. Patients were seen more frequently in the initial phase of their treatment
pathway, leading to improved experience.30% of participants heard of mindful
Objectives
eating prior to our course, with 90% finding it a useful concept for weight
Neurogenetical predictors of psychological disturbances in children with severe
management on completion. Patients became more confident, compassionate and
obesity.
felt more in control. Eating styles were assessed by a validated questionnaire.
Methods
Paired t-test was applied to analyse results. Statistically significant improvement
We examined 254 pubertal obese children: group1 (simple obesity) 187 children,
was found in emotional eating (PZ0.010), food fretting (PZ0.022), unappetizing
14.3G2.0 yrs, 30.4G2.8 kg/m2; group2 (severe obesity) 67 children, 14.7G2.1,
atmosphere (PZ0.042) and overall eating style (PZ0.017). This holistic course
39.1G3.8. Control 80 children, 14.4G2.0 yrs, 19.7G1.7 kg/m2. Dopamine levels
equipped patients with new skills to change eating behaviours, coping strategies
were determined. Genotyping was performed on polymorphic genes COMT,
and changed their mindset and will be incorporated into the standard service for
MAOA, A1 Tag 1A allele of DRD2/ANKK1 polymorphism (rs1800497).
all bariatric patients. However, the results of this project have global implications
Results
as management of obesity should incorporate holistic approach and utilize
A statistically significant difference between dopamine levels were in patients
mindfulness in future.
with simple (8.8(4.8; 20.7)) and severe obesity (48.8(29.8, 163.9)) ng/ml and AA
DOI: 10.1530/endoabs.49.EP668
genotype (PZ0.05). We found the significant increasing of dopamine levels (82.5
[61.3; 116.3]) in boys with severe obesity and 3-3 MAOA genotype comparison
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
to 4-4 genotype (35.7 [23.2; 54.9]) (UZ4.0; PZ0.03). We determined more
EP672
frequent occurrence of GA (Val/Met) genotype COMT gene in children with
Unfavourable blood pressure and lipid levels in obese individuals from
severe obesity (54.3%) compared to simple disease (32.7%) (c2Z6.9; PZ0.03).
the general population
AA genotype frequency was 21.7% in patients with severe obesity, which were
Bruce Wolffenbuttel, Sandra Slagter, Robert van Waateringe,
higher than control (16.6%) (c2Z14.6; PZ0.006). We revealed significantly
Jana van Vliet-Ostaptchouk, André van Beek & Melanie van der Klauw
higher BMI in children with severe obesity and the presence of GA genotype
Univ Med Ctr Groningen, Groningen, The Netherlands.
(41.3G4.5 kg/m2) compared to GG (37.4G3.1) (PZ0.006) and AA (38.6G2.8)
(PZ0.04) genotypes. The more frequent presence of A1 allele, associated with
low dopamine D2 receptors density (A1A1 and A1A2) was detected in children
Background
with morbid obesity (17.9%) in comparison with alimentary obesity (4.8%),
Early diagnosis and treatment of high blood pressure (BP) and high cholesterol is
(c2Z9.7, PZ0.008). The positive reliable correlation was found between A1A2
important to reduce cardiovascular mortality risk.
genotype and BMI (rsZ0.8, PZ0.001).
Methods
Conclusions
We assessed actual BP and LDL-cholesterol
(LDL-C) levels in
88,029
A large frequency of AA genotype were found in children with severe and simple
participants (36,122 men), aged 18-80 yrs, without diabetes, from the Dutch
obesity. Higher BMI levels were in children with severe obesity and genotype
Lifelines Cohort study. Participants were categorized according to degree of
GA. The more frequent presence of A1 TaqIA allele, associated with low
obesity
(normal weight, overweight, obese) and age decade group. BP
dopamine D2 receptors density was found in children with morbid obesity.
measurement was rigorously standardized. Mean systolic and diastolic BP were
DOI: 10.1530/endoabs.49.EP670
calculated depending on BP-treatment status for the three BMI classes, and for
each age group. We repeated these evaluations for LDL-C levels.
Results
In total, 13.3% of men and 15.6% of women were obese. BP increased gradually
in each age group, with mean levels of 124/68 mmHg in the youngest and
142/77 mmHg in the oldest male participants, and was significantly higher in
obese vs. non-obese and overweight individuals in all age groups (P!0.01). The
largest difference (10-11 mmHg) between obese and non-obese was observed in
males below 50 yrs. Despite the use of BP-lowering medication (5.1-6.2% in non-
obese,
21% in obese), still
20-50% had elevated systolic BPR140 mmHg.
Overall mean LDL-C was 3.5G0.9 mmol/l in obese vs. 3.2G0.9 mmol/l in non-
obese men (P!0.001), and 3.3G0.9 vs 2.9G0.8 mmol/l in women (P!0.001).
EP671
More untreated obese than non-obese participants had an LDL-C R3.5 mmol/l
Endocannabinoid 2-arachidonoylglycerol plasma level is a BMI-
(men: 56% vs 37%, women: 41% vs 24%, both P!0.001). Only 37% of obese
independent biomarker of cardiometabolic risk in adult males with
men and 28% of obese women treated with statins reached an LDL-C target
higher relevance in lean and aged conditions
!2.5 mmol/l. A small percentage of obese individuals treated with BP-lowering
Flaminia Fanelli, Marco Mezzullo, Margherita Baccini, Elena Casadio,
drugs also were using statins (33% in men, 16% in women).
Daniela Ibarra Gasparini, Valentina Vicennati, Renato Pasquali &
Conclusions
Uberto Pagotto
Obese individuals have higher BP and LDL-C compared to non-obese, and
Endocrinology Unit and Center for Applied Biomedical Research
especially obese men younger than 50 yrs have elevated BP levels. There is
Department of Clinical and Surgical Science, University of Bologna,
considerable undertreatment of elevated BP and elevated LDL-C in the general
S.Orsola-Malpighi Hospital, Bologna, Italy.
population.
DOI: 10.1530/endoabs.49.EP672
Context
Ageing and obesity are similarly characterized by metabolic impairment in terms
of visceral fat, dyslipidaemia, insulin resistance and hypertension. Obesity is
featured by endocannabinoid system (ECS) hyperactivation. Increased levels of
endocannabinoid 2-arachidonoylglycerol (2AG) found in obesity were variously
associated to dysmetabolic features, however, it is not clear whether such
EP673
associations exist in normal weight conditions. Moreover, ageing contribute in
Relation of insulin resistance to neurocognitive function and
modulating 2AG tone and involvement in worsening metabolic profiles was not
electroencephalography in obese chıldren
addressed. The study aimed at defining 2AG relevance as BMI-independent
Onur Akın, İbrahim Eker, Mutluay Arslan, Suleyman Tolga Yavuz,
biomarker of metabolic impairment in males and whether its relevance is
Sevil Akman, Mehmet Emre Ta¸c¸ılar & Bulent Unay
modified by ageing.
Gulhane Education and Research Hospital, Ankara, Turkey.
Methods
Unmedicated, disease-free male volunteers (nZ144) aged 18-84yo were stratified
in normal weight (NW, BMI:18.5-24.9 kg/m2, nZ61), overweight (OW; BMI:
Background
25.0-29.9 kg/m2, nZ61) and obese (BMI R30.0 kg/m2, nZ22) classes. Plasma
This study aimed to investigate neurocognitive functions and electroencephalo-
2AG, anthropometric and metabolic parameters were assessed.
graphy (EEG) parameters in normoglycemic obese children.
Results
Method
Age did not influence 2AG levels in the overall cohort nor within BMI classes.
A total of 73 obese children (38 male and 35 female) and 42 healthy children (21
2AG levels increased with BMI (PZ0.019), however, significance was lost after
male and 21 female) were recruited. Biochemical disturbances and insulin
adjustment for each metabolic parameter.
2AG displayed age- and BMI-
resistance (IR) were investigated. The Wechsler Intelligence Scale for Children-
independent positive relationships with SBP (PZ0.020), insulin (PZ0.011),
Revised (WISC-R) and EEG were performed for all children. Obese participants
HOMA-IR (PZ0.006), total cholesterol (PZ0.001) and triglycerides (P!0.001)
were classified according to the presence of IR. Data were compared between
and negative with HDL-cholesterol (PZ0.046). 2AG correlation with triglycer-
these subgroups.
ides was confirmed in each BMI class (NW and OW: P!0.001; OB: PZ0.029).
Results
Positive 2AG correlation was found with SBP (PZ0.023) and DBP (PZ0.048)
Verbal scores on the WISC-R of the IRC Group were significantly lower than the
within OB, and with total cholesterol within OW (P!0.001) class. Finally, within
control group and the IR- Group. There were no differences between groups with
the NW class, 2AG negatively associated with HDL-cholesterol (PZ0.004) and
respect to other parameters of the WISC-R and EEG. Verbal and total scores of
positively with glucose
(PZ0.015), insulin
(PZ0.003) and HOMA-IR
the WISC-R were negatively correlated with HOMA-IR values. In the EEG study,
(PZ0.001); notably, the last two correlations were positively influenced by age
slowing during hyperventilation was seen significantly more frequently in obese
(both PZ0.004). No associations were detected between
2AG and waist
children than non-obese children.
circumference.
Conclusion
Conclusions
Neurocognitive functions, particularly verbal abilities, were impaired in obese
Plasma 2AG is a valuable biomarker of clustering hypertension, insulin resistance
children with IR. On the other hand, EEG results did not differ in terms of obesity
and dyslipidemia in male gender. Results in lean males may suggest a causative
and IR. IR may be associated with neurocognitive abnormalities in obese
role for 2AG in age-related insulin resistance.
children.
DOI: 10.1530/endoabs.49.EP671
DOI: 10.1530/endoabs.49.EP673
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP674
(P:0,85), before and after surgery, respectively. We didn’t find any correlation
between BMI and BMD but there was a negative correlation between 25-OH D
and PTH (r: K0,298 P:0,0003)
Abstract withdrawn.
DOI: 10.1530/endoabs.49.EP676
EP677
Effects of mediterranean diet in obese patients with metabolic syndrome
and depression
Vesna Dimitrijevic-Sreckovic1,5, Hristina Janeski2, Branko Sreckovic3,
EP675
Ivan Soldatovic4,5, Nevena Nesovic1 & Milica Vujovic1
Lipid profiles and vitamin D receptor polymorphisms in overweight/
1Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical
obese dialysis patients
Center of Serbia, Belgrade, Serbia;2University Children’s Hospital,
Gokhan Bagci1, Can Huzmeli2, Binnur Bagci3, Ferhan Candan2,
Belgrade, Serbia;3Clinical Center Bezanijska Kosa, Belgrade, Serbia;
Lale Akkaya2 & Mansur Kayatas2
4Institute for Medical Statistics and Informatics, Belgrade, Serbia;5Faculty
1Cumhuriyet University, Medical Biochemistry, Sivas, Turkey;
of Medicine, Belgrade University, Belgrade, Serbia.
2Cumhuriyet University, Nephrology, Sivas, Turkey;3Cumhuriyet
University, Nutrition and Dietetics, Sivas, Turkey.
Introduction
Central obesity is the source of inflammatory factors, causing endothelial
Background
dysfunction. In central nervous system, inflammatory factors mediate neuro-
Vitamin D receptor (VDR) is present on adipocytes, and many studies were
transmitter metabolism promoting excitotoxicity and increase oxidative stress,
carried out to investigate the association between single nucleotide polymorph-
and a major clinical symptom is depression. Mediterranean diet (MD) resulted as
isms (SNPs) in VDR gene with obesity. However, little is known about the role of
a good prevention method for depression.
VDR gene polymorphism with obesity in dialysis patients. Therefore, we aimed
Aim
to investigate lipid profile and VDR gene TaqI, ApaI and FokI SNPs in
To examine the relationship of depression with abdominal obesity and metabolic
overweight/obese dialysis patients.
syndrome (MS) criteria, blood pressure, lipids, glycaemia and inflammation
Methods
factors. Analysing effects of MD on weight correction, abdominal obesity and
Seventy one normal weight and 68 overweight/obese patients were included in
consequent less score points in Hamilton scale for depression.
study. PCR-RFLP method was used for genotyping.
Methods
Results
Study included 36 adolescents and youth (16-30 years) and 22 adults over 30
For all three SNPs, no significant association was found between normal and
years, overweight and obese patients with MS, diagnosed with depression using
overweight/obese patients (PO0.05). The level of LDL, total cholesterol and
Hamilton scale. MS was diagnosed using ATP III classification criteria. The
triglycerides was found significantly high, and HDL level was found significantly
following parameters were observed: BMI, waist circumference (WC), blood
low in overweight/obese patients compared to normal weight patients (P!0.05).
pressure, lipids, CRP and basal glycaemia and insulin. Seven day scheduled MD
In overweight/obese patients, patients carrying ApaI CC genotype have higher
was used by patients.
triglyceride levels compared to AA and AC genotype (CC vs AA PZ0.001;
Results
CC vs AC P!0.001) and CC Z627G653; AC Z193G85; AA Z233G156).
Correlation is found between Hamilton’s scale score and body weight, BMI, WC
No significant association was found between other SNPs and lipid profiles.
(P!0.01) and CRP (P!0.05) in adolescents and youth. Implementation of MD
Conclusions
resulted in reduction of body weight and WC (P!0.05), Hamilton’s scale score
Our results suggest that ApaI polymorphism are associated with high triglyceride
(P!0.001), insulinemia, HOMA-IR and CRP (PO0.5). Hamilton’s scale and
levels in overweight/obese dialysis patients.
Hamilton’s scale score correlated with insulin
(P!0.05) and glycaemia
DOI: 10.1530/endoabs.49.EP675
(P!0.05), basal insulin correlated with CRP (P!0.05). After MD values of
Hamilton’s score, WC, insulin and CRP were lower (PO0.5).
Conclusions
Mediterranean diet resulted with reduced values of Hamilton’s scale score, waist
circumference, insulinemia and CRP in patients with MS and depression. Positive
correlation of Hamilton’s scale score with glycaemia and insulinemia suggest
importance of insulin resistance and glucoregulation disorder on occurrence and
stage of depression in obese patients with metabolic syndrome. CRP is useful
marker for low grade inflammation in obese patients with MS, hence depression.
EP676
Keywords: metabolic syndrome; obesity; depression; Mediterranean diet;
Bone mineral density and bone turnover markers after bariatric
hyperinsulinism
surgery
DOI: 10.1530/endoabs.49.EP677
Meliha Melin Uygur & Dilek Gogas Yavuz
Marmara University School of Medicine, Endocrinology and Metabolism
Disease Department, Istanbul, Turkey.
Although bariatric surgery has beneficial effects on obesity related complications,
rapid weight loss might have negative effects on skeletal health. The objective of
our study was to evaluate changes in bone mineral density (BMD) and bone
EP678
biochemical markers in patients, before and 1 year after bariatric surgery.
Visceral obesity in youth followed by decreased testosterone leading to
Methods
erectile dysfunction and risk of early atherosclerosis
One hundred and two morbidly obese subjects (mean 43G15 years, BMI
Vesna Dimitrijevic-Sreckovic1,5, Hristina Janeski2, Branko Sreckovic3,
48,5 g/cm2) performed either Roux en Y gastric bypass
(n:9) or sleeve
Ivan Soldatovic4,5, Milica Pajovic1 & Marko Stojanovic1
gastrectomy (n:93) were included in the study. Serum vitamin D, calcium,
1Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical
parathyroid hormone (PTH), C-terminal telopeptide (CTX), osteocalcin levels
Center of Serbia, Belgrade, Serbia;2University Children’s Hospital,
were measured with immunochemiluminescence method. BMD measured with
Belgrade, Serbia;3Clinical Center Bezanijska Kosa, Belgrade, Serbia;
Dual X ray absorbsiometry (DEXA) before and after first year of the surgery.
4Institute for Medical Statistics and Informatics, Belgrade, Serbia;5Faculty
Results
of Medicine, Belgrade University, Belgrade, Serbia.
BMI decreased significantly after surgery compared to baseline (30,5G8.5kg/m
versus 48.5G9.08 P:!0.0001). Serum CTX levels were significantly higher at 1
year (P:!0,0001). Changes in calcium, PTH, 25 OH vitamin D, CTX and
Background
osteocalcin at baseline and first year of the surgery. Lumbar BMD was 1,284
Abdominal obesity, which in fact is a metabolic syndrome (MS), is related to
versus 1.260 g/cm2 (P:0,32), femoral neck BMD was 1.034 versus 1.030 g/cm2
decreased testosterone, insulin resistance (IR), increased inflammatory factors,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
non-alcoholic fat liver disease
(NAFLD) and risk of early atherosclerosis.
controlling body weight. It is possible to prevent most of the morbidities and
Elevated inflammatory markers
(CRP) may interfere with insulin signal
mortality related to obesity by preventing weight gain. Every effort should be
transduction at the neuronal level inducing hypogonadotropic hypogonadism.
made to increase the level of education about healthy nutrition habbits and
Objective
importance of regular physical activity.
To examine testosterone relationship with abdominal obesity, lipid status, blood
DOI: 10.1530/endoabs.49.EP679
pressure, IR and NAFLD in obese young males with pre-MS and MS.
Methods
The study included 52 obese male individuals with pre-MS or MS (age16-30)
classified in two groups: I-with low testosterone
!12.0 nmol/l; II-with
testosterone R12,0 nmol/l. The following parameters were observed: waist
circumference (WC), blood pressure, lipids, microalbuminuria. SGOT, SGPT and
g-GT were liver function parameters. ATP III classification was applied for
EP680
diagnosing MS. Patients with less than three above criteria were considered pre-
MS. IR was determined by HOMA IR. OGTT was used to evaluate
Effect of Vitamin D supplementation on body composition in overweight
glycoregulation disorder. Testosterone was determined by radioimmunoassay.
men: A randomized controlled trial
Christos Karefylakis1,2, Annaclara Ariander2, Stefan Särnblad2, Peter Rask3
Results
& Eva Rask1,2
BMI:I-35.7G35, II-33.0G4.9 kg/m2; WC:I-117.3G15.5, II-109.9G14.2 cm;
1Department of Internal Medicine, Division of Endocrinology and Diabetes,
HDL:I-0.96G0.18, II-1.04G0.2 mmol/l; triglycerides: I-2.74G1.6, II-1.8G
Orebro University Hospital, Orebro, Sweden;2Faculty of Medicine and
1.0 mmol/l; insulin
0’:I-113G128. II-40.1G61.2 IU/l; insulin
30’:I-199.8G
Health, School of Health and Medical Sciences, Orebro University, Orebro,
124.II-124.1G90 IU/l; insulin 120’:I-119.8G114. II-53.9G70.8 IU/l; HOMA
Sweden;3Department of Clinical Physiology, Orebro University Hospital,
IR:I-26.8G31, II-9.1G14 mmol/mU/ml; SGOT:I-50.5G39.3, II-26.8G
Orebro, Sweden.
7.8;SGPT:I-81.8G48.2, II-40.2G18.0 U/l; g-GT:I-49.8G19.3 U/l, II-39.7G
21.9 U/l.CRP:I-5.2G2.5, II- 5.25G5.8 mg/l.
Correlations
Introduction
Testosterone negative with body weight, BMI and WC (P!0.05). Decreased
The prevalence of vitamin D deficiency is higher in obese individuals but it is
testosterone
(!12.0 nmol/l) was found in 13.5% obese young males (8.5G
unclear whether vitamin D deficiency impacts body composition or if body
2.6 nmol/l), with normal FSH, LH and estradiol. A statistically important
composition impacts the vitamin D status. The research regarding vitamin D
difference between groups was found for 0, 30 and 120 minute insulin values
supplementation and weight loss in obese individuals is ambiguous. One
(P!0.05) and for liver function parameters SGOT and SGPT (P!0.001).
hypothesis for the presumed fat reductive effect of vitamin D is that vitamin D
Conclusion
inhibits adipocyte differentiation.
Low testosterone is characterized by obesity, MS parameters, hyperinsulinism, IR
Aim
and NAFLD. Negative correlation of testosterone with WC and statistical
To investigate if treatment with vitamin D can reduce fat mass in obese men with
importance of insulinemia and liver function parameters differences confirm the
vitamin D deficiency.
important effect of visceral obesity and IR on the occurrence of erectile
Methods
dysfunction, NAFLD and risk of early atherosclerosis in obese adolescents and
This study was designed as a randomized prospective, placebo controlled, double
youth.
blind intervention. Thirty eight overweight men (BMI O 25 kg/m2) with vitamin
DOI: 10.1530/endoabs.49.EP678
D deficiency (25(OH)D ! 55 nmol/l) were randomized to receive 2000 IU
Cholecalciferol drops or the equivalent amount of placebo drops for 6 months. At
baseline and after 6 months body composition and BMI was measured and blood
samples were obtained; body composition was measured using bioelectrical
impedance analysis (BIA).
Results
The mean change in body fat percentage for the vitamin D group and the placebo
EP679
group was a 0.6%-units (baseline compared to follow up; PZ0.222) and a 0.1%-
The prevalence of obesity and related factors: An urban survey study
units (PZ0.857) increase, respectively. The mean change in BMI in the vitamin
Ayla Gokmen Salici1, Pinar Sisman2, Ozen Oz Gul3, Tugce Karayel4,
D g roup was a 0.2 kg/m2 decrease (PZ0.272) and for the placebo group a mean
Soner Cander3 & Canan Ersoy3
decrease in BMI of 0.5 kg/m2 (PZ0.049). There was no statistically significant
1Department of Internal Medicine, Usak State Hospital, Usak, Turkey;
difference between the placebo group and the intervention group regarding
2Department of Endocrinology, Kars State Hospital, Kars, Turkey;
change in fat percentage or BMI (PZ0.544, PZ0.256, respectively). Moreover
3Department of Endocrinology and Metabolism, Uludag University Medical
no statistically significant difference was observed between the groups regarding
School, Bursa, Turkey;4Department of Internal Medicine, Uludag
change in any of the metabolic laboratory values.
University Medical School, Bursa, Turkey.
Conclusion
We conclude that treatment with 2000 IU vitamin D daily for 6 months does not
impact BMI or fat percentage in overweight men with vitamin D deficiency.
Objectives
Obesity is a chronic and progressive disease that limits physical activity, causes
DOI: 10.1530/endoabs.49.EP680
psychological problems, and finally leads to social isolation of the person.
Detecting the factors affecting obesity and its prevalence in the populaton are
important steps in dealing with the problem. In this study, we aimed to evaluate
the obesity prevalence and the factors affecting this prevalence in randomly
selected volunteers from residents of the city of Bursa.
Methods
EP681
A questionnaire consisting of 40 questions evaluating the sociodemographic
Intensified telematic treatment for obesity using the web platform
aspects, healthy nutrition and exercise habbits and comorbidities of the subjects
PREDIRCAM2, descriptive basal characteristics and preliminary
was performed face to face to
528 volunteers
(414
females,
114 males)
results
participating in our study. Height, weight, waist, hip, neck and wrist
Valeria Alcantara-Aragon1, Susana Rodrigo-Cano2,5, Maria José Martínez1,
circumferences and random blood glucose levels were measured. BMI and
Carmen Martínez1, José Tapia3,6, José Iniesta3,6, Ascension Lupia
˜ez1,
waist to hip ratio were calculated for each participant.
Susana Tenés2,5, M Elena Hernando3,6, J Francisco Merino-Torres2,5,
Results
Alberto de Leiva1,4 & Cintia Gonzalez1,4
The mean age of the whole study population, female and male participants were
1Endocrinology and Nutrition Department, Hospital de la Santa Creu I Sant
39.6G12.8, 40.2G12.7 and 37.1G12.9 years, respectively. According to BMI
Pau, Barcelona, Spain;2Endocrinology and Nutrition Department, Hospital
values 23.5% of the whole study population, 25.8% of females and 14.9% of
Universitari i Politècnic La Fe, Valencia, Spain;3Telemedicine and
males were obese. For the female subjects, the obesity prevalence was found to be
Bioengineering Group, Universidad Politécnica de Madrid, Madrid, Spain;
increasing with age, being married, being housewife and having lunch at home
4Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales
and decreasing with higher education level and income. When we investigated the
y Nanomedicina (CIBER-BBN), and Eduab-HSP Group, Universitat
male subjects, the only factor related to and found to be increasing the obesity
Autònoma de Barcelona, Barcelona, Spain;5Unidad Mixta de Investigación
prevalence was having lunch at home.
Endocrinología, Nutrición y Dietética. Instituto Investigación Sanitaria La
Conclusions
Fe-Universitat de Valencia, Valencia, Spain;6Centro de Investigación
Obesity is a worldwide problem. Its prevelance is increasing in our city and
Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
country. Education level of the subjects seems to be the most important factor in
(CIBER-BBN), Madrid, Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
model which included AST/ALT and BARD was 0.75. BARD and APRI were
PREDIRCAM2 is a web platform for obesity treatment and follow-up. It contains
significant factors (PZ0.03, PZ0.04) on stepwise regression for F3/4 cirrhosis
modules for: dietary prescription and registry with nutritional analysis based on
and they were included in the final model, which had AUROC 0.73. Only Fib4
individualized and mediterranean dietary goals, physical activity prescription and
scoring was independently associated with cirrhosis
(F4) on multivariate
tracking with individualized targets, and anthropometric tracking. An ongoing
regression analysis (PZ0.04) and AUROC for the final model incorporating
multicenter randomized clinical trial evaluates the intervention’s effectiveness in
this factor was 0.70. In contrast to observations in non-bariatric patients, the NFS
obesity treatment and cardio-metabolic-risk prevention.
was of limited value and not an independent factor in predicting NASH, advanced
Methods
fibrosis or cirrhosis.
Inclusion criteria: 18-65 years-old, BMI 30-39.9 kg/m2, no medication for type-2
Conclusion
Diabetes Mellitus (DM), dyslipidemia (DLP) or hypertension (HT). Randomiz-
Currently used non-invasive serum-based scoring systems have only a modest
ation to intensified technological intervention (TI) supported by PREDIRCAM2
predictive value for staging the severity of NAFLD in patients undergoing
platform, or traditional non-technological face-to-face intensified treatment
bariatric surgery. Intra-operative liver biopsy to detect and subsequently manage
intervention
(NTI). Both groups receive one year follow-up through
12
advanced liver disease therefore remains of value. There is a need to develop and
appointments with health-care professionals, 4 of which are exclusively telematic
validate non-invasive biomarkers of disease that offer better predictive value in
in the TI group.
the bariatric population.
Basal characteristics
DOI: 10.1530/endoabs.49.EP682
183 participants have been included, BMI 34.74G2.74, age 44.27G10.62, 84%
female (31% postmenopausal, 6.5% history of gestational DM),
54% high
education level, 54% married. Comorbidities: 2.2% type-2 DM, 5.5% HT, 11.5%
DLP, 6.5% Depression,
2.7% diagnosed eating disorders.
56% received
medication, most frequently antidepressants (24.5%) followed by vitamin D
supplements (11.8%). 68% reported anxiety towards food, overeating in the form
of: pecking 84.7%, binge-eating 35.5%, binge-and-vomiting 3.2%.
Preliminary results
EP683
119 participants have completed 3-month follow-up: 60 TI, 59 NTI. Both groups
Discussion with cases: Could we achieve the goal with non-surgical
have lost weight significantly (P!0.0001). 26.7% TI, and 25.4% NTI have
treatments in morbid obese patients?
achieved at least a 5% weight-loss (PZ0.88). 81 participants have completed
Aydin Cifci1, Senay Arikan Durmaz2, Askin Gungunes2, Irfan Karahan3,
6-month follow-up: 41 TI, 40 NTI. Both groups have lost weight significantly
Selim Yalcin4 & Kubra Ozdemir1
(P! 0.0001). 46.3% TI, and 32.5% NTI have achieved at least a 5% weight-loss
1Department of Internal Medicine, School of Medicine, Kirikkale
(PZ0.20). Both groups have achieved a reduction in HbA1c levels (P!0.0001),
TI K0.81G1.9% and NTI K1.36G2.2% (PZ0.24).
University, Kirikkale, Turkey;2Department of Endocrinology and
Conclusion
Metabolism, School of Medicine, Kirikkale University, Kirikkale, Turkey;
Our study population is mostly composed of highly educated females who report a
3Department of Internal Medicine, Yenimahalle Traning and Research
high frequency of anxiety towards food and eating. PREDIRCAM2 shows to be a
Hospital, Ankara, Turkey;4Department of Oncology, School of Medicine,
promising tool for obesity treatment and cardio-metabolic-risk prevention.
Kirikkale University, Kirikkale, Turkey.
DOI: 10.1530/endoabs.49.EP681
Objective
Diet, lifestyle changes, medical agents and surgical approaches are treatment
options in obese patients. We reported two morbid obese patients who lost 25 and
21% of their previous weight respectively with only lifestyle changes and orlistat
therapy.
Case 1
Forty nine year-old woman had type 2 diabetes mellitus for 20 years. She took
premix insulin twice a day. Her height was 157 cm, her weight was 120 kg, body
EP682
mass index was 48.6 kg/m2. One month later, she lost 3 kg with diet and exercise
Suboptimal prediction of advanced fibrotic liver disease by standard
and then orlistat was started. After seventh month of orlistat therapy, her weight
non-invasive scoring systems in obese patients undergoing bariatric
reduced to 85 kg and body mass index was 34.4 kg/m2.
surgery
Case 2
Niall Dempster1,3, Michael Watson4, Rachel Franklin1, Maciej Juszczak2,
Fifty-four year-old man has type 2 diabetes mellitus and took metformin for 10
Lisa Rickers3, Caroline Fletcher3, Bruno Sgromo3, Richard Gillies3,
years. His height was 168 cm, his weight was 118 kg, BMI was 41.8 kg/m2. One
Jeremy Cobbold4, Leanne Hodson1, Jeremy Tomlinson1 & John Ryan4
month later, he lost 2.5 kg with diet and exercise and then orlistat was started.
1Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill
After seventh month of orlistat therapy, his weight reduced to 93 kg and body
Hospital, Oxford, UK;2Department of Vascular Surgery, John Radcliffe
mass index was 32.9 kg/m2. Both patients lost their weight
35 and 25 kg
Hospital, Oxford, UK;3Department of Bariatric Surgery, Churchill
respectively with lifestyle changes and orlistat therapy. First year of treatment,
Hospital, Oxford, UK;4Department of Hepatology, Churchill Hospital,
patients maintain their weight without any gain.
Oxford, UK.
Conclusion
The number of patients undergoing obesity surgery has increased at the present
Introduction
time. Patients prefer surgery instead of lifestyle changes. Our results of patients
Non-Alcoholic Fatty Liver Disease (NAFLD), is present in over 90% of obese
with morbid obese emphasize importance of lifestyle changes and orlistat therapy.
patients undergoing bariatric surgery. It is a spectrum of pathology ranging from
DOI: 10.1530/endoabs.49.EP683
steatosis through to inflammation (Non-Alcoholic Steatohepatitis, NASH) and
fibrosis. Bariatric surgery is currently the most effective treatment for NAFLD,
but post-operative hepatic decompensation can occur and therefore pre-operative
stratification of liver disease severity is beneficial. Several non-invasive scoring
systems have been developed to stage NAFLD, but validation in the bariatric
surgical population has been limited.
Methods
135 consecutive patients who underwent bariatric surgery in a tertiary referral unit
EP684
from November 2014 to December 2016 were identified and the following
Body compositions in obesity may corralete the minimal change of
NAFLD risk scores calculated: AST/ALT, APRI, BARD, Fib4 and NAFLD
tyhroid functions within normal range
Fibrosis Score (NFS). All patients had an intraoperative liver biopsy performed
Veysel Urun1, Kemal Ureten2, Ozlem Gul Utku4, Askin Gungunes3 &
for accurate histological staging of disease. Logistic regression analysis was used
Senay Arikan Durmaz3
to determine their efficacy in detecting NASH (NAFLD Activity Score R5),
1Department of Internal Medicine, School of Medicine, Kirikkale
advanced fibrosis (Brunt F3/4) and cirrhosis (F4) identified on liver biopsy using
university, Kirikkale, Turkey;2Department of Rheumatology, School of
R software.
Medicine, Kirikkale University, Kirikkale, Turkey;3Department of
Results
Endocrinology and Metabolism, School of Medicine, Kirikkale University,
BARD and AST/ALT were independent predictors of NASH on multivariate
Kirikkale, Turkey;4Department of Gastroenterology, School of Medicine,
logistic regression analysis. However, only AST/ALT ratio was significant in the
Kirikkale University, Kirikkale, Turkey.
final model (AST/ALT PZ0.04, BARD PZ0.08). AUROC for the regression
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction and aim
Conclusions
Overt thyroid dysfunction is well recognized to affect weight, but the influence of
1. FGF-21 and TGF-b reduction were associated with CHD in patients with
minor perturbations of thyroid function remains unclear. There is ongoing debate
obesity.
regarding the influence of minor changes in thyroid hormones status within the
2. Increased TGF-b may play a protective role in atherosclerosis in patients with
normal range and BMI. The aim of this study was to investigate the association
diabetes and obesity.
between thyroid function within normal ranges and obesity via BMI and body
DOI: 10.1530/endoabs.49.EP685
compositions analyzed by bioelectrical impedance.
Materials and methods
One hundred twenty persons with normal thyroid functions were included in our
study. According to the BMI, the patients were divided into 5 groups. Group1;
normal weight (nZ40), group 2; overweight (nZ20), group3; classI obesity
(nZ20), group4; class II obesity (nZ20), group 5 morbid obesity (nZ20).
Measurements of serum TSH, free T3, free T4 and lipid profile were recorded.
EP686
Body compositions and BMI were evaluated by bioelectrical impedance
The dynamics of anthropometric data in fertile age women by various
(TANITA).
types of the treatment
Results
Maryam Abduvakhabova & Saidganikhoja Ismailov
In group 1, TSH was negatively correlated with BMI (rZK0.430, PZ0.006). On
Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.
the contrary, TSH was positively correlated with percentage of body fat (BF%)
(rZ0.391, PZ0.014). Free T3 was positively correlated with BF% (rZ0.333,
PZ0.038). In group 2, free T3 was positively correlated with BF% and fat mass
The aim
(rZ0.657, PZ0.010, rZ0.751, P!0.001 respectively). In group 3, free T3 was
To study efficiency of pathogenetic therapy and dynamics of anthropometric
positively correlated with BF%, fat mass, HOMA-IR and LDL (rZ0.521,
indexes for women with obesity of fertile age at different endocrinopathies to and
PZ0.018; rZ0.543, PZ0.013; rZ0.512, PZ0.021; rZ0.469, PZ0.037,
through 6 months after treatment.
respectively). Similarly, TSH was positively correlated with BMI (rZ0.553,
Material and research methods
PZ0.011). In group 5, free T4 was negatively correlated with LDL (rZK0.485,
On the etiologic factor of patient with obesity were up-diffused on three groups:
PZ0.030).
1 g. are patients with obesity at the polycystic syndrome of ovaries (PCOS) - 30
Conclusion
patients, 2 g. are patients with hypothalamic obesity - 21 cases and 3 g - patient
We demonstrated that differences in thyroid function within the normal range
with endocrine obesity (at a primary hypothyroidism) - 20 patients. Age of
may correlate with differences in BMI and body compositions in subjects within
patients in a 1th group hesitated 39 from 20 to and 28.3G0.64 averaged year. To
different BMI categories. Further large scale data from the population is required
all patients have been conducted spectrum of investigations, which include
to confirm our findings.
clinical, biochemistry, hormonal analysis of the blood. Besides of this,
DOI: 10.1530/endoabs.49.EP684
electrocardiography, ultrasound investigation of uteri and ovarium during 11-
14 days of periods, and MRY of pituitary. For the
1 g. we administered
combination of Syofor 1000 mgs C spironolacton 100 mgs C yodmarinum
100 mgs CL-thyroxine 50 mgs in the morning C antiandrogens C antidepress-
ants. For the 2 group: combination of Syofor 1000 mgs C spironolacton 100 mgs
C Yodmarin 100 mgs CL-thyroxine 50 mgs iC methaboliks C Reduxine
(Sibutramin)
15 mgs C antidepressants. For the 3 groups: combination of
Yodmarin 100 mgs CL-thyroxine 50 mgs.
The results
EP685
In 1 and 2 groups of patients marked reliable decline of BMI 1 and 2 degrees after
Association of Transforming growth factor b and Fibroblast growth
6 months of treatment, while for patients 3 groups of reliable changes of BMI
factor 21 with cardiovascular diseases in obese patients
through 6 months of treatment were not attained at none of degree of BMI Thus,
Teona Shvangiradze1, Ekaterina Troshina1, Irina Bondarenko1,
for patients 1 and 2 groups with BMI 3 degrees through 6 months a tendency was
Marina Shestakova1,2 & Larisa Nikankina1
attained to the decline of BMI. In addition, renewal of fecundity and pregnancy
1Endocrinology Research Centre, Moscow, Russia;2I.M. Sechenov’s First
was attained for the patients of a 1 group - in 19.5% cases (at 10 patients).
Moscow State Medical University, Moscow, Russia.
Conclusions
Optimization of treatment of obesity for the women of reproductive age is based
on drafting of the individual programs, the choice of that is determined by the
Introduction
values of anthropometric indexes, state of hormonal and metabolic status, features
Obesity and type 2 diabetes mellitus (T2DM) are associated with cardiovascular
of food behavior and personality-emotional sphere, state of menstrual and
diseases (CVD). Fibrotic changes in obesity include several molecular processes,
reproductive function.
including activation of Transforming growth factor b (TGF-b). Recent data
indicate the involvement of Fibroblast growth factor 21 (FGF-21) as an important
DOI: 10.1530/endoabs.49.EP686
metabolic regulator, and even biomarker of metabolic changes in obesity and
T2DM.
Aim
To determine TGF-b and FGF-21 level in patients with obesity and T2DM.
Methods
TGF-b and FGF-21 were identified in peripheral blood of 66 patients, aged 48-65
years with obesity. They were divided into 3 groups. 1st - 21 patients with
coronary heart disease (CHD) (confirmed by coronary angiography (CAG)) and
EP687
T2DM, the 2nd - 22 patients with T2DM, in the 3rd - 23 patients without T2DM
Effects of IL-1b on the hypothalamic-pituitary-gonadal axis in men with
and CHD. CHD was excluded in the 2nd and 3rd groups by Tredmil test. Control
obesity and metabolic syndrome - A randomized, double-blind,
(4th) group included 14 healthy person matched by age and sex.
placebo-controlled trial
Results
Fahim Ebrahimi1,2, Philipp Schuetz2,3, Beat Mueller2,3, Sandrine
TGF-b was significantly different in the studied groups (PZ0.046). We found
A Urwyler1,2, Marc Y Donath1,2 & Mirjam Christ-Crain1,2
that TGF-b was significantly lower in patients with CHD (group 1) compared with
1Department of Internal Medicine, Division of Endocrinology, Diabetes and
the group of
“metabolically healthy” obesity
(PZ0.02). TGF-b negatively
Clinical Nutrition, University of Basel Hospital, Basel, Switzerland;
correlated with. atherogenic fractions of cholesterol
- LDL (rZK0.426,
2Department of Clinical Research, University Hospital Basel, Basel,
PZ0.043) and with the degree of internal carotid artery 0stenosis (rZK0.426,
Switzerland;3University Department of Medicine, Kantonsspital Aarau,
PZ0.039) in patients with T2DM. In contrast, patients with verified CHD
Aarau, Switzerland.
demonstrated a negative correlation with the duration of obesity (rZK0.395,
P!0.033), and the processes of heart muscle remodeling (thickness of the left
ventricular posterior wall (rZK0.386, PZ0.029) and interventricular septum
Background
(rZK0.335, PZ0.031). FGF-21 and TGF-b in the 1st group showed a negative
Low testosterone levels in men appear to be an independent cardiovascular risk
correlation with the number of significantly affected vessels according to CAG
factor closely associated with the metabolic syndrome. Reciprocally, the
(rZK0.73, PZ0.041 and rZK0.52, PZ0.036, respectively). All patients with
metabolic syndrome leads to a decrease in testosterone levels, suggesting a
obesity had significantly increased level of FGF-21 compared with the control
bidirectional relationship. It has been hypothesized that increased inflammation is
group (PZ0.03) and FGF-21 positively correlated with BMI (rZ0.47, PZ0.021)
causative for the development of obesity-associated hypogonadism. However,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
clinical evidence supporting this hypothesis is lacking. The aim of the present
EP689
study was to determine whether anti-inflammatory treatment may restore
Clinical and metabolic markers of X-syndrome
endogenous testosterone production in obesity-associated hypogonadism.
Irina Savasteeva1, Yana Navmenova1, Yulia Yarets1, Alena Makhlina2,
Methods
Marina Kaplieva2, Tamara Yeudachkova1 & Elena Vaschenko1
This is a randomized, placebo-controlled, double-blind, trial including
70
1Republican Scientific and Practical Center for Radiation Medicine and
hypogonadal men with the metabolic syndrome. Patients were randomly assigned
Human Ecology, Gomel, Belarus;2Gomel State Medical University, Gomel,
to either receive
100 mg of a recombinant human interleukin-1-receptor
Belarus.
antagonist subcutaneously twice daily for 4 weeks or to receive placebo. The
primary endpoint was the change in total testosterone levels between baseline and
4 weeks. Predefined secondary end points included a change by week 4 in insulin
resistance, body composition, muscle strength, hypogonadal symptoms and
We identified factors that significantly influenced the development of the
hemodynamic parameters.
X-syndrome. A significant influence on the development of X-syndrome
Results
have increase the level of total cholesterol (bZ0.65; PZ0.036; Exp (b) Z
From April 2016 to January 2017, 66 patients have been enrolled at two tertiary
1.92
(1.04O3.54)). Increases the risk of X-syndrome increase the level of
care centers in Switzerland. Median age was 51 years (IQR 41-65) and patients
apo-B-protein (bZ4.79; PZ0.014; Exp (b) Z12.69 (2.68O54.41)). The
had a median BMI of 37 kg/m2 (34-39 kg/m2). Patients had hypogonadotropic
increase in linear dimension of preperitonialy fat increased the risk of
hypogonadism with median baseline testosterone levels of 8.8 nmol/l (231 ng/dl)
developing X-syndrome (bZ1.14, PZ0.036; Exp (b)Z3.14 (1.08O9.16)).
(7.6-10.1), median LH levels of 3.7 IU/l (3-5.2 IU/l), and median C-reactive
By reducing the level of free thyroxine was a consistent trend of formation of
protein levels of 2.9 mg/l (1.4-4.0 mg/l) mirroring a low-grade inflammatory
X-syndrome (bZK0.25; PZ0.09; Exp (b) Z1.08 (0.57O1.10)). When
state. Final results will be available in March 2017 and will be presented first at
using the ROC analysis were obtained by the cut-off point, allowing to
the ECE 2017.
calculate the relative risk. The critical cut-off point for preperitonealny fat
Significance
figure was more linear size 2.1 sm (P!0.02); total cholesterol - more than
This study will show whether there exists causality between obesity-associated
6.36 mmol/l (P!0.02), apo-B-protein - more than 1.15 g/l (P!0.001), free
inflammation and hypogonadism.
thyroxine - less than 13.40 pmol/l (P!0.001). If the linear dimension
DOI: 10.1530/endoabs.49.EP687
preperitonealny fat more 2.1sm RR X-syndrome was 3.00 [0.87O10.39].
When total cholesterol level of more than 6.36 mmol/l RR X-syndrome was
16.50
[2.05O33.05]. When damage apo-B protein over
1.15 g/l RR
X-syndrome was 22.00 [2.49O94.44]. By reducing the thyroxine levels
below 13.40 mmol/l RR X-syndrome was 13.00 [1.53O110.51].
DOI: 10.1530/endoabs.49.EP689
EP688
Demographic and baseline characteristics of an obese population
admitted for bariatric surgery in a secondary care centre
Daniela Gallo1, Silvia Ippolito1, Giovanni Veronesi1, Eugenia Dozio1,
Francesco Frattini2, Eugenia Trotti1, Adriana Lai1, Lorenza Sassi1,
Jessica Sabatino1, Elvira Masiello1, Paola Premoli1, Eleonora Bianconi1,
Claudio Cusini1, Sara Rosetti1, Maria Laura Tanda1, Gianlorenzo Dionigi2,
EP690
Luigi Bartalena1 & Eliana Piantanida1
Impact of weight changes on the incidence of diabetes mellitus: a
1Department of Medicine and Surgery, University of Insubria, Varese, Italy;
Korean nationwide cohort study
2Research Center for Endocrine Surgery, University of Insubria, Varese,
Eun Sook Kim, Jee Sun Jeong, Kyungdo Han, Mee Kyoung Kim,
Italy.
Seunghwan Lee, Yong-Moon Park, Ki-Hyun Baek, Sung Dae Moon,
Je-Ho Han, Ki-Ho Song & Hyuk-Sang Kwon
Catholic University of Korea, Seoul, Republic of Korea.
Obesity has become one of the greatest public health concerns and is known
to be a major risk factor for cardiac, respiratory and metabolic diseases.
Objective
Bariatric surgery is the most effective treatment for morbid obesity.
Obesity is a well-known risk factor for type 2 diabetes, but few data exist on the
According with guidelines, surgery is indicated for treatment of patients
association between weight changes and future diabetes risk in non-obese
with BMI greater than 40 kg/m2 or above 35 kg/m2, with at least one
subjects. This study aimed to investigate the effect of weight changes on the
obesity-related comorbid condition, such as as type 2 diabetes, hypertension,
incidence of type 2 diabetes in Korea, using prospective nationwide data.
dyslipidemia, sleep apnea, osteoarthritis. Nowadays, sleeve gastrectomy is
Research design and methods
one of the most common techniques, able to cure metabolic disorders,
A total of 51 405 non-diabetic subjects were included who had undergone health
allowing a shorter convalescence and fewer complications. We herein
examinations in 2002 and completed follow-up in 2006.
describe the baseline characteristics of 38 adults (35 women, mean age 41G
Results
13 years), suitable for surgery. Patients were referred by Surgeons or other
Individuals who developed type 2 diabetes were more likely to be older and male,
Specialists such as Cardiologists, Pulmonologists, Nephrologists or
to have high BMI, blood pressure, fasting plasma glucose, and total cholesterol, to
Orthopedicians. Three patients were admitted for the conversion of
be a current smoker, to consume larger amounts of alcohol, to be hypertensive and
laparoscopic adjustable gastric banding, to achieve additional weight loss.
hyperlipidemic, and to have a family history of diabetes, compared to those
In keeping with guidelines, BMI was 43.3G6 Kg/m2 (71% R40 kg/m2,
without type 2 diabetes. Compared with the consistently non-obese group, there
23.5% 35-39.9 kg/m2, 5.3% !35 kg/m2), with a visceral pattern of obesity
was a higher hazard ratio for incident diabetes (95% confidence interval) in
(waist circumference
123G11 cm). Half of the patients suffered from
subjects becoming obese (1.50 (1.27-1.78)), losing weight (1.89 (1.61-2.22)),
metabolic syndrome, defined according to IDF/AHA/NHLB harmonized
and remaining obese (2.60 (2.56-3.05)), over 4 years, after adjustment for
definition. Actually,
29% had diabetes,
37% hypertension and
53%
confounding factors. When stratified by BMI categories, risks for incident
dyslipidemia. Among the others, arthropathy was the most frequent
diabetes were significantly decreased with lower BMI and the trends were more
comorbidity (21%), followed by respiratory diseases (chronic obstructive
evident in the non-obese group. However, there was no significant association of
or restrictive pulmonary disease, 19%), chronic venous insufficiency (11%)
high BMI with incident diabetes.
or heart diseases (5.3%). We observed gastric diseases in almost half of the
Conclusions
population (44%), and, as expected, 24% had hiatal hernia. Beyond these,
Weight loss was significantly associated with decreased diabetes risk both in non-
71% of patients emerged to have thyroid disease, with a high prevalence of
obese and obese Koreans, but particularly in the non-obese. Further long-term
non-toxic goiter and Hashimoto’s thyroiditis. During the screening,
studies are needed to establish weight reduction as a preventive strategy for type 2
papillary thyroid cancer was disclosed in two patients (5.3%). According
diabetes.
to the literature, these data underscore the high prevalence of obesity-related
DOI: 10.1530/endoabs.49.EP690
morbilities and the need for an effective and urgent treatment.
DOI: 10.1530/endoabs.49.EP688
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP691
mice deficient in HSD17B13 (HSD17B13KO). The data revealed normal serum
sex steroid concentrations and proper reproductive performance in both male and
Metabolic profile reversal after bariatric surgery
female HSD17B13KO mice, indicating a minor role for HSD17B13 in sex steroid
Daniela Gallo1, Silvia Ippolito1, Giovanni Veronesi1, Eugenia Dozio1,
metabolism and reproduction. In line with the strong expression in the liver,
Francesco Frattini2, Eugenia Trotti1, Adriana Lai1, Lorenza Sassi1,
histological analysis showed the presence of liver steatosis in HSD17B13KO
Jessica Sabatino1, Elvira Masiello1, Paola Premoli1, Eleonora Bianconi1,
mice that was associated with inflammation. The phenotype was more
Sara Rosetti1, Claudio Cusini1, Maria Laura Tanda1, Gianlorenzo Dionigi2,
pronounced in males than females. The severity of the phenotype progressed
Luigi Bartalena1 & Eliana Piantanida1
with aging, and accumulation of triglycerides was observed in the livers of the
1Department of Medicine and Surgery, University of Insubria, Varese, Italy;
male mice from 3 months onwards. Furthermore, metabolic profiling showed a
2Research Center for Endocrine Surgery, University of Insubria, Varese,
tendency for increased hepatic phospholipid content in the
9
month-old
Italy.
HSD17B13KO males with two acylcarnitines (C16:0 and C18:1) showing the
most profound increase (w2-fold). Additionally, presence of microgranulomas
(Kupffer cell aggregations) with increased portal inflammation and ductular
Bariatric surgery is the most-effective treatment for morbid obesity, superior
proliferation was observed in liver specimens from HSD17B13KO mice. This
to medical treatment. Metabolic syndrome (MS) is a condition characterized
was associated with increased expression of immune response genes in the
by multiple major risk factors for coronary heart disease, diabetes, fatty
HSD17B13KO male liver. In conclusion, the lack of HSD17B13 impairs hepatic
liver, and several cancers; the main, diagnostic, components of MS are low
lipid metabolism in mice, resulting in liver steatosis and inflammation. The data,
HDL-cholesterol
(!40 mg/dl in man,
!50 mg/dl in woman), raised
thus, indicate that HSD17B13 is involved in fatty acid metabolism in the liver,
triglycerides
(O150 mg/dl), blood pressure O130/85 mmHg, fasting
while the enzyme does not play a major role in the regulation of reproductive
plasma glucose O100 mg/dl and waist circumference O94 cm in man
functions.
and O80 cm in woman. Indeed, in addition to weight loss, changes in
DOI: 10.1530/endoabs.49.EP692
metabolic profile after bariatric surgery could improve long-term outcomes.
Complete demographic, clinical and laboratory data from 38 people (35
women, mean age 41G13 years) undergoing bariatric surgery and followed
by a dedicated clinical team were analyzed. Descriptive statistics detailed
clinical characteristics of the cohort of patients. Paired T-test compared
baseline clinical parameters, lipid and glycemic profile index at three (T3)
and six (T6) months after surgery. General Linear Model for Repeated
Measure compared the five conditions defining MS over time. Weight, BMI,
waist circumference and systolic blood pressure decreased significantly at
T3 and T6, compared to baseline [all P!0.05]. Triglycerides and LDL
cholesterol decreased at T3 and T6, HDL notably raised at T6 [all P!0.05].
EP693
Fasting plasma glucose and HbA1c decreased at T3 and T6; HOMA index
Visceral vs subcutaneous white adipose depots response to insulin
improved over time
[all P!0.05]. Prevalence of MS according to
treatments in rats
IDF/AHA/NHLB harmonized definition in our population was 50% at
Milica Markelic1, Aleksandra Jankovic2, Igor Golic1, Marija Aleksic1,
baseline, 10 times higher for age than average prevalence in literature; at 6
Ana Stancic2, Vesna Otasevic2, Sava Masovic2, Marija Marin1, Bato Korac2
months such prevalence decreased to 16%. In conclusion, in our population
& Aleksandra Korac1
of patients undergoing bariatric surgery and a dedicated follow-up program,
1University of Belgrade, Faculty of Biology, Belgrade, Serbia;2University
we observed a trend towards a noticeable improvement of the metabolic
of Belgrade, Institute for Biological Research “Sinisa Stankovic”, Belgrade,
profile in the mid-term.
Serbia.
DOI: 10.1530/endoabs.49.EP691
White adipose tissue (WAT) has an important role in the regulation of metabolic
homeostasis. It is well known that two distinct WAT depots in mammals,
subcutaneous WAT (sWAT) and visceral WAT (vWAT) display different
metabolic roles and it could be presumed that exert different response to various
hormones. Numerous studies revealed leading role of insulin in both fat
accumulation (lipogenesis) and adipocyte differentiation (adipogenesis) although
it is not clear is there a difference in response among these two depots. The aim of
this study was to reveal effects of insulin treatments on sWAT and vWAT
EP692
morphology. Male Wistar rats were treated acutely (1 day) or chronically (3 days)
with low (0.4 IU/kg bm) or high (4 IU/kg bm) dose of insulin. Saline-treated
Hydroxysteroid (17beta) dehydrogenase 13 knockout mice present with
animals served as controls. The portions of retroperitoneal, epididymal and
inflammation associated liver steatosis
subcutaneous WAT (rWAT, eWAT, sWAT, respectively) were removed and
Hanna Heikela1, Marion Adam1, Dorothea Portius2, Jenni Mäki-Jouppila1,
prepared for microscopic and Western blot analyses. Tissue components
Arfa Mehmood1,3, Prem Adhikari1, Irene Esposito4, Laura Elo3,5,
(adipocytes, blood vessels and stroma) volume density and cell profile density
Fu-Ping Zhang1, Suvi T Ruohonen1, Leena Strauss1, Michelangelo Foti2 &
per unit area were determined. To establish adipogenic origin of multi-
Matti Poutanen1
locular/paucilocular cells PCNA immunoexpression was examined, while protein
1Department of Physiology, Institute of Biomedicine and Turku Center for
expression and cell presence of phosphorylated form (phospho-IR) of insulin
Disease Modeling University of Turku, Turku, Finland;2Department of Cell
receptor (IR) was used to analyze insulin signaling. Our results demonstrate
Physiology and Metabolism, Faculty of Medicine, Centre Médical
slightly higher number of adipocytes and adipogenic cells and increased
Universiatire, Geneva, Switzerland;3Turku Centre for Biotechnology,
capillarization in vWAT depots. A stronger response of vWAT to insulin
University of Turku and
˚boAkademiUniversity,Turku,Finland; 4Institute
treatment in comparison to sWAT is due to higher phospho-IR expression in
of Pathology, Technische Universitat Munchen, Munich, Germany;
endothelial and multilocular/paucilocular cells of analyzed vWAT depots.
5Department of Mathematics and Statistics, University of Turku, Turku,
Namely, in hyperinsulinaemia canonical insulin-signaling pathway favors
Finland.
adipogenesis and capillary remodeling in vWAT to a greater extent than in
sWAT depot. Our results suggest that insulin-induced differences in remodeling
of sWAT and vWAT depots may contribute to visceral obesity and development
Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a group of enzymes
and progression of insulin resistance and diabetes type 2 among other visceral
that are characterized by their sequence similarity at the active site, and their
obesity-associated metabolic diseases.
ability to catalyze the conversion between the weak 17keto- and the highly active
DOI: 10.1530/endoabs.49.EP693
17beta-hydroxysteroids. To study the physiological role of HSD17B13, a lipid
droplet associated protein, we characterized the phenotype of knockout (KO)
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP694
detected in patients with obesity and hypogonadism as compared with the 1st
group. There were a significant activation of CD16C lymphocytes (19.0[16.0;
Association between obesity and glomerular hyperfiltration: impact on
23.0] vs 12.0[9.0; 15.0]%) and reduction of the CD25C cells number (1.4[1.0;
metabolic risk factors
1.7] vs 1.9[1.8; 2.11]%), which reflects the early T-lymphocyte activation, in
Mirjana Sumarac-Dumanovic1,2, Ana Gligic-Kuzmanovic2,
patients of the 2nd group (P!0.0001).
Danica Stamenkovic-Pejkovic1,2, Snezana Polovina2, Danka Jeremic2,
Conclusion
Goran Cvijovic1,2, Svetlana Zoric2 & Dragan Micic1,2
The excessive accumulation of adipose tissue leads to dysfunction of the helper-
1School of Medicine, University of Belgrade, Belgrade, Serbia;2Clinic for
cell immunity. Hypogonadism with obesity aggravates the imbalance of cell
Endocrinology, Diabetes and Diseases of Metabolism, Center for Obesity,
immunity, which could contribute to the formation of additional metabolic and
Clinical Center of Serbia, Belgrade, Serbia.
immunological disturbances.
DOI: 10.1530/endoabs.49.EP695
Abstract
Glomerular hyperfiltration has been suggested as a possible mechanism linking
obesity and chronic kidney disease, independently of classical risk factors such as
diabetes. In terms of determining the creatinine clearance has numerous
drawbacks, in clinical use are predictors of glomerular filtration rate (GFR)
which show varying degrees of accuracy in obese patients. The aim of our study
was to determine whether it is in our group of obese patients without type 2
EP696
diabetes, glomerular hyperfiltration associated with metabolic disorders. This
GLP-1 therapy and the immune system - can we predict responders
cross-sectional study included 30 obese patients at the beginning of treatment in
from non-responders?
Center for Obesity. Excluded were patients with type 2 diabetes, moderate/severe
Donal O’Shea1,2, Laura Tobin2,3, Declan Cody3, Arimin Mat1,2,
hypertension and cardiovascular comorbidity. We analyzed metabolic parameters
David Kinlen1,3 & Andrew Hogan1,3
(fasting glucose and insulin, HOMA-IR, HbA1c, liver enzymes and renal function
1University College Dublin, Dublin, Ireland;2St Vincent’s University
(GFR, proteinuria and albuminuria). According to the degree of GFR determined
Hospital, Dublin, Ireland;3National Children’s Research Centre, Dublin,
by: 1. the creatinine clearance (CCR); 2. The use of predictors GFR - MDRD and
Ireland.
Cockcroft-Gault (CGO) equation, patients were divided into two groups: with
hyperfiltration and with normal levels of glomerular filtration rate. According
to the level of GFR,
44.4% (CCR),
25.9% (MDRD), 66.7% (CCE) had
Abstract
hyperfiltration, while 55.6% (CCR), 74.1% (MDRD) 33.3% (cGO) patients had
Obesity has reached epidemic proportions globally. At least 2.8 million people die
normal filtration. Patients with hyperfiltration had significantly higher fasting
each year as a result of being overweight or obese, the biggest burden being
glycemia (CCR: 4.9G0.8 vs 4.7G0.5, PZ0.038; MDRD: 5.1G0.3G0.9 vs 4.9,
obesity-related diseases. Glucagon like peptide 1 (GLP-1) targeted therapies show
PZ0.039; cGO: 5.2G0.9 vs 4.7G0.5, PZ0.049) and HbA1c (CCR: 6.1G0.4 vs
the greatest potential for intervention and are approved as weight loss agents.
5.6G0.6, PZ0.015; MDRD: 5.8G0.9 vs 5.3G0.3, PZ0.022; cGO: 6.1G0.4 vs
However not all patients respond to GLP-1
therapy. Understanding the
5.3G0.3, PZ0.038) compared to patients with normal filtration. The value of
mechanisms of bodyweight regulation and their role in GLP-1 responders vs.
gamma-GT was significantly higher in the group of patients with hyperfiltration
non-responders is essential to better serve our patients. We have previously shown
compared another group [CCR: 30 (18-80) vs 24 (15-58), PZ0.080; MDRD:
that invariant natural killer T (iNKT) cells, which resides in adipose tissue, and
29.5
(19-80) vs 24.5 (15-58), PZ0.006; CGO: 41 (15-80) vs 18 (15-27),
acts as adipose tissue regulators are required for the full weight loss effect of GLP-
PZ0.003]. In our group of patients has been shown that obese patients with
1, a licensed weight loss therapy. In the absence of iNKT cells, GLP-1 therapy is
glomerular hyperfiltration had significantly higher values of the parameters of
30% less effective at inducing weight loss, due to a loss of FGF-21
and
glycemic control and gamma-GT compared to those with normal levels of
thermogenic reprogramming. In the current project we have extended our findings
filtration, regardless of age and BMI, which could suggest important
from murine models into humans investigating the adipose tissue metabolic
interrelationship among the initial development of chronic kidney disease with
pathways induced by GLP-1 therapy in patients who display significant weight
rediabetes and nonalcoholic fatty liver disease in obesity.
loss and a subset who fail to lose weight. We have also investigated if two
DOI: 10.1530/endoabs.49.EP694
immune cell derived proteins associated with obesity and insulin resistance
(soluble CD163 and Galectin-3) could be used to predict responses to intervention
(GLP-1 therapy or RYGB). We show that sCD163 but not Gal-3 is elevated in
obesity from childhood through to adulthood, and within 1 week of RYGB and
8 weeks of GLP-1 therapy sCD163 levels are significantly reduced. Overall this
project sheds light on novel mechanisms of bodyweight regulation and highlights
the possible use of sCD163 in mapping the progression of obesity and predicting
responders from non-responders to intervention.
EP695
DOI: 10.1530/endoabs.49.EP696
Characteristics of cellular immunity in men with obesity and
hypogonadism
Elizaveta Dzantieva, Irina Khripun, Zalina Gusova, Sergey Vorobiev,
Yanina Allakhverdieva, Natalia Kuzmenko & Ekaterina Petrovskaya
Rostov State Medical University, Rostov-on-Don, Russia.
Abstract
EP697
There are few studies of the cellular immunity in men with obesity and
An assessment of the relationship between abdominal obesity and the
hypogonadism. The aim was to study the parameters of cellular components of the
severity of upper extremity lymphedema
immune system in patients with obesity and hypogonadism.
YunKyung Jeon, MyungJun Shin, YongBeom Shin, InJoo Kim &
Materials and methods
BoHyen Kim
The study included 120 men aged 40-65 years with obesity (mean BMI - 35G
Pusan National University Hospital, Busan, Republic of Korea.
5.6 kg/m2). Patients were divided into two groups depending on the level of total
testosterone (T). The first group included 56 patients with T levelO12.1 ng/ml
(mean T
-
16.3G3.8 ng/ml), the second group
-
64
patients with T
Abstract
level%12.1 ng/ml (mean T - 8.3G1.9 ng/ml). The control group consisted of
Obesity is one of the well-known initiating and aggravating factor of
25 healthy men with BMI up to 25 kg/m2. Levels of CD3C,CD4C,CD8C,
lymphedema. BMI is typically used to define obesity, but in Asian populations,
CD16C,CD25C lymphocytes were analysed. Statistical data were analysed
health risks are elevated at lower BMI levels and abdominal fat may be a better
using Mann-Whitney U-test.
obesity metric. Thus, we assessed the potential association between abdominal
Results
obesity and lymphedema severity in postoperative breast cancer patients. Thirty-
Level of CD4CT helper cells was significantly lower in the 1st group as
three women with breast cancer-related lymphedema participated in this study.
compared to the control group (41[38; 45]% vs 46[44; 47]%, P!0.005). Level of
Arm circumference was measured at four locations per arm to identify the
cytotoxic lymphocytes CD16C was higher in the 1st group as compared to the
maximal circumference difference (MCD) between the affected and unaffected
control (12.0[9.0; 15.0] vs 9.0[9.0; 10.0]%, (P!0.005). Significant changes in
sides. All patients underwent lymphoscintigraphy and we calculated the
other parameters were not found. Changes in T-cell immune system, namely in
quantitative asymmetry index (QAI) of both arms. A computed tomography
reduction of CD4C lymphocytes (32[28; 39] vs 41[38; 45]%, (P!0.001) and
(CT) was also performed to assess abdominal obesity after lymphedema.
increasing of CD8C lymphocytes (28[26;30] vs 24[20; 29]%, (P!0,05), were
Abdominal obesity was classified as a visceral fat cross-sectional area larger than
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
70 cm2. Fourteen women (42%) were obese (BMIR25 kg/m2) and 18 women
involvement with cardiovascular disease (CVD), however, has not yet been
(54%) had increased abdominal fat. BMI obesity and abdominal obesity were
elucidated. The aim of the current study was to shed light on the potential
significantly correlated, but five patients were classified with abdominal obesity
association with irisin and cardiovascular risk.
despite a BMI below 25 kg/m2. There were no significant differences in age, time
Methods
after surgery, cancer stage, history of axillary lymph node dissection,
Eighty patients with obesity (BMI R 30 kg/m2) and mean age 50,4G10,6 years
chemotherapy, or radiotherapy between patients with and without obesity. The
were included in the study which was realized in a third level university endocrine
mean arm circumference difference was 2.8G2.4 cm. Decreased axillary QAI
department. Biochemical measurements consisted of fasting plasma glucose,
was significantly correlated with obesity, and increased arm edema
serum immunoreactive insulin, serum uric acid, lipid profiles, liver enzymes.
(MCDR2 cm) was significantly correlated with abdominal obesity. Abdominal
Measurements of weight, height, waist circumference and arterial blood pressure
obesity was significantly correlated with increased MCD and should be
were performed. Cardiovascular risk was estimated by means of Framingham
considered along with obesity as an aggravating factor for lymphedema severity.
Risk Score calculation and a measurement of mean carotid intima media
DOI: 10.1530/endoabs.49.EP697
thickness (CIMT) as measured by an automated software via B-mode ultrasound.
Ankle-brachial index (ABI) measurement was also performed. Circulating serum
irisin was measured by a commercially available ELISA kit.
Results
Among parameters of interest, circulating irisin correlated positively with BMI
(rZ0, 246, P!0,05) and negatively with age (rZK0,457, P!0,001), total
EP698
cholesterol (rZK0,246, P!0,05), LDL-cholesterol (rZK0,234, P!0,05), ABI
(rZK0,272, P!0,05). CIMT (rZK0,353, P!0,01) and with Framingham Risk
Associations between the dysregulation of splicing machinery
Score (rZK0,400, P!0,01). Associations with CIMT, Framingham Risk Score
components and the development of hepatic steatosis in obese women
and ABI persisted after adjustment for age and sex. In a ROC-curve analysis
Mercedes del Río-Moreno1, Sergio Pedraza-Arévalo1, Sandra González-
circulating serum irisin was of use
(AUCZ0,665, 95%CI:
0,525-0,804,
Rubio2, Gustavo Ferrín2, Manuel Rodríguez-Perálvarez2, Rhonda
PZ0,037) for distinguishing subjects with CIMT R 75th percentile, which was
D Kineman3, Alejandro Ibán˜ez-Costa1, Manuel de la Mata2, Justo
found in 32,5% of the study participants
P Castan˜o1, Raúl M Luque1 & Manuel D Gahete1
Conclusions
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina
Circulating irisin levels were negatively associated with established CVD
Sofia University Hospital (HURS); Department of Cell Biology, Physiology
estimates. Irisinaemia could be useful for distinguishing subjects with increased
and Immunology, University of Cordoba (UCO); CIBER Physi, Cordoba,
CIMT. Larger, prospective studies are required to establish the particular
Spain;2Department of Hepatology and Liver Transplantation, HURS/I-
mechanisms for these observations.
MIBIC; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd),
Cordoba, Spain;3Research and Development Division, Jesse Brown
DOI: 10.1530/endoabs.49.EP699
Veterans Affairs Medical Center and Department of Medicine, Section of
Endocrinology, Diabetes, and Metabolism, University of Illinois at Chicago,
Chicago, Illinois, USA.
Hepatic steatosis is a common obesity-associated pathology characterized by the
accumulation of fat within the liver, which can progress to liver fibrosis, cirrhosis
EP700
and ultimately lead to hepatocellular carcinoma. Remarkably, obesity and cancer
course with a profound dysregulation of the genetic expression patterns and,
Circulating adipomyokines, inflammatory marker, insulin resistance,
particularly, with the aberrant expression of splicing variants that could contribute
and physical fitness among severely obese Korean children and
to the aggressiveness and comorbidities of these pathologies. Since the
adolescents
appearance of alternative splicing variants could be related to a dysregulation
Kyung Hee Park1, Young-Gyun Seo1, Hye Ja Lee2, Han Byul Chang2, Sang
of the cellular machinery responsible for this process ((spliceosome core elements
Ick Park2, Yoon Myung Kim3 & Hyun Jung Lim4
and splicing factors (SFs)), the objective of the present study was to determine the
1Hallym University Sacred Heart Hospital, Anyang-si, Republic of Korea;
association between the expression pattern of the components of this machinery
2National Institute of Health, Cheongwon, Republic of Korea;3Yonsei
and hepatic steatosis of obese patients. To this end, we collected clinical and
University, Seoul, Republic of Korea;4Kyung Hee University, Seoul,
demographic data and liver biopsy samples from obese women (IMCO30) with
Republic of Korea.
(nZ32) and without (nZ9) hepatic steatosis. RNA from liver samples was
extracted and retrotranscribed to determine the expression levels of selected
Background
components of the major (nZ13) and minor spliceosome (nZ4), and associated
Associations between obesity and adipomyokines, inflammatory marker, and
SFs (nZ28) using a qPCR-based array. Results revealed that the liver of steatotic
level of physical fitness have not been well evaluated in severe obesity in children
patients exhibit a profound dysregulation of certain spliceosome components and
and adolescents.
SFs compared to non-steatotic patients (e.g. RNU6, SF3b1, etc.). Although these
Method
alterations were not associated with the hepatic steatosis level, the expression
Data on leptin, irisin, FGF21, hsCRP, glucose, insulin, physical fitness measured
pattern of the components of this cellular machinery could define discrete groups
by arm curl test for upper extremity)and wall sit test for lower extremity were
of steatotic patients that presented similar alterations in certain spliceosome
obtained in 266 participants who were recruited for ICAAN study, community-
components and SFs. Interestingly, these groups of patients were also
based multidisciplinary weight control program in severely obese Korean
characterized by particular hepatic and clinical-metabolic alterations (e.g. ALT,
children and adolescents. Participants were classified into 3 groups according to
hyperglicemia, hyperinsulinemia, etc.). Therefore, although further confirmatory
their BMI status based on sex and age-specific BMI percentiles: severely obese
studies are needed, these results could suggest that the development of hepatic
(SO,R120% of the 95th percentile), overweight or obse (OB, 85th-!120% of the
steatosis and its associated comorbidities could be linked to the dysregulation of
95th percentile), and non-obese (NW,!85th). Levels of circulating adipomyo-
certain components of the splicing machinery, which may provide novel
kines, inflammatory marker, insulin resistance (HOMA-IR), and physical fitness
diagnostic/therapeutic tools for this pathology.
were compared across the groups adjusted for sex and age. Cross-sectional
DOI: 10.1530/endoabs.49.EP698
associations between obesity status and biomarker levels and physical fitness
were assessed.
Results
Participants in SO group tended to have higher levels of leptin(NW, 12.19G1.05:
OB, 25.64G1.05: SO, 40.77G1.09), hsCRP (NW, 0.37G1.09: OB,1.18G1.09:
EP699
SO,1.82G1.16), and HOMA-IR (NW, 1.78G1.06: OB, 3.55G1.06: SO, 6.28G
1.10) compared to participants in NW or OB(all P for trend !0.001). Levels of
Irisin and cardiovascular risk
physical fitness tended to be significantly decreased across the BMI groups (P for
Yavor Assyov1,2, Antoaneta Gateva1,2 & Zdravko Kamenov1,2
trend, arm curl test 0.03: wall sit test !0.001). Circulating levels of irisin showed
1Medical University, Sofia, Bulgaria;2University Hospital Alexandrovska,
overall significance (P for trend 0.04), but did not show significant difference
Sofia, Bulgaria.
between groups. FGF-21 did not show significant difference across the BMI
groups.
Aims
Conclusions
Irisin is a recently discovered myokine that has been implicated in the
Severe obesity in children and adolescents compared with NW or OB is
pathogenesis of type
2 diabetes
(T2D) and metabolic syndrome (MS). Its
associated with higher levels of leptin, inflammatory marker and insulin
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
resistance and lower levels of physical fitness, which implies problems with
positively related with E/A ratio (rZ0.26 P!0.001) and inversely with left
further weight gain and cardio-metabolic health risks.
ventricular mass index (LVMi) (rZK0.20 P!0.01) and carotid intima-media
DOI: 10.1530/endoabs.49.EP700
thickness (cIMT) (rZK0.24 P!0.005). Urinary free cortisol was positively
related with EFT (rZ0.22 P!0.001). Circulating IGF1 levels were positively
related to E/A ratio (rZ0.27 P!0.001) and negatively correlated with EFT
(r-0.14 P!0.001), LVMi (rZK0.16 P!0.001), end diastolic left ventricular
diameter (rZK0.16 P!0.001), cIMT (rZK0.25 P!0.001), and left atrial
diameter
(rZK0.14 P!0.001). All the echocardiographic and hormonal
parameters evaluated showed significant correlation with the degree of weight
excess and the duration of obesity (P!0.001). In conclusion, cardiac function and
EP701
morphology associate with weight excess, duration of obesity and anabolic
Genetic variants of the adiponectin gene and its association with
hormones deficiencies.
adiponectin level in metabolic syndrome women
DOI: 10.1530/endoabs.49.EP702
Abhishek Gupta1,2, Sunita Tiwari1, Suraksha Agrawal3,
Arun Kumar Singh1, Bhola Nath Paul4 & Katherine Cianflone5
1Department of Physiology, King George’s Medical University, Lucknow,
Uttar Pradesh, India;2Department of Molecular and Clinical Medicine,
University of Gothenburg, Gothenburg, Sweden;3Department of Medical
Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences,
Lucknow, Uttar Pradesh, India;4Immunobiology Division, Indian Institute
of Toxicology Research, Lucknow, Uttar Pradesh, India;5Department of
EP703
Medicine, Institut Universitaire de Cardiologie et de Pneumologie de
Are there any associations between vitamin D levels and insulin
Québec, Quebec, Canada.
resistance in obese patients?
Omercan Topaloglu1, Bahri Evren1, Saim Yologlu2 & Ibrahim Sahin1
1
Inonu University Medical Faculty, Department of Endocrinology, Malatya,
Background
Turkey;2Inonu University Medical Faculty, Department of Biostatistics,
Adiponectin is an adipocyte-derived adipokine, down-regulated in obesity linked
Malatya, Turkey.
disorders. Here, we investigated the genotypic variability of adiponectin (at
position; CT45G and CG276T) and its association with circulating adiponectin
and metabolic syndrome in North Indian adult women.
Introduction
Methods
Most of the human studies suggested an association between obesity and low
We compared metabolic syndrome (MetS; 269) women to without metabolic
25(OH)D3 0levels. It has been proposed that co-existence of vitamin D deficiency
syndrome (wMetS; 272) women of North India. Genotype frequencies of the
may have a role in the development of IR in obesity. We aimed to reveal whether
adiponectin gene were performed using PCR-RFLP method and circulating
any association was present between IR and 25(OH)D3.
adiponectin estimated by sandwich ELISA method.
Materials-methods
Results
223 obese patients referred to our clinics were evaluated for the study. 24 patients
Low level of adiponectin (P!0.001) and high HOMA-IR were found (P!0.001)
with known diabetes mellitus were excluded. Finally, 199 patients were included
in MetS women. Gene frequency of combined mutant genotype (TGCGG) at
and anthropometric (height, body weight, body mass index) and biochemical
position C45T/G of adiponectin was found to be significantly less (PZ0.017)
(fasting blood glucose, HbA1c) and hormonal (fasting insulin, C-peptide, 25(OH)
while mutant G allele was significantly high (PZ0.008) in MetS women as
D3) measurements were assessed. We evaluated IR by ‘homeostasis model
respective to wild type. However, frequency of mutant T allele in MetS women
assessment of IR’ (HOMA-IR). The patients having HOMA-IR value of equal to
was found to be significantly (PZ0.027) less as compared to wMetS at position
or greater than 2.5 were accepted as insulin resistant. The patients were grouped
C276G/T of adiponectin gene. The mutant genotype GG of C45T/G and TT of
according to body mass index (BMI), HOMA-IR, and 25(OH)D3.
C276G/T of adiponectin were significantly associated with lower adiponectin
Results
level and higher HOMA-IR (all P!0.001) in adult metabolic syndrome.
25(OH)D3 levels were significantly lower in the groups of BMI O50 kg/m2 and
Conclusions
BMI 40-50 kg/m2 in comparison to the group of BMI!40 kg/m2 (mean 25(OH)
Results suggest that adiponectin gene variants might be associated with lower
D3 levels
12.0,
12.12,
17.02 ng/dl; respectively)
(PZ0.042, PZ0.025;
adiponectin level and metabolic syndrome.
respectively). BMI levels were significantly lower in the group of 25(OH)D3O
DOI: 10.1530/endoabs.49.EP701
30 ng/ml in comparison to the group of 25(OH)D3!10 ng/ml (mean BMI 42.27
; respectively) (PZ0.05). Likewise, there was significant negative
vs 45.59 kg/m2
correlation between BMI and 25(OH)D3 (PZ0.045, rZK0.142).There was no
difference between 25(OH)D3 levels in patients with IR (HOMAR2.5) and not
IR (HOMA!2.5) patients (PZ0.071). Similarly, there was no significant
correlation between HOMA-IR values and 25(OH)D3 levels (PZ0.98).
Conclusion
Our study showed that 25(OH)D3 levels decreased in obesity; and 25(OH)D3
EP702
levels were not different in patients having IR or not. These findings suggest
Obesity, cardiomyopathy and anabolic hormones
that decreased vitamin D levels in obesity may be result of increasing BMI rather
Elena Gangitano, Daniela Costantini, Rossella Tozzi, Francesca De Giorgi,
than IR.
Eleonora Poggiogalle, Stefania Mariani, Elisa Petrangeli, Lorenzo
DOI: 10.1530/endoabs.49.EP703
Maria Donini, G. Barbaro, Lucio Gnessi & Carla Lubrano
Sapienza University, Department of Experimental Medicine, Rome, Italy.
Obesity is associated with hemodynamic alterations that may lead to heart failure
(HF), through the development of cardiac structural abnormalities and
impairment of ventricular function. Obesity-related neurohormonal and meta-
bolic disturbances may predispose to HF, even in the absence of comorbidities.
EP704
Excess adipose tissue and in particular visceral adiposity contributes to the altered
Elevated serum adiponectin in Alzheimer’s disease as neuroprotective
production of a number of anabolic hormones also involved in the regulation of
strategy
the cardiac function. The aim of the present study was to evaluate cardiac
Liliana Letra1,2, Tiago Rodrigues1, Paulo Matafome1, Diana Duro2,
morphology and function by echocardiography and the relationships between
Raquel Lemos2, Miguel Patrício4, Miguel Castelo-Branco3, Inês Baldeiras5,
echocardiographic parameters, BMI and hormonal status in a population of obese
Raquel Seiça1 & Isabel Santana2,6
patients. 1821 patients (mean age 46.94G13.62 yrs, 1331 females and 490 males)
1Physiology Laboratory, IBILI, Faculty of Medicine, University of
were studied. 157 were normal weight (BMI 22.14G1.83), 247 overweight (BMI
Coimbra, Coimbra, Portugal;2Neurology Department, Centro Hospitalar e
27.76G1.45), and 1417 obese (BMI 39.39G6.88). Anthropometric data, blood
Universitário de Coimbra, Coimbra, Portugal;3IBILI, Faculty of Medicine,
pressure, lipid and glycemic parameters and a complete hormonal status were
University of Coimbra, Coimbra, Portugal;4Laboratory of Biostatistics and
recorded. Two-dimensional echocardiography and carotid intima/media thickness
Medical Informatics, IBILI, Faculty of Medicine, University of Coimbra,
measurement were performed. Total testosterone in males and SHBG in both
Coimbra, Portugal;5Laboratory of Neurochemistry, Centro Hospitalar e
sexes were significantly and inversely correlated with epicardial fat thickness
Universitário de Coimbra, Coimbra, Portugal;6Faculty of Medicine,
(EFT) (rZK0.33 and rZK0.44, P!0.001). Circulating levels of DHEAS were
University of Coimbra, Coimbra, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
therapeutic use gets more difficult, because it was restricted to dietetic
Several studies have highlighted the contribution of adipose tissue dysfunction to
modifications and not having medicines that have indication by FDA during
the development and progression of Alzheimer’s Disease (AD), which may
pregnancy.
depend on alterations in adipokine secretion. Leptin and adiponectin are the most
DOI: 10.1530/endoabs.49.EP705
abundant adipokines in circulation, with recognized systemic effects, but also able
to cross the blood-brain barrier and influence cognitive-related structures, such as
the hippocampus.
Objective
To determine if serum and CSF adiponectin and leptin/adiponectin ratio are
correlated with AD biomarkers and can constitute predictors of progression.
Methods
EP706
A total of 53 AD and 71 aMCI subjects (mild cognitive impairment amnestic
Folate: a new player in metabolic syndrome?
type) were included and underwent a thorough clinical and neuropsychological
Silvia Paredes1,2, Marta Alves1, Maria Lopes Pereira1, José Maia da Costa1,
evaluation (MMSE, MoCA, ADAS-Cog). Serum and CSF adiponectin and leptin,
Aline Fernandes1, Fernando Manso1, Olinda Marques1 & Laura Ribeiro2,3
serum insulin and AD biomarkers (CSF Ab42, t-tau, p-tau and hippocampal
1Hospital de Braga, Braga, Portugal;2Faculty of Medicine, University of
formation volumetry) were also performed. Sixty-seven MCI patients had clinical
Porto, Porto, Portugal;3I3S-Instituto de Investiga
¸
˜o e Inova
¸a˜o em Saúde,
and neuropsychological follow-up in order to identify progression to AD.
Universidade do Porto, Porto, Portugal.
Results
Serum adiponectin was 33% higher in AD when compared to MCI. In CSF, leptin
and t-tau showed a negative correlation in AD patients (rZK0.597, PZ0.026)
Introduction
while adiponectin was positively correlated with Ab42 (rZ0.590, PZ0.002), but
Bariatric surgery (BS) candidates display several nutritional deficiencies that can
only in women. A robust association between CSF adiponectin and hippocampal
aggravate after surgery. Metabolic syndrome (MS) is a cluster of cardiovascular
volume was observed in a subgroup of patients with CSF-based AD diagnosis.
risk factors with several disturbed metabolic pathways. Therefore, individuals
However, no correlation was found with total cognitive scores. Twenty-seven
with MS submitted to BS are probably more prone to nutritional deficiencies.
MCI progressed to AD upon a mean follow-up of 38.2G18.83 months, whereas
Objective
40 maintained the diagnosis. Baseline serum and CSF adipokine levels were
To evaluate the prevalence of nutritional deficiencies and eventual differences
similar in both groups. Only serum adiponectin positively correlated with time of
between BS candidates with and without MS.
progression (rZ0.484, PZ0.049), though incapable of predicting progression to
Materials and methods
dementia.
Retrospectively, databases of 385 patients who underwent BS between 01/2011
Conclusions
and 07/2015 were analyzed. Nine subjects were excluded due to missing data on
Higher CSF adiponectin levels are associated with less Ab42 deposition and
MS parameters. Subjects with R3 criteria according to the NCEP ATP III report
higher hippocampal volume. Accordingly, higher adiponectinemia observed in
were classified as having MS.
AD could be looked as a strategy to maintain its central levels and, consequently,
Results
its beneficial effects.
A total of 181 individuals with MS (150 females, body mass index (BMI) 44.56G
DOI: 10.1530/endoabs.49.EP704
6.4, mean age 45.14G10.9) and 195 without MS (174 females, BMI 42.98G5.9,
mean age 39.44G9.3) were included. No significant differences were found in
iron metabolism (iron/ferritin/hemoglobin), vitamin B12, vitamin D, albumin and
homocysteine between males and females with and without MS. However, both
males and females with MS had significantly higher levels of folate than
individuals without MS. Males with MS exhibited significantly lower levels of
magnesium comparing to males without MS. In females, folate was positively
associated with glucose
(rZ0.206; P!0,001), glycated hemoglobin
(A1c)
EP705
(rZ0.294; P!0,001), total cholesterol (rZ0.153; PZ0.006) and low-density-
Late dumping syndrome in pregnant women after ROUX-EN-Y gastric
lipoproteina cholesterol (rZ0.117; PZ0.037). In males, folate was positively
bypass (RYGB) surgery
associated with glucose (rZ0.402; PZ0.003), A1c (rZ0.362; PZ0.012) and
Lucía Vera Pacheco1, María Teresa Gallego García2, Cristina Del Peso
triglycerides
(rZ0.372; PZ0.007), whereas magnesium was negatively
Gilsanz2, Lorena Rentero Redondo2, Carles Iniesta Navalón2, Noelia
associated with glucose
(rZK0.437; PZ0.01) and A1c
(rZK0.298;
Victoria García-Talavera Espín2, Ma Bienvenida García-Talavera Espín2,
PZ0.042).
Manuel Romero Mun˜oz1 & Amparo Meoro Avilés2
Conclusion
1University Hospital Rafael Mendez, Lorca,Murcia, Spain;2University
There were no significant differences in nutritional deficiencies between
Hospital Reina Sofía, Murcia, Spain.
individuals with and without MS. However, in our study individuals with MS
presented significantly higher folate levels than individuals without MS.
Interestingly enough, folate levels positively associated with lipid and glucose
Introduction
metabolism. The metabolic and clinical significance of our results warrants
Dumping syndromes are common after bariatric surgery and can present
further investigation.
diagnostic and therapeutic challenges in pregnancy.
DOI: 10.1530/endoabs.49.EP706
Case report
A 23-year-old female who underwent a RYGB surgery because of morbid obesity
in 2013. She had no medical history of diabetes nor any other comorbidity related
to obesity. Two years later, her weight had reduced from 128 to 76 kg and also her
body mass index
(BMI) from
43.8
to
26 kg/m2. She was treated with
multivitamins, iron vitamin B12
and calcium. She remained clinically
EP707
asymptomatic. In 2016, she got pregnant and on the 24th gestational week she
Evolution of body composition 3 years after sleeve gastrectomy
checked herself post prandial capillary blood glucose (CBG) that confirmed
Silvia Paredes1,2, Marta Alves1, Maria Lopes Pereira1, José Maia da Costa1,
hypoglycemia, with glucose levels from 55 mg/dl to 30 mg/dl, accompanied
Aline Fernandes1, Fernando Manso1, Olinda Marques1 & Laura Ribeiro2,3
by clinical intense asthenia. Fasting plasma glucose was 71 mg/dl and insulin
1Hospital de Braga, Braga, Portugal;2Faculty of Medicine of the University
5 mIU / ml (2.6-24.9). Dietary modification with frequent intakes every 3 hours,
of Porto, Porto, Portugal;3I3S-Instituto de Investiga
¸
˜o e Inova
¸
˜o em
with low glycaemic index food and avoidance of physical activity immediately
Saúde, Universidade do Porto, Porto, Portugal.
after oral intake were recommended. At the beginning, the episodes were reduced,
but on the 35th gestational week hypoglycemia episodes had increased in severity
and frequency, raising concerns of the risk of maternal neuroglycopenia and
Background
fetal hypoglycemia, that’s why it was decided to treated with Diabetes-specific
Sleeve gastrectomy (SG) has effective results on weight loss, which should result
Oral Nutritional Supplement (low in carbohydrates with no added sucrose, high
from fat mass loss and efforts should be made to preserve lean mass. Few studies
in protein and contains soluble fiber) twice a day between the main meals.
have evaluated body composition (BC) changes after SG for periods O2 years.
Finally, on the 39th gestational week an induced birth was planned of a healthy
Objective
31oo-g infant, with a nearly complete remission of the dumping syndrome after
To investigate the impact of SG on weight and BC, comparing by gender.
giving birth.
Materials and methods
Conclusions
Retrospectively, databases of patients who underwent SG between 2011 and 2013
Dumping syndromes in pregnant women that have gone through a RYGB surgery
were analyzed. Data was obtained before and 1, 2 and 3 years after SG. BC was
need to be distinguished from common symptoms of a normal pregnancy. Its
measured by bioelectrical impedance.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Introduction
Fifty-five females, mean age 42.11G10 years, mean body mass index (BMI)
Phthalates are ubiquitous endocrine disruptors (EDs). EDs induce obesity. MEP
44.59G4.9 Kg/m2 and 11 males, mean age 39.55G10.9 years, mean BMI
and MEHP affect thyroid function.
44.66G5.4 Kg/m2 were included. One year after SG, males had lost 36% of
Aim
weight, 67% of fat mass and 18% of lean mass. In females, 1 year after SG, weight
Estimation of burden of MEP and MEHP in our population, evaluation of leptin in
decreased 32%, fat mass 52% and lean mass 12%. Two and 3 years after surgery,
obese MEP and MEHP positive and negative subjects and evaluation of
males had lost 33% and 30% of weight, 59% and 53% of fat mass and 20% and
connection between leptin, MEP, MEHP and thyroid indicators in that subgroup.
19% of lean mass, respectively. In females, 2 and 3 years after surgery weight
Materials and methods: a cross-sectional study, with 201 subjects divided into
decreased 33% and 30%, fat mass 52% and 48% and lean mass by 14% and 13%,
MEP/MEHP positive and negative, subdivided in obese and lean. Anthropometric
respectively. Males presented the lowest weight and fat mass 1 year after surgery;
parameters done: body height, weight, waist and body mass index. Laboratory
females had the lowest weight and fat mass 2 years after SG.
tests: morning urine sample for MEP/MEHP and venous sample for free
Conclusion
thyroxine (FT4), free tri-iodothyronine (FT3), thyroid stimulating hormone (TSH)
Despite both genders show a weight loss of 30% 3 years after SG, males initially
and leptin. Statisycal analysis was done in SPSS. Results: Mean age of
lose more weight that is regained after the first year. Males also present a greater
36.74
participants was
(G8.55) years, 86 (42.8%) males and 115 (57.2%)
loss of lean mass. Our results highlight the need to develop strategies to avoid
females. There were 64 (31.2%) MEPC, and 44 (22%) MEHPC participants,
weight regain, which seems to start 1 and 2 years after SG, respectively for males
and 5 (5.05%) positive for both. There were 93 (46.3%) participants in obese
and females. Efforts should be also made in order to avoid lean mass loss.
subgroup, MEHP- 64 (68%), MEHPC29 (32%; MEPK 58(62%), MEPC38%).
DOI: 10.1530/endoabs.49.EP707
Independent t-test and Mann Whitney U test did not show statistical significance
in leptin level neither in MEPC and MEPK (t K0.316, P!0.753; Z K0.242,
P!0.809), nor in MEHPC and MEHPK obese participants
(t K1.049,
P!0.297; Z K1.377, P!0.169). Pearson correlation for leptin and FT4 in
obese MEPC subgroup was statistically significant (r K0.347, P!0.041). No
significant correlations were found for leptin with FT3 (r K0.123, P!0.48) and
EP708
TSH (r 0.078; P!0.655). In MEHPC obese patients we did not find any
Comparative study between laparoscopic gastric bypass and
significance (FT4: r 0.189, P!0.25; FT3: r K0.023, P!0.897; TSH r 0.062,
laparoscopic sleeve gastrectomy
P!0.928).
Aurora Aragón-Alonso, Mercedes Ferrer Gómez, José Ramón
Conclusion
Cuenca Sánchez, David Ruiz de Angulo Martín, María Dolores
Half of our population is exposed to MEHP and MEP. In obese subjects higher
Frutos Bernal, María Ángeles Campillo Espallardo, Pedro Segura Luque &
leptin correlates with lower FT4.
Antonio Hernández Martínez
DOI: 10.1530/endoabs.49.EP709
Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
Introduction
Bariatric surgery is currently considered the most effective treatment for morbid
obesity. Laparoscopic gastric bypass (LGB) and laparoscopic sleeve gastrectomy
(LSG) are the most widely used bariatric procedures today.
EP710
Objectives
Using diaserein on the patients with glucose intolerance
In this study we compared LGB and LSG in order to establish whether there is any
Kenan Cadirci1,2 & Kadri Yildiz1,2
superiority of one or the other in effectiveness and complications.
1Erzurum Regional and Educational Hospital, Erzurum, Turkey;
Methods
2Erzurum Palandoken State Hospital, Erzurum, Turkey.
We included all the patients who underwent bariatric surgery in Hospital
Universitario Virgen de la Arrixaca during one year (nZ101) of which 62
received LGB and 39 LSG. Both groups were comparable in age, body max
Diaserein is used in the spesific and long-term treatment of degenerative joint
index, rates of hypertension (HT), type 2 DM (T2DM), hypercholesterolemia
diseases (as osteoarthritis). In vitro studies have showed that Diaserein and its
(Hchol), hypertriglyceridemia
(HTG) and obstructive sleep apnea syndrome
active metabolyte Rheinin inhibate production and activity of interleukin-113
(OSA). A higher percentage of women was present in the LGB group. We
(IL-113), some proinflamatuar and pro-catabolic cytokines. Interleukin-113 play
retrospectively compared postoperative complications and excess weight loss
important role to trigger production of more pro-inflamatuar factors as cytokines,
(EWL) and comorbidity resolution (HT, T2DM, Hchol, HTG and OSA) at one
cyclo-oxygeneas, prostogalandines, nitric oxide, matrix metalloproteinases in
year after surgery.
chondrocyte degradation, snobial enflamation, remodelling of subchondral bone.
Results
Diaserein stimulates Transformic Growth Factor 13 (TGF-13) even if IL-113
LGB was superior to LSG in HT remission (75% vs 43.8%, PZ0.046) and Hchol
exists. Diaserein stimulates synthesis of chondral matrix components as
remission (96.3% vs 33.3%, P!0.001). We found no significant differences
proteoglicans, glicoseaminoglicans, hyaluronic asids. After all Diaserein
between LGB and LSG regarding EWL (77.7%G23.3 vs 76.9%G17.8), T2DM
decreases the lost of chondral components continuously. We present 41 case
remission (78.6% vs 75%), HTG resolution (86.7% vs 75%) and OSA remission
series of patients that is used Diaserein on the treatment of osteoarthritis in
(55.6% vs 16.7%). Also, both techniques were comparable regarding rate of
various joints
(gonarthroisis, coxarthritis, dejenerative lomber diseases).
41
postoperative complications (17.7% vs 10.3%).
patients have followed up clinically in 2014-2016. 17 patients in this serie have
Conclusions
show intolerance to medicine by diarrhea, vomitting and some clinical
At one year postsurgery, LGB was superior to LSG in HT and Hchol remission.
compliants. At the research of these intolareted patients 16 patients have glucose
However, both techniques are comparable in terms of safety, weight loss and
intolerance as Diabetes Mellitus Type 1 and 2. At the researching of literature,
resolution of other comorbidities (T2DM, HTG and OSA).
Diaserein were not advised severe renal insufficiency, gastrointestinal disorder
(Chrone, Ulserative Colit.), hepatic insufficiency and also glucose intolerance.
DOI: 10.1530/endoabs.49.EP708
Diaserein must be used carefully on the patients that have renal and hepatic
insufficiency and failure. And also it must not be preferred on the patients which
have glucose intolerance because of seein severe side effects.
DOI: 10.1530/endoabs.49.EP710
EP709
Prevalence of mono-ethyl-hexyl phthalate and mono-ethyl phthalate in
Serbian population and their influence on leptin and thyroid function in
obesity
EP711
Ivana Bajkin1,2, Natasa Milic2,3, Jovanka Novakovic-Paro1,2, Tijana Icin1,2,
Bone mineral density in obese patients
Jovana Prodanovic1, Nikola Curic2,4, Bojan Vukovic1,2 &
El Ansari Nawal, Fatima Zahra Zaher & Ghizlane Elmghari
Milica Medic-Stojanoska1,2
Department of Endocrinology, Diabetes, Metabolic diseases and Nutrition,
1Clinic of Endocrinology, Diabetes And Metabolic Disorders, Clinical
Mohammed VI University Hospital, Marrakesh, Morocco.
Center of Vojvodina, Novi Sad, Vojvodina, Serbia;2Faculty of Medicine,
University of Novi Sad, Novi Sad, Vojvodina, Serbia;3Department of
Pharmacy, University of Novi Sad, Novi Sad, Vojvodina, Serbia;4Center for
Background
Laboratory Medicine, Clinical Center of Vojvodina, Novi Sad, Vojvodina,
Obesity and osteoporosis are two public health problems with an increasing
Serbia.
prevalence and high impact on morbidity and mortality which, during the last two
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
decades, have become major health threats worldwide. However, obesity has long
lean body mass. The aim of the present study was to explore muscle strength (as a
been considered as a protective factor against osteoporosis. The purpose of our
functional consequence of sarcopenic obesity) and muscle quality
(namely,
study was to evaluate the bone mineral density in obese patients followed at
myosteatosis) in women with and without the Metabolic Syndrome (MetS).
Mohammed VI university hospital.
Methods
Methods
Study participants were enrolled at the Sapienza University, Rome, Italy. Body
Our study has included 35 patients followed for obesity. Bone mineram density
composition was assessed through DXA. The Handgrip strength test (HGST) was
was ordered in all patients.
performed to assess muscle strength using a dynamometer (Dynex, Akern).
Results
HGST was normalized to arm lean mass; intramuscular adipose tissue (IMAT)
The mean age was 40 years, ranging between 21 and 69 years, 94.2% of our
and intramyocellular lipid content (IMCL) were measured by magnetic resonance
patients were female, mean body mass index was 43.9 kg/m2 with an average
spectroscopy, and used as indicators of myosteatosis. The MetS was diagnosed
waist circumference of 120 cm, over two thirds of the patients were morbidly
according to the NCEP-ATPIII criteria. HOMA-IR was calculated; C-reactive
obese, 31.4% had diabetes and 14.2% had hypertension, 18.1% of our female
protein
(CRP) levels were measured. The International Physical Activity
patients were postmenopausal. One female patient had osteopenia with a T score
Questionnaire (IPAQ) was administered to assess the physical activity level
of K1.2 at the spine. The rest of our patients had normal bone mineral density
(PAL).
with a mean T score at the spine and the femur of 0.65 and 1.39 respectively.
Results
Conclusion
54 women (age: 48G14 years, BMI: 37.9G5.4 kg/m2) were included. MetS was
Obesity is associated with normal bone mineral density even in postmenopausal
diagnosed in 54% of subjects. HGST/arm lean mass was lower in women with the
obese women, suggesting a protective effect of obesity against osteoporosis that
MetS compared to their counterparts without the MetS (6.3G1.8 vs 7.8G1.6,
was highlighted in several literature studies. That said, this beneficial effect
PZ0.03). HGST/arm lean mass was negatively associated to HOMA-IR (beta:
should always be weighed against its adverse effects especially the metabolic and
K0.37, S.E.:0.16, PZ0.02), after adjustment for age, body fat, CRP levels, and
cardiovascular ones.
PAL. IMAT (2655G1710 vs 1614G642 mm2) and IMCL (25.0G21.4 vs 23.1G
DOI: 10.1530/endoabs.49.EP711
20.6%) were not different in obese women with the MetS compared to women
without the MetS (PO0.05). No association emerged between HGST/arm lean
mass and IMAT or IMCL.
Conclusion
Insulin resistance, and not muscle fatty infiltration per se, may play a role in the
decline of muscle strength in subjects with obesity, leading to the phenotype of
dynapenic obesity.
EP712
DOI: 10.1530/endoabs.49.EP713
Role of cognitive-behavioral therapy in the treatment of obesity
Snjezana Popovic-Pejicic
Faculty of Medicine, University of Banja Luka, Republic of Srpska, Banja
Luka/Republic of Srpska, Bosnia and Herzegovina.
Dietary therapy, programmed physical activity and cognitive-behavioral therapy
are basic measures in the treatment of obesity. Cognitive-behavioral therapy
applies methods which change eating habits of obese persons, aiming to remove
EP714
barriers relating dietary therapy and programmed physical activity. The goal is to
Concern about body image, impulsiveness and personality traits in the
try efficiency of applying cognitive-behavioral therapy in the program for the
morbidly obese before bariatric surgery and in patients who have
reduction of body mass of obese persons, versus the application of dietary therapy
undergone surgery
and programmed physical activity alone. The study included 60 obese persons,
Isabel Mateo-Gavira1, Daniel Medina-Rivero1, José Pedro Novalbos-Ruiz2,
who were divided into two groups with 30 patients in each group, 20 to 58 years of
Amelia Rodríguez-Martín2, María José Santi-Cano3, D Ogalla de Castro3 &
age with the body mass index R30 kg/m2 and hyperlipidemia (LDL cholesterol
Manuel Aguilar-Diosdado1
R 4.2 mmol/l). Patients from both groups were on hypocalorie diet, individually
1Endocrinology. Puerta del Mar Hospital, Cádiz, Spain;2Preventive
designed and had programmed physical activity every day. Patients in group II
Medicine and Public Health, University of Cadiz, Cádiz, Spain;
underwent group cognitive-behavioral therapy under the supervision of
3Nursing and physiotherapy, University of Cadiz, Cádiz, Spain.
psychiatrist once a week with the duration of 120 min. Both groups also went
to see an endocrinologist 6 times, on which occasions their body weigh, blood
pressure, parameters of lipid status serum and level of glucose in serum were
Objectives
mesured. Results showed that in group II the medium value of body mass
To analyse the levels of anxiety, depression, impulsiveness, bulimic behaviour,
reduction after twelve weeks of treatment was 9.5 kg (8.9%) and in group I 4.4 kg
concern about body image and the quality of life of patients included in the care
(4.1%). In group II, LDL cholesterol decreased for 34.5% and in group I for 5.0%;
process following bariatric surgery, in our field.
HDL cholesterol increased for 2.7% while in group I it decreased 2.5%; total
Methods
triglycerides decrased for 15.3% and in group I for 5.4%; values of glicaemia
Observational study of the patients included in the care process for bariatric
decreased for 14.8% while in group I they remained unchanged. Cognitive-
surgery at University Hospital Puerta del Mar. Two cohorts were identified
Behavioral therapy affected the improvement of motivation and readiness of
according to their situation before or after surgery. Studies were made of variable
patients to stick to the dietary regime and programmed physical activity. In
antropometrics, clinics, personality traits and quality of life. The instruments used
designing the program for the reduction of obesty it is necessary to include
were: Anxiety inventories
(BAI) and Depression
(Beck); Body Sharp
cognitive-behavioral therapy, which brings significantly better therapy outcomes.
Questionnaire
(BQ21); BULIT-R test of bulimic behaviour, impulsiveness
(BIS) and SF12 questionnaire on quality of life.
DOI: 10.1530/endoabs.49.EP712
Results and conclusions
A total of 198 patients were studied, women constituted 69.2% of the subjects; the
average age was 45 without differences in the cohorts before/after 12 months; the
BMI in patients before surgery was 48 (S.D. 7) and in patients post surgery, 34 (S.D.
6). The patients on waiting lists presented higher levels of concern with regard to
their body image (BQ21: 65), bulimic behaviour (BULIT: 62) and depression
(BECK: 15). The SF12 reflected good mental health but scored lower on points
EP713
for physical health. The levels of impulsiveness were not high (BIS: 53), so no
Dynapenic obesity and myosteatosis in women with and without the
patient reached the cut off point (104). The cohort of post-surgery patients
metabolic syndrome
presented high levels of concern about body image (BQ21: 65) and anxiety (BAI:
Eleonora Poggiogalle, Lorenzo Donini, Lucio Gnessi, Stefania Mariani,
34). Impulsiveness was moderate (BIS: 58). It was noted that the proportion of
Michele Di Martino, Barbara Ciccantelli, Cecilia Mancini, Marcello Arca,
patients with extreme concern about their body image (BQ21 O 105) was higher
Andrea Lenzi & Carla Lubrano
in patients who had already undergone surgery (12.5 vs 6.5%). Attending to the
Sapienza University, Rome, Italy.
depressive state of patients (BECK) prior to surgery required professional care for
35.9% for the morbidly obese, against 16.7% of post-surgery patients; severe
depression was detected in 11.7% and 4.8% of patients respectively.
Introduction
Insulin resistance is a well-known hallmark of the metabolic syndrome (MetS),
DOI: 10.1530/endoabs.49.EP714
and it detrimentally affects also protein metabolism, favoring to the decline of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP715
sensitivity, glucose tolerance and reduced MWAT inflammatory cytokines
content, which are known to induce insulin resistance.
Lifestyle of morbidly obese patients awaiting bariatric surgery and in
Conclusions
the cohort of patients who have undergone surgery
The present data provide evidence that thyroid function is reduced in obese rats
Isabel Mateo-Gavira, Daniel Medina-Rivero1, Amelia Rodríguez-Martín2,
and reinforce the role of T3 treatment on improvement of insulin sensitivity by its
José Pedro Novalbos-Ruiz2, María José Santi-Cano3, A Díaz-Yelamos3
negative modulation of inflammatory cytokine expression in metabolic disorders
& Manuel Aguilar-Diosdado1
as obesity or diabetes mellitus.
1Endocrinology, Puerta del Mar Hospital, Cádiz, Spain;2Preventive
Medicine, University of Cadiz, Cádiz, Spain;3Nursing and Physiotherapy,
DOI: 10.1530/endoabs.49.EP716
University of Cadiz, Cádiz, Spain.
Objectives
To determine the habits and lifestyle of the morbidly obese before and after
bariatric surgery.
Material and methods
Transversal study of two groups of morbidly obese patients attending the
Endocrinology Unit of Puerta del Mar, Cádiz: one group before and the other after
bariatric surgery. Clinical and analytical data of the patients was collected: socio-
EP717
demographic and lifestyle characteristics, Bulit-R Questionnaire (Bulimia), BIS
Predictive factors of outcome in bariatric surgery
(impulsiveness), BQ1 (body image), BAI (anxiety), BECK (depression) and
Aurora Aragón-Alonso, Mercedes Ferrer Gómez, José Ramón
quality of life through questionnaire SF12.
Cuenca Sánchez, David Ruiz de Angulo Martín, María Dolores
Results
Frutos Bernal, María Ángeles Campillo Espallardo, Pedro Segura Luque
111 morbidly obese were studied before surgery (31.5% men, 68.5% women) and
& Antonio Hernández Martínez
87 morbidly obese post-surgery (29.9% men and 70.1% women). Before surgery
Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
mean weight was 133.4 (S.D. 24.4) and BMI 48.6 (S.D. 7.0), and post-surgery 94.9
(S.D. 19.8) and BMI 34.5 (S.D. 6.5). In both groups there was a predominance of
primary and lower secondary education (25.8% of total); the greater proportion of
Introduction
subjects with a higher level of education was in the post-surgery group (3.6% vs
Bariatric surgery is currently considered the most effective treatment for morbid
13%). Only 25% were actively in work before surgery, rising to 36.5% in the post-
obesity, although rates of weight loss and comorbidities resolution differ among
surgery group. Significant differences were observed between the two groups in
bariatric techniques and depending on preoperative factors.
relation to habits and lifestyle sucha as tobacco consumption (21.1 vs 7.1%),
Objectives
alcohol consumption (21.1 vs 17.4%), physical exercise (55 vs 82.6%), hours of
In this study we analyse possible factors that influence the outcome of bariatric
physical exercise (4.75 hours/week vs 5.9) and increase in meals per day from 3 to
surgery (weight loss and improvement in metabolic comorbidities) in order to
5. Family support is greater for the post-surgery group (90 vs 83.8%), excluding
identify those patients most likely to benefit from surgery.
differences in professional support services (14%).
Methods
Conclusions
We included all the patients who underwent bariatric surgery in Hospital
Significant differences were observed in patients’ habits and lifestyle before and
Universitario Virgen de la Arrixaca during one year (nZ101) of which 62
after bariatric surgery; factors which could contribute to the care, prognosis and
received LGB and 39 LSG. We retrospectively analysed which preoperative
evolution of the patients. Social and family support is greater for post-surgery
factors were related to percentage of excess body mass index
(BMI) loss
patients.
(%EBMIL), type 2 diabetes remission (T2DM), and higher rates of hypertension
(HT) and hypercholesterolemia (Hchol) persistence one year after surgery.
DOI: 10.1530/endoabs.49.EP715
Results
%EBMIL one year after surgery was significantly higher (PZ0.016) in patients
with preoperative BMI %50 kg/m2 vs BMIO50 kg/m2 (79.4G21.3 vs 65.6G
15.4). Age, sex and presurgery T2DM were not associated with %EBMIL one
year after surgery. Absence of insulin treatment at baseline
(89% vs 50%,
PZ0.03), less than five years after diagnosis of T2DM (100 vs 53.8% PZ0.017)
were associated with higher T2DM remission one year post surgery. Age, sex,
EP716
presurgery BMI, HbA1c and smoking status were not associated with higher
Thyroid hormone treatment reduces inflammatory cytokines in
remission rates. HT persistence one year after surgery was significantly associated
mesenteric adipose tissue improving insulin sensitivity of obese rats
to age O50 (30.3% vs 8.2% PZ0.005) and baseline T2DM (30.8% vs 10.3%,
Ana Carolina Panveloski-Costa, Caroline Serrano-Nascimento,
PZ0.015). HChol persistence one year after surgery was significantly associated
Leonice Poyares, Gabriela Souza Viana, Paula Bargi-Souza &
to ageO50 (28.1% vs 8.5%, PZ0.013) and baseline T2DM (28% vs 10.6%,
Maria Tereza Nunes
PZ0.04). Sex, baseline BMI nor smoking status were not associated with HT nor
University of Sao Paulo, Sao Paulo, SP, Brazil.
HChol persistence.
Conclusions
There is a heterogeneous pattern of presurgical factors that predict the outcomes
Thyroid hormone plays an important role on carbohydrate and lipid metabolism.
of bariatric surgery.
In hypothyroidism is observed reduction of glucose transporter-4 expression and
insulin sensitivity and in hyperthyroid states the key enzymes of gluconeogenesis
DOI: 10.1530/endoabs.49.EP717
and glycogenolysis are induced, and both conditions lead to glucose intolerance.
It has been reported an increased prevalence of thyroid dysfunction in obese and
diabetic patients. Recently we have demonstrated a hypothyroid state in alloxan-
induced diabetic rats, in which the treatment with triiodothyronine (T3) improved
glycemia control and insulin sensitivity. These alterations were accompanied by
reduction of inflammatory cytokines in white adipose tissue and skeletal muscle.
The present study aimed at evaluating the thyroid function of cafeteria diet-
EP718
induced obese rats and the effects of thyroid hormone treatment on their glycemia
Prevalence of obesity in Algeria
control, insulin sensitivity and subclinical inflammation.
Nadira Fafa1,2, Djamila Meskine1,2, Saida Fedala1,2 & Lamia Kedad1,2
Methods
1Laboratory of Endocrinology and Metabolism LEM1, Algiers, Algeria;
Obesity was induced in male Wistar rats by cafeteria diet. A subset of the obese
2Ibn Ziri Bologhine Hospital, Algiers, Algeria.
rats was treated with T3 (1.5 mg per 100 g body weight) for a 28-day period (DT3).
Thyroid function was evaluated by molecular
(TG, NIS, TSHR and TPO
expression in thyroid gland) and biochemical parameters (serum TSH, T4 and T3
Introduction
concentrations). Cytokines concentration was measured in mesenteric white
The epidemiological transition has resulted in a major increase in the prévalence
adipose tissue (MWAT) (MILIplex assay kit).
of obesity in our country. Obesity is closely associated with chronic diseases such
Results
as type 2 diabetes, hypertension and dyslipidemia. The aim of our study is
Obese rats exhibited decreased insulin sensitivity, thyroid function and serum
assessing the prevalence of general obesity, central obesity (OA), associated risk
TSH concentration, and increased MWAT inflammatory cytokines, NIS and
factors
(D2, HTA and dyslipidemia) and tries to provide information on
TSHR expression in thyroid gland. Thyroid hormone treatment improved insulin
determinants of obesity in Algerian adult.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
EP720
This was a cross sectional study conducted among 2210 subjects (1583 women
Anthropometric and metabolic effects of a milk-based intensive lifestyle
and 627 men) aged 18 to 64 years old, living in Algiers (Algeria). Subjects were
intervention in severely obese adults
randomized, anthropometric parameters, socio demographique situation; infor-
Iulia Andrada Ioana, Faraz Rafey Mohammed, Conor Murphy,
mations about food habits and physical activity were collected using a
Katriona Kilkelly, Colm Brassil, Katie Cunningham, Robert Mcgrath,
questionnary. Fasting blood glucose, cholestrol, triglycerids and blood presure
Helena Griffin, Paula O’Shea & Francis M Finucane
were mesured.
Galway University Hospital, Galway, Ireland.
Results
The prevalence of obesity (BMI O 30 kg/m2) was 24, 9% (12, 7% for males and
66, 4% for females). The prevalence of central obesity (WC O 80 cm for women
Therapeutic options for patients with severe obesity are limited. Low energy meal
and 94 cm for men) was 66, 4%, 41% for males and 76, 4% for females. Multi
replacement regimes can induce significant short-term weight loss and
variable logistic regression showed that elderly, female gender, low educationnal
improvements in metabolic variables. We sought to estimate the effect size on
level, a history of familial or personnal obesity and menopause were at risk of
adiposity and cardiovascular risk factors of a relatively inexpensive 24-week
obesity classified by BMI or WC. Wheras a young age, a higher level of
regime based on meal replacement with semi-skimmed milk in severely obese
education, male gender, current smoking, celibacy and hight physical activity
adults. A retrospective cohort analysis showed that of 206 patients in our hospital-
were at low risk of obesity. Obeses subject’s definied by BMI or Waist
based bariatric medicine service who started,
112
(54%) completed the
circumference had an increased risk of type
2 diabetes, hypertension and
programme and underwent an initial milk-based weight loss phase, followed by
dyslipidemia.
weight stabilization and weight maintenance phases, each lasting
8 weeks.
Conclusion
Patients were seen every two weeks by the bariatric physician, nurse and dietitian.
The caracterization of these factors will contribute to defining more effective and
We compared outcomes in completers (who had similar baseline characteristics to
specific strategies to screen and control obesity.
non-completers) at time 0, 8, 16 and 24 weeks, with repeated measures ANOVA.
DOI: 10.1530/endoabs.49.EP718
50.9% of completers were female, 40.2% had diabetes, mean age was 50.9G10.3
years. BMI decreased from
52.7G9.3 to 46.9G8.7, 44.8G8.6 and 43.8G
9.2 kg/m2 at 0,
8,
16 and 24 weeks, respectively (P!0.001 with repeated
measures ANOVA), equivalent to 24.8 kg weight loss and a reduction in excess
body weight from 110.6G37.2 to 75.2G36.9%, P!0.001 over 24 weeks.
In patients with diabetes, HbA1c decreased from 63G18.3 to 48G14.5 mmol/mol,
PZ0.01. There were very significant reductions in all diabetes medications,
except for metformin. These preliminary findings suggest that a 24-week milk-
based meal replacement programme can have large effect sizes on important
outcomes in severely obese. However, attrition was high. A more formal
assessment of the efficacy of the intervention as well as its safety, feasibility and
EP719
cost-effectiveness seems warranted.
Testosterone deficiency in obese males: is insulin resistance the one to
DOI: 10.1530/endoabs.49.EP720
blame?
Pedro Souteiro1,2, Daniela Magalha˜es1,2, Jorge Pedro1,2,
Sofia Castro Oliveira1,2, João Sérgio Neves1,2, Sandra Belo1,2,
Maria Manuel Costa1,2, Rita Bettencourt-Silva1,2, Ana Varela1,2,
Joana Queirós1,3, Paula Freitas1,2, Davide Carvalho1,2 & Group AMTCO3
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-
EP721
talar São João, Porto, Portugal;2Faculty of Medicine of University of Porto,
Association of cortisol, DHEA-S and cortisol/DHEAS ratio with insulin
Porto, Portugal;3Multidisciplinary Group for Surgical Management of
resistance in overweight and obese women
Obesity, Centro Hospitalar São João, Porto, Portugal.
Adam Maciejewski1, Monika Litwinowicz2, Emilia Marcinkowska2,
Marian Grzymislawski2 & Katarzyna Lacka1
1
Department of Endocrinology, Metabolism and Internal Medicine, Poznan
Introduction
University of Medical Sciences, Poznan, Poland;2Department of Internal
Obesity is a growing worldwide public health issue and it is associated with
Medicine, Metabolic Diseases and Dietetics, Poznan University of Medical
multiple comorbidities, namely the so called Male Obesity-associated Secondary
Sciences, Poznan, Poland.
Hypogonadism (MOSH). However, the mechanisms that explain this association
are not fully understood.
Methods
HPA axis that plays important controlling and modulating functions in organism
Cross-sectional study of 163 obese men that were evaluated for several clinical
is also linked with insulin resistance and weight control. The number of evidences
and analytic parameters. Testosterone deficiency was defined as: total
linking cortisol secretion with obesity and other metabolic complication increase,
testosterone !2.8 ng/ml and/or free testosterone calculated by the Vermeulen
but still there is a lack of definitive results. Therefore the aim of our study was to
formula !50 pg/ml.
compare adrenal function parameters between high and normal insulin resistant
Results
overweight and obese women. This retrospective analysis was performed on the
The studied population had a mean age and BMI of 40.8G10.5 years-old and
group of 70 adult polish Caucasian overweight and obese women with the mean
45.8G6.7 kg/m2, respectively. Testosterone deficiency prevalence was 47.2%.
age of 40 years. Mean BMI for the whole group was 38 kg/m2. Exclusion criteria
The majority (96.1%) of these men had hypogonadotropic dysfunction and 2.9%
were: pregnancy or breastfeeding, history of any pituitary or adrenal gland
presented high gonadotrophins. When only calculated free testosterone was
disorders, current or previous usage of any glucocorticoid-containing medi-
considered, the deficiency prevalence was 18.1%. Higher BMIs correlated with
cations, other drugs known to affect cortisol level and patients with diagnosis of
lower levels of SHBG (sex hormone binding globulin): rZK0.19; P!0.05. BMI
severe liver or kidney dysfunctions and acute or chronic inflammatory disorder at
(rZK0.26; P!0.001), age (rZK0.21; P!0.05) and HOMA-IR (rZ0.39;
the time of measurements. Patients were divided into two groups according to
P!0.001) had a negative correlation with calculated free testosterone levels,
HOMA-IR value (cut-off point of 3.8). Statistical analysis was performed using
while SHBG levels exhibited a positive correlation (rZ0.18; P!0.05). There
Statistica software. Differences between lower HOMA-IR and higher HOMA-IR
was no significant correlation between oestradiol levels and free/total testosterone
groups were determined by student t test and Mann-Whitney U test when
or BMI. When the aforementioned significant variables were included in a linear
appropriate. To analyze correlations between measured values Spearman
regression model, HOMA-IR (bZK0.33; P!0.001) and SHBG levels (bZ0.20;
correlation coefficiency was calculated. P value
!0.05 was considered
P!0.01) could predict the free testosterone levels, while age (PZ0.07) and BMI
statistically significant. Patients with higher HOMA-IR have higher morning
(PZ0.23) lost their significance after the adjustment. In accordance, males with
cortisol concentration (504.36 vs 425.82 nmol/l) and lower DHEA-S concen-
normal glucose tolerance had higher free testosterone levels than those with pre-
tration (170.18 vs 227.49 mg/dl), although these differences were not statistically
diabetes or diabetes even after adjusting for age and BMI (bZ0.22; P!0.01).
significant. There was statistically significant difference between higher and
Conclusions
lower HOMA-IR groups in evening cortisol concentration
(248.28
and
Testosterone deficiency is frequent in obese males, with most of them presenting
186.02 nmol/l, respectively, PZ0.007) and cortisol/DHEA-S ratio
(5.73
vs
hypogonadotropic dysfunction. SHBG levels and mainly insulin resistance, and
2.73, PZ0.003). For the whole group studied there was statistically significant
not obesity per se, seem to be the true mediators of this interplay. We found no
positive correlation between cortisol/DHEAS ratio and HOMA-IR (rZ0.39,
correlation between oestradiol and testosterone levels suggesting that androgen
PZ0.001). There is a significant association between evening cortisol secretion
aromatization in adipose tissue is not a key determinant as previously thought.
and HOMA-IR and between cortisol/DHEA-S ratio and HOMA-IR.
DOI: 10.1530/endoabs.49.EP719
DOI: 10.1530/endoabs.49.EP721
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP722
Paediatric Endocrinology
Obesity and fruit and vegetables consumptions in children
EP724
Bruno Sousa1,2
Intracranial lesions in children and adolescents with morbid obesity;
1Universidade Lusófona de Humanidades e Tecnologias, Lisboa, Portugal;
results of long-term follow-up
2Research Center for Biosciences and Health Technologies, Lisboa,
Ayca Torel Ergur1, Sevinc Odabasi Gunes1, Sinan Tan2 &
Portugal.
Umit Ayse Tandircioglu2
1Department of Pediatric Endocrinology, Kirikkale University Faculty of
Introduction
Medicine, Kirikkale, Turkey;2Department of Radiology, Kirikkale
Obesity is associated with the low consumption of fruit and vegetables.
University Faculty of Medicine, Kirikkale, Turkey.
Objective
Evaluate the obesity and the fruit and vegetables consumptions in children after
Introduction
an intervention of school food education program.
Childhood obesity has become an important health problem nowadays.
Methodology
Intracranial lesions
(IC) can affect the hypothalamic
- hypophyseal axis
It was implemented a food education program in three classes (nZ55) of 1st
depending on the localization of the lesion and lead to hypophyseal hormone
cycle, on school year (2016/2017) and the evaluation of this action was done
deficiencies, especially growth hormone. Although IC lesions are important in the
comparing fruit and vegetables consumptions and nutritional status of this
etiology of obesity, There’s limited data in the literature about this subject. Aim of
children between beginning and the end of the program (after 12 weeks). Fruit and
this study is to evaluate the incidence of IC lesions and their role in clinical
vegetables consumptions were assessed through the application of a food
symptoms and etiology in cases with morbid obesity (MO) in childhood.
frequency questionnaire and the nutritional status was determined by BMI.
Materials and methods
Weight and height were assessed in all children and BMI was calculated. To
One hundred twenty cases admitted with the complaint of MO in 13 years (2002-
determine the obesity was used CDC criteria. The educational intervention
2015) were included in this study. Anthropometric evaluation and detailed
consisted in promoting fruit and vegetables consumptions at school environment,
physical examinations were performed. Biochemical and hormonal parameters
involving formative and recreational activities, as well as a greater supply of fruit
(glucose, lipid metabolism, adrenal steroids and diurnal cortisol) were evaluated.
and vegetables in school.
Contrast-enhanced dynamic magnetic resonance imaging (CDMRI) technique
Results
was used to assess the hypothalamo-hypophyseal field. Height of hypophysis was
This sample had between 6 and 8 years old and 54.5% were girls. Fruit
evaluated according to age and sex.
consumption increased and considering the
3-5
pieces of fruit per day
Results
recommended by the Portuguese Food Wheel, the consumption in these students
In our study, 16.6% of the MO patients had an IC lesion. Most of the cases had
evolved from 16.3% to 41.8%. Vegetables consumption also increased. At
adenoma of the hypophysis (55% of the cases with IC lesion.) Six of the patients
beginning 54.5% ate two or more servings per day of vegetables, and at end
with IC lesion had high prolactin levels. Prolactin levels were increased in the
74.5%. In nutritional status, it was observed that obesity decreased from 20% to
6 patients but front hypophyseal hormone levels were in between normal range
16.4%.
in the rest of the patients. None of the patients had decreased growth velocity.
Conclusions
Conclusion
This type of educational intervention in schools increased fruit and vegetables
In this long-term study, the important result is that; IC lesion frequency was
consumptions and reduce the prevalence of obesity in children.
significantly higher in children and adolescents with MO than those of the normal
DOI: 10.1530/endoabs.49.EP722
population. Moreover, these lesions show no other endocrinological or
neurological symptom besides obesity. Furthermore; due to this study; we
suggest that cranial imaging with CDMRI in these cases, even if the physical-
neurological examination is normal, will contribute greatly to the early diagnosis
and treatment of lesions without causing other symptoms.
DOI: 10.1530/endoabs.49.EP724
EP723
Neuromedin B receptor: role in adipogenesis and a possible target for
obesity treatment
Gabriela Paula1, Marianna Wilieman1, Luana Souza1, Karina Ribeiro2,
Leandra Baptista2 & Carmen Cabanelas1
1Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil;
EP725
2National Institute of Metrology, Quality and Technology, Duque de Caxias,
Congenital hyperinsulinism in two siblings due to the same ABCC8
Rio de Janeiro, Brazil.
mutation: the clinical importance of an early diagnosis and treatment
Francisco Sousa Santos1,3, Helder Simo˜ es2, Lidia Castro-Feijóo3,
Neuromedin B (NB) is a peptide highly expressed in adipose tissue (AT) but its
Paloma Cabanas Rodríguez3, Ana Fernández-Marmiesse6, Rebeca
function remains unclear. We showed that NB receptor (NB) knockout mice
Saborido Fian˜o6, Teresa Rego4, Angel Carracedo5 & Jesús Barreiro Conde3
(NBR-KO) are resistant to diet-induced obesity compared to wild type (WT) and
1Serviço de Endocrinologia, Centro Hospitalar Lisboa Ocidental, Lisboa,
now we aimed to analyze NBR influence in adipocytes. Mesenchimal cells from
Portugal;2Serviço de Endocrinologia, Instituto Português de Oncologia de
perigonadal AT of WT and NBR-KO mice were isolated and maintained in
Lisboa, Lisboa, Portugal;3Unidad de Endocrinología Pediátrica y
growth medium (GM) as control group or in differentiation medium (DM) as
Crecimiento, Pediatría, Hospital Clínico Universitario y Universidad de
induced group. After 2 weeks cells were fixed and lipid accumulation was
Santiago de Compostela, IDIS, Santiago de Compostela, Spain;4Serviço de
evaluated by Oil Red O staining. NBR-KO cells accumulated 56% less lipids than
Endocrinologia, Centro Hospitalar Lisboa Central, Lisboa, Portugal;
WT cells in DM. To analyze NBR antagonist intervention during adipogenesis
5Fundación Publica Galega de Medicina Xenómica, Hospital Clínico
3T3-L1 cells were cultured in GM (GMC), or in DM in the absence (DMC) or
Universitario de Santiago de Compostela, Universidad de Santiago de
presence of 3 mM of NBR antagonist (DMA), during 21 days. In parallel NBR
Compostela, Santiago de Compostela, Spain;6Pediatría, Hospital Clínico
antagonist was added to DMC group for 6 days after 21 days in culture to verify
Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
its influence after differentiation. Cells were fixed and stained with Dapi and
Bodipy for cell and lipid measurements. After 21 days DMC group exhibited 2.7
Introduction
times more cells number than GMC but DMA group presented similar cell
Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin
number as GMC. DMC group reached 83% of well area as lipid while DMA did
secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected
only 7% although it was corrected by cells area. When NBR antagonist was added
genes. It can present as focal or diffuse pancreatic disease, which is mainly
for 6 days to DMC it decreased cells number by 40% and lipid accumulation
determined by the genotype. Diazoxide is the first-line medication in diffuse
diminished 10%. In conclusion NBR-KO AT cells have impaired induced-
cases, however many do not respond satisfactory. Second-line options include
adipogenesis and NBR antagonist promoted less adipogenesis, reduced
somatostatin analogues and surgery, which is curative in case of focal CHI.
adipocytes number and decreased lipid accumulation. Data demonstrate, for the
Case report
first time, a role for NBR in adipocyte differentiation, suggesting it is a possible
We report the case of two siblings that presented with hypoketotic
target for obesity treatment. Presently, we are analyzing hormones and factors
hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis
involved in adipogenesis, lipogenesis and cell death to clarify mechanisms.
of diffuse CHI due to an ABCC8 compound mutation (c3576delG and c742COT)
DOI: 10.1530/endoabs.49.EP723
was concluded. They did not benefit from diazoxide therapy (or pancreatectomy
performed in patient no
1 when he was 3 months old) yet responded to
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
somatostatin analogues. Patient no 1 developed various cognitive deficits and
Introduction
epilepsy, however patient no 2 experienced an entirely normal neurodevelopment.
11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has been associated with
Conclusion
several human metabolic disorders and is converted from inactive 11-keto form to
We report the case of two siblings with diazoxide-resistant CHI caused by the
glucocorticoid (GC or cortisol). GC overproduction or hypercortisolism is a major
same compound ABCC8 mutation (which was never before described, to the best
diagnostic factor of Cushing syndrome and Anorexia. GCs regulate carbohydrate,
of our knowledge). Their phenotype and therapeutic management had some
fat, and protein metabolism.
differences and this could offer a potential explanation for the distinct
Materials and methods
neurological outcomes, despite the same genetic basis for the disease. Molecular
Previously we established porcine fibroblasts overexpressing 11b-HSD1. Based
diagnosis and better knowledge of the disease behaviour seemed to contribute to a
on these, transgenic piglets overexpressing 11b-HSD1 were born through somatic
better medical care in patient no 2, which ultimately resulted in a better outcome.
cell nuclear transfer (SCNT) and re-cloning methods. Transgenic piglets were
This highlights the importance of early recognition and diagnosis of this disease.
identified by PCR methods using specific primers for the targeting cassettes from
DOI: 10.1530/endoabs.49.EP725
the genomic DNA of piglets. HepG2 cell line overproducing 11b-HSD1 (11b-
HSD1-HepG2) was established for in vitro model. In vivo porcine and in vitro
hepatic models were analyzed by real-time PCR, immunohistochemistry and
Western blotting methods.
Results
Six live piglets were born. Integration of target gene into the genomic DNA was
confirmed from all of them. Excessive expression of
11b-HSD1 induced
up-regulation of gluconeogenesis
(G6PT, G6Pase, PEPCK and etc.) and
lipogenesis related genes (FASN, ACC, and SCD) in in vivo and in vitro models.
EP726
To compensate for energy loss by anabolism, it stimulates AMPK and SIRT
Association between oxidative stress and bone turnover markers in the
signaling, which controls energy balance and mitochondrial biogenesis.
obese children
Conclusions
Pawel Matusik1, Magdalena Olszanecka Glinianowicz2, Jerzy Chudek2
These results suggest that the overproduction of 11b-HSD1 induce activation of
& Ewa Malecka-Tendera1
complementary energy gaining processes through mitochondrial respiration. Our
1Department of Pediatrics and Pediatric Endocrinology, Medical University
in vivo and in vitro models will be useful for further study and potential
of Silesia, Katowice, Poland;2Department of Pathophysiology, Medical
application in metabolic diseases.
University of Silesia, Katowice, Poland.
DOI: 10.1530/endoabs.49.EP727
Background
Recent data have been showed that free radicals are involved in either bone
resorption and atherosclerosis development in adults. In paediatric population the
important risk factor for the early atherosclerosis development is obesity, which
can be also associated with the disturb bone turnover.
Objective and hypotheses
The aim of the study was to evaluate the interrelationship between oxidative stress
EP728
and bone turnover markers in obese children vs lean controls and correlated them
Hepatic and adipose tissue insulin resistance as a consequence of
with the anthropometrical status and metabolic activity of adipose tissue.
intermittent hypoxia are exacerbated by glucocorticoid receptor
Method
antagonism in man
Bone turnover markers (osteocalcin (OC), N-terminal telopeptide of type I
Jonathan Hazlehurst, Catriona Charlton, Diana Mantripp, Leanne Hodson
collagen (NTx)), oxidative stress markers (TAC - total antioxidative capacity,
& Jeremy Tomlinson
glutathione peroxidase, oxLDL) and leptin were determined in 50 obese children
Oxford Centre for Diabetes, Endocrinology & Metabolism and NIHR
and 79 healthy controls. Anthropometrical status by BMI calculation and body
Biomedical Research Centre, University of Oxford, Oxford, UK.
composition parameters as: fat mass (FAT), fat-free mass (FMM), predicted
muscle mass
(PMM) and total body water
(TBW) were evaluated using
bioelectrical impedance analyzer (BIA) in all children.
Introduction
Results
Obstructive sleep apnea (OSA) affects up to 20% of a Western population and is
OC was significantly lower in obese children and correlated significantly
associated with non-alcoholic fatty liver disease and type 2 diabetes (T2D). OSA
(negatively P!0.01) with BMI in the lean group. There was also significant
is characterized by intermittent episodes of hypoxia (IH) that occur during sleep.
positive correlation between OC and TAC in obese children. NTx correlated
It is not yet known if IH is directly linked to insulin resistance within key
significantly with oxy-LDL (positively) in either, obese and lean group (P!0.05
metabolic target tissues (adipose; liver and skeletal muscle) and what the potential
and P!0.01 respectively). In the lean group only, there were significant relations
underlying mechanism may be. It has been suggested that individuals with OSA
between NTx vs leptin and body composition parameters (rZ0.245 vs leptin,
have high circulating glucocorticoid levels which may be linked to the
rZ0.245
vs FAT%, rZK0.252 vs PMM%, and rZK0.245 vs FFM%
development of IR and T2D.
respectively).
Methods
Conclusion
17 healthy male volunteers were recruited and underwent detailed metabolic
Bone turnover seems to be disturbed in the obese children and pathophysiological
phenotyping in a fasted state including a hyperinsulinaemic-euglycaemic clamp,
factor with can be involved in that mechanism may be an increase oxidative stress
incorporating the use of stable isotopes of glucose and palmitate to measure fatty
level. Osteocalcin and NTx levels seem to be related to the anthropometrical
acid partitioning. Initial assessments were made in normoxic conditions;
status and adipose tissue activity (leptin level).
volunteers were then randomised either to no treatment (nZ9) or treatment
DOI: 10.1530/endoabs.49.EP726
with the glucocorticoid antagonist Mifepristone (600 mg once a day) (nZ8).
After 1 week of treatment, assessments were repeated under conditions of IH (12
desaturations/h to arterial saturations of 85-91%).
Results
Global insulin sensitivity as measured by M/I values was unchanged by IH or by
IHCMifepristone (control: 8.65G4.1; IH: 9.13G5.4; control (pre_drug): 8.9G
3.7; MifeprisoneCIH: 10.13G3.3). However, IH impaired the ability of insulin
to suppress TAG, an effect that was worsened by Mifepristone ((insulin mediated
suppression of TAG: control: K449G124; IH: K218G131 (PZ0.0034); control
(pre_drug): K339G201; MifeprisoneCIH: K76G128; (PZ0.008). In addition,
Steroid Metabolism C Action
adipose tissue IR, as measured by a reduction in the ability of insulin to suppress
EP727
circulating NEFA, was worsened by Mifepristone under conditions of IH (insulin
In vivo porcine and in vitro HepG2 models with 11b-HSD1
mediated change in plasma NEFA control: K501G164; IH: K411G187 (PZns);
overproduction
control (pre_drug): K549G130; MifeprisoneCIH: K367G109; (PZ0.03)).
Hee Young Kang, Jae Hwan Lee, Jin Yong An, Dinh Nam Tran &
Conclusion
Eui-Bae Jeung
Acute IH causes insulin resistance in liver and adipose tissue. These effects are
Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
worsened rather than improved by antagonism of the glucocorticoid receptor,
highlighting the importance of understanding tissue specific glucocorticoid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
actions and suggesting activation of the HPA axis is not the link between OSA
EP730
and metabolic risk
Gender specific metabolic phenotype in the 5b-reductase knockout
DOI: 10.1530/endoabs.49.EP728
mouse
Laura Gathercole1,2, Petra Klusonova3, Nikolaos Nikolaou1,
Jonathan Hazlehurst1, Ahmad Moolla1, Niall Dempster1, Trevor Penning5,
Roger Cox4, Alex Odermatt3 & Jeremy Tomlinson1
1
University of Oxford, Oxford, UK;2Oxford Brookes University, Oxford,
UK;3University of Basel, Basel, Switzerland;4Medical Research Council
EP729
Harwell, Oxfordshire, UK;5University of Pennsylvania, Philadelphia, USA.
Dexras1 regulates MSC-derived adipogenesis and osteogenesis
Jo Woon Seok1, Daeun Kim1, Hye min Lee1, Bo kyung Yoon1,
Hyo Jung Kim1 & Jae-woo Kim1,2
Steroid hormones and bile acids are potent regulators of metabolism. The enzyme
1Department of Biochemistry and Molecular Biology, Integrated Genomic
5b-reductase
(AKR1D1) has a crucial role in bile acid synthesis and also
Research Center for Metabolic Regulation, Institute of Genetic Science,
generates 5b-reduced dihydrosteroid metabolites, regulating intra-cellular steroid
Yonsei University College of Medicine, Seoul, Republic of Korea;
availability though the clearance of cortisol, testosterone, androstenedione, and
2Severance Biomedical Science Institute, Yonsei University College of
progesterone. As AKR1D1 sits at the interface of bile acid synthesis and steroid
Medicine, Seoul, Republic of Korea.
metabolism, we have hypothesised that it plays a key role in metabolic
homeostasis and have generated and characterised an entirely novel, global
AKR1D1 knockout (KO) mouse. As expected AKR1D1 KO mice had altered
Mesenchymal stem cells
(MSCs) are multipotent stromal cells that can
hepatic steroid (in vitro cortisone clearance: 100% (WT), 70% (KO); in vitro
differentiate into various types of cells including chondrocytes, osteoblasts and
5a-cortisone/cortisol metabolite generation increased 3.9-fold (KO)) and bile
adipocytes. Since these types of cells are simultaneously derived from the same
acid metabolism (hepatic bile acid concentration males: 1164G626 pmol/mg
precursor cell, adipogenesis and osteoblastogenesis are thought to be counter-
(WT), 122G42 pmol/mg (KO) P!0.05; females: 310G67 pmol/mg (WT),
related. It is well-known that chronic treatment of steroid can induce Cushing’s
113G23 pmol/mg (KO) P!0.01). At
30
weeks male, but not female,
syndrome which has phenotypes like visceral adiposity and osteoporosis. Cell fate
AKR1D1KO animals were lighter than wildtype (WT) littermates
(males:
of differentiation into either adipocytes or osteoblasts is one of the critical factors
35.6G0.9 g (WT), 33.2G0.6 g (KO) P!0.05; females: 25.3G0.6 g (WT),
of these symptoms, but the molecular mechanism of cell fate decision of MSCs
24.9G0.4 g (KO) PZns) with lower total (9.7G0.7 g (WT), 7.4G0.5 g (KO)
under the streroid treatment is unclear. Recently, we showed that Dexras1
P!0.05) and % (29G1.4% (WT), 24G1.5% (KO) P!0.05) fat mass, as
mediates glucocorticoids and IGF-I signaling followed by MAPK activation and
determined by DEXA. At termination, male AKR1D1 KO mice had smaller
results in increased adipogenesis while its abolishment decreases adipogenesis.
subcutaneous adipose depots (1.0G0.1 g (WT), 0.7G0.1 g (KO) P!0.05) and,
Now we established that lack of Dexas1 exhibited increased osteogenesis in
despite no difference in body weight or composition, female KO animals had
mesenchymal stem cells including both bone marrow derived stem cells (BMSCs)
smaller gonadal fat depots (0.5G0.1 g (WT), 0.3 gG0.03 g (KO) P!0.05). Both
and mouse embryonic fibroblasts (MEFs). Corroborative to our previous data,
male and female AKR1D1KO mice had enhanced insulin sensitivity (ipITT AUC
decreased adipogenesis in MSCs was also observed in the absence of Dexras1.
males:
793 mMol min (WT), 647 mMol min (KO); ipITT AUC females:
Despite less dramatic change in differentiation, it is also shown that lessened
663 mMol min (WT), 568 mMol min (KO)), without changes in glucose
mature osteoblasts in Dexras1-overexpressing preosteoblast cell line, MC3T3-E1,
tolerance. AKR1D1 KO mice display a sexually dimorphic metabolic phenotype.
down regulating Smad signaling in the early period of differentiation.
Whereas both male and female AKR1D1 KO mice have increased insulin
Furthermore, we found that Dexras1 is involved in increased central obesity
sensitivity, only male AKR1D1 KO mice have a lean phenotype. Although the
associated with chronic treatment of steroids but rescued steroid-induced
underpinning mechanisms remain to be fully defined, AKR1D1 may represent a
osteoporosis in mouse model treated with dexamethasone for 8 weeks followed
future novel therapeutic target for the treatment of metabolic disease.
by increased gene expression related to osteoblast in the murine bone. Above all
DOI: 10.1530/endoabs.49.EP730
these results, we suggest that Dexras1
is a key molecule which stimulates
adiposity and down regulates osteogenesis via counter regulating action.
DOI: 10.1530/endoabs.49.EP729
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations: Environment,
Society and Governance
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Cardiovascular Endocrinology and Lipid Metabolism
consider confounding factors such as time taken from the dictation of letters to
typing and postal delays, and observer effect from trainees. The endocrine
EP731
meeting is not happening every week, and trainees are not attending it
Measuring of quality of life and health characteristics among 40-79 old
consistently due to other clinical commitments. We are actively looking to
population in Hungary
rectify these issues.
Anita Zubrecki1, Ivan Devosa2, Maria Jako1, Attila Vass3, Klara Deak3,
DOI: 10.1530/endoabs.49.EP732
Sandor Kolosszar1, Melinda Vanya4,5, Imre Foldesi6 & Gyorgy Bartfai1
1Department of Obstetrics and Gynaecology, University of Szeged, Szeged,
Hungary;2Athene Pallasz University, Kecskemét, Hungary;3Department of
Ophtalmology, University of Szeged, Szeged, Hungary;4Mediteam Zrt,
Szeged, Hungary;5Department of Obstetrics and Gynaecology, Kalman
Pandy Hospital Gyula, Gyula, Hungary;6Department of Laboratory
Developmental Endocrinology
Medicine, University of Szeged, Szeged, Hungary.
EP733
Endocrinology training programs in member countries of the
Introduction
International Society of Endocrinology (ISE): a pilot survey evaluation
Life expectancy is increasing in most developed countries, in part due to
comparing regions and cultures
improved socio-economic conditions and in part to advances in healthcare. It is
Maite P Bastyr & Juan C Galofré
widely acknowledged that the promotion of healthy ageing by delaying,
Department of Endocrinology, University of Navarra, Pamplona, Spain.
minimizing or preventing disabilities or diseases is one of the most important
public health objectives in this century.
Methods
Background
243 Women and 181 men aged 40-79 years were recruited in Szeged (Hungary)
Endocrinology is a relatively young subspecialty of internal medicine. No
consensus on international standards for training has been established, and hence
Subjects were recruited from population registers and those who agreed to take
the variability between training programs and endocrinologist qualifications may
part completed a detailed questionnaire including aspects of personal and medical
be great.
history, lifestyle factors. Objective measures of body size, cognition, vision,
Methods
skeletal health and neuromuscular function were obtained. Internal consistency of
A standardized questionnaire was constructed to explore individual national
the questionnaire was also investigated (Cronbach alfa: 0.715).
standards for endocrinology training, evaluating the responding programs for
Results
physician entry criteria for each program, medical content, duration of the
Mean age of participants was 59.17 S.D.:10.71 years. There were significant
programs, procedural competency, and qualification and re-qualification
correlation between the quality of life and systolic blood pressure of the right &
requirements. Representatives from member societies of the ISE were solicited
left hand
(PZ0.007
and PZ0.013) and smoking use
(PZ0.002) The
to provide specific characteristics of their respective national training programs
cardiovascular risk was significantly higher in the 40-50 age groups compared
via a questionnaire on SurveyMonkey.
to the older age groups (PZ0.002).
Results
Conclusion
Sixteen of 54 (30%) ISE member countries responded regarding training program
We provide new data among the health characteristics of older population in
characteristics. Spanish-speaking (SS) countries were more likely to have an
South Hungary. Such information is an important prerequisite to develop effective
entrance exam compared with non-SS countries (80 vs 27%, c2Z3.88, PZ0.049).
strategies to reduce age-related disabilities and optimise health and well-being
On average 62-85% of programs included all general endocrinology knowledge
into old-age.
content with the exception of endocrine surgery (15%) and genetics (31%).
DOI: 10.1530/endoabs.49.EP731
Genetics was included more frequently in SS vs non-SS countries (60 vs 13%,
c2Z3.26, PZ0.071) and less frequently in European Union (EU) vs non-EU
countries
(17
vs
43%, c2Z3.61, PZ0.057). Pediatric endocrinology was
included more frequently in SS vs non-SS countries (100 vs 43%, c2Z4.29,
PZ0.038). Endocrinology research was included less frequently in EU vs non-
EU countries (50 vs 86%, c2Z3.26, PZ0.071). Thyroid procedures were taught
Clinical Case Reports - Thyroid/Others
only 33-38% of the time across programs while diabetes-related procedures and
EP732
DEXA were required by 62-69% of the programs, and both were included more
Does standardising the dynamic endocrine testing process improve
frequently in the SS vs non-SS countries
(c2Z8.70, PZ0.003, c2Z5.08,
patient communication and safety?
PZ0.024, respectively). While
100% of countries required certification to
Rahat Tauni1,2 & Ritwik Banerjee2
practice endocrinology, only 38% had a certifying examination, with significantly
1Cambridge University Hospitals, Cambridge, UK;2Luton and Dunstable
lower administration in EU vs non-EU (17 vs 57%, c2Z5.08, PZ0.024).
University Hospital, Luton, UK.
Conclusion
The questionnaire identifies differences in endocrinology training, which can be
addressed by ISE member countries in the hope of an overall improvement in the
Background and objectives
quality of training and international harmonization of the discipline of
Ineffective communication is one of the leading causes of medical errors and
endocrinology.
patient dissatisfaction. We implemented an initiative for dynamic endocrine tests
DOI: 10.1530/endoabs.49.EP733
to enhance communication with primary care colleagues and patients.
Methods
We introduced a comprehensive system of organising dynamic tests, structured
documentation, weekly endocrine meeting to discuss the results and standardised
escalation process for suspected abnormal results. We retrospectively analysed 50
tests prior to and 50 after the initiative was introduced (nZ100). Most were
EP734
routine short synacthen tests (SST) with a small proportion of other tests including
The basic characteristics of delivery of endocrinologic care in Slovakia
urgent/semi-urgent SST, dexamethasone suppression tests, TRH and GnRH
from outpatients care perspective
stimulation tests, prolonged oral glucose tolerance test and prolonged supervised
Jan Bielik1 & Peter Glatz2
fast.
1Trencin University of Alexander Dubcek, Trencin, Slovakia;2Consultancy,
Results
Bratislava, Slovakia.
The mean time from the date of test and the letter to general practitioner/patient
of routine tests reduced from 22.07 days to 13.92 days for normal SSTs and
The prevalence of endocrinologic diseases in Slovak Republic in 2015 was about
5.16 days to 4.83 days for abnormal SSTs, although the latter was not statistically
390 000 patients e.g. the prevalence was about 7.1%. The objective of this study
significant. The other test numbers were too small to establish significance. There
was to find out the basic relevant characteristics of delivery of endocrinologic care
was no significant difference in time taken for organising the tests and no patient
based on data from General Insurance Company with covering cca 63% of all
inhabitants.
harm was reported in both groups. Anecdotal reports from trainees suggested that
Methods
there were more training opportunities with the introduction of the new process.
Discussion
The combined analysis from the GIC data was used.
Our data suggests that streamlining the dynamic endocrine function test system
Results
reduces the delay in communicating normal routine dynamic endocrine test
246 195 patients, 212 977 women and 33 597 men, were examined in this study.
results and can increase the training opportunities for trainees. We aim to perform
The patients visited 150 endocrinologic outpatients departments (EOD). The
another analysis with a larger sample and analyse patient satisfaction data and
number amounted from 1100 to 2800 patients per one department. The prevalence
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
of endocrinologic diseases differed from 6.1% to 9.3% compared 8 administrative
Goal
regions. The ratio of EOD varied between
2.9% and
6.7% per
100 000
Decrease a number of lower limb amputations in PDM in Uzbekistan by
inhabitants. The migration of patients among regions varied from 3% to 10%.
improvement of specialised help given to patients with DFS.
The thyreoid diseases represented 88.4% of all patients, metabolic diseases
Materials and methods
- 8.3%, bone diseases - 6.5%, all other diseases - 5.4% (1 patients had one and
Prior to 2010 there were only 2 ‘Diabetic foot’ rooms in Tashkent, Uzbekistan. In
more diseases). The prevalence of benign tumors in patients was cca 1.85% and
2010-2012, CPA ‘UMID’ jointly with Uzbekistan Ministry of Health and
malignant tumors about 1.7%. Some endocrinologic diseases were treated by
Research Centre for Endocrinology implemented a project ‘Prevention of lower
more than 50 other specialists like internal specialists etc. In this thyreoid diseases
limb amputations in people with diabetes mellitus in Uzbekistan’ granted by the
represented about 21.9%, bone diseases - 686%, metabolic diseases - 18.6% and
World Diabetes Fund (WDF).
all others diseases - 65.4%. From 2013 to 2015 y. was observed an increase of
Results
patients with thyreoid diseases in 7.0%, bone diseases - 4.5%, other diseases
Within the framework of the project for the first time in Uzbekistan, 288 ‘Diabetic
5.3%. Together 21 activities from daily practice were observed and evaluated.
foot’ rooms were set up under 14 endocrinological dispensaries and in 274 rural
The most often were: first and followed examination, blood taking, evaluation
district clinics which were also equipped with a medical armchair for feet
of laboratory exams, ultrasonography, advice to the patients, densitometry,
examination, a tuning fork, monofilament, percussion hammer, kit of dressing
biopsy, etc.
materials. To work in these rooms, 615 podiatrists were trained who render a
Conclusions
qualified medical help to PDM and teach them rules of foot care. Annually over
The prevalence of endocrinologic diseaseas in Slovakia is high. There are some
28 800 PDM undertake feet examination and training in these rooms. A twofold
non explanable differences among administrative reasons in access to
decrease in a number of amputations and increased awareness of PDM in foot care
endocrinologic outpatients care and high level of overlapping among
proves improvement of specialised help to people with DFS. Within the
endocrinology and other medical specialties.
framework of the project, 288 multidisciplinary teams (surgeon C endocrinol-
DOI: 10.1530/endoabs.49.EP734
ogist C podiatrist) were trained throughout the country and now they render a
specialised help to patients with DFS.
Conclusions
Implementation of the project ‘Prevention of lower limb amputations in people
with diabetes mellitus in Uzbekistan’ improved a specialised help to people with
DFS due to launching a network of ‘Diabetic foot’ rooms and an effective work of
podiatrists and multidisciplinary teams trained on sites and that lowered a number
of amputations in PDM by two times; increased awareness of people with diabetes
on prevention of DFS.
Diabetes (to include Epidemiology, Pathophysiology)
DOI: 10.1530/endoabs.49.EP736
EP735
Gestational diabetes risk in three Israeli population subgroups
Anat Jaffe1, Shmuel Giveon2, Carmit Rubin3, Ilia Nvokov3, Arnona Ziv3 &
Ofra Kalter-Leibovici2,3
1Hillel Yaffe Medical Center, Hadera, Israel;2Sackler School of Medicine,
Tel Aviv, Israel;3Gertner Institute for Epidemiology and Health Policy
Research, Ramat Gan, Israel.
EP737
Assessment of the prevalence of type 1 diabetes microvascular
complications in young adults in the repablic of Belarus with regard to
Objective
the duration of the disease
Israeli Ethiopian Jews (EJ) and Arabs have at reproduction age higher incidence
Yuliya Dydyshka1, Alla Shepelkevich1, Vladislav Yurkovets1,
of diabetes than other Israeli Jews. We aimed to compare gestational diabetes
Elena Brutskaya-Stempkovskaya1,2 & Marina Mantachik1
(GDM) risk among these population subgroups.
1Belarusian State Medical University, Minsk, Belarus;231th city polyclinic
Methods
in Minsk, Minsk, Belarus.
The study cohort included age-matched EJ, non-Ethiopian Jews (NEJ) and Arab
women age 20-45 years. GDM diagnosis was based on the two step screening
method of 50 and 100 g oral glucose load tests. Univariate comparisons and the
Background and aims
association between population subgroups and the risk for GDM were tested in
According to current recommendations of the American Diabetes Association
multiple logistic regression analysis, adjusted for age, parity and pre-gestational
expedient screening of microvascular complications in all patients with type 1
levels of the metabolic syndrome components.
diabetes (T1D) with a duration of 5 years of the disease. Therefore, the aim of
Results
study was to assess the prevalence of microvascular complications in T1D
The study included 13 943 women (2938 EJ, 5156 NEJ and 5849 Arabs). During
patients aged 30K45 years with regard to the duration of the disease 5K10 years
the years 2008-2011, birth rate was 0.358, 0.475 and 0.526 (P!0.001), diabetes
and over 10 years.
screening was performed in 84, 81, 85 and GDM prevalence was 4.3, 2.2 and 2.9%
Materials and methods
among Ethiopian, non-Ethiopian and Arab women respectively. The multivariate
We examined 360 patients with type 1 diabetes, 196 (54.4%) men and 164
odds ratios (OR) for GDM were age 2.9-per 10 years (95% CI 2.1-4.1), BMI 1.12
(45.6%) women. The average age of the patients was 37.9G4.5 (37.4K38.4)
(95% CI 1.1-1.2), triglycerides 1.05-per 10 mg/ml (95% CI 1.0-1.1), systolic
years, the age of onset of diabetes - 28.1G6.2 (27.5K28.8) years, duration of the
blood pressure 1.05-per 10 mmHg (95% CI 1.02-1.1), parity 0.8 (95% CI 0.7-
disease - 9.0 (7.0K12.0) years, BMI - 24.8G3.95 (23.6-25.2) kg/m2, HbA1c -
0.9) and Ethiopian ethnicity 2.55 (95% CI 1.6-4.1). Arab-ethnicity 1.4 (95% CI
8.37G1.83 (8.18K8.56). In the study, carried out a detailed clinical examination
0.95-2.15) and HDL-c 0.99 (95% CI 0.91-1.08) were not associated with risk for
of patients with medical records analysis.
GDM.
Results
Conclusions
Diabetic peripheral neuropathy (DPN) was diagnosed in 133 (36.9%) patients;
Ethiopian ethnicity is an independent risk for GDM. The higher GDM prevalence
diabetic retinopathy (DR) K 78 (21.7%) patients, diabetic nephropathy (DN) K
in Arab women is mainly explained by higher obesity rates.
in 146 (40.6%) patients, albuminuria was detected in 137 (38.1%) persons. In
DOI: 10.1530/endoabs.49.EP735
general, microvascular complications of diabetes were set at 270 (75%) patients.
With increasing duration of the disease for more than
10 years showed a
significant increase in microvascular complications: DPN 30.6 vs 47.1% (c2Z
9.91; PZ0.002); DN K 34.2 vs 50.7% (c2Z9.60; PZ0.002); albuminuria K
31.9 vs 47.8% (c2Z9.06; PZ0.003); DR - 40.1 vs 71.7% (c2Z34.2; P!0.005);
any microvascular complications K 67.6 vs 86.9% (c2Z17.06; P!0,001).
Diabetes Complications
However, no significant differences in HbA1c:
8.32G1.83 vs 8.45G1.82%
(PZ0.539).
EP736
Conclusions
Improvement of specialised help to patient with diabetic foot syndrome
Patients with type 1 diabetes with disease duration 5K15 years microvascular
in Uzbekistan
complications recorded in 75% of cases. The increase in the prevalence of
Nilufar Ibragimova, Telman Kamalov, Hamidulla Shakirov,
microvascular complications associated with the duration of the disease, but not
Oxana Platonova & Lyudmila Kokareva
with the level of HbA1c.
Charity Public Association of the Persons with Disabilities and People with
DOI: 10.1530/endoabs.49.EP737
DM ‘UMID’, Tashkent, Uzbekistan.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Endocrine Disruptors
EP741
EP738
24 hrs chronomics of BP/HR in terms of double amplitude, acrophase,
hyperbaric index and its relation with circadian rhythm of 6-sulfatoxy
Endocrine disrupting chemicals exacerbate type 1 diabetes mellitus
melatonin in night shift nursing professionals: A Case-control study
model
B Anjum1,2, Narsingh Verma1, Sandeep Tiwari3, Ranjana Singh2 &
Changhwan Ahn, Jin Yong An, Dinh Nam Tran, Seon Young Park &
Abbas Mahdi2
Eui-Bae Jeung
1Department of Physiology, King George’s Medical University, Lucknow,
Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
UP, India;2Department of Biochemistry, King George’s Medical
University, Lucknow, UP, India;3Department of Surgery (Gen), King
It has been proposed that cellular Ca2C signals activate hormone secretion. In
George’s Medical University, Lucknow, UP, India.
pancreatic b cells, which produce insulin, Ca2C signals have been known to
contribute to insulin secretion. In previous study, demonstrated that endocrine
The present study was aimed to investigate the 24 hours chronomics of BP/HR in
disrupting chemicals (EDCs) such as bisphenol A (BPA) and Octylphenol (OP)
terms of Double amplitude, Acrophase and Hyperbaric index and its relation with
could cause increase in insulin level and insulin transcription factors. But in
circadian rhythm of 6-sulfatoxy melatonin in night shift nurses and actual day
regulations of plasma glucose level were not decreased as much as insulin increase.
workers. 56 night shift nurses, aged 20-40 years, performing day and night shift
For identifying this phenomenon, we evaluate the HOMA-IR which is used for
duties were recruited from the Trauma Center, KGMU, India, and 56 age sex
calculating insulin resistance, trace that EDCs has ability to increase insulin
matched actual day workers were also enrolled as controls. BP and HR were recorded
resistance. We hypothesized that EDCs disrupts calcium homeostasis and the
by ABPM at every 30 min intervals in day time and each hour in night time
altered intracellular calcium levels may induce insulin resistance. The expression
synchronically with circadian rhythm of 6-sulfatoxy melatonin during shift duties.
of genes involved in transporting calcium ions to the endoplasmic reticulum (ER)
Highly significant difference was found in double amplitude (2DA) of SBP between
was decrease while the expression of those affecting the removal of calcium from
night (23.10G14.68) and day shift (34.27G16.44) (P!0.0005). In night shift,
the ER was increased. Depletion of calcium from the ER leads to ER-stress and can
hyperbaric index (HBI) of mean SBP was found to be increased at 00-03 am
induce insulin resistance. Taken together, these results imply that the disruption of
(midnight) while during day shift, peak was found at 06-09 am. HBI of mean HR was
calcium homeostasis by EDCs induces ER-stress and leads to the insulin resistance.
found to be increased at 18-21 pm during night shift while in controls, peak was
Additionally, findings from this study suggest that imbalances in calcium
found at 09-12 & again 15-18 pm of SBP, DBP & HR. Alterations in Acrophase of
homeostasis due to EDCs such as BPA and OP could promote insulin resistance
BP/HR were very common among night shift workers and Ecphasia was found in
and its harmfulness especially to the Type I diabetes mellitus patients.
few night shift workers. Alteration in morning and night melatonin level was also
DOI: 10.1530/endoabs.49.EP738
found during night shift as compare to their day shift and in actual control group.
Reverse pattern of Acrophase and HBI of BP & HR along with 6-sulfatoxy melatonin
during night shift represents desynchronization. It indicates that the circadian rhythm
was disrupted during night shift and recovery occurs during day shit.
DOI: 10.1530/endoabs.49.EP741
EP739
Stimulating effect of 17b-estradiol and TCDD and on the protein
expression of cytochrome P450 1A1 gene in cellular and xenografted
models of breast cancer
Ryeo-Eun Go, Kyung-A Hwang & Kyung-Chul Choi
EP742
Laboratory of Biochemistry and Immunology, Veterinary Medical Center
The effects of halogenated-hydrocarbon uron herbicides, as endocrine
and College of Veterinary Medicine, Chungbuk National University,
disruptor compounds on the oxytocin (OT) hormone regulation in vitro
Cheongju, Chungbuk, Republic of Korea.
Krisztian Sepp1, Zsuzsanna Valkusz1, Zsolt Molnar2, Anna Laszlo4,
3, Marianna Radacs2 & Marta Galfi2
Tunde Alapi
Cytochrome P450 (CYP) 1A1 plays a major role in the metabolic activation of
1First Department of Medicine, University of Szeged, Szeged, Hungary;
procarcinogens to carcinogens via aryl hydrocarbon receptor (AhR) pathway.
2Department of Environmental Biology and Education of Gyula Juhasz
Especially, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known as an agonist of
Faculty of Education, University of Szeged, Szeged, Hungary;3Department
AhR. In estrogen responsive cancers, 17b-estradiol (E2) may influence on AhR
of Inorganic and Analytical Chemistry of Faculty of Science and
dependent expression of CYP1 family via the interaction between estrogen receptor
Informatics, University of Szeged, Szeged, Hungary;4Department of
(ER) and AhR. In the present study, the effect of E2/ER on the expression of AhR and
Biometrics and Agricultural Informatics Szent Istvan University, Godoll
˝,
CYP1A1 genes was investigated for MCF-7 clonal variant (MCF-7 CV) breast
Hungary.
cancer cells expressing ER. In reverse transcription (RT)-PCR and western blot
analysis, mRNA level of AhR was not altered, but its protein level was increased by
The biological organisms are complex systems regulated by the homeostatic
TCDD or E2. The transcriptional and translational levels of CYP1A1 appeared to be
back-end network. In these days the growing environmental loads (from industry,
increased by TCDD or E2. The increased expression of AhR and CYP1A1 induced
household, etc.) contain chemical exposure eg. halogenated hydrocarbons
by E2 was restored to the control level by the co-treatment of ICI 182,780, indicating
(monuron: MU (C9H11ClN2O), diuron: DU (C9H10Cl2N2O)), which can be
that E2 induced the protein expression of AhR and CYP1A1 like TCDD via an ER
endocrine disruptor compounds (EDCs). Synthesis, release of hormones and cell
dependent pathway. In an in vivo xenograft mouse model transplanted with MCF-7
processes of endocrine cells, and the biochemical properties of hormones can be
CV cells, the protein levels of AhR and CYP1A1 of tumor masses were also
changed by these agents. The disturbance of endocrine regulation by the EDCs
increased by E2 or TCDD. Taken together, these results indicate that E2 may
can induce different diseases for example in the reproductive-, neurological,
promote AhR dependent expression of CYP1A1 via ER dependent pathway in MCF-
and/or psychical, and/or immunological system. In this study the aim was to
7 CV cells expressing ER in the absence of TCDD, an agonist of AhR. The relevance
investigate the effects of uron herbicides (fenuron: PU (C9H12N2O); MU, DU) on
of E2 and ER in CYP1A1 activation of estrogen responsive cancers may be targeted
the monoamine activated ocytocin (OT) release from neurohypophysis (NH)
for developing more effective cancer treatments. (This research was supported by a
cells. The primary monolayer NH cell cultures were prepared from the evidenced
grant (14182MFDS977) from Ministry of Food and Drug Safety in 2016.)
Wistar rats (_) for the experiments. The separated NH tissues were dissociated
Keywords: Dioxin, 17 b-estradiol, breast cancer, xenograft models, CYP1A1
by enzymatic (trypsine, collagenase, DNA-se I; II) and mechanic methods. The
DOI: 10.1530/endoabs.49.EP739
14 days old cultures were standardized for cell-viability and OT content. The NH
cells were tested for functionally OT hormone volume by aspecific stimulus
(30 mM [KC]). The untreated cultures were the controls, and the treating system
was the consequential: A: 1 hour 0.1 mg/ml EDCs; B: 10-6M monoamines
(epinephrine, norepinephrine, dopamine, histamine, serotonine) alone; C:
EP740
combined the monoamines agents with EDCs. The OT content was measured
from supernatant media by RIA method. The results showed that the uron
herbicides alone did not have significant effects on the OT release in the primary
monolayer NH cell cultures. The EDCs caused alteration of the monoamine
Abstract withdrawn.
activated hormone release. The uron herbicides can play as strong environmental
stress factors in the homeostatic system regulation. This work was supported by:
TÁMOP-4.2.2.D-15/1/KONV-2015-0010, TÁMOP-4.2.4.A/2-11-1-2012-0001.
DOI: 10.1530/endoabs.49.EP742
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP743
Conclusion
In conclusion, our study demonstrates consistently that several behavioral traits
The protective role of Zingiber officinale extract against methyl
and fat-soluble vitamins may have detrimental effects on BMD, while reinforcing
thiophanate induced toxicity in male rats
the benefit of physical activity for skeletal health.
Rachid Mosbah1,2, Malika Bahri1, Said Azzoug3, Zouhir Djerrou4 &
Alberto Mantovani5
DOI: 10.1530/endoabs.49.EP744
1Department of Biology, University of Boumerdes, Boumerdes, Algeria;
2Laboratory of Eco-biology, ENS Kouba, Algiers, Algeria;3Hospital of
Lamine Debaghine B.E.O, Algiers, Algeria;4University of Skikda, Skikda,
Algeria;5Istituto Superiore di Sanità, Rome, Italy.
In this study, we attempted to assess the toxicity of Methyl Thiophanate (MT) on
the biochemical and reproductive parameters in male Wistar rats as well as the
possible protective role of Zingiber officinale (Ginger, Ging) extract against
MT-induced toxicity. Hence, forty adult Wistar rats were allocated into four
EP745
groups of 10 rats for each; the first group served as control, groups 2, 3 and 4 were
Quantitative image based analysis of endocrine disruptor effects on
treated orally (5/week) for 8 weeks by MT (150 mg/kg bw), Ging (100 mg/kg bw)
mitochondria morphology-function in prostate cancer cells
and MT plus Ging respectively. At the end of experiment, blood samples were
Aurélie Charazac1, Célia Deconde Le Butor1, Mamadou Gueye1,
collected under anesthesia for measuring the biochemical parameters and
Jérôme Gilleron1, Kévin Giulietti3, Patrick Fenichel2, Xavier Descombes3,
testosterone level, while, the reproductive organs were excised and used for
Frédéric Bost1, Stéphan Clavel1 & Nicolas Chevalier2
semen quality analysis and histopathological examinations. Results indicated that
1Institut National de la Santé et de la Recherche Médicale (INSERM) UMR
MT exposure increases the level of blood glucose, cholesterol, triglycerides, urea,
U1065/UNS, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice,
uric acid, AST, ALT and total protein, whereas, no clear impact on testosterone
PACA, France;2Centre Hospitalier Universitaire de Nice, Hôpital de
level was noted compared to the control. Semen analysis showed a decrease in
l’Archet 2, Service d’Endocrinologie, Diabétologie et Médecine de la
spermatids number, sperm count, motility and viability. Moreover, a marked
Reproduction, Nice, PACA, France;3INRIA CRI-SAM, Nice, PACA,
histopathological damage in testis and epididymis was detected which reflect a
France.
poor semen quality. Ginger extract co-treatment with MT alleviates and/or repairs
all adverse toxic effects caused by MT on the reproductive, biochemical and
hispathological parameters. This amazing preventive role may be related to its
Persistent organic pollutants
(POPs) are environmental contaminants that
potential antioxidant properties. In conclusion, ginger extract supplementation
interfere with normal hormonal homeostasis and act as endocrine disrupting
plays crucial protective role against MT-induced toxicity in male rats.
compounds (EDC). These molecules can mimic hormone effects on metabolism.
The links between metabolism and cancer are now well established. Metabolism
DOI: 10.1530/endoabs.49.EP743
generates reactive oxygen species (ROS), which contribute to mutations and
induces oncogenic transformation. In turn, cancer cells display high metabolic
flexibility allowing them to grow in various cellular environments and favoring
their proliferative and invasive capacities. Mitochondria are key players in this
complex interplay since they produce ROS, generate energy, and participate in
nucleotide synthesis and in glutamine metabolism of cancer cells. Regarding the
importance of hormones on prostate cancer risk and outcomes, we are developing
a multiple parameters in vitro assay conducted in a high-throughput screening
format relevant for prostate cancer metabolism and aggressiveness. This
screening method includes, inter alia a microscopy based analysis of
mitochondria structure and function. We analyzed the effects of five EDCs
EP744
(Aldrin, BDE28, TCDD, PCB153, PFOA) identified in the plasma of patients on
Systematic screening for environmental and behavioral determinants
two prostate cancer cell lines,
22RV1 (androgen-responsive) and DU145
identifies factors detrimental to skeletal health
(androgen-unresponsive). Each compound was tested in a dose dependent
Ling Oei1,2, Joy Wu3, Edwin Oei4, Fernando Rivadeneira2,5,
manner to determine its effects on ROS production, mitochondrial membrane
Andre Uitterlinden2,5, John Ioannidis6, Michael Snyder1 & Chirag Patel7
potential, mitochondrial biogenesis and mitophagy. In addition, we performed an
image based computational analysis of the mitochondrial network morphology
1Department of Genetics, Stanford University School of Medicine, Stanford,
and dynamics. This strategy allows us to extract some quantitative parameters on
CA, USA;2Department of Internal Medicine, Erasmus MC, Rotterdam,
the mitochondrial network as fragmentation index, compactness, average volume,
The Netherlands;3Division of Endocrinology, Stanford University School
of Medicine, Stanford, CA, USA;4Department of Radiology and Nuclear
etc. When combined, morphological and functional parameters allow us to
Medicine, Erasmus MC, Rotterdam, The Netherlands;5Department of
discriminate subtle perturbations of the mitochondrial structure-function induced
Epidemiology, Erasmus MC, Rotterdam, The Netherlands;6Stanford
by EDCs in prostate cancer cells. We are confident that this multiparameter
University School of Medicine, Stanford Prevention Research Center, USA;
analysis strategy could represent a new perspective in identification and
7Department of Biomedical Informatics, Harvard Medical School, Boston,
characterization of EDCs based on their effects on cell metabolism (phenoscore)
MA, USA.
in order to estimate their potential risk on human health.
DOI: 10.1530/endoabs.49.EP745
Background
An increasing amount of biomedical data is becoming available, and methods are
needed to tackle these “big data”.
Methods
We performed a systematic evaluation of 138 environmental and behavioral
factors in relation to bone mineral density (BMD) in the National Health and
Nutrition Examination Survey (NHANES). Dual energy X-ray absorptiometry
(DXA) scans were available for total body, head, pelvis and lumbar spine for
27,259 participants from NHANES surveys 1999-2000 (A), 2001-2002 (B),
Endocrine Tumours and Neoplasia
2003-2004 (C) and 2005-2006 (D). A discovery Environment-Wide Association
Study (EWAS) was performed on cohorts B and D, and replication was sought in
EP746
cohorts A and C.
NENs, NETs, NECs: Accessing expert care
Results
Nicola Jervis & Catherine Bouvier
Higher serum levels of a-tocopherol (per S.D. bZK0.25% for lumbar spine) and
NET Patient Foundation, Leamington Spa, UK.
of g-tocopherol (bZK0.54% for total body), forms of vitamin E, were associated
with decreased BMD. In contrast, retinol serum levels were related to higher
BMD (per S.D. bZC0.21% for total body). Serum lead levels had a negative
Endocrine tumours are a heterogenous group of tumours, that are frequently
relationship to BMD of the lumbar spine (per S.D. bZK0.43%) and head (per S.D.
described as “complex”, “diverse”and, with few exceptions, “rare”. According to
bZK0.87%). Higher levels of physical activity were associated with higher
the Giwice Position Statement (as issued by the European Task Group for
BMD (total body: per MET C1.2%). Being a current or past smoker was
Endocrine Tumours): Endocrine Tumours are defined.as malignant tumours
associated with decreased BMD of the total body, pelvis and head.
arising from endocrine organs including thyroid, adrenal, parathyroid, as well as
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
neuroendocrine tumours in general. The research supported recommendation, to
Pituitary - Clinical
improve care, experience and outcomes, is for patient-centric endocrine cancer
EP748
care in specialist centres, by multidisciplinary teams (Box: MDT members), with
access to enrolment into clinical and translational research. Specialism being
Learning from adult growth hormone deficient patients’ advisory panel
determined by patient volume (geographical prevalence and incidence) and
Judith Hey-Hadavi1, Cecilia Camacho-Hubner1 & Nicky Kelepouris2
centre/MDT experience in disease subtype. The Taskforce points to the ENETs
1Pfizer Inc, Endocrine Care, New York, NY, USA;2Pfizer Inc, US
Centre of Excellence Programme as an exemplar of specialist accreditation.
Endocrine Care, Collegeville, PA, USA.
Neuroendocrine neoplasms (NENs) can be found in endocrine glands and more
diffusely throughout the body, including respiratory, digestive and urinary tracts,
Introduction
breast, skin and nerve structures. They display a variety of functional and
Adult Growth Hormone Deficient (AGHD) patients have often a difficult path
infiltrative behaviours, and growth patterns. Nomenclature varies but in general is
from diagnosis to treatment. A patient advisory panel was conducted to better
based on site of origin, grading
(utilising morphology and proliferation),
understand the AGHD patient journey and how this could be supported. This
functionality then staging - though determining malignancy for some types is
format was chosen to allow for direct patient to patient interactions and
based predominantly on the presence
/ absence of metastases. The global
discussions and for physicians to learn.
incidence of NENs is rising. However despite expert recommendations and
Findings
European guidelines, NET Patient experience reports suggest ongoing care
A total of nine patient advisors (three childhood-onset; six adult-onset, age 33-67
deficits related, amongst other issues, difficulty in accessing clinically appropriate
years; 4M: 5W) were invited through different US endocrinology offices for a one
diagnostics, treatment and psychosocial care, including information and support.
day meeting. All had multiple pituitary hormone deficiencies (MPHD) and
received daily GH. Six HCPs attended the meeting to learn from the interactions.
An independent moderator facilitated the meeting and discussion. All patients
reported that their journey was challenging regardless of age at diagnosis or
DOI: 10.1530/endoabs.49.EP746
MPHD. They felt that there is a lack of AGHD knowledge, and unawareness
among physicians and patients. Symptoms went unrecognized for years prior to-
diagnoses/treatment: and included: weight gain, arthralgia, social withdrawal/a-
pathy and extreme fatigue (labelled ‘laziness’). The majority was misdiagnosed:
mainly with depression and treated with antidepressants for variable period of
time. The patients felt their ‘life caving in’. Some were too fatigued to go to the
doctor. After diagnosis, it sometimes took months to get on GH replacement
therapy due to insurance issues and finding a physician who would treat.
Support was very limited without the opportunity to learn about AGHD or
connect with other patients. The advisors proposed several ideas to improve their
experience, i.e. education of HCPs, and patients, patient ambassador programs,
patient panels etc.
Female Reproduction
Conclusions
EP747
Hearing live from patients is an innovative way of learning outside the traditional
clinical setting. We identified a major need for more education, awareness, and
The accuracy of lifestyle management information on websites for the
resources for AGHD patients as well as physicians to improve their care.
management of PCOS
Thaw Dar Htet1, Samatha Cassar2, Millicent Burggraf1, Jacqueline Boyle1,
DOI: 10.1530/endoabs.49.EP748
Melanie Gibson-Helm1, Nigel Stepto1,2 & Lisa Moran1,2
1Monash Centre for Health Research Implementation, School of Public
Health and Preventive Medicine, Monash University, Melborune, Australia;
2Clinical Exercise Science Program, Institute of Sport Exercise and Active
Living, Victoria University, Melbourne, Australia.
Thyroid (non-cancer)
Background
Lifestyle approaches (diet, physical activity and/or behavioural) play an integral
EP749
part in Polycystic Ovary Syndrome (PCOS) management. The internet is widely
Iodine supplementation in children and pregnant women from rural
used as a resource for health information. However, the accuracy of lifestyle
areas of Belarus in 2015-2016
information on PCOS websites is unknown. This study aimed to assess the
Tatsiana Mokhort1, Sergey Petrenko2, Boris Leushev2, Olga Bartoshevich3,
accuracy of lifestyle recommendations on PCOS websites.
Nataliya Kolomiets4, Elena Mokhort1 & Ekaterina Fedorenko5
Methods
1Belarusian State Medical University, Minsk, Belarus;2International
The internet search was conducted through three search engines across different
Sakharov Environmental Institute, Minsk, Belarus;3Liakhovichy Central
web browsers and countries. Keywords “PCOS”, “Polycystic Ovary Syndrome”
Regional Hospital, Brest Region, Belarus;4Belarusian Medical Academy of
and “Polycystic Ovarian Syndrome” were used to identify websites using a
Post-Graduate Education, Minsk, Belarus;5Republican Research and
previously defined internet search protocol. Websites providing lifestyle
Practical Center ‘Hygiene’, Minsk, Belarus.
information in less than
10 sentences were excluded. The accuracy of the
information was assessed through a checklist of 29 questions developed based on
National and International guidelines for diet, physical activity or weight
The efficiency of the Belarusian model for iodine deficiency elimination based on
management for the general population and PCOS with higher scores indicating
obligatory use of iodized salt in the industrial food production and bread baking
greater accuracy. Websites were scored by two independent reviewers.
has been often challenged in other countries. In support the facts are presented
Results
evidencing of insufficient iodine intake in groups of increased risk of iodine
Fifteen websites were eligible from 72 websites in total (20%). The total accuracy
deficiency in children and pregnant women from the rural areas of Belarus. The
score was 56G13 (potential range K29 to 87) comprising 23G6 for diet
goal of the recent study is to compare the dynamics of iodine supplementation for
(potential range K11 to 33), 15G5 for physical activity (potential range K9 to
the period of 2015-2016 in groups of increased risk in Brest region. The iodine
27) and 14G3 for weight management (potential range K8 to 24). A moderate
status of the body was determined by the iodine urine concentration. The study
proportion of websites provided general information on appropriate diet (40-
included
30 pregnant women examined in
2015 and 40 pregnant women
80%) or weight management strategies (47-60%) but only 10-40% of the
examined in 2016 aged 23-32 years, and 51 children examined in in 2015 and 44
websites provided information on aspects such as core food, discretionary foods,
children examined in 2016 aged 8-14 years. Statistical processing was performed
exercise quantity/intensity, specific energy deficits or behavioural strategies.
by nonparametric statistics.In
2015
in the rural area ioduria median was
Conclusion
165.7 mg/l in children and 107.5 mg/l in pregnant women. Iodized salt was used by
A limited number of Internet sites for PCOS contain information on lifestyle
86.2% of schoolchildren and only 66.7% of pregnant women. In 2016 ioduria
management. Of these, the majority provided information on general diet,
median in children of the same region increased to 233.0 mg/l, and in pregnant
physical activity and weight recommendations but less information on a healthy
women to 152.4 mg/l. Iodized salt in 2016 was used by 89.4% of schoolchildren
lifestyle implementation. These findings suggest that PCOS-related websites need
and 78.8% of pregnant women. Thus, the Belarusian model of iodine deficiency
elimination having been used since 2001 has demonstrated its long term efficiency
to be improved to provide more detailed and practical information for consumers
even in the risk groups of iodine deficiency development.
to apply to their PCOS management.
DOI: 10.1530/endoabs.49.EP749
DOI: 10.1530/endoabs.49.EP747
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations:
Interdisciplinary Endocrinology
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Adrenal Cortex (to include Cushing’s)
Conclusion
In recipients who underwent Ptx before and after KT, PTx provided sustained
EP750
decrease in serum Ca and PTH levels without affecting graft function.
Comparison of 17-OH-Progesterone results by a radioimmunoassay
DOI: 10.1530/endoabs.49.EP751
and a chemiluminescent assay
Conceicao Godinho & Isaura Rodrigues
Centro Hospitalar Lisboa Central, Lisboa, Portugal.
Introduction
The major clinical importance of 17-OH-Progesterone is related to the diagnosis
EP752
and therapeutic monitoring of Congenital Adrenal Hyperplasia
(CAH).
Radioactive assays are widely used in clinical laboratories for measuring
The effect of corticosteroids on development of femoral head
17-OH-Progesterone. The appearance of a non-isotopic, chemiluminescent
osteonecrosis in patients after kidney transplantation
automatic assay, may be an interesting alternative if the performance of the
Enis Gursel1, Omer Faruk Bilgen1, Sadik Bilgen1, Basak Erdemli Gursel2,
assay remains the same or higher.
Canan Ersoy3 & Alparslan Ersoy4
Obective
1Department of Orthopedics, Uludag University Medical Faculty, Bursa,
Turkey;2Department of Radiology, Uludag University Medical Faculty,
To compare the 17-OH-Progesterone results by a radioimmunoassay (RIA) and a
chemiluminescent assay (CLIA) and to analyze the clinical impact taking into
Bursa, Turkey;3Endocrinology and Metabolism, Uludag University
account the % concordance.
Medical Faculty, Bursa, Turkey;4Department of Nephrology, Uludag
Material and methods
University Medical Faculty, Bursa, Turkey.
We studied 74 patients, aged 6 months to 83 years old, observed at CHLC
endocrinology appointments, in Lisbon. The serum samples were analyzed by
Corticosteroid-induced osteonecrosis is seen in 3-4% of patients undergoing
‘17a-Hydroxyprogesterone
(17-OHP)-RIA-CT’, DIASource
(wr:
0.04-
kidney transplantation (KT), especially at the head of the femur. The use of
12.5 ng/ml) and
‘Maglumi
17-OH Progesterone
(CLIA)’ Snibe
(wr:
0.1-
corticosteroids for any reason is responsible for approximately 41% of total hip
20 ng/ml). An excel tool was used for statistical treatment and the clinical
arthroplasty performed due to osteonecrosis. In this study, we investigated factors
concordance of patients was analyzed according to the reference values of both.
affecting osteonecrosis development after KT
For statistical comparison nine patients were excluded and to analyze the clinical
Methods
impact we divided patients into groups according to age and gender.
Among 205 recipients who underwent KT, 32 (15.6%) had symptomatic femoral
Results
head osteonecrosis (FHO group). Fifty patients who were similar in terms of age,
Pearson correlation coefficient rZ0.90 and the equation of linear regression
sex, and posttransplant follow - up period constituted the non-FHO group.
was:yZ0.46xC0.17. Group 1Z24 both gender (6m-11y); Group 2: 12 male
Results
(12 y-47y); Group 3: 38 female (13y-83y). For the group 1 and 2: % agreement
The gender, age and pre-transplant BMI of both groups were similar. In patients
was 62.5 and 66; It was impossible to classified 25% of group 1 because CLIA has
who developed FHO, the onset of symptom was median 6 months (range: 1-40).
no reference values for age. Group 3 had insufficient clinical data.
In patients who developed bilateral FHO, the mean duration of symptomatic
Conclusion
change in the other hip was 2.1 months (range: 0-6). The median value of the
There is a good correlation but in order to become an alternative to RIA it is
patients’ diagnosis time was 9 months (range: 1-40). The serum creatinine,
fundamental to have reference values between 3 months and 3 years for a further
calcium, phosphorus, ALP and PTH values at 1st, 6th and 12th after KT in both
reassessment since its main usefulness is the diagnosis and monitoring of CAH.
groups did not differ. There was no significant difference in hip and lumbar
DOI: 10.1530/endoabs.49.EP750
DEXA values between the groups in terms of osteonecrosis development. Three
patients (9.4%) in the FHO group and seven patients (14%) in the non-FHO group
had steroid treatment before KT. Cumulative steroid doses taken after KT the
FHO and non-FHO groups were 6366 mg (range: 3230-10947) and 5664 mg
(range: 3717-13887) at 12th month (PZ0.068). A total of 17 hips total hip
prosthesis were performed in 11 patients (six female, five male, mean age 45.2)
who developed FHO.
Calcium and Vitamin D Metabolism
Conclusion
We did not find any association between post-transplantation FBO development,
EP751
lumbar and femoral bone density measurements, and steroid doses.
The effect of parathyroidectomy on graft function in kidney transplant
DOI: 10.1530/endoabs.49.EP752
recipients with persistent hypercalcemia
Aysegul Oruc1, Alparslan Ersoy1, Ozen Oz Gul2 & Canan Ersoy2
1Department of Nephrology, Uludag University Medical Faculty, Bursa,
Turkey;2Endocrinology and Metabolism, Uludag University Medical
Faculty, Bursa, Turkey.
Although serum calcium (Ca), phosphorus and parathyroid hormone (PTH) levels
Cardiovascular Endocrinology and Lipid Metabolism
tend to normalize after successful kidney transplantation
(KT), persistent
EP753
hyperparathyroidism (PHPT) can have deleterious effects on graft function. We
aimed to evaluate the effect of parathyroidectomy (PTx) on graft function in
Resveratrol increases hepatic SHBG expression through human
recipients after KT.
constitutive androstane receptor: a new Contribution to the French
Methods
Paradox
This retrospective study conducted in 319 adult KT recipients. PHPT is defined as
Cristina Saez-Lopez1, Laura Brianso-Llort1, Javier Torres-Torrenteras2,
serum corrected Ca level O10.2 mg/dl (at least twice in a 6 month period) and
Rafael Simo1, Geoffrey Hammond3 & David Selva1
PTH O150 pg/ml at 6th month of KT.
1Diabetes and Metabolism Research Unit, Vall Hebron Institut de Recerca
Results
(VHIR), Barcelona, Spain;2Research Group on Neuromuscular and
The mean follow up time was 49.4G1.4 months. Mean serum PTH levels before
Mitochondrial Diseases, Vall Hebron Institut de Recerca (VHIR),
and at 12th month of KT and prevalence of hyperparathyroidism were 529G474
Barcelona, Spain;3Cellular & Physiological Sciences, University of British
and 212G236 pg/ml, and 83.9% and 51.9%, respectively. Fifteen recipients with
Columbia, Vancouver, British Columbia, Canada.
PHPT received cinacalcet for an average of 14.2G5.7 months. After cessation of
cinacalcet therapy, serum Ca levels increased within 6 month. Mean serum Ca
Sex hormone-binding globulin (SHBG) carries sex steroids in blood regulating
levels at 1st, 6th and 12th months of 12 recipients who underwent PTx before KT
their bioavailability. Red wine consumption increases plasma SHBG levels, and
were 9.3G1.2, 9.6G0.8 and 9.2G1.2 mg/dl, respectively. The duration between
we have discovered that resveratrol, a polyphenol enriched in red wine, acts
PTx and KT in 16 recipients who underwent PTx after KT was 17.1G8.9 months
specifically through the human constitutive androstane receptor
(CAR), a
(range 5-41 months). Two of 16 had operation at 5th and 1 at 7th month of KT
drug/xenobiotic detoxification gene regulator, to increase hepatic SHBG
because of severe hypercalcemia. Mean serum Ca levels of 16 recipients at 1st,
production. Chromatin immunoprecipitation and luciferase reporter gene assays
6th and 12th months of KT were 10.5G0.9, 10.8G0.9 and 10.6G0.9 mg/dl,
show that human CAR binds to a typical direct repeat 1 nuclear hormone
respectively. There was no significant difference in graft function between post-
receptor-binding element in the human SHBG proximal promoter. Resveratrol
transplant follow-ups in both groups.
also increased hepatic SHBG production in humanized SHBG/CAR transgenic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
mice. Moreover, SHBG expression correlated significantly with CAR mRNA
CVD, Diabetes 18.2%, smokers 18.2%,HTA 36.4%, high lipoprotein(a) 45.5%,
levels in human liver biopsies. We conclude that the beneficial effects of red wine
early CVD 54.6%. 72.7% treated with statins (73.6% rosu and 9.1% atorvastatin)
on the metabolic syndrome and it associated co-morbidities, including
and ezetimibe. 44.4% had elevated transaminases with at least two statins and
cardiovascular disease and type
2 diabetes, may be mediated in part by
27.3% did not tolerate any statin. Patients performed regular physical exercise (at
resveratrol acting via CAR to increase plasma SHBG levels.
least 180 min per week) and diet (100% BMI!30).100% of the subjects had LDL
DOI: 10.1530/endoabs.49.EP753
levels at least 60 mg/dl above therapeutic target. The mean pre and postreatment
levels were: TC: 243.8G27.7 vs 148.5G47.4 mg/dl (P 0.01), LDL-C: 159G23.9
vs 69.9G39.3 (P 0.01), 100% in therapeutic objective, HDL-C 58.5G14.4 vs
56.6G16.1 (P 0.7), non-HDL-C 185.3G21.5 vs 91.8G32.7 (P 0.01), 100% on
therapeutic target, TG 130G46.2 vs 109G54.8 (P 0.3), Apo B 136G19.9 vs
64.3G11.04 (P 0.01), lipoprotein (a) 133.1G9.9 vs 112.5G5.1 (P 0.04). Only 2
patients had mild side effect: one patient with pseudogripal syndrome that
spontaneously disappeared in 2 days and another patient with injection site
EP754
reaction.
Therapeutic potentials of small molecular weight allosteric agonist of
Conclusion
relaxin receptor
PCSK9 inhibitors were well tolerated and significantly reduced levels of TC,
Alexander Agoulnik1, Irina Agoulnik1, Xin Hu2, Elena Kaftanovskaya1,
LDL-C, ApoB, non-HDL C and lipoprotein a, with 100% of patients achieving
Zaohua Huang1, Courtney Myhr1, Jingbo Xiao2, Mariluz Soula1, Brian Ho1,
therapeutic goals after 3 months of treatment.
Elena Barnaeva2, Noel Southall2, Marc Ferrer2 & Juan Marugan2
DOI: 10.1530/endoabs.49.EP755
1Herbert Wertheim College of Medicine, Florida International University,
Miami, Florida, USA;2NIH Chemical Genomics Center, National Center
for Advancing Translational Sciences, National Institutes of Health,
Rockville, Maryland, USA.
The anti-fibrotic, vasodilatory, and angiogenic therapeutic properties of relaxin
EP756
peptide have been shown in several animal models of human diseases and in
clinical trials. Using high-throughput screening of small molecule library,
Non-lipidic effects of PCSK9 inhibitors in real life
structure-activity relationship (SAR) studies, ligand-receptor interaction model-
Inmaculada Gonzalez-Molero, Viyu Doulatram, Marta Domínguez,
ing, site-specific mutagenesis, and transgenic animal studies we discovered the
Francisco Sanchez Torralvo, Ignacio Ruiz García, Gabriel Olveira &
first series of small molecule agonists of relaxin GPCR, RXFP1. The lead
Francisco Tinahones
compound ML290 is a selective RXFP1 agonist with low cytotoxicity, preferred
Hospital Regional de Málaga, Malaga, Spain.
in vitro ADME and in vivo pharmacokinetic properties. ML290 displays efficacy
similar to the natural hormone in several functional assays in vitro. ML290
Objective
activates human, macaque, pig, and rabbit RXFP1, but not rodent receptors.
Analyse possible effects on physical examination, blood count, liver and kidney
Computational modeling of small molecule binding with human RXFP1 and
function, and steroidogenic hormones synthesis. Know the satisfaction of patients
related receptors in combination with site-directed receptor mutagenesis studies
with the first injectable treatment for hypercholesterolemia approved in our
indicated that the small molecules activated RXFP1 through an allosteric site and
country.
did not compete with relaxin binding to RXFP1. To test agonist activity in vivo we
Material and methods
produced mice with knock-in of human RXFP1 into mouse gene. The analysis of
Data were collected from patients with heterozygous familial hypercholester-
transgenic mice showed that the human receptor fully complement the deletion of
olemia treated with PCSK9 inhibitors. Clinical, physical and analytical data were
mouse gene. Intravenous injection of relaxin led to a rapid increase in heart rate in
collected at baseline, 1 month and 3 months. Satisfaction test (TQ21M-9) was
unconscious WT and humanized mice, but not in Rxfp1 deficient animals. The
performed 3 months after treatment.
ML290 injection increased heart rate in humanized but not in WT animals
Results
suggesting specific target engagement by small molecule agonist in vivo. Similar
Data were obtained from 13 patients, 45.5% male. Mean age: 49.5 years (26-74).
to relaxin IV injections of ML290 caused increased blood osmolality. Therapeutic
Mean pre and postreatment levels were: TC: 243.8G27.7 vs 148.5G47.4 mg/dl
potentials of the small molecular weight relaxin receptor agonist can be now
(P 0.01), LDL-C: 159G23.9 vs 69.9G39.3 (P 0.01), non-HDL-C 185.3G21.5 vs
tested in various preclinical cardiovascular and fibrotic models of human diseases.
91.8G32.7 (P 0.01), Apo B 136G19.9 vs 64.3G11.04 (P 0.01), lipoprotein (a)
DOI: 10.1530/endoabs.49.EP754
133.1G9.9 vs 112.5G5.1 (P 0.04). HbA1c 5.9G0.4 vs 5.70.3 (NS), creatinine
1.01G0.3 vs 0.92G0.2 (NS), GOT 34.7G34.2 vs 34.6G21.9 (NS), GPT 29.8G
18.7 vs 28.2G13.9 (NS). Weight: 70.9G11.2 vs 73.5G11 kg (NS). No effects
were detected in blood count, systolic, diastolic BP or heart rate. The mean levels
of hormones were: Testosterone 4.3G1.4 vs 4.04G1.8 ng/ml (NS), TSH 2.2G0.8
vs 2.14G0.8 mU/l (NS), T4l 16.3G1.1 vs 14.8G0.4 (NS) ACTH 24.2G17.7 vs
30.2G25.2 (NS), Cortisol 14G2.9 vs 16.6G2.1 (NS) Vitamin D3 41.5G49.1G
18.2 ng/ml (NS). Patients showed a high level of satisfaction with treatment, with
EP755
mean scores of 75.9% for effectiveness items, 80.2% convenience items and
85.2% overall satisfaction.
PCSK9 inhibitors effects on lipid profile in familial
Conclusion
hypercholesterolemia in a specific Lipid Unit: experience in first year
Despite the decrease in TC and LDL C levels, there were no significant changes in
commercialization
the levels of stereogenic hormones or vitamin D levels. Treatment with PCSK9
Inmaculada Gonzalez-Molero, Viyu Doulatram, Monserrat Gonzalo Marin,
inhibitors did not change hemogram, hydrocarbon metabolism, kidney, liver
Jose Abuin, Virginia Morillas, Gabriel Olveira & Francisco Tinahones
function, or physical examination parameters. Patients show a high satisfaction
Hospital Regional de Málaga, Malaga, Spain.
with this injectable treatment for hypercholesterolemia.
DOI: 10.1530/endoabs.49.EP756
Objective
Analyse the features of first patients treated with PCSK9 inhibitors in a specific
Familial dyslipidemia Unit and the effects on lipid profile in first months of
treatment.
Material and methods
Data from patients with heterozygous familial hypercholesterolemia treated with
EP757
PCSK9 inhibitors were reviewed. Clinical data, physical examination and
Renal function preservation with Manidipine vs Amlodipine in type 2
analytical data were collected at baseline, one month and 3 months.
diabetic hypertensive patients with persistent microalbuminuria
Results
Sara Quintana-Arroyo1, Claudia Arnas-Leon1, Ana Delia Santana-Suarez1,
Data were obtained from 13 patients, 45.5% male. Mean age: 49.5 years (26-74).
Manuel Nivelo-Rivadeneira1, Agnieszka Kuzior1, Carmen Acosta-Calero1,
Mean follow-upin our Unit:12 years. Diagnosis by DLC: 100% score higher
Margarita Saiz-Satjes3 & Francisco Javier Martinez-Martin2
than 6. 54.6% had been detected with family cascade screening, 45.5% cases with
1Endocrinology Department, Hospital Universitario de Gran Canaria
mutation detected in LDL-R. Initial levels in our clinic: CT: 313.5 mg/dl, TG:
Dr Negrin, Las Palmas de Gran Canaria, Spain;2Outpatient Hypertension
102 mg/dl, LDL 228 mg/dl, HDL: 52 mg/dl, non-HDL C: 202 mg/dl, despite
Clinic, Hospital Universitario de Gran Canaria Dr Negrin, Las Palmas de
45.5% had already started treatment. 72.7% had a family history of premature
Gran Canaria, Spain;3CAP Rambla HUMT, Terrassa, Barcelona, Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Objectives
EP759
The AMANDHA randomized study (PROBE design) showed that the addition of
Anthropometric measurements, nutrition and exercise habits in kidney
Manidipine 20 mg vs Amlodipine 10 mg for 2 years in 91 hypertensive type 2
transplant recipients
diabetic patients with persistent microalbuminuria, uncontrolled with a renin-
Alparslan Ersoy1, Nizameddin Koca1, Tuba Gullu Koca1 & Canan Ersoy2
angiotensin system inhibitor (given full-dose for at least the 6 previous months)
1Uludag University Medical Faculty, Department of Nephrology, Bursa,
was more effective in reducing albuminuria in spite of similar blood pressure
Turkey;2Uludag University Medical Faculty, Endocrinology and
control. Patients with significant renal impairment (PlCr O1.4 mg/dl in women
Metabolism, Bursa, Turkey.
and O1.5 in men) had been excluded. However, no data were published on the
progression of renal dysfunction, with only PlCr values reported, which were not
significantly different. We undertook to establish if there were differences in
After a successful kidney transplant, the nutrition of patients is improved and they
glomerular filtration rate (GFR) progression.
gain weight. Increased appetite due to medication, age of transplant, gender, race,
Methods
pre-transplant obesity story and dialysis type increase the obesity frequency. We
Post-hoc analysis of AMANDHA. GFR was estimated by the MDRD-4 equation
aimed to evaluate the effect of gender on nutrition and exercise habits on
for each individual measurement. Point-to-point GFR were compared by unpaired
transplant recipients.
t-test and progression was compared by the Kruskal-Wallis test. (non-parametric
Methods
ANOVA). Values are given as mean (GS.E.M).
Stable patients were divided into two groups according to gender: 29 males and 33
Results
females. Their nutrition and exercise habits of recipients were questioned by a
Baseline GFR were
67.3
(G5.2) and
70.2
(G5.0) ml/min/1.73 m2
with
survey. The 3-day dietary regimen of all patients was studied using the BEBISe
Manidipine and Amlodipine, respectively; at 6 months they were 68.6 (G5.6)
programme.
and 69.5 (G5.3), and at two years 66.9 (G4.7) and 65.5 (G5.0). During follow-
Results
up, patients treated with Manidipine lost 0.4 (G3.9) ml/min per 1.73 m2 of FGR
Charateristics of groups similar. BMI, blood pressure, hip circumference,
vs 4.7
(G5.2) with Amlodipine. Point-to-point GFR were not significantly
suprailiac and suprascapular fold thicknesses of the groups were not different.
different between the groups, but GFR loss after two years was lower with
The waist (90.3 vs 98.2 cm, PZ0.01), mid-arm (27.2 vs 28.9 cm, P!0.05),
Manidipine (PZ0.032).
triceps
(16.1
vs
11.8 cm, P!0.01) and neck (36.6 vs 41.5 cm, P!0.001)
Conclusions
circumferences in female recipients were lower than those of males. The body fat
The previously published data of AMANDHA showed a markedly greater
percentage of females (30.9 vs 23.8, P!0.01) were lower. HDL levels in males
albuminuria reduction (about 40% more) with Manidipine vs Amlodipine, which
are significantly lower among lipid and apolipoprotein levels. The ratios of eating
was attributed to efferential arteriole dilatation. The present post-hoc analysis also
at home, using oils and exercising in both groups were similar. When recipients’
shows a better preservation of renal function with Manidipine. These results
daily diets were evaluated, intake of fat in males was higher than that of females
strengthens the case for combined treatment with Manidipine and a renin-
(63.3G4.1 vs 70.1G3.1 g, P!0.05). There was no difference in total energy
angiotensin system blocker in hypertensive type 2 diabetic patients with persistent
(1645G68 vs 1681G62 kcal), water
(1590G79 vs 1665G76 ml), protein
microalbuminuria.
(70.4G4 vs 75.8G3.5 g), carbonhydrate (197.7G9 vs 191.8G11.4 g), fiber
(25.7G2.4 vs 24.1G1.7 g) and polyunsaturated fatty acid (12.8G1 vs 13.4G1)
DOI: 10.1530/endoabs.49.EP757
intakes between females and males, respectively. Also vitamin intake of both
groups were comparable except carotene intake of females (5.3G0.4 vs 4G0.3,
P!0.05).
Conclusion
We observed no difference in nutrition and exercise habits between male and
female recipients. Although the percentage of body fat in males was lower, the
amount of fat consume in their diets was higher. The waist and neck
circumferences, which is important for the risk of cardiovascular disease, were
EP758
higher in males.
Effects of calcineurin inhibitors on abdominal obesity in kidney
DOI: 10.1530/endoabs.49.EP759
transplant recipients
Emel Isiktas Sayilar1, Alparslan Ersoy1 & Canan Ersoy2
1Department of Nephrology, Uludag University Medical Faculty, Bursa,
Turkey;2Endocrinology and Metabolism, Uludag University Medical
Faculty, Bursa, Turkey.
Calcineurin inhibitors (CNI, cyclosporine A: CsA and tacrolimus: Tac) cause
posttransplant diabetes mellitus, hypercholesterolemia and hypertension. Post-
transplant weight gain can be related to the type of CNIs. Distribution of obesity is
one of the major predictors of cardiovascular diseases. Several indices assessed
EP760
upper body obesity such as waist circumference (WC) and waist to hip ratio
Hyperglycemia as a factor changing the level of the patient’s
(WHR) are more accurate than whole body obesity (body mass index: BMI). This
rehabilitation after ischemic stroke
study aimed to compare the effects of CNIs on obesity after kidney
Irina Dzherieva, Natalia Volkova, Natalia Maslova & Nikolay Krivonosov
transplantation.
Rostov State medical University, Rostov on Don, Russia.
Methods
The 133 consecutive transplant patients were randomized into 2 groups: CsA
(nZ62) and Tac (nZ71) for two years. In all patients, BMI, body fat percentage,
The aim of the study was to defined the level of rehabilitation after the stroke
WC, hip circumference (HC) and WHR were measured.
depending on the type of hyperglycemia.
Results
Materials and methods
The weight, BMI, body fat percentage, WC and HC were significantly increased
The retrospective analysis of 122 (54 female and 68 men) cases of ischemic stroke
up to month 24 in both groups. There was no significant difference in increases of
(IS) has been done. The diagnosis of IS was confirmed by computer tomography.
BMI, WC, WHR and body fat percentage between both groups. The ratio of
According to the level of hyperglycemia at the debut of IS the patients were
diabetics in CsA group was higher than Tac group (21% vs 1.4%, P!0.001). The
divided into three groups. Group 1 (60 patients) - with normoglycemia, group 2
ratios of de novo diabetics (4.8% vs 12.7%) and hypertensives (29% vs 26.8%)
(27 patients) - with stress hyperglycemia and group 3 (35 patients) with chronic
were similar in the CsA and Tac groups, respectively. Although the abdominal
hyperglycemia. At the beginning and the end of hospitalization the level of
obesity ratios in the CsA and Tac groups increased, the ratios were comparable in
neurological deficit was determined according to NHSS scale. The comparison of
the preoperative (17.7% vs 23.9%), after 12 (37.3% vs 39.3%) and 24 (40% vs
averages was carried out using the Kruskal-Wallis test (a posteriori pairwise
45.9%) months of transplant, respectively. There was no significant difference in
comparisons were made using the method of Niemen), program R Foundation for
glucose and lipid profile between CsA and Tac groups.
Statistical Computing, Vienna, Austria (Version 3.2).
Conclusion
Results
The type of calcineurin inhibitor used did not affect anthropometrical
The patients with normoglycemia and stress hyperglycemia have had the same
measurements throughout two years although both of them caused weight gain
level of rehabilitation (50% (CI: 45-75%) and 50% (CI: 32-73%) respectively).
after transplant.
The statistical significant difference has been found between groups 1 and 3. In
DOI: 10.1530/endoabs.49.EP758
patients with chronic hyperglycemia the average relative level of rehabilitation
was 33% (CI: 22-50%, PZ0.023). The level of rehabilitation of patients 60 years
old was 57% and between 60-75 years old and older this level was 50%.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
woman without special history who was diagnosed to have autoimmune hepatitis,
The negative influence of chronic hyperglycemia has been revealed. The stress
celiac disease, autoimmune pancreatitis and sclerosing cholangitis. The patient
hyperglycemia does not influence on the level of rehabilitation The age exerts on
was put on a gluten-free diet, corticosteroid therapy, azathioprine and
the regress of neurological deficit regardless of the hyperglycemia kinds.
ursodeoxycholic acid. Observation 3: A 37-year-old man, with a history of
DOI: 10.1530/endoabs.49.EP760
vitiligo and Hashimoto’s thyroiditis, presented asthenia and normocytic
normochromic anemia. Biermer’s disease and celiac disease have been
diagnosed. Observation 4: A 41-year-old woman with a history of Hashimoto
thyroiditis presented a dry syndrome and asthenia and liver cytolysis. The anti-
nuclear, anti-SSA and anti-SSB antibodies were positive and labial biopsy
showed a lymphocytic sialadenitis stage III of Chisholm confirming the
EP761
association autoimmune hepatitis and syndrome of Gougerot Sjogren. Obser-
An investigation into role of circulating concentrations of vitamin D and
vation 5: A 29-year-old female patient with a history of Type 1 diabetes, Basedow
calcium in the development of hypertension and related cardiovascular
and Addison diseases was diagnosed to have a celiac disease revealed by diarrhea
diseases
and abdominal pain. Observation 6: A 31-year-old woman follwed for Systemic
Saba Nazir1, Nadia Afzal1, Maleeha Akram1, Zubaria Iqbal1, Abida Raza2,
erythematosus lupus and Gougerot Sjogren syndrome presented a persistent
Mazhar Qayyum1, Afzaal Ahmed Naseem1, Syed Ali Raza Kazmi3,
anemia. Anti-transglutaminase antibodies were positive and duodenal biopsies
Faheem Tahir4, Kiran Afshan5, Sarwat Jahan5 & Syed Shakeel Raza Rizvi1
showed subtotal villous atrophy confirming celiac disease.
1Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University
Conclusion
Rawalpindi, Rawalpindi/Punjab, Pakistan;2Department of Biophotonics,
Patients with autoimmune diseases have a tendency to develop additional
National Institute of Laser and Optrionics (NILOP), Nilore/Islamabad,
autoimmune disorders indicating the need for continued surveillance for the
Pakistan;3Aga Khan Health Centre, Rawalpindi/Punjab, Pakistan;
development of new autoimmune disease in predisposed patients.
4Reproductive Physiology, Public Health Laboratories Division, National
DOI: 10.1530/endoabs.49.EP762
Institute of Health (NIH), Islamabad, Pakistan;5Department of Animal
Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Vitamin D plays a key role in the control of cardiovascular diseases (CVDs), acting
as negative regulator of renin-angiotensin-aldosterone-system (RAAS), whereas
EP763
calcium directly affects central blood pressure (BP) control center, nucleus tractus
Endocrine complications in a female patient with b-thalassemia major
solitarus. We investigated associations between plasma concentrations of vitamin D
following bone marrow transplantation
and calcium and BP in 100 hypertensive CVDs patients and 100 normotensive
Luminita Nicoleta Cima1, Ioana Maria Lambrescu1, Lavinia Stejereanu1,
subjects of 21-60 years. Vitamin D concentrations were measured using ECLIA
Anca Colita1,3 & Simona Fica1,2
system, whereas calcium concentrations were determined using spectrophotometric
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
system. Data were analyzed using Student’s t-test, ANOVA and Pearson correlation
2Endocrine Department, Elias Hospital, Bucharest, Romania;3Hematology
r. Out of 10 RAAS inhibitors (RAASi) treated patients, nine were vitamin D
Department, Fundeni Hospital, Bucharest, Romania.
deficient and one was vitamin D insufficient. Of 29 non-RAASi treated patients, 28
were vitamin D deficient and one was vitamin D insufficient. Among 36 patients
treated with combination of RAASi and non-RAASi, 35 were vitamin D deficient
We report the case of a 14-year-old female patient with b-thalassemia major (b-
and one was vitamin D insufficient. Out of 25 untreated patients, 22 were vitamin D
TM) that presented numerous endocrine complications following bone marrow
deficient and three were vitamin D insufficient. Ninety one control subjects were
transplantion (BMT). The patient was admitted in our department for endocrine
vitamin D deficient, eight were vitamin D insufficient and one was vitamin D
evaluation 3 years after BMT. She was diagnosed with b-TM at 1 year of age and
sufficient. In patients treated with RAASi, calcium concentrations were at lower
received chronic blood transfusions and oral chelating therapy until 2012 when
limit of normal range in 7 and at upper limit in 3. In non-RAASi treated patients,
BMT was performed. The patient developed acute skin and intestine graft-versus-
calcium concentrations were at lower limit in 13 and at upper limit in 16. In both
host-disease remitted with glucocorticoids and suffered severe convulsions as a
RAASi and non-RAASi treated patients, calcium concentrations were at lower limit
result of cyclosporine administration with two subsequent vertebral fractures
in 27 and at upper limit in 9. In untreated patients, calcium concentrations were at
appearance (T5-T6). At first admission in our department she complained of
lower limit in 15 and at upper limit in 10. In control subjects, calcium concentrations
irregular menses. The physical exam revealed HZ148.4 cm (K2.33 S.D.), BMIZ
were at upper limit in 21, at lower limit in 77 and below lower limit in 2. There were
20.17 kg/m2, Tanner P5B5. The laboratory tests were normal, except for low
weak correlations between vitamin D and calcium concentrations and mean BP and
normal estradiol
(34.4 pg/ml) with elevated FSH
(57.9 mIU/ml), low
systolic and diastolic BP in all patients.
25-OH-vitamin D and high titre of thyroid antibodies with normal thyroid
DOI: 10.1530/endoabs.49.EP761
hormones level. The thyroid ultrasonography showed a hypoechoic, hetero-
geneous thyroid with increased vascularity. DXA whole-body revealed low bone
mineral density (Z scoreZK2.2 S.D.) and the vertebral MRI showed reduced
vertebral height at T6-T8 and L3-L5. She started treatment with Duphaston and
vitamin D. At 1 year follow-up, she presented normal menses, both FSH and
estradiol normalized
(FSHZ5.11 mUI/ml, E2Z76.37 pg/ml) and no further
Clinical Case Reports - Thyroid/Others
fractures occurred.
EP762
Conclusion
Endocrinopathies are a common late effect of both b-TM and BMT, resulting in
Multiple autoimmune syndrome: about six observations
thyroid dysfunction, impaired growth, ovarian insufficiency and decreased bone
Soumaya Mrabet1, Aya Hammami2, Elleuch Nour2, Jaziri Hanen2,
mineral density. Because of the possible endocrine complications, lifelong
Ben Slama Aida2, Braham Ahlem2, Ajmi Salem2, Mehdi Ksiaa2,
endocrine follow-up is necessary in these patients.
Jmaa Ali2 & Ben Jazia Elhem1
1Farhat Hached University Hospital, Sousse, Tunisia;2Sahloul University
DOI: 10.1530/endoabs.49.EP763
Hospital, Sousse, Tunisia.
Introduction
Autoimmune disorders are known to be more frequent in women and often
EP764
associated each others, but it is rare to see multiple autoimmune diseases in a
single patient. Multiple autoimmune syndrome
(MAS) is defined as the
Association of Basedow disease with pernicious anemia: a case report
combination of at least three autoimmune diseases in the same patient. The
Mihai Radu Diaconescu & Smaranda Diaconescu
pathogenesis of MAS is not known. Genetic, infectious, immunologic and
‘Gr T Popa’ University of Medicine and Pharmacy, Iasi, Romania.
psychological factors have all been implicated in its development.
Observations
Introduction
We report six new observations of MAS.
Immunologic background often present different association of two or more
Results
autoimmune diseases. However the coexistence of Basedow disease (BD) - the
Observation
1: A
24-year-old female patient followed for Hashimoto’s
prototype of these disorders - with pernicious anemia (PA), sometimes as a
thyroiditis, Addison disease and celiac disease. The patient was explored for
component of pancytopenia, is rarely described. Between 50 patients operated on
cytolysis. The diagnosis of autoimmune hepatitis was retained and the patient was
immunologic hyperthyroidism in a 20 years period only one case related this
treated with oral corticosteroid and azathioprine. Observation 2: A 61-year-old
uncommon combination.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Case report
Conclusion
AB, a 46-year-old woman with a long standing BD treated from 1 year with
Our case confirms that, Thiazides can induce hyponatremia, especially in elderly
antithyroid drugs
(propylthiouracil) and b-blockers
(propranolol) recorded a
female patients. Chronic hyponatremia, must be seriously evaluated, to find out
notable clinical improvement but with stationary or even increase size of her
the cause and to be corrected if possible. Correction of hyponatremia can improve
diffuse goiter. In addition she charged in the last three months palled skin,
cognitive performance and life quality. We must be careful while treating an older
giddiness, tiredness, anorexia and coldness of the extremities. Laboratory workup
female patient with Thiazides.
showed TSHZ4.6 mU/l, fT4Z38 pmol/l, fT3Z9 pmol/l, TRABZ1.8Z1.8 UI/l.
DOI: 10.1530/endoabs.49.EP765
Current thyroid scan and US objectifies a diffuse
8!6 cm homogeneous,
hypervascularised gland with uniform uptake. Though full blood count indicate
pancytopenia with normochromic, normocytic anemia (HbZ9 g/dl, MCVZ
88 fL, MHCHZ34 q/l). Also total white count was 3400 m/l, platelet count was
48 000 m/l and reticulocyte count was
1%. Peripheral smears show oval
macrocytes, hypersegmented granulocytes and anisopoikilocitosis so a diagnosis
EP766
of megaloblastic anemia secondary to Vitamin B12 deficiency was established.
Raynaud phenomenon in a young PCOS patient
The standard treatment with intramuscular cyanocobalamin obtained substantial
Martina Eva Leczycka1, Johannes Ohrman1 & Hisham Maksoud2
resolution of woman’s symptomatology. However maintained thyroidomegaly
1Medical University of Gdansk, Gdansk, Poland;2Nottingham Woodthorpe
prompted our patient to undergo surgery. An adjusted near total thyroidectomy
Hospital, Nottingham, UK.
(Dunhill technique) was practiced followed by a smooth postoperative course.
Histological examination of the operative piece (150 g) showed all stygma of
Polycystic ovarian syndrome presents in 4-8% of women worldwide, making it
thyrotoxicosis. Astoningshly endocrine equilibration was obtained together with
the most common reproductive age endocrinopathy. Rheumatological concomi-
positive hematological response occuring gradually within few months and
tant diseases are extremely rare in PCOS patients, especially Raynaud’s
maintaining further.
phenomenon. Condition that, lowers the quality of life in patients, suggesting
Discussions and conclusion
hormonal imbalances despite years of treatment. Studies show that oestrogen
1-3% of patients with immunogenic hyperthyroidism (BD) have associated
plays a role in the vasculature, it is exogenous administration increases the
hematological disorders as single-cell lineage abnormalities like pernicious
endothelium dependent dilation. Treatment of the phenomenon is symptomatic,
anemia and related troubles or pancytopenias. In all cases BD precedes the blood
wearing gloves, avoiding triggering factors, and lastly pharmacotherapy or
disease. Causes of these pathologic coincidences reside unlikely as pure
sympathetic blockade in severe cases to avoid digital ischemia. We are presenting
coincidence but rather from reciprocal influence, immune-mediate effects,
a rare case of dermato-rheumatological involvement in a PCOS patient. 24-year-
outcomes of antithyroid therapy or vitamin B12
deficiency. Appropriate
old woman, diagnosed with PCOS in 2010 was treated with multi drug therapy
surveillance of all cases of untreated or treated BD is mandatory, recommended
including: Metformin up to 1500 mg daily, oral contraceptive pill, spironolactone
for early detection of pernicious anemia as for other autoimmune disorder.
up to
150 mg daily, Topiramate
50 mg daily for migraine headaches and
DOI: 10.1530/endoabs.49.EP764
Liraglutide 0.6 mg with varying regimens throughout the years. In winter 2014
she presented with the first symptom of Raynaud’s phenomenon (RP). However
that has been ignored until 2016; - 1 year after the discontinuation of oral
contraception, the patient reported; pain upon dishwashing, hand washing, and
increased frequency of the phenomenon despite wearing double winter gloves.
She was then referred to a rheumatology department, underwent capilaroscopy
exam, which revealed dilated capillary nail beds. The following laboratory tests;
EP765
ANA-HEp2 was elevated - 1:640 (!1:80 norm) of a granular type. Antibody
Chronic hyponatremia caused by Thiazide diuretic: A case report
panel characteristic for connective tissue diseases was all negative except for -
Marjeta Kermaj1, Dorina Ylli1, Anisa Zeqja4, Violeta Hoxha1,
DFS 70 being mildly elevated. The antibody is typical for an autoimmune rather
Thanas Fureraj1, Renta Sanxhaku1, Ermira Muco2, Adela Shkurta3,
than rheumatological ethology. No other abnormalities were found in the blood
Enalda Demaj5 & Agron Ylli1
morphology, rheumatoid factor nor erythrocyte sedimentation rate. Syndrome as
1UHC Mother Teresa, Endocrinology Department, Tirana, Albania;2UHC
common as PCOS should be of a concern across different hospital departments,
Mother Teresa, Department of Infectious Diseases, Tirana, Albania;3Vila
the complexity of the pathomechanism and treatment regime should alert us for
Maria Hospital, Endocrinology Department, Tirana, Albania;4UHC Mother
further clinical consequences.
Teresa, Department of Psychology, Oncologic Hospital, Tirana, Albania;
DOI: 10.1530/endoabs.49.EP766
5Kucova Hospital, Endocrinology Department, Tirana, Albania.
Introduction
Hyponatremia (defined as a serum sodium level !135 mmol/l), is seen in in 15-
30% in hospital setting, especially in intensive care units. Certain drugs
EP767
(e.g.Thiazides diuretics) used in everyday clinical practice, may induce
hyponatremia, more frequently in elder women.
Polyglandular autoimmune syndrome type III-case report
Case report
Jelena Malinovic Pancic1,2 & Bojana Caric1,2
A 76-year-old woman presented at emergency unit with complaints: physical
1University Clinical Center of Republic of Srpska, Banja Luka, Bosnia and
weakness, nausea, vomiting, extreme fatigue and abdominal pain. She was under
Herzegovina;2Medical Faculty Banja Luka, Banja Luka, Bosnia and
arterial hypertension treatment with Valsartan/Hydroclortiazide
160/25 mg
Herzegovina.
2 pills/day for 4 years. She was presented many times at emergency unit, during
last 4 years with the same complaints, but she was never evaluated about the cause
The term polyglandular autoimmune syndrome (PAS) is used when there is a
of hyponatremia. Her life quality and cognitive performance were getting worse
dysfunction of two or more endocrine glands associated with circulating
during this time. Objective examination: Overall condition poor, pale face, stupor,
antibodies directed at organspecific included glands. Neufeld and Blizzard
incoherent answers to different questions, TA 170/80 mmHg, Fc 80/min, SO2
classified PAS into two categories: type I and type II with the newly added
97%, lungs normal, abdomen soft, liver, spleen, kidneys were normal, legs free of
category, type III, which does not include the adrenal cortex. PAS III includes
edema. Laboratory examinations revealed: Severe hyponatremia, hypokalemia,
several autoimmune diseases
(autoimmune thyroiditis, immune-mediated
hypochloremia and metabolic alcalosis (NaC102 mmol/l; KC2.8 mmol/l; Cl-
diabetes mellitus, pernicious anemia, vitiligo, alopecia areata, and many others)
71 mmol/l,PhZ7.49), others biochemical blood test and hemograme were
and is divided into four sub-categories. We report a 44-year-old patient who was
normal. Urine analysis: density 1007,pH 7. Imagery examination: Head CT:
hospitalized in August 2016 at our department with suspected polyglandular
showed no acute lesions, hypodens areas, cortical subatrofi. Chest CT: normal.
autoimmune syndrome. In 2013 he was repeatedly evaluated at gastroenterology
EKG normal. She was treated for 2 days in Intensive unit care with 3% NaCl sol,
department where were established the diagnoses of primary hemochromatosis
KCl 7.5%, MgSO4 25%iv, correcting NaC, 10 mmol/l daily. After initial
(homozygous mutation in the gene p C282Y HFE), Crohn’s disease and celiac
improvement, she was transferred to Endocrinology Unit for further treatment.
disease, as well as candidiasis in May
2016. In our department, the
After normalization of blood electrolytes, we looked for the cause of
endocrinological testing establish the existence of autoimmune thyroiditis (anti
hyponatremia. In literature treatment with Hydrochlortiazide was reported as
-TG 207.1 IU/ml; antiTPO 141.0 IU/ml) without disorders of thyroid function and
the cause of hyponatremia and hypokalemia especially in elder women. She was
the presence of insulin resistance.
informed about the drug adverse effect and the importance of never using it again.
DOI: 10.1530/endoabs.49.EP767
She dehospitalized with overall improved conditions. During follow up, blood
electrolytes resulted normal and her life quality and cognitive performance were
improved.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP768
existence, because some may falsify the results
(underestimating or over-
estimating HbA1c, such as J-Camaguey). The use of alternative glycemic markers
Resistance of SIAD to tolvaptan despite initial control in progressive
may be helpful in these cases.
small cell lung cancer
Aoife Garrahy & Chris Thompson
DOI: 10.1530/endoabs.49.EP769
Academic Department of Endocrinology, Beaumont Hospital/ RCSI
Medical School, Dublin, Ireland.
A 58-year-old male was admitted through the emergency department with
symptomatic severe euvolemic hyponatremia. Biochemistry was consistent with
EP770
SIAD (plasma sodium (pNa) 107 mmol/l, plasma osmolality 230 mOsm/kg, urine
Myasthenia gravis associated with Graves’ disease and adrenal
sodium 36 mmol/l, urine osmolality (UOsm) 638 mOsm/kg, 0900 h plasma cortisol
insufficiency
484 nmol/l and thyroid function tests normal). Chest X-ray was normal but CT thorax
Mouna Elleuch, Hamza Elfekih, Faten Hadjkacem, Mahdi Kalthoum,
confirmed a lung mass suspicious for malignancy. As the patient had symptoms of
Mouna Ammar, Nabila Rekik, Wajdi Safi, Mouna Mnif & Mohamed Abid
cerebral irritation, including drowsiness and confusion, he was treated with
Hedi-Chaker University Hospital, Sfax, Tunisia.
hypertonic (3%) saline infusion; pNa rose by 13 mmmol/l over the 48 h and
symptoms resolved. Water deprivation caused no further rise in pNa so the patient
Introduction
underwent tolvaptan challenge; pNa rose from 121 to 125 mmol/l over 12 h,
Multiple autoimmune syndrome (MAS) is a rare condition, first described by
associated with a rise in plasma vasopressin (pAVP) from 4.4-9.3 pmol/l. Tolvaptan
Humbert and Dupond in 1988 and characterised by three or more autoimmune
7.5 mg daily was commenced on day 5 and pNa rose gradually to 130 mmol/l with an
disorders in the same individual.
eventual tolvaptan dose of 15 mg daily. Over 6 weeks, the patient developed
Case description
persistent hyponatremia despite escalating doses of tolvaptan to 60 mg daily. UOsm
Here we present a case of 14-year-old female patient diagnosed with ocular
while on tolvaptan was O800 mOsm/kg and AVP levels between 8 and 16 pmol/l
myasthenia gravis. The diagnosis of Graves’ disease was suspected on the basis
indicating unopposed action of AVP. Systemic chemotherapy led to temporary
of hyperthyroidism symptoms and confirmed by undetectable TSH level
improvement in plasma sodium and tolvaptan dose was reduced to 15 mg over the
(!0.01 mUI/l) with high FT4 level (27.8 pmol/l). The adrenal insufficiency
subsequent three months. Six months after initial presentation, pNa fell again and
was suspected also clinically (extreme fatigue, weight loss, hyperpigmentation
tolvaptan dose was increased to 60 mg; noncompliance was excluded by supervised
and low blood pressure) and accepted with a low cortisol level (37.4 ng/ml). The
tolvaptan challenge, during which pAVP rose to 178 pmol/l, and UOsm remained
patient has improved after taking an anticholinesterase agent and corticosteroid
O909 mOsm/kg, suggesting renal resistance to tolvaptan. Imaging confirmed
replacement therapy. For the hyperthyroidism, a radical treatment is
progressive liver and bony metastases and the patient died 10 months after
recommended and the Beta-blockers should be avoided.
presentation, due to metastatic malignancy. This is the first report of escape of SIAD
Conclusion
from tolvaptan therapy, despite increasing doses. With progression of malignancy,
The MAS-3 in our case is characterized by the association of myasthenia gravis,
and rising pAVP conentrations tolvaptan may have been insufficient to compete with
Graves’ disease and adrenal insufficiency in which every condition has a different
tumour associated AVP for renal receptors.
treatment and prognosis in addition to a multidisciplinary care.
DOI: 10.1530/endoabs.49.EP768
DOI: 10.1530/endoabs.49.EP770
EP769
EP771
Overestimation of HbA1c by an unusual hemoglobin variant
Incidental asplenia in a patient with presumed type 2 autoimmune
Fernando García Pérez1, Sandra Isabel Villanueva-Herraiz1, José Ignacio
polyglandular syndrome (APS-2): misclassification or overlap?
Fernández Pen˜a1, Inés Camacho Benítez1, Juan Manuel García de Quirós1,
Thomas Georgiou, Fotini Adamidou, Gesthimani Mintziori & Marina Kita
Guillermo Martínez de Pinillos Gordillo1, Antonio Moro Ortiz1, Mariana
Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece.
Tomé Fernández-Ladreda2 & María Victoria Cózar León1
1Hospital Universitario de Valme, Sevilla, Spain;2Hospital Punta de
Europa, Gibraltar, Spain.
Introduction
Asplenia has been reported in 10% of patients with type 1 APS (APS-1), but has
never been reported in APS-2. We describe a patient with presumed APS-2 and
Glycosylated haemoglobin (HbA1c) is considered the Gold Standard parameter
aplenia.
for evaluating long-term glycemic control in individuals with Diabetes Mellitus
Case report
(DM). The presence of hemoglobin variants or others conditions that modify its
A 69-year-old woman was diagnosed with B12 deficiency with severe anemia at
glycosylation, can affect the veracity of its measurement. The detection of these
age 21 and insulin dependent diabetes mellitus at age 33, following routine
hemoglobinopathies and his knowledge by the clinicians is very important for the
testing. At 59, she was hospitalized with salt wasting and a diagnosis of Addison’s
correct diagnosis and follow-up. We present the case of a patient who presented a
disease was made, which was subsequently confirmed by an inadequate response
hemoglobinopathy that interferes with the determination of HbA1c by HPLC, one
to tetracosactide stimulation. The diagnosis of subclinical Hashimoto’s thyroiditis
of the methods most used in laboratories. The case is about a man of 17 years old
was concurrently made. The patient had chronic onychomychosis of one
referred for evaluation by Endocrinology because in the context of a study of
fingernail and multiple toenails, but never of the mucous membranes and has
syncopal episodes and possible hypoglycaemia presents HbA1c of 6.5% with
never reported tetany. The diagnosis of APS-2 was made, based on the presence
repeated blood fasting glucose between 70 and 75 mg/dl. A new HbA1c with a
of the complete tri-glandular syndrome. The patient was under active surveillance
result of 7.0% and other exams were requested, which were normal: oral glucose
for other autoimmune manifestations, but none has so far been detected. Her past
tolerance test, negative autoantibodies
(GAD, IA-2
and insulin), plasma
history is negative for serious illnesses or infections and has never had abdominal
C-peptide and insulinemia. Blood count parameters were also normal. He had
surgery. Of note, she had never received a pneumococcal vaccine. Her family
no family history of DM to suspect Monogenic Diabetes. Levels of fructosamine
history is negative for autoimmune disorders. An abdominal CT scan was
(alternative marker for assessing glycemic control of the last 2-3 weeks, based on
requested for complaints of non-specific abdominal discomfort and an incidental
glycoproteins measurement) were requested, resulting in
240 mmol/l, which
observation regarding the absence of an orthotopic spleen was made. An
correlated with a calculated HbA1c of 5.6%. In addition to the incongruity
abdominal ultrasound found evidence of a hypoplastic splenic vessel. Functional
between the HbA1c values and the rest of the study, an abnormal peak in the
imaging of the spleen using 99mTC-colloid failed to reveal a functional spleen.
HbA1c chromatogram (HPLC assay) was observed. HbA1c was measured again
Relevant laboratory investigations including peripheral blood smear revealed
by a different method (boronate affinity chromatography) resulting in a very
Howell-Jolly bodies. Parathormone and electrolytes were normal. Quantitative
different result (HbA1c 5.3%). Due to the suspicion of hemoglobinopathy that
measurements of major immunoglobulin classes and T lymphocyte sub-
overestimates HbA1c, it was sent to the reference laboratory for molecular
populations were normal. HLA II haplotypes DQB1*05 and DQA1*01 were
characterization. Finally, the patient presented hemoglobin J-Camaguey
indentified. AIRE sequencing is pending.
heterozygous (ArgOGly; HBA1: c.424COG). The mother also presented the
Conclusion
same hemoglobinopathy in heterozygous.
Asplenia in the context of well-defined APS-2 and in the absence of clinical
Conclusions
immunodeficiency, is a novel finding that challenges our current understanding of
Many patients may present simultaneously a hemoglobinopathy and DM. Some
APS and needs to be further investigated.
hemoglobinopathies, without clinical repercussion are detected incidentally
during the measurement of HbA1c. It is important for clinicians to be aware of its
DOI: 10.1530/endoabs.49.EP771
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP772
thyroglobulin antibody (TgAb), negative peroxidase (TPOAb) and TSH-receptor
antibodies
(TRAb). He was treated with methimazole for 3.5 months. He
Immune checkpoint inhibitors related thyroiditis - a report of two cases
maintains normal thyroid function since antithyroid drug withdrawal. (iv) Male,
Sara Donato, Pedro Antunes, Joana Sim
˜es-Pereira & Hélder Sim
˜es
64-year-old, without previous thyroid disease, treated with nivolumab for
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,
metastatic lung adenocarcinoma. After 5 cycles, he developed thyrotoxicosis
Portugal.
with TSH 0.003 mUI/ml and normal FT4 and FT3. He had spontaneous remission
of thyrotoxicosis within 2 months and then developed hypothyroidism with TSH
Introduction
7.78 mUI/ml, FT4 0.48 ng/dl, FT3 2.19 pg/ml and positive TPOAb and TgAb.
Immune checkpoint inhibitors
(ICPIs) are recent approved drugs used in
Levothyroxine was initiated, compatible with the possible diagnosis of
malignant melanoma, non-small-cell lung cancer and renal cell cancer. They
nivolumab-associated thyroiditis.
act by activating host T cell against malignant antigens. Immune checkpoint
Conclusion
blockade can lead to breaking of immune self-tolerance, thereby inducing
Health providers must be aware of endocrine disorders that may be associated
autoimmune/autoinflammatory side effects, such as endocrinopathies. It may
with immunomodulatory therapies for a timely diagnosis and correct treatment.
affect thyroid, adrenal and pituitary. We present two ICPIs induced thyroiditis
DOI: 10.1530/endoabs.49.EP773
cases.
Case 1
Sixty-eight-year-old female diagnosed with a conjunctival malignant melanoma
at the age of 64. She was first surgery treated and then submitted to radiotherapy.
Due to bone, lung and hepatic metastasis she started Ipilimumab 3 mg/kg on
21-day cycle. Eleven days after the third Ipilimumab administration she was
EP774
asymptomatic but was found to have thyrotoxicosis (TSH 0.04 mUI/ml; FT4
Meigs’ syndrome in a 63 year-old woman - case report
1.31 ng/dl). Thyroid peroxidase and thyroglobulin antibodies were elevated and
Alina Mihaela Pascu, Mircea Daniel Hogea, Marius Alexandru Moga,
thyroid stimulating immunoglobulin was low. Four months after suspension of
Lorena Dima, Petru Iulian Ifteni & Claudia Gavris
Ipilimumab a spontaneous recovery of the thyroid axis was seen.
Faculty of Medicine, Transilvania University of Brasov, Brasov, Romania.
Case 2
Sixty-two-year-old female diagnosed with a foot malignant melanoma one year
Introduction
before. She was first surgically treated. Due to lung, breast and lymph node
Meigs’ syndrome is defined as the presence of a benign ovarian tumour (fibroma),
metastases she started Nivolumab 3 mg/kg on 15-day cycle. Before starting this
in association with ascites and hydrothorax. The characteristic feature of this
drug she had a diffuse thyroid uptake on PET-scan with normal thyroid function.
condition is the resolution of the effusions once the tumour is surgically removed.
Twelve days after the first administration of Nivolumab she described a painless
Case report
increase of anterior cervical volume, fatigue and had thyrotoxicosis on the blood
A 63 year-old female patient was admitted to the Surgery Clinic with metroragia,
test (TSH 0.02 mUI/ml; FT4 2.50 ng/dl). One month after she was found to have
abdominal distention, and a recent history of minor breath shortness. Pulmonary
asymptomatic hypothyroidism
(TSH 9.96 mUI/ml; FT4
0.49 ng/dl). Thyroid
clinical examination showed all the signs of right pleural effusion, which was also
ultrasound showed a thyroiditis pattern. She started levothyroxine therapy and
confirmed by the chest X-ray. The abdominal examination revealed a round
one month after stopping Nivolumab she was still on hypothyroidism.
irregular mass arising from the right pelvic cavity. Abdominal ultrasound showed
Conclusions
a large pelvic mass (23 cm in diameter) more on the right pelvic cavity, a
ICI may induce autoimmune thyroiditis or may worsen a pre-existing one. These
polyfibromatous uterus, and a small quantity of ascites. A complete blood count
patients should be monitored for signs and symptoms of thyroid dysfunction,
was carried out, with normal results. Surgical intervention was decided and the
since it can cause significant morbidity if not promptly recognized and treated.
laparotomy confirmed a large pelvic mass which was part of the left ovary,
DOI: 10.1530/endoabs.49.EP772
dislodged in the right side of the peritoneal cavity. Also, 100 ml of ascitic fluid
and a polyfibromatous uterus were found. The ovarian mass was removed and
also a hysterectomy with bilateral adnexectomy was performed. The macroscopic
appearance: giant polynodular tumoral mass (23 cm in diameter), with compact
structure, microcysts, and haemorrhagic areas. No residual ovarian tissue was
EP773
observed in the subcapsular portion of the tumour. Microscopically, a compact
tissue, consisting of pleomorphic fusiform cells, and discrete mitotic activity (less
Nivolumab-associated pituitary, adrenal and thyroid autoimmune
than 3 divisions/10 fields) was described. The cells were arranged in fascicles,
disorders
with hyaline and myxomatous areas. Dilated vessels with thrombotic material
Rita Bettencourt-Silva1,2, Joana Oliveira1,2, César Esteves1,2,
were noted. The absence of malignancy of the tumour and of the ascitic and
Venceslau Hespanhol2,3, Gabriela Fernandes3, Cláudia Caeiro4,
pleural effusions was confirmed by cytomorphologic study. In conclusion, the
Joana Queirós1 & Davide Carvalho1,2
histopathological examination demonstrated an ovarian tumour with a fibroma
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-
aspect. Postoperative evolution was favorable and the patient was discharged after
talar São Joa˜o, E.P.E., Porto, Portugal;2Faculty of Medicine, University of
12 days. The controll chest X-ray revealed the resolution of the hydrothorax.
Porto, Porto, Portugal;3Department of Pulmonology, Centro Hospitalar São
Conclusion
Joa˜o, E.P.E., Porto, Portugal;4Department of Medical Oncology, Centro
Even though Meigs’ syndrome mimics an aggressive malignant ovarian tumour,
Hospitalar São Joa˜o, E.P.E., Porto, Portugal.
in the presence of pleural and peritoneal effusions, after surgical removal of the
tumour the patient has a good prognosis and the life expectancy is similar to
Background
normal healthy population, even if recurrence was also reported.
Nivolumab is a monoclonal antibody specific for human PD-1 (programmed cell
DOI: 10.1530/endoabs.49.EP774
death protein-1), a checkpoint molecule highly expressed in several cancers.
Nivolumab is an immunotherapeutic strategy for human cancer, but it can
interfere with endocrine system.
Case reports
We report four cases regarding nivolumab-associated endocrinopathies: (i) Male,
55-year-old, with previous normal cortisol and adrenocorticotropic hormone
Developmental Endocrinology
(ACTH) levels, treated with nivolumab for metastatic lung epidermoid
EP775
carcinoma. After
14 cycles, he developed asthenia, anorexia, weight loss,
GH influences plasma fasting adropin concentration in patients with
hypotension and hyponatremia, resulting in hospital admission. Adrenal
turner syndrome
insufficiency was confirmed by morning cortisol !1.0 mg/dl; hydrocortisone
Beata Wikiera1, Magdalena Krawczyk2, Anna Noczynska1 &
treatment was started with clinical improvement. (ii) Male, 78-year-old, with
Jacek Daroszewski3
previous normal cortisol and ACTH levels, treated with nivolumab for stage 3B
1Department of Endocrinology for Children and Adolescents, Medical
lung epidermoid carcinoma. After 15 cycles, he developed adrenal insufficiency
University, Wroclaw, Poland;2Cardiology Department, 4th Military
with morning cortisol!3.0 mg/dl and ACTH!5.0 ng/l. He had recent weight
Hospital, Wroclaw, Poland;3Department of Endocrinology, Diabetes and
loss, but was hemodynamically stable, without electrolyte imbalance. He started
Isotope Therapy, Wroclaw, Poland.
hydrocortisone with clinical improvement.
(iii) Male,
70-year-old, without
previous thyroid disease, treated with nivolumab for metastatic clear cell renal
carcinoma. After 2 cycles, he developed thyrotoxicosis with thyroid-stimulating
Background
hormone (TSH) 0.01 mUI/ml (ref:0.35-4.94), free thyroxine (FT4) 1.82 ng/dl
Increased adiposity and insulin resistance are conditions frequently observed
(ref:0.70-1.48), free triiodothyronine (FT3) 3.68 pg/ml (ref:1.71-3.71), positive
nowadays. Many hormones are involved in the pathogenesis of the condition but
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
therapeutic options we can offer to the patients are still scant. Each newly
EP777
discovered peptide give us hope. Adropin (Ad) is a newly discovered metabolic
Erk- and Akt-mediated osteocalcin signaling in human pancreatic
hormone involved in energy homeostasis. This homeostasis is frequently
b-cells does not directly involve GPRC6A activation
disturbed in patient with Turner Syndrome (TS). Patient with Turner syndrome
Silvia Perego1, Veronica Sansoni1, Martina Faraldi1, Giuseppe Banfi1,2 &
are unique model for studies of an effect of the treatment with supraphysiological
Giovanni Lombardi1
doses of growth hormone (GH).
1IRCCS Istituto Ortopedico Galeazzi, Milano, Italy;2Vita-Salute San
Objective and hypotheses
Raffaele University, Milano, Italy.
We studied adropin dependance and response in a group of TS patients treated
with supraphysiological doses of growth hormone (rGH).
Method
Osteocalcin (OC) is the main non-collagenous protein of the bone and it has a
The study group consisted of 36 TS patients aged 3.2-16.07 years (mean 8.2
regulatory role in mineralization. Extra-skeletal roles have been recently
years) diagnosed by karyotyping. The rGH was applied in a dose 0.05 mg/kg per
hypothesized for OC (e.g., modulation of glucose-induced insulin secretion by
day Prior to and following the treatment anthropometrical data were recorded as
interacting with GPRC6A in b-cells). However, OC-mediated GPRC6A activation
well as biochemical parameters were measured: adropin, OGTT, insulin, lipids,
has been demonstrated only in rodents and heterologous systems. In this study we
IGF-1, and IGFBP-3.
aimed at evaluating the dose-dependent response to OC and the eventual activation
Results
of the GPCR-dependent pathways in a physiologic-like model of human pancreatic
The increase of IGF-1 concentration at the end of observation was significant
b-cells. 1.1B4 cell line, derived from electrofusion of PANC-1 cell line and
(from 119.4G62.46 to 413.37G204.38 ng/ml, meanGS.D., PZ0.000). The GH
primary human b-cells, were treated for 5 and 30 min with different concentrations
treatment influenced insulin resistance revealed by increased HOMA values
of OC (20 to 100 ng/ml) either alone or in combination with 10 mM NPS2143, a
(median 0.64G0.45 before and 0.92G0.97 after, PZ0.02). rGH treatment cause
non-competitive antagonist of GPRC6A. mRNA and protein expression were
a significant rise in Ad level. The correlation between adropin and IGF-1 and IGF-
evaluated in order to assess the expression of GPRC6A and the activation profile of
1 SDS levels was not significant neither before nor on the treatment (rZ0.17 and
Erk and Akt pathways. As for human b-cells in vivo, which physiologically express
rZ0.004 respectively). Adropin concentration correlated with IGFBP3 level
nearly undetectable levels of GPRC6A, 1.1B4 cells displayed undetectable levels
before rGH treatment but not on rGH therapy. Ad also correlated with insulin
of GPRC6A protein. On the contrary, GPRC6A mRNA was slightly detectable. A
level before GH applying. Correlation with glucose levels at 30’ of OGTT was
slight increase (1.5 fold) of pErk/tErk was induced by OC 40 ng/ml at 30 min.
stable and even rise on GH treatment (PZ0.33 vs PZ0.48). Similar observation
Instead, pAkt was dose-dependently induced within 5 min with a 2-fold peak with
was noticed for lipids, but close correlations between Ad adropin and total
OC 80 ng/ml; at 30 min a residual activation was evident for OC 20 and 40 ng/ml.
cholesterol, LDL cholesterol, triglycerides (TG) before GH applying changed on
NPS2143 did not affect the activation profile of Erk and Akt if not for a slight peak
rGH therapy. The only correlation noticed in GH treated patients was between Ad
activation of both pathways with OC 60 ng/ml, instead of 40 ng/ml for Erk and
adropin and TG (PZ0.34).
80 ng/ml for Akt. In summary: i) GPRC6A is not expressed (or it is expressed at
Conclusion
very low levels) by human pancreatic b-cells; ii) the common OC signaling
Result of the study showed an increase in adropin level following rGH application
pathways, identified in heterologous expression systems, are only slightly induced
is not mediated by IGF-1. rGH treatment changes adropin influence on lipid
in human pancreatic b-cells; iii) the inhibition of GPRC6A do not affect the
metabolism, but ameliorates insulin action.
activation profile of Erk and Akt and, hence, GPRC6A may not be involved in
DOI: 10.1530/endoabs.49.EP775
physiological OC signaling in human b-cells.
DOI: 10.1530/endoabs.49.EP777
Diabetes (to include Epidemiology, Pathophysiology)
EP776
Diabetes Complications
Diagnosis of cystic fibrosis related diabetes
EP778
Ángel Rebollo-Román1, Paloma Moreno-Moreno1, Ana Barrera-Martín1,
Aura-Dulcinea Herrera-Martínez1, José-Manuel Vaquero-Barrios2 &
The comparison of cardiovascular events in kidney transplant
Alfonso Calan˜ as-Continente1
recipients with and without type 2 diabetes mellitus
1Endocrinology Service, Hospital Universitario Reina Sofía, Córdoba,
Alparslan Ersoy1 & Canan Ersoy2
Spain;2Pneumology Service, Hospital Universitario Reina Sofía, Córdoba,
1Department of Nephrology, Uludag University Medical Faculty, Bursa,
Spain.
Turkey;2Uludag University Medical Faculty, Endocrinology and Metab-
olism, Bursa, Turkey.
Aim
To describe the prevalence of abnormal glucose tolerance and diabetes in patients
Diabetes melliuts (DM) presents particular challenges after kidney transplant (KT).
with cystic fibrosis (CF) depending on the diagnostic criteria.
These challenges contribute to cardiovascular disesases among diabetic recipients.
Methods
We assessed frequency of posttransplant cardiovascular events in diabetic patients.
Observational, cross-sectional, clinical research on patients with CF evaluated at
Methods
Hospital Universitario Reina Sofía (Córdoba).
This retrospective study conducted in 399 kidney recipients at our center. The
Results
patients were divided into two groups: DM (n:59, 52.5% females) and non-DM
Twenty-eight patients were selected for the study. Age: 31.85G8.78 years, with a
(n:340, 46.5% females).
CF evolution time of 21.77G9.37 years. 64% women. 55.6% of the subjects
Results
presented with the deletion of phenylalanine in position 508 (DF508), known to
The median KT duration was 4 years. The median age and BMI of DM group were
be a severe one. Most patients (85.2%) suffered from pancreatic insufficiency. We
higher than those of non-DM group (51 vs 42 years and 28.6 vs 25.8 kg/m2,
compared the three ADA classical diabetes diagnostic criteria. With the fasting
respectively, P!0.001). The mean creatinine levels of both groups were similar.
plasma glucose 3.6% of patients were diagnosed with impaired glucose tolerance
Hypertension (76.3 vs 62.4%, PZ0.04), coronary artery disease (15.3 vs 4.1%,
(IGT) and 3.6% with cystic fibrosis-related diabetes (CFRD). Using the glycated
PZ0.001), obesity (39.7 vs 20.9%, PZ0.007) and dyslipidemia (32.3 vs 15.4%,
haemoglobin (HbA1c) 28.6% of patients had (IGT) and 3.6% CFRD. After the
PZ0.002) co-morbidities in DM were more frequent than those of non-DM groups.
oral 75g-glucose test (OGTT) with intermediate blood glucose measurements,
There was no significant difference between the ratios of myocardial infarction (3.4
25.1% were diagnosed with IGT and 7.1% with CFRD. We found different
vs 2.6%), cardiac arrhythmia (3.4 vs 9.4%), congestive heart failure (3.4 vs 1.2%),
prevalence of abnormal glucose tolerance depending on the diagnostic criteria
stroke (1.7 vs 0.6%), transient ischemic attack (1.7 vs 4.1%) and peripheral vascular
used. OGTT with intermediate blood glucose measurements is the most sensitive
disease (3.4 vs 0.6%) in DM and non-DM groups. The ratio of patients underwent
criteria for IGT and CFRD compared to fasting glucose (PZ0.002) and HbA1c
angioplasty was higher than that of non-DM group (23.7 vs 12.1%, PZ0.016)
(PZ0.289).
while the ratios of patients underwent coronary stenting (1.7 vs 1.8%) and coronary
Conclusions
by-pass operation (3.4 vs 1.2%) were similar. The graft loss and mortality rates in
- In our series, there are statistically significant differences among the criteria used
DM and non-DM groups did not differ (5.1 vs 5.6% and 5.1 vs 1.8%, respectively).
to diagnose the abnormal glucose tolerance and CFRD
Conclusion
- OGTT was the most sensitive test to establish the abnormal glucose tolerance
We observed that there was no difference in new cardiovascular events, graft loss
and CFRD in our series, in agreement with published evidence.
and mortality between recipients with or without DM after KT.
DOI: 10.1530/endoabs.49.EP776
DOI: 10.1530/endoabs.49.EP778
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Endocrine Disruptors
Conclusion
In the presence of autoimmune endocrinopathies the search of associated
EP779
autoimmune diseases in particular celiac disease is necessary in order to avoid any
The adrenal gland after diosgenin application in a rat model of the
therapeutic delay which can alter the prognosis of the patient.
menopause
DOI: 10.1530/endoabs.49.EP780
Vladimir Ajdzanovic1, Ivana Jaric1, Jasmina Zivanovic1, Marko Miler1,
Natasa Ristic1, Dragana Miljic2, Florina Percinic-Popovska3 &
Verica Milosevic1
1Institute for Biological Research “Sinisa Stankovic”, University of
Belgrade, Belgrade, Serbia;2Department of Neuroendocrinology, Clinic for
Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia,
EP781
Belgrade, Serbia;3Faculty of Veterinary Medicine, Ss. Cyril and Methodius
Characterization of murine Leydig cell lines as tools to study androgen
University in Skopje, Skopje, Macedonia.
synthesis disruption by xenobiotics
Roger Engeli, Cornelia Furstenberger, Denise Kratschmar & Alex Odermatt
University of Basel, Basel, Switzerland.
Diosgenin, a steroidal sapogenin of natural origin, demonstrated some
therapeutic effects when it comes to the treatment of cardiovascular issues,
malignancies and the menopausal symptoms. In this study, we have
Mammalian Leydig cells produce the majority of the systemic levels of the
investigated histological changes and corticosterone secretion of the adrenal
primary male sex hormone testosterone. Testosterone plays a crucial role
gland after diosgenin application in a rat model of the menopause. Middle-
during development of male reproductive tissues, onset of puberty, and
aged, acyclic female Wistar rats were divided into control (C; nZ6) and
maintaining health state. The final step of testosterone synthesis is catalyzed
diosgenin treated (D; nZ6) groups. Diosgenin (100 mg/kg b.w./day) was
by
17b-hydroxysteroid dehydrogenase
3
(17b-HSD3). Disruption of
orally applied for 4 weeks, while C group received the vehicle alone. Our
testosterone synthesis is associated with many diseases. Due to the lack of
approach considered using the design-based stereology, histochemistry and
a human Leydig cell line, two different murine Leydig cell lines (MA10,
the hormonal assay. The adrenal cortex volume decreased in D females by
BLTK1) were studied for their suitability as screening tools for testosterone
15% (P!0.05) while the volume of adrenal medulla increased (P!0.05) by
synthesis disruption by xenobiotics. The endogenous expression and activity
64%, compared to the same parameters in C group. Volume density of zona
of murine 17b-HSD3 was studied in both cell lines. Further, cells were
glomerulosa (expressed per absolute adrenal gland volume) in D rats
stimulated using br-8-cAMP and forskolin to study testosterone production.
increased (P!0.05) by 22% in comparison with C animals. Diosgenin
Cell supernatants were analyzed using LC-MS. Unstimulated cells showed
treatment decreased
(P!0.05) volume density of zona fasciculata
no or very low endogenous 17b-HSD3 activity. Stimulated MA10 cells
(expressed per volume of adrenal cortex) by 15% and caused vasodilatation
showed low but concentration-dependent increases of testosterone levels in
within this zone, when compared to C females. Circulating corticosterone
supernatants after 24 h. BLTK1 cells did not produce any testosterone. This
was also decreased by 16% compared to the C group. Absolute volume of
study emphasizes the necessity of analyzing steroid using sensitive
zona reticularis in D group decreased (P!0.05) by 38% in comparison with
MS-based methods and shows that MA10 and BLTK1 cells produce a
the same parameter in C rats. Also, after diosgenin application, volume
variety of steroids but only low amounts or no testosterone.
density of zona reticularis (expressed per absolute adrenal gland volume)
DOI: 10.1530/endoabs.49.EP781
and zona reticularis cell volume were decreased by 40% and 20% (P!0.05)
respectively, compared to C animals. Our results, reflecting a decrease of the
numerous adrenocortical stereological parameters, indicate that diosgenin
took over the role of corticosteroid precursors and got incorporated into the
steroidogenesis.
EP782
DOI: 10.1530/endoabs.49.EP779
Identification of chemicals disrupting adrenal steroid production by
steroid profiling in H295R cells
Petra Strajhar1, David Tonoli2, Fabienne Jeanneret2, Raphaella Imhof1,
Vanessa Malagnino1, Melanie Patt1, Denise Kratschmar1, Julien Boccard2,
Serge Rudaz2 & Alex Odermatt1
1
University of Basel, Basel, Switzerland;2University of Geneva, Geneva,
Switzerland.
EP780
Association of autoimmune endocrinopathies and celiac disease
Human adrenal H295R cells are applied according to the validated OECD
Mrabet Soumaya1, Akkari Imen1, Ach Taieb2, Ach Koussay2 &
test guideline
456 to identify potential endocrine disrupting chemicals.
Ben Jazia Elhem
Testosterone and estradiol production serves as read-out although these are
1Gastroenterology Department Farhat Hached University Hospital, Sousse,
not steroids typically produced by the adrenals. The current study attempted
Tunisia;2Endocrinology and Diabetology Department Farhat Hached
to optimize conditions for using H295R cells to detect chemicals disturbing
University Hospital, Sousse, Tunisia.
the synthesis of key adrenal steroids. Culture supernatants of H295R cells
were analysed by LC-MS-based steroid quantification. The impact of
experimental conditions including time and serum content on steroid
Introduction
profiles was assessed. Steroid profiles were measured before and after
Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs
incubation with reference and test compounds for potential disruption of
in genetically susceptible people. It is significantly associated with other
adrenal steroidogenesis. The results revealed that H295R cells cultivated
autoimmune disorders represented mainly by type 1 diabetes and autoimmune
according to the OECD test guideline produced progestins, glucocorticoids,
dysthyroidism.
mineralocorticoids and adrenal androgens but only very low amounts of
Material and methods
testosterone. However, testosterone contained in Nu-serum was metabolized
We report 23 observations of patients with autoimmune endocrinopathies
during the 48 h incubation. Therefore, inclusion of positive and negative
associated with celiac disease.
controls and a steroid profile of the complete medium prior to the
Results
experiment was needed to characterize steroid synthesis and indicate
There are 23 patients with an average age of 31 years. All patients had chronic
changes occurring upon exposure to chemicals. Among the test chemicals,
diarrhea associated with abdominal pain in 15 cases and malabsorption syndrome
octyl methoxycinnamate and acetyl tributylcitrate resembled the corticos-
in five cases. The diagnosis of celiac disease was made on serological (Anti-
teroid induction pattern of the positive control torcetrapib. Gene expression
transglutaminase, anti-endomysium and anti-gliadin antibodies positive respect-
analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate
ively in 20, 18 and 15 cases) and histological criteria (Partial villous atrophy in 13
enhanced CYP11B2 expression; however, less pronounced compared with
cases and total villous atrophy in
10 cases). Autoimmune endocrinopathies
torcetrapib. In conclusion, the extended profiling and appropriate controls
associated to celiac disease were: type
1 diabetes in
14 cases, Hashimoto
allow detecting chemicals that act on steroidogenesis and provide initial
thyroiditis in seven cases and Addison disease in one case. One patient had type 1
mechanistic evidence for prioritizing chemicals for further investigations.
diabetes, Basedow disease and Addison’s disease associated to celiac disease. All
DOI: 10.1530/endoabs.49.EP782
patients were treated with gluten-free diet and specific endocrinopathy treatment
with favorable evolution.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP783
diagnostic. When studying the relationship between the department of origin and
tumor type, we found a statistically significant difference between the cases
Endocrine dysfunctions associated with Hodgkin Lymphoma treatment
presented by the department of Endocrinology and the surgical departments
Daniela Dias, Joana Simo˜ es-Pereira, Sara Donato & Conceição Pereira
(General Surgery and Otolaryngology) and the remaining departments (c2 46.55;
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,
P!0.001). No significant association between the type of decision and tumor
Portugal.
type was found (c2 9.79; N.S.).
Conclusion
Introduction
Multidisciplinary teams are feasible and needed to make reliable, shared, patient-
Hodgkin lymphoma
(HL) survivors may develop a range of long-term
centered and evidence-based decisions. Endocrinology department remains the
complications that arise years after therapy. Among these, the endocrine
cornerstone that allows the flow of patients across the team.
dysfunctions are a major concern. Aim: To investigate the long-term endocrine
DOI: 10.1530/endoabs.49.EP784
effects of HL treatment.
Methods
Revision of the HL patients’ medical files who were followed at our Endocrine
Late-effects Clinics.
Results
We studied 178 patients (86 (48.3%) were female), whose mean age at HL
EP785
diagnosis was
18.07G10.79
(2-56) years. Chemotherapy was offered to
ER status heterogeneity in breast cancer: role in response to endocrine
177(99.4%) patients and radiotherapy to 157 (88.2%). Hypothyroidism was
treatment
identified in
76(42.7%) patients; women were not more affected than men
Teresa Gagliano, Angeliki Ditsiou, Arnhild Grothey & Georgios Giamas
(PZ0.083). Mean time between radiotherapy and hypothyroidism diagnosis was
Department of Biochemistry and Biomedicine, University of Sussex,
7.76G6.96 (1-39) years. Seven patients who developed hypothyroidism did not
Brighton, UK.
receive directed cervical radiotherapy and only 3 of them evidenced positive
thyroid antibodies. Thyroid nodules were present in 41 (23%) patients. Mean time
Tumor heterogeneity affects diagnosis, prognosis and response to therapy.
between radiotherapy and thyroid nodules development was 13.41G7.90 (1-35)
Heterogeneity is found in both normal and neoplastic human mammary gland. For
years. Although women were more affected (PZ0.01), they were not diagnosed
example, luminal estrogen receptor (ER)-negative cells can give rise to various
earlier (PZ0.842). Six (3.4%) patients developed thyroid cancer. Mean age at
phenotypes, including ER-negative and ER-positive mammary tumors,
thyroid cancer diagnosis was 24.4G8.36 (17-34) years. Patients who developed
suggesting that the cell-of-origin does not necessarily reflect the tumor type.
thyroid cancer were significantly younger when they underwent radiotherapy
Regarding ER status, heterogeneity can challenge endocrine therapies;
(10.2G2.9 vs 20.3G9.8/PZ0.024). Mean time between radiotherapy and thyroid
elimination of responsive clones can increase resistance of the survived ones
cancer diagnosis was 16.25G5.5 (11-21) years. Ten (11.63%) women developed
and ultimately reduce treatment efficacy leading to tumor relapse. The aim of our
breast cancer, 16.7G6.03 (7-25) years after HL therapy. Hypogonadism was
study is to investigate breast tumor heterogeneity and its role in endocrine
observed in 32 women and 12 men; mean age at hypogonadism diagnosis was
resistance onset. For this purpose, we co-cultured ER-positive (T47D, CAMA1)
28.07G8.92 (13-48) and 40.5G17.19 (14-66) years, respectively. Women
and triple negative breast cancer (TNBC) (MDA-MB231, HCC70) cell lines,
(P!0.001) and men (PZ0.001) who developed hypogonadism were older when
using 2D and 3D models. CAMA1 were sensitive to tamoxifen in term of cell
they received HL therapy. Median time between HL therapy and hypogonadism
viability, however this sensitivity was reduced when CAMA1 were co-cultured
was significantly shorter in women (1(0-18) vs 11.5 (3-39) years; (P!0.001)).
with TNBC cells. Interestingly, following co-culture with TNBC cells, the
Women who recovered their gonadic function were younger when they received
expression of ER in CAMA1 decreased while the anti-apoptotic protein Mcl-1
lymphoma therapy (17.5G7.0 vs 20.46G9.8/PZ0.026).
increased. On the other hand, T47D are slightly sensitive to tamoxifen; however,
Conclusion
this sensitivity was completely abolished when T47D were co-cultured with
Given the high relevance of endocrine dysfunctions in these patients, in order to
TNBC. In addition, the expression of ER in T47D was significantly increased
early identify and manage them, a long-term endocrine follow-up is needed, with
following co-culturing with TNBC cells, while the doubling-time of T47D was
adequate protocols.
significantly reduced, suggesting an increase in cell proliferation rate. Our results
DOI: 10.1530/endoabs.49.EP783
demonstrate that ER status appears to be modulated when ER positive cells are
co-cultured with TNBC cells, leading to a different response to endocrine therapy.
In addition, ER positive cells’ doubling time is modified after exposure to TNBC
cells. Further experiments are needed to fully understand the molecular
mechanisms behind these findings.
Endocrine Tumours and Neoplasia
DOI: 10.1530/endoabs.49.EP785
EP784
Multidisciplinary committee on endocrine tumors: an analysis of 6-year
experience
Juan J Díez1,2, Pedro Iglesias1, Teresa Alonso-Gordoa1, Enrique Grande1 &
Pablo Gajate1
EP786
1Hospital Universitario Ramón y Cajal, Madrid, Spain;2Universidad de
Potential role of vitamin D in restoring sensitivity to mTOR inhibitors
Alcalá de Henares, Madrid, Spain.
in hepatocellular carcinoma (HCC): 1,25(OH)vitamin D (VitD) reverts
everolimus (EVE) resistance in a hcc cell line
Claudia Pivonello1, Donatella Paola Provvisiero1, Mariarosaria Negri1,
Aim
Gilda Di Gennaro1, Cristina de Angelis2, Chiara Simeoli1,
Multidisciplinary approach is mandatory in the management of endocrine tumors.
Giacomo Galdiero1, Maria Cristina De Martino1, Annamaria Colao1 &
Herein, we summarize the healthcare activity performed during the last 6 years at
Rosario Pivonello1
the multidisciplinary committee for endocrine tumors of a tertiary and University
1Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,
Hospital.
Università Federico II di Napoli, Naples, Italy;2I.O.S. and COLEMAN
Methods
S.r.l., Naples, Italy.
A search of clinical-care activity of the endocrine tumors committee of our
hospital from 2011 to 2016 was performed. Clinical and demographic data of all
patients were recorded. The committee’s decisions were analyzed by tumor type
HCC is a difficult-to-treat- cancer with poor prognosis. Despite EVOLVE-1 trial
and the type of decision (diagnostic or therapeutic). Clinical protocols approved
demonstrated that EVE did not improve overall survival in molecularly and
by the committee were quantified.
clinically unselected patients with advanced sorafenib resistant HCC, in selected
Results
patients, the established antitumor effect of EVE could make this drug a potential
Two hundred and sixty seven decisions, affecting 205 patients (72.2% women,
adjuvant therapy. Unfortunately, the acquired EVE resistance due to the tumour
mean age 53.3G16.9 years) with endocrine tumors, were made. Thyroid tumors
adaptation to chronic drug use is a current challenge. VitD has been deemed as
accounted for the main workload of the committee, with 61.8% of all decisions, a
potential regimen to treat a variety of cancers alone or in combination with other
percentage that has not substantially changed over the years. The rest of decisions
drugs. The aim of this study was to assess the antiproliferative effect of the
dealt with neuroendocrine
(14.6%), pituitary
(13.5%), adrenal
(6.0%) and
combined treatment with EVE and VitD in JHH-6, a model of HCC cell line, and
parathyroid tumors
(4.1%). Most cases came from the Departments of
to explore the role of VitD pre-treatment in the re-sensitization to EVE in JHH-6
Endocrinology (52.8%) and General Surgery (18.0%). 75.7% of the committee’s
cell line resistant to EVE
(JHH-6 EveR). JHH-6 EveR were obtained after
decisions were therapeutic and 15.7% diagnostic. The committee developed 29
4 months of EVE 10-8M treatment. Messenger and protein VitD receptor (VDR)
clinical protocols for local use. 65.5% of them were therapeutic and 34.5%
expression was confirmed by RT-qPCR and immunofluorescence. DNA assay
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
was established to evaluate the proliferation rate in parental and EveR cells after
Objective
EVE treatment (from 10-14 M to 10-8 M) alone or in combination with VitD
The objective of the study was to describe the endocrine outcomes of 764 patients
(10-7 M). In parental cells, EVE significantly reduced the proliferation index in a
followed during a 20 years period in our out-patient clinic.
dose-dependent manner after 6 days of treatment and VitD did not improve EVE
Design
effect. JHH-6 EveR cells no longer responded to EVE treatment but 12h and 24h
The design was a retrospective medical records review.
of VitD pre-treatment was sufficient to significantly restore the efficacy of EVE at
Patients
concentration ranging from 10-14 M to 10-8 M with a maximum effect of 3.3%
The study included 764 patients whose oncological or hematological dangerous
at
10-8 M (P!0.001). Moreover, the liver miRNA PCR Array study
diseases appeared before
18 years old. Larger groups were constituted by
demonstrated that VitD treated JHH-6 EveR showed an increased expression of
Leukaemias, Central Nervous Tumors and Lymphomas.
miR-375 compared to JHH-6 EveR, suggesting a role of miR-375 in EVE
Outcome measures
re-sensitization. These preliminary data suggested the use of VitD to overcome
The frequency and types of endocrine conditions were measured.
the acquired resistance to EVE in HCC.
Results
DOI: 10.1530/endoabs.49.EP786
One thousand and ninety one endocrine conditions were observed in all groups.
The most common types of endocrine conditions were problems with growth and
thyroid. We found puberty abnormalities and bone problems in third and fourth
places of frequency. ACTH insufficiency was found in seventh place.
Conclusion
Endocrine dysfunctions are very common in survivor’s population. Endocrinol-
EP787
ogists should be aware of international guidelines and to make an effort to
Comparisson of subtraction and two-phase parathyroid scintigraphy
optimize screening and treatment of endocrine effects of cancer therapy. The
conserning histological type of hyperfunctioning parathyroid tissue
crucial period is the pubertal with growth spurt failure and acceleration puberty
Sanja Dugonjic1, Boris Ajdinovic2, Snezana Cerovic3 & Zoran Hajdukovic4
maturity wisch of them can bring future social and professional difficulties.
1Military Medical Academy, Institute of Nuclear Medicine, Belgrade,
DOI: 10.1530/endoabs.49.EP788
Serbia;2Military Medical Academy, Institute of Nuclear Medicine,
Belgrade, Serbia;3Military Medical Academy,Institute of Pathology and
Forensic Medicine, Belgrade, Serbia;4Military Medical Academy,
Clinic of Endocrinology, Belgrade, Serbia.
The aim of this study was comparison of sensitivity of subtraction parathyroid
scintigraphy (SBPS), vs. two-phase parathyroid scintigraphy (2FPS), related to
EP789
histological type of hyperfunctioning parathyroid tissue.
Magmas modulates chemoresistance in endocrine-related cancers
Materials and methods
Eleonora Riva1, Federico Tagliati1, Teresa Gagliano1, Claudio Trapella2,
Fifty patients, thirty with primary hyperparathyroidism and twenty on dialysis and
Sonia Missiroli3, Paolo Pinton3, Cristiano Bertolucci4, Ettore degli Uberti1
secondary hyperparathyroidism underwent parathyroid scintigraphy (PS) before
& Maria Chiara Zatelli1
surgery. Static scintigrams of neck and chest were performed, fifteen minutes and
1Section of Endocrinology, Department of Medical Sciences, University of
two hours after iv. injection of 740 MBq of Tc99m-MIBI. Four hours latter, after
Ferrara, Ferrara, Italy;2Department of Chemical and Pharmaceutical
iv. injection of 185 MBq Tc99m, thyroid scintigraphy was performed. After
Sciences, University of Ferrara, Ferrara, Italy;3Department of Morphology,
normalization and motion correction, subtraction Tc99m from Tc99m-MIBI
Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy;
scintigrams was done. Scintigraphic results of both PS methods were graded from
4Department of Life Sciences and Biotechnologies, University of Ferrara,
one to five: grade 1-normal finding, grade 2-probably normal finding, grade
Ferrara, Italy.
3-suspicious finding, grade 4-probably abnormal finding and grade 5-abnormal
finding. Scintigraphic findings graded 3, 4 and 5 were considered as pathologic.
Pathohistological analyses were done microscopically on standard haematoxylin-
eosin stained slides to determine the substrate: adenoma and type of hyperplasia.
Magmas, a gene encoding for the mitochondrial import inner membrane
Results
translocase subunit, Tim16, protects different cell lines from the antitumoral
Postoperatively 96 hyperfunctioning paratiroid glands (PG): 24% adenomas,
effects of several pro-apoptotic stimuli (i.e. chemicals and chemotherapeutic
62.5% with nodular hyperplasia (NHPL) and 13.5% with diffuse hyperplasia
agents). The synthetic Compound 5 is capable of sensitizing chemoresistant
(DHPL), were found. Overall sensitivity of SBPS was 74%; 91.3% for adenoma,
tumor cells overexpressing Magmas to proapoptotic stimuli, indicating that this
molecule may be useful to overcome tumor chemoresistance. The aim of our
70% for NHPL and 61.5% for DHPL, with no statistically significant difference in
sensitivity between groups of PG. Overall sensitivity of 2FPS was 67.7%; 100%
study was to evaluate whether Compound 5 targets Tim16 and is cytotoxic
for adenoma, 61.5% for NHPL, and 38.5% for DHPL. Statistically significant
in vivo. We found that Compound 5 enhances the antiproliferative effects of
difference was found in sensitivity of 2FPS findings between these three groups,
doxorubicin in MCF7 cells, while it fails to do so in two independent MCF7 cell
P!0.0001. SBPS had statistically significantly higher sensitivity of 61.5% for
clones where Magmas was silenced by specific shRNA. Then, the normal breast
diffuse hyperplasia, comparing to 2FPS, with sensitivity of 38.5%, P!0.0001.
MCF12 cells were transfected with two differently tagged vectors, tim16-ddktag
Conclusion
encoding for Tim16 and tim14-hatag, encoding for its partner Tim14. We found
SBPS and 2FPS showed similar sensitivity in detection of PG adenoma and
that Tim16 co-immunoprecipitates with Tim14 and that their interaction is
nodular hyperplasia of parathyroid glands. Superiority of subtraction parathyroid
reduced in the presence of Compound 5. However, Tim16 levels appear to be
scintigraphy in detection of PG with diffuse hyperplasia is important finding,
reduced in cells treated with Compound 5. The toxicity of this molecule was then
knowing that these glands are the smallest one and often remain undetected prior
tested in vivo by the Fish Embryo toxicity assay, employing Zebrafish eggs:
surgery, both in secondary, and importantly in primary hyperplasia.
Compound 5 is not toxic in vivo at the concentrations employed in vitro (5 and
10 mM), while its toxicity increases dose-dependently at higher concentrations.
DOI: 10.1530/endoabs.49.EP787
These data support the hypothesis that Compound 5 targets Tim16 and that Tim16
levels modulate the chemosensitizing effects of Compound 5, that need to be
confirmed by in vivo studies.
DOI: 10.1530/endoabs.49.EP789
EP788
Endocrine health problems detected in 764 patients evaluated in a late
effects clinic
Conceiçao Pereira, Joana Pereira, Daniela Dias, Sara Donato &
EP790
Dauarte Salgado
Portuguese Cncer Institute, Lisbon, Portugal.
Altered expression of the components of the splicing machinery is
associated to increased malignancy and expression of aberrant splicing
variants in prostate cancer
Context
Juan M Jiménez-Vacas1, Manuel D Gahete1, Sergio Pedraza-Arévalo1,
Many pediatric cancer survivors have endocrine conditions. After alkylating
Mercedes del Río-Moreno1, Daniel Hormaechea-Agulla1,
agents, steroids, methotrexate and radiation, several endocrine dysfunctions may
Enrique Gómez-Gómez1,2, Julia Carrasco-Valiente2, María del Mar
appear. Surveillance for late effects is recommended by worldwide guidelines.
Moreno3, María José Requena-Tapia2, Justo P Castan˜o1 & Raúl M Luque1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina
EP792
Sofia University Hospital (HURS); Department of Cell Biology, Physiology
Chronic stress and somatotroph axis in breast cancer more than a
and Immunology, University of Cordoba (UCO); CIBER Physi, Cordoba,
simple association
Spain;2Service of Urology, HURS/IMIBIC, Cordoba, Spain;3Service of
Iulia Crumpei1,2, Ioana Armasu1,2, Mihai Danciu1,5, Mariana Tofan3,
Anatomical Pathology, HURS/IMIBIC, Cordoba, Spain.
Constantin Volovat3, Alina Belceanu1,2, Felicia Crumpei4,
Valentina Adomnicai2 & Carmen Vulpoi1,2
1
University of Medicine and Pharmacy, Iasi, Romania;2Department of
Endocrinology, Sf. Spiridon Hospital, Iasi, Romania;3Department of
Prostate cancer (PCa) is the most common cancer among men in developed
Onclogy, Victoria Hospital, Iasi, Romania;4Department of Radiology,
countries. Unfortunately, the heterogeneity of this malignancy hinders the finding
of new biomarkers and therapeutic tools. A potential factor contributing to PCa is
Sf. Spiridon Hospital, Iasi, Romania;5Department of Morphopathology,
alternative splicing, which can generate the appearance of oncogenic variants
Sf. Spiridon Hospital, Iasi, Romania.
involved in PCa aggressiveness. Thus, we hypothesized that the alteration of the
splicing machinery (spliceosome components and splicing factors (SFs)) could be
Introduction
associated to the expression of tumorigenic splicing variants and malignancy of
Epidemiological and clinical studies have proven direct correlations between
PCa. Accordingly, we characterized the expression pattern of key components of
chronic stress, inflammation and cancer progression. The inflammatory
the major (nZ13) and minor spliceosome (nZ4) and associated SFs (nZ28) in
environment preexisting the malignant change and elevated IGF-1 levels are
51 PCa biopsies and 15 normal prostates, by using a microfluidic-based qPCR-
associated with higher cancer risk, especially through GH effects on cell
array. The results revealed a downregulation of two key components of the
proliferation and inhibition of apoptosis.
spliceosome responsible for the recognition of and binding to the branching site of
Aim
the target introns (RNU2 and RNU12) in PCa samples compared to controls,
To evaluate the relationship between biological and hormonal stress markers,
which might explain the prevalence of intron retention events found in PCa. In
growth factors and breast cancer (BC).
addition, expression of other components of the minor spliceosome (i.e. RNU11,
Patients and Methods
RNU4atac or PRPF8) was also significantly reduced in PCa, suggesting a
Biological markers (fibrinogen, C-reactive protein (CRP), ESR), endocrine stress
profound dysregulation of the minor spliceosome function and a consequent
markers
(urinary free cortisol, ACTH and urinary metanephrines) and
alteration in the processing of U12-introns. Furthermore, this analysis also
somatotroph axis: growth hormone (GH), insulin-like growth factor-1 (IGF1)
revealed a marked alteration of certain SFs (i.e. SRSF5, SRSF9, MAGOH or
were determined in a population-based sample of 79 female patients diagnosed
TIA1) in PCa, whose expression was associated with the expression of relevant
and treated for breast cancer.
splicing variants
(i.e. In1-ghrelin variant) and with malignancy features
Results
(metastasis, PSA levels, etc.). Finally, functional assays (proliferation, migration,
Among the inflammatory markers the increase of fibrinogen has been connected
etc.) with PCa cell lines confirmed the pathophysiological role of some of these
to high levels of IGF1 (rZ0.231, PZ0.045), low GH (rZK0.220, PZ0.062) and
SFs. Altogether, these results indicate that the splicing machinery is drastically
low cortisol (rZK0.226, PZ0.058); elevated ESR correlates with the increase in
dysregulated in PCa, which could help to explain the predominance of intron
GH secretion (rZ0.243, PZ0.039) and high CRP was directly linked to higher
retention events and the appearance of tumorigenic splicing variants in this
values of ACTH (rZ0.417, PZ0.00). Both cortisol (rZK0.265, PZ0.025) and
pathology, providing novel tools to develop diagnostic markers or therapeutic
urinary metanephrines
(rZK0.311, PZ0.016) have proven to negatively
targets.
correlate to IGF-1. While advancing in age, both ACTH levels (rZK0.225,
DOI: 10.1530/endoabs.49.EP790
PZ0.052) and IGF1 (rZK0.223, PZ0.051) tend to decrease.
Conclusion
The chronic inflammatory status, frequently found in patients suffering from
breast cancer, seems to be linked to the increase of the endocrine stress and
growth markers. This augmentation of IGF1 levels could be a negative predictive
factor for the further evolution and prognostic for the disease. However, our study
EP791
has shown that high levels of stress hormones correlate to lower IGF1.
Polyglandular autoimmune syndrome type III b
DOI: 10.1530/endoabs.49.EP792
Raquel Vaz de Castro1, José Maria Aragués2, Florbela Ferreira1,
Vânia Gomes1, Ana Wessling1, Lurdes Tavares1, Joana Ribeiro1,
Irina Alves1, Afonso Camilo Fernandes1 & Maria Joa˜o Bugalho1
1Santa Maria Hospital, Lisbon, Portugal;2Beatriz Ângelo Hospital, Lisbon,
Portugal.
Female Reproduction
EP793
We report the case of a 57-year-old female diagnosed with Grave’s disease fifteen
years before (TSH !0.001 U/ml; FT4 2.3 ng/dl; FT3 7.2 ng/dl, TSAbs 17 U/l).
Cynicism and common endocrine diseases in pregnancy
Persistency of hyperthyroidism despite antithyroid therapy led to total
Ioannis Ilias1, Anastasia Linardi1, Charalambos Milionis1,
thyroidectomy three years after the diagnosis. Thereafter, thyroid function
Evangelia Venaki1, Athanasios Tselebis2, Stamatina Nikopoulou1 &
remained normal under hormonal replacement with levothyroxine. The patient
Eftychia Koukkou1
had also been diagnosed with Pernicious Anemia at 47 years of age after
1Department of Endocrinology, Diabetes & Metabolism, El. Venizelou
investigation for complaints like fatigue and shortage of breath. Hemoglobin
Hospital, Athens, Greece;2Department of Psychiatry, Sotiria Hospital,
levels were 10.2 g/dl and Intrinsic Factor antibody titer was positive. She was
Athens, Greece.
treated with cobalamin and folic acid and hemoglobin levels became stable in the
low-normal range. A year ago, the patient presented with left upper quadrant
Introduction
abdominal pain and asthenia, raising the suspicion of gastric disease. Specific
Cynicism (or cynical distrust) is described as a state of mind and belief that most
blood tests were performed and the presence of high titers of gastric parietal cells
people are selfish. Cynicism is an attitude characterized by general distrust of the
antibodies (PCA), elevated gastrin (O1000 pg/ml; normal range: 13-115 pg/ml)
motives of others, and some experts describe it as a form of chronic anger.
and chromogranin A (936 ng/ml; normal range !102 ng/ml) confirmed the
Negative emotions, especially cynicism, may be harmful to physical health.
hypothesis of autoimmune gastritis. Furthermore, an elevated NSE level of
Aim
13.2 ug/l was detected. Endoscopy of the gastrointestinal tract found a
The assessment of cynicism in pregnant women with common endocrine diseases.
pedunculated polypoid lesion in the stomach fundus which was resected.
Subjects - Methods
Histological results revealed a well differentiated neuroendocrine tumor (NET)
We examined 54 Greek pregnant women (mean age C S.D.: 35C5 years), 18
with no evidence of vascular invasion or necrosis and Ki-67 index !2%;
with hypothyroidism diagnosed during pregnancy (HT), 18 with gestational
immunohistochemical studies for gastrin, somatostatin and serotonine were
diabetes mellitus (GDM) treated with medical nutrition therapy and 18 with HTC
negative; atrophic gastritis was also documented. The association of Graves’
GDM. They all responded to the validated Greek version of the Cook-Medley
disease, pernicious anemia and gastrointestinal neuroendocrine tumor suggests
questionnaire (by T Anagnostopoulou & G Kioseoglou) (minimum possible
the diagnosis of the very rare type IIIb polyglandular autoimmune syndrome.
score: 8, maximum: 40). The validity of the responses was assessed by calculating
Gastric NETs associated to chronic atrophic gastritis (Type 1) are often small
Cronbach’s alpha and the differences between the three groups of women, taking
(!1-2 cm) multiple in 65% of cases and polypoid in 78% of cases, often G1 and
into account their age, were assessed with analysis of covariance (ANCOVA).
with an excellent prognosis.
Results
DOI: 10.1530/endoabs.49.EP791
The validity of the questionnaire was satisfactory (Cronbach alpha Z0.77).
Women with HT had mean cynicism scoreCSE: 19.4C1.3, with GDM: 21.6C
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1.3 and HTCGDM; 24.7C1.3 (PZ0.02 for HT vs HTCGDM). The cynicism
score had no correlation with age (PZ0.34).
n
Age
Agreement Disagreement
% concordance
Discussion
Female
50
16-73
49
1
98
In our study we found that coexistence of HTCGDM acted cumulatively in
Male
26
13-60
19
7
73.1
cynicism score. It has been found that cynicism raises the risk of developing DM
type 2, and so does GDM. Given such negative consequences, we discern the need
of women with GDM to reassess their life attitudes and possibly to seek help to
improve their life and their prognosis.
Conclusion
There is a good agreement between the two methods. The absence of age-
DOI: 10.1530/endoabs.49.EP793
stratified reference values by CLIA’ method may explain the discordant results.
Despite the small sample size, Maglumi free testosterone may be considered a
good alternative to the RIA assay, although it is fundamental to have reference
values according to age and gender since the concentration of free testosterone
varies throughout life from childhood to adulthood.
EP794
DOI: 10.1530/endoabs.49.EP795
Thyroid ultrasonography findings in patients with polycystic ovary
syndrome
Anice Bergamim, Cristiane Perazo, Ivan Cruz, Simone Austgulen,
Patricia das Oliveiras, Roberto Perrotta & Flávia Concei
¸
˜o
Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Growth Hormone IGF Axis - Basic
Polycystic ovarian syndrome (PCOS) affects 6-10% of women of childbearing
EP796
age. The pathophysiology of PCOS is related to increased insulin resistance (IR).
Impact of new standardization on IGF-I assay IMMULITE 2000
Obesity, the leading cause of high IR, is present in 50% of women with PCOS, but
Isaura Rodrigues & Conceicao Godinho
lean women with PCOS also have higher IR than women with the same BMI
Centro Hospitalar Lisboa Central, Lisbon, Portugal.
without PCOS. Recent studies have correlated high IR with presence of thyroid
nodules (TN), which motivated us to evaluate the occurrence of TN in patients
with PCOS. 50 women with 18-45 years with PCOS according to the Rotterdam
Introduction
criteria were submitted to: evaluation of BMI and presence of acanthosis nigricas
IGF-I is a clinically relevant protein in the diagnosis and monitoring of treatment
(AN): laboratory tests for blood glucose and thyroid hormones; and thyroid
of growth disorders. The Growth Hormone Research Society and the International
ultrasound (made by the same examiner with the same device). Laboratory and
IGF Research Society have encouraged the adoption of a universal calibration for
imaging results were compared between patients with (group 1) and without
immunoassays to improve standardization of IGF-I measurements.
(group 2) TN through the Student’s T-test. The prevalence of TN was 36%. We
Objectives
observed that weight, BMI and glycemia were significantly higher in group 1 with
Comparison of new standardization IGF-I assay with IGF-I assay currently used
the following p-values, respectively: 0.003; 0.01; and 0.028. The prevalence of
in CHLC, Lisbon; To study whether the introduction of the new assay would lead
AN was also higher in group 1 (50!37.5%). Among patients with TN, 13 had a
to different clinical interpretations, verifying the concordance of results.
single nodule and only 5 had multinodular disease (2 patients with 4 and 3 with 3),
Material and Methods
totalizing 30 nodules identified. 13 of these were %1 cm and 7 were suspicious,
A random sample of 186 patients regularly assisted at CHLC, mostly in
indicating that further investigation would be necessary. Our prevalence of TN
Endocrinology Departments, comprising both genders, ages 2 months-85 years.
was higher than that found by other authors in obese women at the same age
Determinations on IMMULITE 2000 (Siemens). Chemiluminescent assays: new
without PCOS (21.4%). Although prevalence of TN increases with age, a Finnish
standardization (1st IS WHO, 02/254 NIBSC) and old (1st IRR WHO, 87/518
study evaluating healthy middle-aged women (49-58 years) also showed a lower
NIBSC); An Excel tool was used for statistical treatment. For comparison
prevalence (30.69%). These data suggest that patients with PCOS have a higher
statistics we excluded 9 patients.
risk of developing TN.
Results
Comparison statistics: rZ0.994; SlopeZ0.63; interception
(ng/ml)Z22.4;
DOI: 10.1530/endoabs.49.EP794
nZ177; range 27.2-938.0 ng/ml. According to assay and age-specific reference
values specified by the manufacturer, we found concordance between 78.3 and
90.4%, regardless of gender, with the exception of 0-3 year age group, in which
concordance fell below 33.3 and 50%.
Conclusions
Comparison statistics revealed data overlapping with those of the manufacturer.
Although there was a good agreement between assays results, caution should be
EP795
exercised in the interpretation of a single IGF-I value and of the impact of the new
Comparison of free testosterone results by a radioimmunoassay and a
standardization. Discrepancies require posterior evaluation in the evolution of the
chemiluminescent assay
disease, mainly in group 0-3 years. Clinicians should be aware of the tendency to
Conceicao Godinho & Isaura Rodrigues
reduce IGF-I values with the new calibration, so that they do not attribute it to a
Centro Hospitalar Lisboa Central, Lisboa, Portugal.
change in patient status.
DOI: 10.1530/endoabs.49.EP796
Introduction
Radioactive assays are widely used in clinical laboratories for measuring free
testosterone. The appearance of a non-isotopic, chemiluminescent automatic
assay, may be an interesting alternative if the performance of the assay remains
the same or higher.
Objective
To compare the free testosterone results by radioimmunoassay
(RIA) and
Male Reproduction
chemiluminescent assay (CLIA) and to analyze the clinical impact taking into
EP797
account the % concordance.
Rare case of manifestation of erectile dysfunction soon after
Material and Methods
thyroidectomy because of thyroid cancer in 56-year-old man with
We studied 76 patients, aged 13-73 years old, and observed at CHLC medical
diabetes mellitus type 2 and diabetic neuropathy
appointments, in Lisbon. The serum samples were analyzed by “Free TESTO-
Natia Katamadze & Zurab Marshania
RIA-CT”, DIASource (0.2-22.1 pg/ml) and “Maglumi Free Testosterone (CLIA)”
V.Iverieli Endocrinology, Metabology, Dietology Center, “ENMEDIC”,
Snibe (1.52-40.62 pg/ml). An excel tool was used for statistical treatment and the
Tbilisi, Georgia.
clinical concordance of the results were analyzed according to the reference
values of both.
Results
Introduction
A strong correlation was observed rZ0.95 and linear regression was calculated:
Erectile dysfunction (ED) is common among men with diabetes mellitus (DM).
yZ1.51xC0.072. The % concordance found was:
Early diagnosis for such patients is essential in case of other multiple serious
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
endocrine disorders like thyroid cancer (TC). The aim of our presentation is to
EP799
demonstrate the case of
56-year-old male with DM and TC when the
Epileptic seizures in patients with large and giant prolactinomas
manifestation of ED had been observed only after thyroidectomy.
Yuliya Sidneva, Luidmila Astafieva, Maksim Kutin & Pavel Kalinin
Clinical presentation
The Burdenko Neurosurgical Institute, Moscow, Russia.
A 56-year-old man attended our clinic with complains of ED and loss of libido.
He also represented the complains characteristic to diabetic neuropathy. The
symptoms of diabetic neuropathy appeared approximately 10 years ago. The
Objective
patient is diagnosed with diabetes mellitus type 2 since the age of 46. So diabetes
To study epileptic seizures in patients with large and giant prolactinomas.
mellitus and diabetic neuropathy was diagnosed at the same time. In November
Patients and methods
2016, total thyroidectomy was performed because of papillary microcarcinoma.
The study group included 45 patients with large prolactinoma (more 36 mm in
After several days of surgical intervention the patient represented complaints of
diameter) and 23 patients with giant prolactinoma (more than 60 mm in diameter).
ED. Laboratory investigations were performed: HbA1c-6.0%, prolactin and total
55 men and 13 women aged 16-67 years (mean 39). Patients were followed by
testosterone within normal range. It had carried out a comprehensive, phased
hormone measurements, magnetic resonance imaging (MRI), electroencephalo-
treatment, which included treatment of diabetic neuropathy and hypothyroidism
gram (EEG) and endocrinological, psychopathological, neurologic examinations.
with carrying out non-specific stimulation
(Yohimbin Hydrochlorid and
Results
L-arginin) as well as the therapy by PDE-5 inhibitor. Above-mentioned treatment
Mean serum prolactin level ranged between 12 990 and 1 038 000 mU/l (mean
led positive results because the treatment of ED was initiated in a timely manner.
198 000 mU/l). Epileptic syndrome was revealed in 14 patients (21%): partial
In our clinical case DM and DN was diagnosed at the same time. It is interesting
seizures with secondary generalization (64%), complex (28%) and simple (14%)
that the patient underwent to thyroidectomy and soon after he attended our Clinic.
seizures or their combinations. Seizures differed in structure depending on growth
The question is: does thyroidectomy and high level of TSH could be the reason of
of the tumor. Partial seizures with secondary generalization were mostly revealed
early manifestation of ED?
in patients with growth of adenoma to temporal region on left (50%) and right
Conclusion
(14%). Complex partial seizures were revealed in patients with growth of the
The early diagnosis of ED is important for successful treatment especially among
adenoma to temporal region on left (21%) and into the III ventricle (7%). Simple
man who had ED and multiple serious endocrine disorders. So it is important to
partial (psychosensory) seizures were in patients with growth of adenoma into
reveal it in the early stage. The easiest way not to miss ED in diabetic patients is
diencephalic region (14%). Diagnosis of epileptic seizures was based on the
the questionnaires, which we use successfully in our clinic.
detection of typical pathological patterns in EEG.
DOI: 10.1530/endoabs.49.EP797
Conclusion
21% patients with large and giant prolactinomas have epileptic syndrome.
Structure of epileptic seizures depends on extension of the adenoma and intrusion
in different regions of the brain.
DOI: 10.1530/endoabs.49.EP799
Neuroendocrinology
EP798
EP800
Dissecting the androgen excess phenotype of women with idiopathic
Prednisolone reinforces the food reward system by bilateral amygdala
intracranial hypertension
activation - an fMRI study
Michael O’Reilly1, Catherine Hornby1, Connar Westgate1,
Georg Serfling1, Macià Buades-Rotger2,3, Birgit Harbeck1, Ulrike Kramer2,3
Hannah Botfield1, Keira Markey1, Carl Jenkinson1, Lorna Gilligan1,
& Georg Brabant1
Mark Sherlock2, James Gibney2, Jeremy Tomlinson3, Wiebke Arlt1 &
1Department of Internal Medicine I, University of Lubeck, Lubeck,
Alexandra Sinclair1
Germany;2Institute of Psychology II, University of Lubeck, Lubeck,
1University of Birmingham, Birmingham, UK;2Tallaght Hospital and
Germany;3Department of Neurology, University of Lubeck, Lubeck,
Trinity College, Dublin, Ireland;3University of Oxford, Oxford, UK.
Germany.
Abstract
Introduction
Idiopathic intracranial hypertension (IIH) is a devastating neurological condition,
A well known side effect of glucocorticoid treatment is abdominally centred
with elevated intracranial pressure of unknown aetiology. IIH is largely a disease
weight gain due to increased sensation of hunger but the underlying mechanism is
of obese females of reproductive age. The clinical phenotype of IIH overlaps with
still only incompletely clarified. To elucidate whether the brain reward system is
polycystic ovary syndrome (PCOS), with prevalent obesity, hyperandrogenism
involved in this regulation we studied here the effects of an acute prednisolone
and anovulation. In this study, we aimed to delineate the androgen excess
infusion on brain centres responding to food stimulation by fMRI in healthy males
phenotype of IIH women compared to those with PCOS and simple obesity.
and correlated these findings to the 24 h food intake of the subjects.
Women with IIH (nZ70), alongside age- and BMI-matched cohorts with PCOS
Methods:
(nZ60) and simple obesity (nZ40), were recruited to an in vivo study. Serum
20 healthy normal-weight men were tested in a prospective randomized cross-
classic and 11-oxygenated androgens were measured by liquid chromatography-
over setting after an overnight fast respectively. They were either infused for
tandem mass spectrometry (LC-MS/MS) and urinary steroid excretion by gas
30 min with 250 mg prednisolone or placebo. fMRI scans were taken 4 h later
chromatography-mass spectrometry. Cerebrospinal fluid (CSF) androgens were
while presenting food and object pictures. At the following morning participants
quantified by LC-MS/MS in IIH women (nZ49) and a female cohort with non-
had a supervised breakfast at a standardized buffet. All were restricted from eating
IIH neurological disease (nZ30). PCOS patients had increased insulin resistance,
during the four hours until fMRI and kept a food diary until the next morning.
as measured by HOMA-IR (P!0.05), while HOMA-IR in IIH and controls did
Results
not differ. Serum testosterone was higher in IIH compared to both PCOS and
When presenting palatable food pictures in contrast to object pictures we obtained
control women (P!0.001 for both); conversely, serum androstenedione was
a significant activation in brain regions known to be part of the food reward
higher in PCOS women than in IIH (P!0.001) and controls (P!0.01). Serum
system like the hippocampus, anterior cingulate cortex, bilateral amygdala and
levels of the 11-oxygenated androgen precursors 11b-hydroxyandrostenedione
insula. Application of prednisolone significantly increased the activity in the
and 11-ketoandrostenedione were increased in PCOS (P!0.0001), while levels
bilateral amygdala and right insula in contrast to placebo. The buffet test did not
in IIH patients did not differ from controls. Systemic 5a-reductase activity, as
reveal any significant difference in calorie intake or preferences of different
measured by the ratio of 5a-tetrahydrocortisol/tetrahydrocortisol, was higher in
macronutrients nor did the food diary.
IIH women compared to both PCOS and controls (P!0.05 for both). IIH women
Discussion
had increased CSF androstenedione and testosterone compared to controls (all
The present imaging results support a direct stimulatory, prednisolone specific
P!0.0001). Using mass spectrometry-based analysis, we show that women with
effect on food reward centres in the bilateral amygdala and the right insula. This
IIH have a distinct androgen excess phenotype compared to PCOS and simple
interaction may represent an increased anticipated reward value of high calorie
obesity, with higher active serum androgens, 5a-reductase activity and increased
food mediated by glucocorticoids, an effect which most likely needs to be present
CSF androgens. Further studies are needed to understand the role of androgen
for a prolonged period of time to relate to a measurably increased food intake
excess in the pathogenesis of IIH.
(supported by DFG).
DOI: 10.1530/endoabs.49.EP798
DOI: 10.1530/endoabs.49.EP800
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Nuclear Receptors and Signal Transduction
peptides, whereas 5aTHB induced weak changes with only 3. Interestingly,
interactions between the MR LBD and its co-regulator peptides were altered
EP801
to a comparable extent by F and 5aTHB treatment (76 vs 41 interactions
18b-glycyrrhetinic acid reduces VLDL secretion as a modulator for
altered, respectively). In addition, both aldosterone (10 nM) and 5aTHB
HNF4a
(5 mM) increased transcriptional activity of a luciferase tagged MR reporter
Qingli Liu, Meng Yang, Minyi Zhang & Min Guan
construct in HEK293 cells (13.50G1.09 fold and 11.20G1.24 fold vs
Shenzhen Institutes of Advanced Technology, Chinese Academy of
vehicle, respectively, both P!0.0001, nZ4). Both effects were antagonised
Sciences, Shenzhen, Guangdong, China.
by spironolactone. In conclusion, the mechanisms underlying the action of
5aTHB differ from those of classical GCs, consistent with its reduced side-
effect profile, and may involve MR as much as GR.
Glycyrrhizin (GL) is a major bioactive triterpene glycoside of licorice root,
DOI: 10.1530/endoabs.49.EP802
a traditional Chinese herbal medicine. GL and primary metabolite 18b-
glycyrrhetinic acid (GA) have been developed as anti-inflammatory and
antiviral drugs for liver diseases in China and Japan. Hepatic VLDL
secretory pathway is not only responsible for lipid homeostasis but also
associated with viral particles assembly and secretion. Hepatocyte nuclear
factor 4a (HNF4a) together with its downstream targets, namely, secreted
phospholipase A2 G12B (PLA2G12B) and microsomal triglyceride transfer
EP803
protein (MTP), regulate VLDL production and secretion. We hypothesized
Development of novel human stable reporter cell line for the assessment
that GA may act through HNF4a to mediate some of its beneficial effects.
of PPARg transcriptional activity
We found that GA inhibits the transcriptional activity of HNF4a.
Peter Illes, Aneta Grycova & Hana Prichystalova
Specifically, promoter reporter expression of PLA2G12B, MTP and ApoB
Department of Cell Biology and Genetics, Faculty of Science, Palacky
activated by HNF4a are dose-dependently suppressed by GA. Through lipid
University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
droplet analysis in vitro, we further found that GA trended to elevate
intracellular triglycerides levels in a dose dependent manner in Huh7 cells,
indicating that VLDL production and secretion is suppressed. To investigate
GA effects in vivo, we fed mice a high-fat diet for 19 weeks. These mice
Endocrine disrupting chemicals (EDCs) are exogenous compounds that
were then gavaged with GA 60 mg/kg (HFD-GA) or vehicle (HFD-ctrl)
affect the endocrine system, disrupt the hormonal balance and consequently
every day for 6 weeks. We found that VLDL secretion rate was lowered
cause the adverse health effects in humans. These compounds persist and
significantly by GA treatment in HFD mice compared to HFD-ctrl mice.
accumulate in the environment and can easily gain entry to the food chain.
Data from blood biochemistry analysis revealed that treatment with GA
Peroxisome proliferator-activated receptor gamma
(PPARg) and its
significantly reduced blood TG, TC, ALT, AST, and glucose. While hepatic
heterodimeric partner retinoid X receptor alpha (RXRa) are very often
TG and TC levels were increased by HFD feeding, GA blunted the amount
targets of EDCs. PPARg play crucial role in lipid and glucose metabolism
elevated by HFD. Oil red O staining showed that the amount of fat droplets
and disturbing of PPARg signaling leads to serious diseases such as obesity,
in HFD-GA hepatocytes were reduced noticeably compared to HFD-ctrl,
diabetes, insulin resistance and cardiovascular diseases. Therefore, it is of
indicating that GA treatment reduced neutral lipid accumulation in the liver.
topical interest to develop reliable, high throughput in vitro system allowing
These evidence collectively suggested that GA acts as a modulator of
screening and identification of compounds affecting PPARg activity. In the
HNF4a, not only alleviating hepatosteatosis but also reducing hepatic
current work, we developed the unique stably transfected human reporter
secretion of TG-rich VLDL implying an underlying mechanism for antiviral
cell line T24/83-PPARgamma for the assessment of PPARg transcriptional
and hepatoprotective properties.
activity. Reporter cell line was prepared by transfecting the human bladder
carcinoma cell line T24/83 with reporter plasmid pNL2.1[Nluc/Hygro]
DOI: 10.1530/endoabs.49.EP801
containing three copies of PPARg response element, coupled with minimal
promoter. Design of response element was based on the sequences of
promoter region of human acyl-CoA-oxidase. In the cells treated with
PPARg ligand 15-deoxy-d12,14-prostaglandin J2 and prostaglandin D2 for
24 h, luciferase activity ranged from 40-fold to 50-fold and from 70-fold to
80-fold, respectively
(RLU 104-105). Application of PPARg selective
antagonist T0070907 resulted in inhibition of luciferase activity, indicating
EP802
specific response of T24/83-PPARgamma cell line. The inducibility of
5a-THB as a novel anti-inflammatory drug: The roles of the
luciferase activity remained unaffected after cryopreservation and even after
glucocorticoid and mineralocorticoid receptors
prolonged cultivation for more than 2 months. Based on these results, the
Amber Abernethie1, A Gastaldello1, RA Morgan1, C Mitchell1,
novel human reporter cell line T24/83-PPARgamma can be considered as a
KJ McInnes1, K Beck4, A Odermatt4, R Houtman3, D Melchars3,
potential tool for screening of compounds affecting PPARg activity,
OC Meijer2, PWF Hadoke1, DEW Livingstone1, BR Walker1 & R Andrew1
applicable in various toxicological and environmental studies.
1University of Edinburgh, Edinburgh, UK;2University of Amsterdam,
DOI: 10.1530/endoabs.49.EP803
Amsterdam, The Netherlands;3PamGene International, Den Bosch,
The Netherlands;4University of Basel, Basel, Switzerland.
Glucocorticoids
(GC) are potent anti-inflammatory compounds, acting
mainly through the glucocorticoid receptor (GR). GC therapy, however, has
debilitating side-effects, necessitating safer new alternative therapies. The
EP804
natural GC metabolite
5a-Tetrahydrocorticosterone
(5aTHB) is anti-
Functional characterization of inherited S127F substitution in V2
inflammatory in vivo in mice, but with fewer side-effects. Its mechanism
vasopressin receptor revealed a loss-of-function mutation leading to
of action is unknown, and here we test signalling via GR and the
nephrogenic diabetes insipidus
mineralocorticoid receptor (MR). 5aTHB displaced dexamethasone (Dex)
László Erdélyi1, András Balla1,2 & László Hunyady1,2
from primary rat hepatocytes (nZ6, Kd (nM): Dex 37G8, corticosterone
1Department of Physiology, Semmelweis University, Budapest, Hungary;
153G59, 5aTHB 268G78) but only negligibly from isolated human GR
2MTA-SE Laboratory of Molecular Physiology, Hungarian Academy of
(nZ3, EC50 (mM): Dex 0.004, cortisol 0.019, 5aTHB 480). GR nuclear
Sciences and Semmelweis University, Budapest, Hungary.
translocation was quantified by western blot after nuclear
(N) and
cytoplasmic (C) separation of steroid-treated A549 cells. Dex (100 nM)
increased the N/C GR ratio, after 30 minutes (0.59G0.26 to 2.97G0.50,
P!0.0001) and 24 h (0.47G0.29 to 2.23G0.72, P!0.05). In contrast, GR
The V2 vasopressin receptor (V2-R) mediates the effect of vasopressin on
translocation was not observed with 5aTHB (1, 3 or 10 mM) at either time
the water reabsorption in the kidney and several mutations in the V2-R have
(nZ6). Similarly, GR Ser211 phosphorylation was increased by (1 mM)
been identified causing nephrogenic diabetes insipidus (NDI). In this study,
corticosterone
(B;
5.00G1.05 fold vs vehicle, P!0.0001) but not by
we investigated a previously not characterized mutation of the. We obtained
(10 mM) 5aTHB (2.74G0.35 fold vs vehicle, not significant). MARCoNI
genomic DNA of a young male patient with NDI, the AVPR2 gene was
(Pamgene) peptide array analysis (nZ3) demonstrated that Dex altered the
amplified with PCR and a missense mutation (S127F) was identified. We
interaction of GR ligand binding domain (LBD) with 75 co-regulator
monitored the cellular localization of the S127F mutant V2 receptor using
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
HA-tagged receptors in confocal microscopy experiments. The S127F V2
1Klinik fur Augenheilkunde - Charité Universitatsmedizin Berlin, Berlin,
receptor was detected only in the endoplasmic reticulum but not in the
Germany;2Institut fur Experimentelle Pädiatrische Endokrinologie, Charité
plasma membrane. We also measured the cAMP signaling capability of the
- Universitatsmedizin Berlin, Berlin, Germany; 3Institute of Anatomy,
mutant receptor with BRET measurements. The S127F receptor was not
Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
able to increase the intracellular cAMP levels in response to vasopressin
stimulation. Certain ER retention mutations can be rescued by pharma-
cological chaperones, which cause misfolded mutant receptors to present in
3-Iodothyronamine
(3-T1AM) is an endogenous metabolite of thyroid
the plasma membrane. We examined the effect of tolvaptan
(V2R
hormone (TH) for which was shown to have various effects. One of the
antagonist) on the S127F V2 receptor. HEK293 cells were transiently
effects is body temperature decline, which may be related with menthol
transfected with the plasmid of the mutant receptor and after one day the
receptor TRPM8. Normally, this ion channel is expressed in neuronal tissue,
cells were incubated for 18 hours with tolvaptan. After the pretreatment, the
where it has a nociceptive role. Functional TRPM8 expression has also been
cells were exposed to vasopressin, and we were able to detect cAMP signal
shown in non-neuronal cells of the eye such as corneal and conjunctival
generation of the mutant receptor. We checked whether the result after
epithelial cells, corneal endothelial cells as well as human corneal
tolvaptan pretreatment was due to restored plasma membrane location of the
keratocytes. Furthermore, we could demonstrate in previous studies that
receptor. We were able to demonstrate significant increase of the mutant
3-T1AM acts as a cooling agent in human corneal epithelial and conjunctival
receptors in the plasma membrane using flow cytometry. Since the tolvaptan
epithelial cells and that it is suppressing TRPV1
channel
(capsaicin
is already used in the treatment of multiple diseases, we plan to carry out
receptor), which plays an important role in dry eye disease. Here, we
clinical studies to assess the potential therapeutic usage of this drug in the
determined in a human corneal endothelial cell line (HCEC-12) and a human
NDI patients with S127F V2R mutation. This work was supported by
corneal keratocyte cell line (HCK) if 3-T1AM also acts as a cooling agent to
National Research, Development and Innovation Fund (NKFI K116954).
directly affect TRPM8 at a constant temperature. Functional activity was
DOI: 10.1530/endoabs.49.EP804
evaluated by comparing the effects of 3-T1AM with those of TRPM8 known
agonists on intracellular Ca2C currents and whole-cell currents using
fluorescent Ca2C-imaging and planar patch-clamping. Menthol (500 mM), a
specific TRPM8 activator, evoked a Ca2C influx as well as an increase of
whole-cell currents. This effect could be blocked by BCTC (20 mM) and
AMTB (20 mM), both selective TRPM8 antagonists. Notably, comparable
effects were observed with 1 mM 3-T1AM. Overall, this study completes our
EP805
previous studies of human corneal and conjunctival epithelial cells.
Effects of human interleukins on transcriptional activity of vitamin D
Interestingly, the effect of 3-T1AM has a similar Ca2C response pattern
receptor in transgenic gene reporter cell lines IZ-VDRE and IZ-CYP24
and similar whole-cell current pattern in all three layers of the cornea.
Iveta Bartonkova, Aneta Grycova & Zdenek Dvorak
Therefore, this might represent a general biological phenomenon. Further
Department of Cell Biology and Genetics, Faculty of Science, Palacky
investigation of 3-T1AM effects on the cornea should be performed in order
University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
to better characterize a potential benefit of 3-T1AM on the treatment of dry
eye disease.
DOI: 10.1530/endoabs.49.EP806
Vitamin D receptor (VDR) signalling can be affected with a variety of
compounds, both endo- or exogenous. However, any disruption of VDR
transcriptional activity can exert severe physiological or pathophysiological
outcomes. It is therefore of a great importance to have a reliable in vitro
screening technique that would provide a tool for efficient identification of
agonists and activators of human VDR. In the current work, we described
two novel human reporter cell lines IZ-CYP24 and IZ-VDRE, constructed
EP807
for the purpose of VDR transcriptional activity detection. Parental human
Cytotoxic activity of plant extracts from Brazilian biome in prostate
adenocarcinoma cell line LS 180 was stably transfected with a reporter
cancer cell lines
construct CYP24_minP-pNL2.1[Nluc/Hygro] containing a sequence from
Sarah Cardoso, Matheus Andrade, Vinicius Cunha, Cristian Silva,
the promoter region of human CYP24A1
gene
(IZ-CYP24), or
Patrícia Rodrigues, Mayra Leão, Christopher Fagg, Eliete Guerra,
VDREI3_SV40-pNL2.1[Nluc/Hygro] containing three copies of VDREI
Francisco Neves, Luiz Simeoni, Dâmaris Silveira & Adriana Lofrano-Porto
from the promoter region of human CYP24A1
gene
(IZ-VDRE),
University of Brasilia, Brasilia, Brazil.
respectively. Both our cell lines remained fully functional in the cell culture
for more than 2 months (corresponding to 30 passages) and even after
Introduction
cryopreservation. Luciferase inductions ranged from 10-fold to 25-fold
Prostate cancer is a public health problem worldwide. The cure is unlikely and
(RLU 106-107) and from 30-fold to 80-fold (RLU 103-104) in IZ-VDRE and
therapeutic alternatives are limited. The Brazilian biodiversity represents a huge
IZ-CYP24 cells, respectively. Time-course analyses revealed the possibility
source of potential discovery of new drugs derived from plants. We therefore
to detect VDR activators as soon as after 8 hours of incubation. Both our cell
aimed to conduct a biomonitoring chemical study of plant extracts from Pouteria
lines were highly selective towards VDR agonists, no cross-talk with
sp. previously shown to be cytotoxic in androgen-sensitive
(LNCaP) and
retinoids, thyroids or steroid was observed. As a proof of concept, the effect
androgen-resistant (PC3) human prostate cancer cell lines.
of 13 human interleukins on VDR transcriptional activity was examined.
Methods
Luciferase assays showed an inhibition of VDR transcriptional activity by
The crude ethanolic extract of Pouteria caimito leaves and hexanic extract of
interleukin-4 and interleukin-13, reaching approximately 60% of calcitriol-
Pouteria ramiflora were tested in PC3 and LNCap human prostate adenocarci-
induced luciferase signal in concentrations about 1 ng/ml after 24 h of
noma cells. The crude extract of P. ramiflora branches and stem was then pre-
incubation in IZ-CYP24 cell line. Similar results were obtained from
fractionated through sintered funnel. The pre-fraction hexane: ethyl acetate 1:1
expression analyses of human CYP24A1 mRNA. Taken together, both of
was fractionated by column chromatography into
649
fractions, grouped
these cell lines provide a tool for reliable, high-throughput and selective
according to the profile in thin layer chromatography into 49 samples. Among
identification of VDR ligands, with possible implications in toxicological
those, four samples were selected for Nuclear Magnetic Resonance (NMR)
and environmental studies.
spectroscopy, based on their abundance and cytotoxicity biomonitored by MTT.
DOI: 10.1530/endoabs.49.EP805
Results
The ethanolic extract of P. caimito showed a dose-dependent cytotoxic effect in
PC3 cells (O50%), with a statistically significant inhibitory effect on the cell
cycle. The hexanic extract of P. ramiflora showed a dose-dependent cytotoxic
effect in LNCaP, with a high selectivity index (5.5 after 48 h of treatment), as
compared to a non-cancerous human cell line (HaCat). Among the 49 samples
obtained from this extract, fraction “8” was purified and the compound epi-
EP806
friedelanol was isolated, whose bioactivity is under evaluation in prostate cancer
3-Iodothyronamine induces transient receptor potential melastatin 8
cell lines.
(TRPM8) channel activation in human corneal endothelial cells and
Conclusion
human corneal keratocytes
Our biomonitored analysis of Pouteria sp. extracts has provided the purification
Nina Ljubojevic1, Noushafarin Khajavi2, Katharina Lohse1,
of a number of cytotoxic fractions. Among those, a triterpenic bioactive
Monika Valtink3 & Stefan Mergler1
compound (epi-friedelanol) was identified by RMN spectroscopy, and deserve
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
further studies regarding its specific cytotoxicity. Triterpens have been shown to
unique gut-derived peptide that has major impact in energy homeostasis and
exert cytotoxic effects on different types of cancer at low activity towards normal
weight regulation, with new emerging implications in tumorigenesis process,
cells, including prostate cancer.
especially in hormone-dependent cancers.
DOI: 10.1530/endoabs.49.EP807
Aim
To evaluate the relationship between ghrelin, clinico-biological parameters of
obesity and gonadotropic axis in breast cancer patients.
Patients and Methods
We assessed the relationship between fasting ghrelin and anthropometric
measures, insulin-resistance, lipid and glucose metabolism parameters, hypo-
thalamic-pituitary-gonadal axis (HPG): FSH, testosterone/estradiol-ratio, SHBG,
and body composition (evaluated by dual-energy X-ray absorptiometry) in 64
Obesity
breast cancer patients. Both acyl-ghrelin (AG) and des-acyl-ghrelin (DAG) were
EP808
evaluated through ELISA; total ghrelin (TG) was calculated as the sum of the two.
Evolution of patients with amyotrophic lateral sclerosis followed in a
Results
nutrition and endocrinology specific unit during 3 years
DAG, but not AG, negatively correlates with BMI (rZK0.280, PZ0.013), waist
Inmaculada Gonzalez-Molero, Monserrat Gonzalo, Viyu Doulatram,
circumference
(rZK0.335, PZ0.006) and waist/hip ratio
(rZK0.302,
Jose Abuin, Francisco Tinahones & Gabriel Olveira
PZ0.015). Concerning body fat distribution, DAG negatively correlates with
Hospital REgional de Málaga, Malaga, Spain.
sub-total (rZK0.326, PZ0.005) and truncal fat mass (rZK0.273, PZ0.02).
Even stronger association of these parameters was observed with TG. Also, DAG
negatively correlates with insulin l
(rZK0.354, PZ0.003) and HOMA-IR
Introduction
(rZK0.343, PZ0.004). Concerning HPG, AG, but especially AG/TG-ratio were
A high percentage of patients diagnosed with Amyotrophic Lateral Sclerosis
positively correlated with FSH (rZ0.354, PZ0.004) and SHBG (rZ0.272,
(ALS) have malnutrition. The nutritional treatment in ALS is essential, affecting
PZ0.03). Even though no direct correlations were found between ghrelin and
muscle strength, quality of life and survival.
HPG, we observed that insulin positively correlates with testosterone/estradiol-
Objective
ratio (rZ0.247, PZ0.039), as with SHBG (PZ0.341, PZ0.004), and that the hip
To describe the nutritional characteristics of patients evaluated in a specific
circumference was positively correlated with free-testosterone levels (rZ0.251,
nutritional Unit in patients with ALS during 3 years.
PZ0.044).
Material and methods
Conclusions
A descriptive study of all patients diagnosed with ALS and evaluated in this
Ghrelin has definitely indirect effects in breast cancer through its roles in obesity
specific consultation since October 2013. The nutritional status is assessed by
and insulin-resistance. We described different connections between ghrelin-
anamnesis, 24-h ingestión count, physical examination (BMI, % lost weight,
obesity-gonadotropic axis in these patients, underlying discreet metabolic and
Plicometry, dynamometry), evaluation of dysphagia by EAT-10 (if positive,
hormonal modifications. However, ghrelin may also play a direct role in breast
volume viscosity test) and analytical tests.
cancer pathogenesis due to its recently discovered anti-aromatase effect in
Results
adipocytes.
Data were obtained from 60 patients. Mean age at diagnosis: 57.5 years (26-79
DOI: 10.1530/endoabs.49.EP809
years),
65% male. Bulbar: 28.6%, spinal: 61.2%. The mean time until the
evaluation in nutrition Unit was 22.1 month (12.6 in bulbar vs 24.7 in spinal,
P!0.05). The initial BMI: 26.4 (18.1 to 36.2), in 78.3%O 25. The nutritional
status in the first consultation was
(VSG): 23% of patients with moderate
malnutrition, 17.1% of severe malnutrition (30.8% of bulbars vs 5.9% of spinal,
P!0.05). The most frequent analytical alterations were vitamin D insufficien-
cy/deficiency
(58.3%) and hypercholesterolemia
(50%). The most frequent
analytical disorders were vitamin D deficiency/insufficiency
(58.3%) and
EP810
hypercholesterolemia
(22.5%). Nutritional intervention at the first visit was
Differences in calcium and thyroid homeostasis and thyroid volume
only diet in 46% (7.1% bulbar vs 69% in spinal, P!0.05), thickening prescription
after bariatric surgery
in 34%, nutritional supplements in seven patients, gastrostomy in three patients
İffet Dagdelen Duran1, Nese Ersoz Gulc¸elik2, Dilek Berker1 &
(all of them bulbar). Of the patients who were offered gastrostomy during follow-
Serdar Guler1
up (56.8%), 68.4% accepted. The main reason for this was weight loss (83%). The
1Ankara Numune Education and Research Hospital, Department of
FVC (Forced vital capacity) at this time was: 58% (23 to 97%) and 100% were
Endocrinology and Metabolic Diseases, Ankara, Turkey;2Ankara
endoscopic. As complications of gastrostomy: three patients had accidental
Education and Research Hospital, Department of Endocrinology and
withdrawal. The mean survival time after gastrostomy was 14 months (2-25
Metabolic Diseases, Ankara, Turkey.
months).
Conclusions
- 40.1% of patients with ALS present moderate/severe malnutrition in the first
Introduction
assessment.
Bariatric surgery would end up with great alterations in homeostatic measures
- BMI and analytical parameters are not early markers of malnutrition, being
such as glucose and lipid metabolism and hormonal regulation, which of all are
weight loss the best marker.
interweaved with some number of ways to each other. The hormonal modulation
- Patients with bulbar ALS present malnutrition more frequently than spinal
extands along a wide span starting from the change in gastrointestinal peptides, to
forms and require an earlier and more aggressive nutritional intervention.
the effect in insulin and other nutrient metabolism regulatory hormones and even
DOI: 10.1530/endoabs.49.EP808
the hormones establishing thyroid and calcium homeostasis. Secondary
hyperparathyroidism is a common finding associated with decreased nutrient,
mineral and vitamin D absorption after gut lumenal loss due to bariatric surgery.
Meanwhile when the adaptation of thyrotropin (TSH) and free t4 (fT4) level
shows variance among studies, in fact TSH frequently was reported to decrease.
Free t3 (fT3) was constantly shown to decrease, used to be correlated with
dysfunction in deiodination. The thyroid volume would also be a candidate of
other parameter that is expected to change over postsurgical period.
EP809
Materials and Methods
Obesity, gonadotropic axis and breast cancer - is ghrelin the
We recruited 67 morbidly obese patients planned to have bariatric surgery. All the
connexion?
subjects were recorded for their body weight, BMI, metformin, insulin and
Ioana Armasu1,2, Iulia Crumpei1,2, Constantin Volovat3, Mariana Tofan3,
levothyroxine(LT4) usage and if used dosage of the drug before the operation.
Valentin Zaharia2, Adrian Aancutei2, Ioana Vasiliu1, Ionela Lacramioara
The patients were examined with hormonal [parathormon(PTH), 25-oh-vitamin
Serban1 & Carmen Vulpoi1,2
d3(25vitD3), TSH, fT3, fT4 and biochemical tests [calcium(Ca), ionized Ca(iCa),
1University of Medicine and Pharmacy, “Gr.T. Popa”, Iasi, Romania;
phosphorus(P), 24 hour(h) urinary Ca]. Thyroid ultrasonography (USG) were
2County Emergency Hospital, “Sf. Spiridon”, Iasi, Romania;3Victoria
performed by one same practitioner and the diameters of each lobe was given as
Hospital, Iasi, Romania.
axbxc(cm). The volume of each lobe was calculated with axbxcx0.524 (cm3), and
total thyroid volume with addition of right to left lobe volume. The number of
Introduction
nodules and the size of largest nodule were also recorded. The antropometric
Obesity and insulin resistance have been identified as risk factors for breast cancer
measures, drug consumption data, laboratory tests and thyroid USG were repeated
and are associated with late-stage diagnosis and poor prognosis. Ghrelin is a
after 12 month of surgery.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
Aim
The mean age of patients was 41.5G9.6 year. 58 (86.5%) subjects were female,
To report the clinical findings in a third case with overgrowth related to a small
while 9(13.5%) were male. After 12 month of surgical approach, mean body
microduplication of 15q26.3 not including the IGF1R region.
weight decreased from 120.3G4.1 kg to 85.4G3.3 kg (P:0.00), BMI from 47.8G
Methods
1.4 kg/m2 to 34.0G1.2 kg/m2 (P:0.00), TSH from 2.3G0.2 to 1.1G0.2 mIU/ml
Comparative genome hybridization was done using an Agilent 180k microarray
(P:0.00), fT4 from 1.0G0.0 to 0.5G0.0 ng/dl (P:0.00), fT3 from 2.5G0.1 to
platform.
1.3G0.1 pg/ml (P:0.00), PTH from 48.6G4.7 to 24.4G4.4 pg/ml (P:0.00), Ca
Results
from 8.0G0.4 to 5.0G0.6 mg/dl (P:0.00), and thyroid volume from 9.6G2.2 to
Accelerated linear growth was observed after the first 3 months with a normal
4.0G0.8 cm3 (P:0.022) significantly. Levothyroxine and insulin requirement
weight increase in a female patient, born at 36 weeks of gestation by normal
decreased after operation nonsignificantly. 25vitD3 increased, 24 h urinary Ca
delivery. At birth weight was 3200 g (O97th centile), length 52 cm (O97th
decreased again nonsignificantly.
centile) and head circumference (HC) 35.5 cm (97th centile). Mother’s and
DOI: 10.1530/endoabs.49.EP810
father’s height was 182 cm. She had transient feeding problems, necessitating
nasogastric feeding in the first week of life. She presented with delayed motor
development. Teeth erupted prematurely. At the age of 2 years, her length was
96 cm (O 97th centile), weight 16 kg (97th centile), HC 51 cm (97th centile) and
armspan 96 cm. She showed a high forehead, mild synophris, epicanthal folds,
deep-set eyes, a flat nasal bridge, mid face flattening, a prominent chin, and
tapering fingers. Ultrasound of the abdomen and heart were normal. Bone
maturation and serum IGF-1 were normal. ArrayCGH analysis showed a de novo
Paediatric Endocrinology
1.6 Mb duplication of 15q26.3 (arr
15q26.3q26.3 (98386658 99753407)x3).
EP811
Speech delay and mild coordination and motor problems were noted later on,
Sebaceous hyperplasia and androgen levels-still controversial
whereas height and weight progressed normally but above the 97th percentile. At
Anca E Chiriac1, Anca Chiriac2,3 & Doina Azoicai1
the age of 4 year, mitral valve insufficiency developed, necessitating a surgical
1University of Medicine and Pharmacy, “Grigore T Popa”, Iasi, Romania;
repair.
2Apollonia University, Iasi, Romania;3Nicolina Medical Center, Iasi,
Conclusions
Romania;4“P Poni” Research Institute, Iasi, Romania.
The previous and this case report highlight the possible involvement of the distal
region of 15q in infantile overgrowth, independent of IFGR1 duplication. Delayed
speech development, tall stature and macrocephaly with a prominent chin appear
constant findings, while cardiac manifestations may be variably present.
Sebaceous glands are very sensitive to androgens which can modify the size but
DOI: 10.1530/endoabs.49.EP812
not the number of sebaceous glands. Sebaceous hyperplasia is a common benign
proliferation of the sebaceous glands seen during the first weeks of life, being
reported in 89.4% of 1000 newborns enrolled in across-sectional prospective
study in the period of November 2007 to May 2009 in India [1] or in 35% of 2938
neonates aged up to three days of life hospitalized in a Brazilian city [2]. Sebum
secretion is high in neonates probably induced by maternal androgen:
dehydroepiandrosterone transferred trans-placental. [3] It is also named “the
miniature puberty of the newborn” along with vaginal bleeding in infant girls and
neonatal acne. Reduced androgen levels in elderly could explain hyperplasia of
sebaceous glands
(slower cell turnover), especially in women while high
androgen-dependent sebum secretion in neonates results in neonatal sebaceous
hyperplasia. The association between sebaceous hyperplasia and androgens has
EP813
been demonstrated in animal models [5], but no correlation was found between
A very rare case of 48, XXYY syndrome
serum androgen levels and the appearance of sebaceous hyperplasia lesions in
Ioana Alexandra Ambarus Popovici1, Cristina Rusu2,3, Alina Andreea
women [6].Controversial data exist and further clinical studies are required.
Oprea1, Laura Feraru1, Raluca Balaceanu1 & Cristina Preda1,3
1University Hospital, “St. Spiridon” Iasi, Iasi, Romania;2University
Hospital for Children “St. Maria” Iasi, Iasi, Romania;3University Of
Table 1 Differences between neonatal and adult form of sebaceous
Medicine and Pharmacy, “Gr. T. Popa”, Iasi, Iasi, Romania.
hyperplasia [4].
Neonatal sebaceous
Adult sebaceous gland
Introduction
gland hyperplasia
hyperplasia
48, XXYY is a rare sex chromosome aneuploidy, being estimated to occur in
1:18000-1:40000 male births. Phenotypically it was considered a variant of
Age of onset
First weeks of life
Middle age-elderly
Klinefelter syndrome (47,XXY), but currently, due to mental deficiency and
persons
behavioural characteristics associated, it’s considered to be a separated genetic
Gender: males/females
1.08/1
condition.
Sites of skin lesions
nose
forehead,genitalia,
Case report
areola, chest
We report a case of a 8-year-old boy, first child of a young non-consanguineous
Androgen levels
high
low/normal
couple, born at term. Due to minor dysmorphic facial features, hypospadias and
(hyper-receptivity)
bilateral talus valgus, a genetic test was conducted and the karyotype identified
Evolution
Spontaneously
progressive evolution
was 48,XXYY. He was frequently hospitalized for upper respiratory infections,
remission within
without treatment
gastro-enteritis, recurrent otitis. He was diagnosed with viral induced asthma and
weeks
IgA and IgG subclass deficiencies, developing food and medication allergies.
Physical examination revealed normal height and weight, dysmorphic facial
features (thick eyebrows, hypertelorism, mongoloid slant of the eyes, convergent
DOI: 10.1530/endoabs.49.EP811
strabismus, thin lips, dental problems), bifid scrotum, hypospadias, sacral sinus,
clinodactyly of the fifth finger, bilateral talus valgus surgically corrected.
Neuropsychiatric evaluation revealed borderline mental retardation, delayed
speaking, aggressive behaviour, learning difficulties. The endocrinologic consult
showed a normal thyroid axe, with a normal-low testosterone level
EP812
(!0.025 ng/ml) associated with a FSH level of 0.98 mUI/ml (0.4-3.8) and LH
Microduplication of 15q26.3 not including IGF1R as a novel genetic
level !0.1 mUI/ml (0-3,8). Thyroid ultrasound was normal, testicular ultrasound
cause of infantile overgrowth
revealed hypoechoic testis, the X-ray of the hand revealed delayed bone age.
Jean De Schepper1,2, Denis Libeert2 & Bert Callewaert2
Conclusions
1UZ Brussel, Brussels, Belgium;2UZ Gent, Ghent, Belgium.
48,XXYY was described as a variant of 47,XXY syndrome. It is very important to
distinguish the two syndromes regarding the associated medical conditions (as in
our case - asthma, food allergies, dental problems, strabismus, recurrent otitis,
Introduction
frequent upper respiratory infections), cognitive and behavioural problems,
Recently, a microduplication of 15q26.3 not including IGF1R was reported in
learning difficulties which are more frequently correlated with
48,XXYY
subjects of two families with overgrowth and variable intellectual disability
syndrome. Due to complexity and specific features of this particular syndrome,
(Leffler M. et al., Eur J Med Gen, 2016).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
it is recommended a thorough evaluation and a different therapeutic attitude for
which was noted to have started in the first few days of life. He had normal serum
each case.
sodium concentration (142 mmol/l), high serum osmolality (311 mOsm/l), low
DOI: 10.1530/endoabs.49.EP813
urinary osmolality (129 mOsm/kg), and hyponatriuria (15 mmol/l) on admission.
The water deprivation test was stopped due to weight loss higher than %3 at 3.5th
hour of the test. The plasma vasopressin (16.75 pmol/l, range:0-13) drawn at the
conclusion of the dehydration test was high, and the urine parameters showed
little insignificant changes. The desmopressin challenge test did not affect the
urine parameters, either. There was a continuous high urine output, low urine
osmolality and impaired ability to increase urine osmolality to normal levels after
ADH administration. The AVPR2 gene of this patient was sequenced with
ABI310 and revealed a novel hemizygous missense mutation causing a
conversion of the histidine residue to tyrosine in the protein sequence, at the
EP814
position 80th in exon 2. We suggest that bioinformatical analysis and functional
Clinical case of early manifestation of autoimmune polyglandular
characterization studies will enlight the function of the mutant AVPR2 protein.
syndrome type 3 A in children
This research was funded by The Scientific and Technological Research Council
Julia Volk & Anzhalika Solntsava
of Turkey (SBAG Project Numbers: 112S513 and 115S499).
Belarusian State Medical University, Minsk, Belarus.
DOI: 10.1530/endoabs.49.EP815
Autoimmune polyglandular syndrome (APS) type 3 - is a rare orphan disease,
which is a combination of autoimmune thyroid disease and diabetes mellitus
(DM) type 1 and/or pernicious anemia, vitiligo, alopecia. Due to the rare
occurrence in pediatric patients we give our own observation of early
manifestation of APS type 3 A in a girl 10 years. Complaints in the primary
treatment: sweating, irritability, cardiopalmus, weight loss. Survey results:
ultrasound examination of the thyroid gland: expressed diffuse changes, the
EP816
increase in volume K22.0 cm3
(normal
2.74-6.76). Indicators: thyroid-
Type 1-like diabetes mellitus in an oncological endocrinology unit
stimulating hormone (TSH) 0.05 mkIE/ml (normal 0.27-4.2), free thyroxine
Sara Donato, Sónia Andrade, Daniela Dias, Joana Simo˜es-Pereira &
(T4) O100.0 pmol/l (normal 12.0-22.0), free triiodothyronine (T3) 43.1 pmol/l
Maria da Concei
¸a˜o Pereira
(normal
3.1-6.8), TSH receptor antibodies
18.0 IU/l
(normal
0-1.75).
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,
Ophthalmologist: ophthalmopathy low degree of both eyes. Primary diagnosis:
Portugal.
Graves’ disease
(GD), goiter grade
2, thyrotoxicosis of medium gravity,
decompensation. Autoimmune ophthalmopathy. Starting treatment: tiamazol
20 mg/day; metoprolol 25 mg/day. 6 months later the patient was hospitalized
Introduction
with complaints during the month of thirst, frequent urination, weight loss of
Asparaginase is a component of chemotherapy regimens used to treat paediatric
4.5 kg, weakness. Survey results: blood glucose level 34.1 mmol/l. Acid-base
acute lymphoblastic leukaemia (ALL). One of its well-known side effects is
balance: metabolic acidosis. Indicators: C-peptide 155.6 pmol/l (normal 160-
hyperglycaemia which is probably related to hypoinsulinemia. Its incidence rises
1100), antibody titer to glutamic acid decarboxylase 93.2 U/ml (normal 0-1.0),
significantly when associated with corticotherapy. We present two cases of
glycated hemoglobin 9.5%. The metabolic compensation of thyrotoxicosis was
diabetes related to asparaginase and corticoid administration.
observed on maintenance therapy (tiamazol 5 mg/day): T4 17.16 pmol/l, TSH
Case 1
!0.05 mkIE/ml. There was a volume reduction 16.2 cm3 on thyroid ultrasound.
Eleven-year-old girl diagnosed with an ALL. Before treatment she had a normal
Final diagnosis: APS type 3 A: DM, type 1, decompensation. GD, medical
body weight and was normoglycaemic. She started the DFCI-2011 protocol and
euthyroidism. Autoimmune ophthalmopathy. Treatment: insulin therapy
22
on the day of the first peg-asparaginase administration she was found to have
U/day; tiamazol 5 mg/day. 2 months later a child was hospitalized due to
polydipsia, polyuria and a glycaemia of 700 mg/dl with no clinical evidence of
worsening indicators of thyroid hormones and severe fluctuations in blood
pancreatitis. She started an intensive insulin scheme of therapy with an average
glucose on the treatment of human genetic engineering insulins. Survey results:
dose of 0.6 U/kg/day. On the 16th day insulin dose started to be reduced. Despite
thyroid ultrasound: negative dynamics - increase to 21.08 cm3. Indicators: TSH
the higher doses of corticosteroids in the following asparaginase infusions she
0.009 mkIE/ml, T4
24.8 pmol/l, T3
10.06 pmol/l. Correction of therapy:
needed lower doses of insulin to maintain euglycaemia.
increasing the dose of tiamazol to 20 mg/day and using insulin analogs. The
Case 2
simultaneous presence of two or more autoimmune diseases of the endocrine
Six-year-old boy diagnosed with an ALL at the age of three. He was first treated
glands (thyroid and DM) aggravates the symptoms of each of them, leads to the
with DFCI-2005 protocol without evidence of hyperglycaemia. A remission
decompensation of patients.
lasting 10 months was achieved with recurrence diagnosed at the age of six. He
DOI: 10.1530/endoabs.49.EP814
started the IntReALL-SR-2010 protocol and before this treatment his body weight
was between P25-50 and he was normoglycaemic. Seven days after the first peg-
asparaginase administration he was found to have a glycaemia of 519 mg/dl with
ketonuria of 5 mg/dl, without clinical evidence of pancreatitis. He started an
intensive insulin scheme with an average dose of 1.5 U/kg/day. Eleven days after
the second peg-asparaginase administration insulin dose started to be reduced and
at the end of induction course was stopped. Peg-asparaginase was administered
one last time without hyperglycaemia.
EP815
Conclusion
A novel p.H80Y mutation in the AVPR2 gene causing congenital
Asparaginase-induced hyperglycaemia may cause diabetic ketoacidosis or
nephrogenic diabetes insipidus
hyperosmolar hyperglycaemic nonketotic syndrome which can be fatal. It is
Tugce Karaduman1, Merve Ozcan1, Aslı Celebi Tayfur2, Emel Saglar1,
recommended a frequent assessment of glycaemia in these patients. Its occurrence
Beril Erdem1, Dilara Sahin1, Aysun Caltık Yılmaz2, Bahar Buyukkaragoz2,
usually does not lead to suspension of therapy. Hyperglycaemia frequently gets
Ayse Derya Bulus3 & Hatice Mergen1
better despite continuous use of asparaginase.
1Hacettepe University, Faculty of Science, Department of Biology, Ankara,
DOI: 10.1530/endoabs.49.EP816
Turkey;2Kecioren Training and Research Hospital, Pediatric Nephrology,
Ankara, Turkey;3Kecioren Training and Research Hospital,
Infant Endocrinology Clinic, Ankara, Turkey.
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease caused by a defect
in the vasopressin V2 receptor in renal collecting duct cells which is encoded by
EP817
the AVPR2 gene (Xq28). More than 200 mutations have been found comprising
P3NP has high-normal values in GHD children and correlates
missense, nonsense, small insertions and deletions, large deletions and complex
negatively with IGF1
rearrangements in AVPR2 gene to date. In this study, a 6-year-old boy was
Mariana Costache Outas1,2, Camelia Procopiuc3, Andra Caragheorgheopol3
referred to the Pediatric Nephrology Department of Kecioren Research and
1,4
& Simona Fica
Training Hospital for abnormal fluid intake (5 l/day) and diuresis (4.3 l/day)
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
congenital heart defects
(29%), renal malformations
(26%), autoimmune
2Coltea Clinical Hospital, Bucharest, Romania;3CI Parhon National
thyroiditis (17%) and celiac disease in one patient. Sixty-nine percent (nZ24)
Institute of Endocrinology, Bucharest, Romania;4Elias Emergency
were eligible for growth hormone (GH) treatment. Among these, 13 reached their
Hospital, Endocrinology Department, Bucharest, Romania.
final stature with a variation of the mean z-score from K2.78 (K4.38-K1.31)
before to K2.16 (K3.85 to 0.00) after treatment. Among patients older than 12
years (nZ21), in 62% puberty was induced by transdermal oestrogens. One
Aim
patient had two spontaneous pregnancies.
Procollagen type III N-terminal peptide (P3NP) occurs during type III collagen
Conclusions
synthesis. Previous studies about the GH misuse in athletes proved the P3NP as a
In our study treatment with GH showed improvement of the height z-score. Some
growth hormone (GH) responsive biomarker. We evaluate the P3NP levels and
girls were diagnosed very late and some of them after attended final height
correlate with IGF1 depending on GH status.
without GH treatment. It is essential to be alert to the main clinical manifestations
Subjects and Methods
of the syndrome and provide an earlier diagnosis to optimize the treatment.
We determined P3NP levels in 81 prepubertal children (35 girls) with a mean age
DOI: 10.1530/endoabs.49.EP818
of 6.2 y.o [3.37-9.95]. The group consists of 37 subjects with normal height, 18
subjects with growth hormone deficiency (GHD) and 26 subjects with non-GHD
short stature. We measured P3NP with a commercially available (for research
purpose) ELISA kit (catalog code: DL-PIIINP-Hu) with the detection range 62.5-
4000 pg/ml.
Results
In 50 subjects with values of IGF1 below 0 SDS, we found a negative correlation
of P3NP and IGF1 (rsZK0.292, PZ0.039). Even not statistically significant,
P3NP correlate negatively with height-SDS (rsZK0.210, PZ0.144). 26 values
of P3NP were out of the reference range for this biomarker. Five of these records
belongs to GHD subjects with conditions that can explain high P3NP levels
Pituitary - Basic
(hypothyroidism in the context of multiple pituitary deficiencies, trauma or
inflammation). We analyzed 55 registrations with P3NP in the normal range
EP819
available for the whole group, according to GH status. We found higher P3NP
Non-functioning pituitary adenomas: association between
levels, expressed as median of SD in the GHD group compared to normal stature
clinical-pathological and molecular parameters
children
(MZ0.7, nZ9 vs MZK0.17, nZ28) and this difference was
Ana Barrera-Martín1, María-Carmen Vázquez-Borrego2, Ángel Rebollo-
statistically significant UZ70.5, zZ1.96, PZ0.049).
Román1, Pedro-Blas García-Jurado3, Paloma Moreno-Moreno1,
Conclusion
María-Rosa Alhambra-Expósito1, Álvaro Toledano-Delgado4,
The lack of GH-IGF1 effect in GHD children could lead to normal -high levels of
Justo-P Castan˜o2, María-Ángeles Galvez-Moreno1 & Raúl-M Luque2
P3NP because this biomarker of collagen synthesis is not effectively incorporated
1Endocrinology Service, Hospital Universitario Reina Sofia, Córdoba,
into collagen supportive tissues.
Spain;2IMIBIC/HURS, Department of Cell Biology, Physiology and
DOI: 10.1530/endoabs.49.EP817
Immunology, University of Cordoba; CIBER Fisiopatología de la Obesidad
y Nutrición (CIBERobn); Campus de Excelencia Internacional Agroali-
mentari, Córdoba, Spain;3Radiology Service. Hospital Universitario Reina
Sofia, Córdoba, Spain;4Neurosurgery Service. Hospital Universitario Reina
Sofia, Córdoba, Spain.
Non-functioning pituitary-adenomas
(NFPAs) represent the most common
pituitary tumor-type. To date, there are not clinical, biochemical, anatomo-
pathological, immuno-histochemical or molecular parameters useful to predict
their remission. Therefore, the aim of this study was to evaluate the potential
EP818
relationship between the clinical, biochemical and pathological characteristics of
patients with NFPAs, the expression profile of these tumours and the clinical
Turner Syndrome (TS): overview of surveillance in a tertiary care
outcomes during their follow-up. An observational/retrospective-study of patients
hospital
with NFPAs evaluated between January 2002-December 2015 was implemented
Ekaterina Popik, Catarina Matos de Figueiredo, Joana Freitas,
at our hospital, by collecting a complete set of clinical/biochemical/radiological-
Helena Cardoso, Maria João Oliveira & Teresa Borges
data from patients
(nZ34; 50% women; age: 56.2G11.9 years-old), and
Centro Materno-Infantil do Norte, Centro Hospitalar do Porto, Oporto,
anatomopathological and molecular (26 genes measured by qPCR) data from the
Portugal.
tumours. Mean follow-up of patients: 5.2G3.9 years. Symptomatology: 38.2%
campimetric alterations, 35.3% headache and 11.8% symptoms derived from
Introduction
hormonal deficits. A predominant expression of Dopamine-receptor 2 (DRD2)
Turner syndrome is one of the most common human chromosomopathy and
followed by somatostatin-receptors (sst) 3 and 2 was found. Furthermore, a
represents an important cause of short stature and ovarian insufficiency. It is
consistent increase in the expression of the majority of receptors analyzed
caused by total or partial loss of X-chromosome and its prevalence is about 1 in
between first and second surgery of the patients was observed. Interestingly,
2000-2500 live female births.
lower expression-levels of sst1 and sst3 were found in patients pre-treated with
Objectives
statins. Correlations between receptors and/or molecular markers (i.e. DRD2 with
To review the patients with TS followed in a Paediatric Endocrinology Unit since
AVPR1b, sst5TMD5 with serum testosterone-levels or sst5TMD4 with p53-
1999.
levels) were observed. Additionally, male sex, lower levels of pre-surgery cortisol
Methods
and testosterone and low sst5, AVPR1b and PTTG1 expression were associated
A retrospective study regarding diagnosis, course, treatment and current status of
with a higher curation of patients. Although further studies with a larger cohort of
patients with TS was performed, based on medical records’ review.
well-characterized patients are needed, our molecular and clinical data suggest
Results
that a putative pharmacological treatment for this pathology might be
Thirty-five female patients were included; 62.9% showed mosaic karyotype;
somatostatin-analogues with affinity for sst3
or dopamine agonists
(e.g.
5 patients had a prenatal diagnosis and 3 during the neonatal period and in the
pasireotide or cabergoline), that statin-treatment might influence the expression
others (nZ27) the mean age of diagnosis was 7.83 years (0.40-16.11). The main
levels of some sst-subtypes (e.g. sst3), and that some clinical/molecular markers
reason for investigation was short stature
(46%); other less frequent and
(i.e. sex, pre-surgery cortisol and testosterone levels and sst5/AVPR1b/PTTG1-
sometimes combined included failure to thrive (nZ5), primary amenorrhea
expression) could be associated with the curation of patients with NFPAs.
(nZ2), foot oedema at birth (nZ2), dysmorphic features (nZ6), cardiomyopathy
DOI: 10.1530/endoabs.49.EP819
(nZ1) and hepatitis (nZ1). The main associated morbidities were: learning
disabilities
(31%), hearing and visual problems (40 and 29%, respectively),
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Steroid Metabolism C Action
260.64G114.81 and 211.44G91.67, respectively, on chorus working day (Group
II) at similar hours. Saliva cortisol levels showed a 33% decrease in Group II
EP820
while an increase of 21% was detected in Group I (P!0.02). Also a reduction
Reference values for the urinary steroid metabolome: the impact of sex
14% in stres scores was observed in Group II (P!0.04); especially remarkable in
and age on human adult steroidogenesis
women, individuals with non-alcoholic, but smokers, active employeers and
Daniel Ackermann1, Belen Ponte2, Menno Pruijm3, Claudia H. d’Uscio1,
people who have less time engaged in music.
Idris Guessous4, Georg Ehret5, Fred Paccaud7, Antoinette Pechére-
Conclusion
Bertschi6, Pierre-Yves Martin2, Michel Burnier3, Bernhard Dick1,
We can say that individuals who perform a two-hour Turkish art music per week,
Bruno Vogt1, Murielle Bochud7 & Nasser A. Dhayat1
are affected positively by music different from the day of their normal life.
1Department of Nephrology and Hypertension, Bern University Hospital,
Particularly due to fact that mucic is very popular, cheap and easly applicable in
University of Bern, Bern, Switzerland and Department of Clinical Research,
daily life, it seems promising to use music in daily life as strategy for stress
University of Bern, Bern, Switzerland;2Nephrology Service, Department of
reduction.
Specialties of Internal Medicine, University Hospital of Geneva, Geneva,
DOI: 10.1530/endoabs.49.EP821
Switzerland;3Nephrology Service, University Hospital of Lausanne,
Lausanne, Switzerland;4Department of Community Medicine, Primary
Care and Emergency Medicine, University Hospital of Geneva, Geneva,
Switzerland;5Cardiology Service, Department of Specialties of Internal
Medicine, University Hospital of Geneva, Geneva, Switzerland;
6Endocrinology Service, Department of Internal Medicine Specialties,
EP822
University Hospital of Geneva, Geneva, Switzerland;7Institute of Social
Inhibition of 11b-hydroxysteroid dehydrogenase 2 by the fungicides
and Preventive Medicine, University Hospital of Lausanne, Lausanne,
itraconazole and posaconazole
Switzerland.
Katharina Beck1, Denise Kratschmar1, Arne Meyer1, Daniela Schuster2 &
Alex Odermatt1
1
Division of Molecular and Systems Toxicology, Department of Pharma-
Background
ceutical Sciences, Pharmazentrum, University of Basel, Basel, Switzerland;
Urinary steroid metabolomics by GC-MS is an established method in clinic and
2Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular
research to describe steroidogenic disorders, but normative data are scarce.
Biosciences Innsbruck (CMBI), Computer Aided Molecular Design Group,
Methods
University of Innsbruck, Innsbruck, Austria.
The 24-hour urinary excretion of 40 steroid metabolites was measured by GC-MS
in 1128 adult participants of the Swiss Kidney Project on Genes in Hypertension
(SKIPOGH), a multicenter, family-based, cross-sectional study. Sex- and age-
Impaired
11b-hydroxysteroid dehydrogenase type
2
(11b-HSD2)-dependent
specific reference ranges were created in the units mg/mol Creatinine and
cortisol inactivation can lead to electrolyte dysbalance, hypertension and
mg/24 hours.
cardiometabolic disease. Furthermore, placental 11b-HSD2 essentially protects
Results
the fetus from high maternal glucocorticoid levels, and its impaired function has
Most urinary steroids showed an age- and sex-specificity. An age- but no sex-
been associated with altered fetal growth and a higher risk for cardio-metabolic
specificity was found for etiocholanolone, 18-OH-11-dehydro-TH-corticosterone,
diseases in later life. Despite its important role, 11b-HSD2 is not included in
TH-cortisol, a-cortol, and b-cortol in the unit mg/mol Creatinine. No sex- but an
current off-target screening approaches. To identify potential 11b-HSD inhibitors
age-specificity was found for 20a-DH-cortisol in mg/24 hours and neither a sex-
amongst approved drugs, a pharmacophore model was used for virtual screening,
nor an age-specificity was found for TH-corticosterone and 18-OH-cortisol in
followed by biological assessment of selected hits. This led to the identification of
mg/24 hours.
several azole fungicides as 11b-HSD inhibitors, showing a significant structure-
Conclusions
activity relationship between azole scaffold size, 11b-HSD enzyme selectivity
Sex- and age-specific reference ranges for 40 steroid metabolites measured by
and inhibitory potency. A hydrophobic linker connecting the azole ring to the
GC-MS were established in a thoroughly characterized general Caucasian
other, more polar end of the molecule was observed to be favourable for 11b-
population and can be used in routine clinical work.
HSD2 inhibition and selectivity over 11b-HSD1. The most potent 11b-HSD2
DOI: 10.1530/endoabs.49.EP820
inhibition, using cell lysates expressing recombinant human 11b-HSD2, was
obtained for itraconazole (IC50 139G14 nM), its active metabolite hydroxyi-
traconazole (IC50 223G31 nM) and posaconazole (IC50 460G98 nM). Interest-
ingly, experiments with mouse and rat kidney homogenates showed considerably
lower inhibitory activity of these compounds toward
11b-HSD2, indicating
important species-specific differences. Thus,
11b-HSD2 inhibition by these
EP821
compounds are likely to be overlooked in preclinical rodent studies. Inhibition of
Does music effect the stress of daily life?
placental 11b-HSD2 by these compounds, in addition to the known inhibition of
Nevin Dinccag1, Coskun Oruc2, Sevim Oncul3, Sevda Ozel Yildiz4 &
cytochrome P450 enzymes and P-glycoprotein efflux transport, might contribute
Cengizhan Sonmez5
to elevated local cortisol levels, thereby affecting fetal programming.
1Istanbul University, Istanbul Faculty of Medicine, Endocrinology and
DOI: 10.1530/endoabs.49.EP822
Metabolism Division, Istanbul, Turkey;2Istanbul University, Istanbul
Faculty of Medicine, Biochemistry Division, Istanbul, Turkey;3Istanbul
University, Istanbul Faculty of Medicine, Physciatry Department, Istanbul,
Turkey;4Istanbul University, Istanbul Faculty of Medicine, Bioistatistics
and Medical Informatics Department, Istanbul, Turkey;5Bahcesehir Music
Society, Istanbul, Turkey.
EP823
Cortisol levels and thyroid hormones in surgical patients with different
sensitivity to pain
Introduction
Anatoli Zhudro
It’s assumed that music has health beneficial effects by its potential stres-reducing
Republican Clinic Medical Center of the Presidential Administration,
life. There are some reports that chorists in choral soceity are influenced by music
Minsk, Belarus.
positively during their activities.
Research design and methods
37 healthy volunteers who perform Turkish art music in Bahcesehir Music
Objective
Society with mean age 50.3G10.3yrs, were included into this study. The state and
To determine the intraoperative levels of cortisol and thyroid hormones in
trait anxiety status of chorists was evaluated by using a Likertscale at the time of
surgical patients with different sensitivity to pain.
beginning (19.00) and the end (21.00) of choir, on chorus working day. After each
Material and methods
assesments, chorists were asked to collect saliva samples for cortisol levels to be
We analyzed the individual sensitivity to pain in 94 people the day before surgery.
measured later by using electrochemiluminescence immunoassay. Participants
Patients were ASA 1-2. Age 46G10.2 years. We used a mechanical stimulus (1!5
were requested to repeat the same procedure at similar times of any day in their
mm wire with stop) and the visual analogue scale of 10 points (color, grayscale,
normal lives. All data was evaluated with SPSS 20 version.
10 fields, from light to black). Incentives applied to the base of the thumb. Patients
Findings
divided into 2 groups, first group - low sensitivity to pain (VAS 1-5). 2nd group -
Although results were within normal limits in all subjects, differences were
high sensitivity to pain
(VAS 6-10). All patients underwent laparoscopic
observed on normal and chorus activity days. While mean cortisol levels (ng/dL)
cholecystectomy under general anesthesia. Anesthesia consisted of premedica-
were detected as 248.69G140.50 and 286.11G179.50, respectively, at hours
tion, induction, myoplegia, intubation, ventilation with a mixture of oxygen
19.00 and 21.00 on the normal day of life (Group I); the levels were observed as
supply, nitrous oxide and sevoflurane, anodyne - fentanyl, paracetamol. We used
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
hemodynamic monitoring and ventilation system. Control thyroid hormones (T3,
oxidation substrate. Aim of this project was to understand whether T3 influence
T4, TSH) and cortisol before operation, 3 times during surgery and after surgery.
skeletal muscle metabolism during fasting.
Statistical analysis was performed using the software package Statistica 7.0
Methods
Results
Adult male BALB/C mice were food deprived for 48h (STV), and daily treated
In all patients, the level of thyroid hormones remained normal throughout the
with intraperitoneal injections of T3 (100 mg/Kg BW) (STVT3) or vehicle as
study period. Not observed any changes of thyroid hormone levels in patients with
controls. At the end of the experiments, Tibilias anteriors were collected and
both high and low sensitivity to pain. Plasma cortisol levels remained within the
firstly laminin stained sections were analyzed for myofiber sizes by IF
normal range in 92% of patients. In 8% of the patients (all patients in the second
microscopy. Secondly, the number of glycolytic, intermediate or oxidative fibers
group, the high sensitivity to pain) noted the excess of normal levels of cortisol.
per cross section area on NADH stained histological sections was analyzed.
After the start of operation of cortisol level was higher than baseline.
Mitochondria content, indicative of a more oxidative metabolism, was then
Intraoperatively, in patients with high sensitivity to pain of the plasma cortisol
analyzed by qRT Syber Green PCR for PGC-1a mRNA.
level was higher than in patients with low sensitivity to pain.
Results
Conclusion
As expected, laminin staining evidenced a reduction in Cross Sectional Area of
Perioperative levels of thyroid hormones and cortisol most surgical patients
the myofibers induced by fasting (STV), as a sign of atrophy. The cited reduction
remains within the normal range. Patients with high sensitivity to pain was higher
was significantly hampered by the presence of T3 in the STVT3 group. Secondly,
cortisol levels after starting operation as compared to the level of cortisol in
T3 was able to significantly reduce the shift in the metabolism towards a more
patients with low sensitivity to pain.
oxidative state (P!0.05) and a less glycolytic one (P!0.01) induced by fasting.
DOI: 10.1530/endoabs.49.EP823
Coherently, T3 reduced the increase in PGC-1a mRNA level induced by fasting in
the STV group (P!0.05).
Conclusions
The decrease of the amount in oxidative muscle fibers during T3 treatment in STV
agrees with a less expression of PGC-1a, a molecular marker of mitochon-
driogenesis and fatty acid oxidation. Therefore, T3 treatment during fasting seems
EP824
to exert a protective role on the metabolism of muscle fibers.
Ritonavir induced Cushing’s Syndrome in a patient under inhaled
DOI: 10.1530/endoabs.49.EP825
corticosteroids
Teresa Alves Pereira1, Inês Furtado2, Ana M Lopes1, Liliana Fonseca1 &
Isabel Palma1
1Endocrinology Department, Centro Hospitalar e Universitário do Porto,
Porto, Portugal;2Internal Medicine Department, Centro Hospitalar e
Universitário do Porto, Porto, Portugal.
EP826
Introduction
False memory in elderly patients with thyroid disease
Cushing’s Syndrome secondary to inhaled or topic corticosteroids is very rare,
Anna Golda1, Agnieszka Sawicka1, Agata Bielecka1 &
although there are reports of a link to cytochrome inhibitors. Ritonavir, a protease
Krzysztof Marczewski1,2
inhibitor used for treatment in human immunodeficiency virus (HIV) infection, is
1Department of Nephrology and Endocrinology Pope John Paul II Regional
a potent inhibitor of cytochrome P450 3A4.
Hospital, Zamosc, Poland;2Faculty of Health Sciences Lublin University of
The case
Economy and Innovation, Lublin, Poland.
A 41 years old man - with personal history of asthma, HIV infection diagnosed in
2002 and hepatitis C infection since 1999 - was sent to an endocrinology consult
in January/2015 for obesity investigation and orientation. The patient presents
Introduction
with a one-year history of truncal and facial obesity and global weakness of the
The phenomenon of false memory is quite prevalent among people with cognitive
lower limbs. Moreover, the patient presented with cushingoid facies, facial
impairment. Cognitive dysfunction and its relationship with the thyroid gland has
plethora, centripetal obesity and hypotrophic upper limbs. At that time, the patient
been described. In contrast, little is known about the phenomenon of false
was under therapy with ritonavir 100mg/day, salmeterol/fluticasone 50/250 mg
memory in patients with thyroid diseases. That is why we want to introduce our
two inhalations per day and a topic betamethasone lotion 0,5mg/g twice a week.
preliminary observation.
Morning total plasma cortisol levels were low
(0,6 mg/dl) and ACTH was
Method
suppressed
(5 pg/ml). Cosyntropin stimulation test confirmed a suppressed
Patients aged 64 to 90 years (average 77) with endocrine disorders were subjected
to tests for typical geriatric assessment and tests investigating the so-called. false
pituitary-adrenal axis. Consequently, ritonavir was concluded and the clinical
picture resolved progressively.
memory, that is. “remembering” the words that were not spoken, according to the
Conclusion
method Roediger and McDermott’s
The present case underlines the importance of cytochrome inhibitors in the
Results
modification of corticosteroid metabolism and their extended effect - as in
We investigated 31 patients, of which 17 had thyroid disease. All patients with
Cushing’s Syndrome.
thyroid diseases, “remembered the” unspoken words. The best result was only 6%
of the words false “recalled”, the worst result was 75%, on average, about 35%.
DOI: 10.1530/endoabs.49.EP824
This result did not differ significantly on the outcome of patients with other
endocrine disorders, but among them were two people without the presence of
false memory. We found a negative correlation between the results of the test of
false memory and mini mental status (P!0,01). We did not find significant
correlations between the results of the tests and TSH.
Conclusion
False memory may prove to be an important problem among older people with
Thyroid (non-cancer)
thyroid disease. Although its clinical significance needs further study.
EP825
DOI: 10.1530/endoabs.49.EP826
Thyroid hormone T3 protects skeletal muscle metabolism during
fasting in mice
Valentina Russi1, Sarassunta Ucci1, Camilla Virili2, Marco Centanni2,
Viviana Moresi3 & Cecilia Verga Falzacappa1,2
1Pasteur Institute, Rome, Italy;2Sapienza, University of Rome, Medical
surgical Sciences and Biotechnologies Department, Rome, Italy;3Sapienza,
University of Rome, Department of Anatomy, Histology, Forensic Medicine
and Orthopedic, Section of Histology, Rome, Italy.
EP827
Orbital disease primer for Endocrinologists-not always thyroid
Background
associated orbitopathy (TAO): a case vignette
Skeletal muscle is known to be a target of THs, regulating oxygen consumption,
Fotini Adamidou1, Christina Manani1, Panagiotis Anagnostis1,
fiber composition, calcium mobilization and glucose uptake. However, a possible
Thomas Georgiou1 & Kostas Boboridis2
role for THs in muscle homeostasis and cellular metabolism under pathological
1Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;
has never been investigated. Food deprivation induces skeletal muscle atrophy,
2Aristotle University of Thessaloniki, Ophthalmology Department,
causing metabolic changes, and forcing the tissue to utilize fatty acid as the main
Thessaloniki, Greece.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
“hand motion”, necessitating two cycles of rituximab at 375 mg/m2 each, two
TAO is a rare disease, seriously involving 5% of patients with autoimmune
weeks apart. Lymphocyte depletion was immediate and sustained and visual
thyroid disease. The clinical presentation may be difficult to distinguish from
acuity improved to 4/10 bilaterally. Three years later CASZ0 and the patient
other orbital conditions.
maintains a visual acuity of 2/10.
Case 1
Case 2
A 63-year-old woman was admitted to the Neurology Service for worsening
A 78-year-old male non-smoker presented with hyperthyroidism initially thought
diplopia over the previous six months, with a working diagnosis of myasthenia
to be due to toxic multinodular goiter and had thyroidectomy four months later.
gravis or multiple sclerosis. The Endocrine Service was consulted because of a
An incidental papillary thyroid carcinoma measuring 1.05 cm, insular type, was
long history of Hashimoto’s thyroiditis. The patient was euthyroid on thyroxine
found at histology in the right lobe. He was referred for management of GO one
replacement. Clinical activity score was 0, but there was restriction in elevation of
month postoperatively, characterized by retrobulbar pain, chemosis and diplopia,
the right eye. Orbital MRI demonstrated thickening of the right inferior rectus.
CASR7, loss of color vision and visual acuity of 1/10 bilaterally. He received
The diagnosis of TAO was made and the patient received intravenous
pulsed methylprednisolone to a cumulative dose of 8 g and orbital radiotherapy,
methylprednisolone with symptomatic improvement.
resulting in mild improvement in inflammation, but worsening of the acuity to
Case 2
light perception on the right only, with relative afferent pupillary defect on the left
A 48-year-old man with a history of Crohn’s disease, was referred for presumed
and fixed globes. The patient then received two infusions of rituximab of 500 mg
TAO, with severe diplopia, right retrobulbar pain and exophthalmos. He was
two weeks apart. He recovered vision to 2.5/10 in the right eye, which allowed his
euthyroid, with negative thyroid antibodies. Orbital MRI demonstrated
return to independent living. He subsequently received 100mCi131I without GO
thickening of all extraocular muscles of the right eye. A diagnosis of orbital
relapse.
myositis was made. The patient received 1.5g intravenous methylprednisolone
Conclusion
with marked improvement, but a month later presented with a red left eye and
Rituximab therapy can benefit vision and quality of life in refractory, severe GO.
diplopia. Orbital CT demonstrated thickening of the superior oblique and the
DOI: 10.1530/endoabs.49.EP828
medial rectus. The patient again received intravenous methylprednisolone with
complete remission and remains asymptomatic from his orbital and bowel disease
one year later.
Case 3
A 45-year-old woman was referred to the Endocrine Service with right sided
EP829
ptosis, for presumed TAO. She was euthyroid, with negative thyroid antibodies.
Evaluation of clinical performance of a new immunoassay in the
Eye exam was normal except for right-sided ptosis. Orbital MRI was normal. On
determination of thyroid stimulating immunoglobulins (TSI)
further questioning, the patient admitted having had botulinum toxin injections on
Isaura Rodrigues & Conceicao Godinho
the forehead and right brow a week before.
Centro Hospitalar Lisboa Central, Lisbon, Portugal.
Conclusion
The differential diagnosis and management of orbitopathy often relies on the
Endocrinologist and spans the spectrum of divergent medical specialties.
Introduction
DOI: 10.1530/endoabs.49.EP827
Anti-TSH receptors (TRAb) are an important marker in the differential diagnosis
of the etiologies of hyperthyroidism. They detect serum TSH receptor
immunoglobulins that interact with the TSH receptor without the functional
discrimination of stimulating from blocking antibodies. A new assay has recently
been released, that utilizes recombinant human TSH receptors (hTSHR) for the
specific detection and quantification of thyroid stimulating autoantibodies (TSI).
Objective
EP828
To evaluate the agreement of a new TSI test by method comparison with a TRAb
RIA, in the assessment of Graves disease (GD) in clinically well defined patients.
Management of very severe Graves’ orbitopathy with low dose
Material and methods
rituximab: report of two cases
We studied 162 patients regularly assisted at CHLC, Lisbon: 104 clinically
Fotini Adamidou1, Christina Manani1, Panagiotis Anagnostis1,
documented GD, 29 with other thyroid diseases and
29 with non-thyroid
Thomas Georgiou1, Kostas Boboridis2 & Marina Kita1
autoimmune disease. The serum samples were analyzed by a RiaRSR TRAb CT,
1Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;
traceable to WHO standard 90/672, and a new automatic chemiluminescent
2Aristotle University of Thessaloniki, Ophthalmology Department,
immunoassay, Immulite 2000 TSI (Siemens), traceable to WHO 2nd IS, NIBSC
Thessaloniki, Greece.
08/204.
Results
Introduction
At manufacturer TSI cut-off (0.55 IU/l), the clinical sensivity and specificity
Although Graves’ orbitopathy (GO) is common in the course of Graves’ disease,
were:
97.1
and
91.4% and at TRAb cut-off
(1.5 IU/l),
80.7
and
94.8%
dysthyroid optic neuropathy and corneal breakdown are rare. We describe two
respectively. The agreement of the results in the range of 0-1.5 IU/l revealed
cases of severe GO treated successfully with rituximab.
the occurrence of 17 positive results in TSI that were negative or gray in RIA.
Case 1
Conclusions
A 50-year-old female smoker with Graves’disease, presented with disfiguring
TSI may prove to be a useful method in clinical practice, by automating and
eyelid edema, exophthalmos and diplopia, preserved visual acuity and clinical
discriminating the functional activity of the TRAb.The high sensitivity of TSI
activity score (CAS) R 5. She received pulsed medroxyprednisolone to a total of
may be of great value in the diagnosis and follow up of GD and a good alternative
6 gr and standard orbital radiotherapy 3 months later with minor improvement.
to the RIA assay.
Thyroid status stabilized on methimazole combined with lithium and an
DOI: 10.1530/endoabs.49.EP829
uncomplicated thyroidectomy followed. However, visual acuity declined to
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations:
Pituitary and Neuroendocrinology
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Adrenal Cortex (to include Cushing’s)
Clinical Case Reports - Pituitary/Adrenal
EP830
EP832
The metabolic impact of ACTH-dependent versus ACTH-independent
Coexistence of TSH-secreting pituitary adenoma, primary
Cushing’s syndrome: a retrospective study of 99 patients
hyperparathyroidism and vitamin D deficiency
Mirela Diana Ilie1 & Corin Badiu1,2
Ibtissem Oueslati, Nadia Mchirgui, Karima Khiari & Néjib Ben Abdallah
1‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;
Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.
Introduction
Introduction
The simultaneous occurrence of central hyperthyroidism and primary hyperpar-
Although the metabolic impact of Cushing’s syndrome and hypercortisolemia are
athyroidism is extremely rare. Few cases of TSH pituitary adenoma in the setting
well known, the metabolic impact of ACTH is less established.
of multiple endocrine neoplasia type 1-associated syndrome were reported in
Objective
literature. Herein, we report a new case of TSH secreting pituitary adenoma
To identify differences in the glucidic, lipid and bone metabolism in ACTH-
particular by the coexisting of primary hyperparathyroidism and vitamin D
dependent versus ACTH-independent Cushing’s syndrome.
deficiency.
Methods
Observation
Retrospective, cross-sectional study of 99 patients with Cushing’s syndrome (54
A 76-year-old woman was referred to our Department with thyrotoxicosis and
with ACTH-dependent Cushing’s syndrome and 45 with ACTH-independent
elevated TSH levels. She presented with an important weight loss, intolerance to
Cushing’s syndrome) admitted to
‘C.I.Parhon’ National Institute of Endo-
heat, restlessness, flapping tremor, diarrhea and vomiting. On examination, she
crinology during 1998-2016. Clinical and paraclinical data were analyzed.
had a body mass index of 19 kg/m2, a clinical signs of dehydration, a blood
Results
pressure of 120/60 mmHg and an irregular pulse of 120 beats/min. Thyroid gland
Type 2 diabetes was found in 39% and prediabetes was found in 31% of the
was asymmetrically enlarged. No proptosis was observed. Electrocardiogram
patients in the ACTH-dependent group; in the ACTH-independent group 31% of
showed an arythmic tachycardia (120/min). Echocardiography revealed moder-
the patients had diabetes and 27% had prediabetes. Regarding lipid metabolism,
ate, asymmetric hypertrophy of the left ventricle. Systolic and diastolic functions
15% of the patients in the ACTH-dependent group were already on lipid-lowering
were preserved. Laboratory tests revealed central hyperthyroidism and primary
drugs compared with 29% in the ACTH-independent group; of the remaining
hyperparathyroidism. The 25 OH vitamin D was 4.6 mg/l (nr: 30-100 mg/l).
patients, who were not on lipid-lowering drugs, 63% had hypercholesterolemia
Serum creatinine was
131 mmol/l and creatinine clearance was
59 ml/min.
and 46% had hypertriglyceridemia in the ACTH-dependent group, compared with
Pituitary hormone explorations revealed hypogonadotropic hypogonadism with
75% having hypercholesterolemia and 50% having hypertriglyceridemia in the
normal lactotropin and corticotropin functions. Pituitary MRI scan showed an
ACTH-independent group. Osteoporosis was found in 31% of the tested patients
invasive pituitary adenoma measuring
21!15!17 mm and causing right
in the ACTH-dependent group and in 60% of the tested patients in the ACTH-
cavernous sinus invasion. Sestamibi parathyroid scintigraphy, cervical and
independent group.
thoracic magnetic resonance imaging were normal. Bone densitometry revealed
Conclusions
osteopenia. The patient was symptomatically treated with intravenous fluid
Lipid and bone metabolism were more affected in the ACTH-independent group,
replacement therapy, antithyroid drugs and beta blockers. Due to the patient’s
while glucidic metabolism was more affected in the ACTH-dependent group.
poor general condition, surgical approach of the TSH-oma was contraindicated
DOI: 10.1530/endoabs.49.EP830
and pituitary radiotherapy was considered.
Conclusion
Although vitamin D deficiency and primary hyperparathyroidism are common
disorders in the elderly population, their association to TSH pituitary adenoma is a
rare condition.
DOI: 10.1530/endoabs.49.EP832
EP831
ACTH-independent subclinical Cushing’s syndrome in patient with
acromegaly and adrenal incidentaloma
Maria Kurowska, Joanna Malicka & Jerzy Tarach
Department of Endocrinology, Medical University, Lublin, Poland.
EP833
Central diabetes insipidus in children: about eight cases
Introduction
Najoua Lassoued, Selmene Ouannes, Afef Jguirim & Mohamed Taher Sfar
It is well established that acromegaly is associated with increased risk of cancer.
Department of Pediatrics, CHU Taher Sfar, Mahdia, Tunisia.
However, it is currently unclear whether patients with acromegaly are at increased
risk of developing adrenal tumors and little is known about the association
between acromegaly and adrenal adenomas. The simultaneous occurrence of
Introduction
preclinical Cushing’s syndrome in patients with acromegaly and adrenal adenoma
Central diabetes insipidus (CDI) is a rare but potentially dangerous dysregulation
is extremely rare, and to our knowledge, so far only 5 such cases have been
of the water balance secondary to an arginine vasopressin (AVP) deficiency.
reported in literature.
Diabetes insipidus may have different manifestations in children compared to
Case report
adults. CDI is more common in children than nephrogenic diabetes insipidus.
73-year-old female with typical acromegalic appearance and acromegaly
Methods
suspected
34 years ago and recognized 16 years ago. She underwent non
A retrospective study of eight patients collected in the pediatric department of
complete transsphenoidal resection of somatotroph macroadenoma 15 years ago.
Mahdia.
Since neurosurgery she is chronically treated with long-acting somatostatin
Results
analogue, currently with lanreotide autogel 120 mg every 28 days. The current
The average age of patients was 2.8 years. The reason for hospitalization was a
GH level is 2.59 ng/ml [n:0.126-9.88] and IGF-1
252.2 ng/ml
[n:29-204].
prolonged fever in three patients, weight stagnation in three patients, severe
Approximately 3 years ago, a focal lesion 22!17 mm was detected in left adrenal
dehydration in one patient and headache and decreased visual acuity in one
gland, with a basal density (K)12HU (tumor density in the adrenal protocol:
patient. A history of polyuropolydypsic syndrome was found in five patients only.
(C)18HU, (C)10HU, (K)1HU respectively), suggesting adenoma. The patient
Diuresis was quantified at 9 ml/kg per hour on average. In biology, the plasma
had long-term arterial hypertension with no cushingoid features. An examination
osmolarity was
296.8 mosmol/Kg and the urinary osmolarity was
95.8
of pituitary-adrenal axis showed lowered ACTH levelZ4,76 pg/ml [n:7.2-63.6],
mosmol/kg with a urinary density at 1001 on average.Water deprivation test
a tendency to lose a circadian rhythm of cortisol [19.6-10.3 mg/dl] and the lack of
was carried out in four patients only confirming the diagnosis of CDI while the
cortisol secretion inhibition by 1 and 2 mg of dexamethasone [8.5 and 5.3 mg/ml,
four remaining patients had underwent directly a Desmopressin stimulation test.
respectively]. Daily excretion of urine cortisol was normal [172.5 and 123.6 mg;
The etiological assessment revealed a cerebral malformation in 4 patients, a
n:55.5-286.0].
Langerhans cell histiocytosis in three patients and a craniopharyngioma in one
Conclusion
patient. Hormonal assessment revealed adrenal insufficiency in one patient and
In order to determine the incidence and the relationship between the adrenal
thyrotropic insufficiency in two patients. Treatment with intranasal Desmopressin
tumors and acromegaly, standard evaluating of the adrenal glands is indicated in
was started at the mean dose of 0.125 ml/day in combination with the etiological
patients with acromegaly.
treatment. The evolution was favorable in most of our patients.
DOI: 10.1530/endoabs.49.EP831
Conclusion
The discovery of a CDI in children leads to an etiological investigation with an
urgent need to identify tumor pathologies (craniopharyngioma, dysgerminoma).
Infiltrative pathologies may be already known or reveal the disease (histiocytosis,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
and more rarely sarcoidosis). The objective of the management is to ensure a
EP835
normal water balance by normalizing the diuresis by the administration of
Pachydermoperiostitis associated with non secrettory pituitary
Desmopressin, to prevent any water retention and therefore any hyponatremia. It
macroadenoma in patient with toxic multinodular goitre
is associated with the treatment of the etiology of the CDI and the hormone
Ramazan Gen
replacement therapy of the associated anterior pituitary insufficiency.
Mersin University, Mersin, Turkey.
DOI: 10.1530/endoabs.49.EP833
Pseudoacromegaly is associated with acromegalic phenotype but normal insulin
like growth factor-1
(IGF-1) levels and suppressed growth hormone levels.
The reasons of this condition may be pachydermoperiostitis insulin resistance,
drug intake such as minoxidil and hypothyroidism (4). We describe pachy-
EP834
dermoperiostitis in a patient with hyperthyroidism and non-secretory pituitary
A hpothyroid case with pituitary hyperplasia mimicking TSHoma
macroadenomas.
H Sebile Dokmetas, Oguzcan Kinikoglu, Y Emre Altintas, Murat Atmaca &
Clinical case
Fatih Kilicli
A 62 year old man presented with palpitation, sweating and weight loss. Physical
Department of Endocrinology, Istanbul Medipol University, Istanbul,
examination revealed that’s multi nodular goitre, acral enlargement, gigantism,
Turkey.
fall in the left eye lid and thickening of the skin (heel-pad thickness was 27 mm on
right foot and 28 mm on left foot) Laboraory results revealed that serum st4
37.7 pmol/l
(12.8!n!20,4), TSH
!0.006 mIU/ml
(0.47!n!4.2), IGF-1
A 36-year-old female patient was referred to endocrinology outpatient clinic due
91.8 ng/ml (75(n(212). We re-evaluated GH-IGF-1 levels after treatment of
to increased TSH levels. Two years ago, she had been diagnosed and treated as
hyperthyroidism. After being euthyroid, GH level 0.379 ng/ml (1!n!9), IGF-1
Graves’ disease with propylthiouracil. Total thyroidectomy was performed in
88 ng/ml (75!n!212). GH level was suppressed after 100 gr oral glucose load.
another center due to ineffective medical treatment and oral levothyroxine sodium
Pituitary magnetic resonance imaging revealed 10.5 mm macroadenoma. All
(LT4) was started. During the follow-up her TSH levels were normal. Thirteen
pituitary hormone levels of patient was normal. Advanced investigation for
months after the last normal TSH value, she consulted the endocrinology
hyperinsulinemia, hypothyroidism and drug use revealed nothing. In contrast
outpatient clinic due to high levels of TSH (23 uIU/ml). She was questioned about
patient has hyperthyroidism. Two sons of the patients physical exam revealed
the proper usage of medication and the LT4 dose was increased. Despite the
acral enlargement, gigantism and thickening of the skin as a patient. GH levels,
higher dose of LT4
(400 mg/day), her TSH level was still increased at
IGF-1 levels and pituitary MRI of the sons of patient was normal. We considered
O100 uIU/ml. Although pituitary function test were normal, pituitary MRI
patient and two sons have autosomal dominant inheritance pachydermoperiostitis.
showed a macroadenoma with suprasellar extension. TSH a-subunit was
Conclusion
4.25 ng/ml (0-0.90 ng/ml). She was hospitalized for operation of TSHoma by
This is a very rare case of pseudacromegaly due to pachydermoperiostitis with
brain surgery department. After endocrinological evaluation request, we advised
nonfunctioning pituitary adenoma in patient with toxic multinodular goitre.
medical treatment because of more likely pituitary hyperplasia. She re-checked
up for ruling out possible malabsorption due to Celiac disease, but symptoms of
DOI: 10.1530/endoabs.49.EP835
malabsorption and Anti- Gliadin antibody (IgA) was negative. Also 200 mg oral
LT4 treatment was given and 2 hours later plasma free T4 level was measured due
to incompliance the medical treatment was not successful and it was found
increased levels of free T4. Intramuscular (i.m) LT4 200 mg/day treatment was
started. Ten days later her TSH level had decreased to 27 uIU/ml. After another
10 days of i.m LT4 treatment every other day, her TSH level decreased to
0.35 uIU/ml, while her fT4 and fT3 rose to slightly above the upper limit. A
control pituitary MRI showed significant regression of hyperplasia. During the
i.m LT4 treatment period the patient was consulted by a psychiatrist to explore
EP836
possible underlying psychiatric causes that could account for the previously
unsuccessful oral treatment and she was convinced to take oral LT4 properly.
Successful management of macroprolactinoma with aromatase
inhibitor in a patient with hypogonadotropic hypogonadism
Feyza Yener Ozturk, Esra Cil Sen, R Selvinaz Erol, Sezin Dogan Cakir,
Seda Erem Basmaz, Emre Sedar Saygili, Adnan Batman & Yuksel Altuntas
Department of Endocrinology and Metabolism, Sisli Hamidiye Etfal
Training and Research Hospital, Istanbul, Turkey.
Introduction
Hypogonadism persisting in man with macroprolactinoma requires exogenous
testosterone replacement therapy (TRT). But TRT may cause secondary elevations
of prolactin. We report here a case of macroprolactinoma and hypogonadotropic
hypogonadism with persistently high prolactin level after initiating TRT.
Case report
A 28 year-old male was admitted to outpatient clinic with complaints of
headache, low libido and blurred vision on left eye for three years. Magnetic
Figure 1 Pretreatment pituitary MRI image.
resonance imaging
(MRI) revealed a pituitary mass
(3.6!3.5!2.3 cm)
occupying entire sella, extending to sphenoid sinus, internal carotid arteries
(ICA), encasing right ICA and deviating stalk to left. Tumor compressed optic
chiasm causing bitemporal hemianopsia. Laboratory tests: prolactin: 133 ng/ml
(1/100 diluted prolactin: 77 ng/ml), cortisol:6.75 mg/dl (unresponsive to low dose
ACTH stimulation test), TSH:2.31 uIU/ml, fT4:0.47 ng/dl, fT3:1.06 pg/ml,
FSH:0.43 mIU/ml, LH:0.29 mIU/ml, t.testosteron!20 ng/dl, GH!0.05 ng/ml,
IGF-1:86.9 ng/ml (n:117-329). Nonfunctional adenoma and panhypopituitarism
was the diagnosis. Transnasal transsphenoidal adenomectomy was performed
after hormone replacement. Pathology revealed prolactin-secreting pituitary
adenoma with Ki67:1-2%. Cabergoline therapy (1 mg/week) was started on
postoperative
15th-day as prolactin was
323 ng/ml. Prolactin decreased to
80 ng/ml on the 2nd-month of therapy but t.testosteron was still low. TRT was
started intramuscularly per 3 weeks for complainment of low libido. After then,
prolactin level increased abruptly to 470 ng/ml. Despite gradual increament of
dosage to 4 mg/week, prolactin remained elevated (451 ng/ml). No enlargement
Figure 2 Pituitary MRI image after 3 weeks i.m LT4 treatment.
of residual mass was noted on new MRI. When TRT was quitted for 3 months,
prolactin decreased to 93 ng/ml. Then TRT was started with selective aromatase-
inhibitor anastrozole 1 mg/day. With cabergoline dosage decreased gradually to
DOI: 10.1530/endoabs.49.EP834
3 mg/week, prolactin decreased to 18.8 ng/ml and t.testosterone was normal
(300 ng/dl).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
asthenic patient with limited lesions of vitiligo and loss of libido. Water
Aromatisation of exogenous testosterone to estradiol and subsequent estrogen-
deprivation test showed the persistence of excretion of highly diluted amounts of
stimulated prolactin release may complicate the control of hyperprolactinemia.
urine, confirming the diagnosis of diabetes insipidus. The patient responded
Aromatase-inhibitor added to therapy may facilitate successful TRT for patients
spectacularly to therapy with sublingual desmopressin, with a decrease of diuresis
with macroprolactinoma.
to under 2500 ml/24 hours and an increase of urine gravity to 1010 under a dose
DOI: 10.1530/endoabs.49.EP836
of 60 mg!3/day, supporting the diagnosis of central diabetes insipidus. Serum
testosterone was of 1.01 ng/ml (normal range - between 2.6 and 10 ng/ml) and
low-normal LH and FSH (LHZ1.5 mU/l and FSHZ2 mU/l) suggesting the
presence of central hypogonadism. Serum fT4 was of 0.545 ng/ml (normal range
- between 0.9 and 1.9 ng/ml) with ‘normal’ TSH (1.6 mIU/l) suggestive for
central hypothyroidism. Corticotroph axis was undamaged (morning plasma
cortisol of 15.5 mg/dl and ACTH of 38.9 pg/ml). Osteodensitometry revealed
osteopenia. MRI investigation of the hypothalamo-pituitary region showed a
small pituitary gland (7/3/6 mm) accompanied by partial empty sella without
images of pituitary adenomas and absence of the native hypersignal of the
EP837
neurohypophysis. The pituitary stalk was deformed, taking a nodular shape with
dimensions of 4/5/6 mm. This image was highly suggestive for neuroinfundibular
Multifocal multisystem langerhans cell histiocytosis - a rare cause of
hypophysitis, most probably of autoimmune origin. Injections with testosterone
panhypopituitarism and diabetes insipidus - a case report
undecanoate every three months and daily oral supplementation of thyroid
Filip Gabalec1,2, Martin Simkovic1,2, Petra Kasparova2,3, Pavel Zak1,2 &
hormones added to desmopressin therapy significantly improved patient’s quality
Jan Cap1,2
of life. Autoimmune associations of the anterior and posterior pituitary are very
14th Department of Internal Medicine, University Hospital Hradec Kralove,
rare and may raise difficulties of diagnosis and therapeutic decisions.
Hradec Kralove, Czech Republic;2Faculty of Medicine Hradec Kralove,
Charles University, Hradec Kralove, Czech Republic;3The Fingerland
DOI: 10.1530/endoabs.49.EP838
Department of Pathology, Hradec Kralove, Czech Republic.
Introduction
Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a
very rare cause of sellar expansion. The clinical presentation can be
heterogeneous, from a single bone lesion to potentially fatal, widespread disease.
We describe the difficulties with the evaluation and the treatment of LCH.
Case
EP839
39 years old woman has had amenorrhea for 2 years and higher intake of fluids
Pituitary apoplexy while treating recurrence of Cushing’s disease with
(5-7 l/day) for 6 years. Non-functioning pituitary expansion with pituicytoma
Pasireotide
appearance was found on MRI. She was followed up for almost 3 years.
Birute Zilaitiene1,2, Aiste Kondrotiene3, Rasa Verkauskiene1,2,
Panhypopituitarism developed during the follow-up and replacement therapy
Lina Barsiene2, Robertas Knispelis2, Valdas Sarauskas4 &
with adiuretin, thyroxin and hydrocortisone was initiated. Finally, she underwent
Annamaria Colao5
biopsy for slow progression of sellar expansion - Langerhans cell histiocytosis
1Institute of Endocrinology, Lithuanian University of Health Sciences,
was confirmed histologically, with S100 a CD1a protein immunohistochemical
Kaunas, Lithuania;2Department of Endocrinology, Hospital of Lithuanian
positivity. Staging of the disease revealed suprasellar expansion, skeletal and
University of Health Sciences Kauno Klinikos, Kaunas, Lithuania;
retrobulbar infiltration, lymphadenopathy along the right internal carotid artery
3Lithuanian University of Health Sciences, Medical Academy, Kaunas,
and retroperitoneal and mediastinal lymphadenopathy with FDG avidity on
Lithuania;4Department of Pathological Anatomy, Lithuanian University of
18-FDG-PET/CT. She received five cycles of cladribine monotherapy with
Health Sciences, Kaunas, Lithuania;5Department of Molecular and Clinic
subsequent PET/CT restaging.
Endocrinology and Oncology, University of Naples Frederico 2,
Discussion
Endocrinology Sector, Naples, Italy.
Hypothalamus-pituitary-adrenal axis infiltration is present in up to 50% of LCH;
the most common disorder is diabetes insipidus (DI). The frequency of DI is 30-
Introduction
40% and 94% if other pituitary hormone deficiencies exist. The diagnosis can be
ACTH producing macroadenoma and pituitary apoplexy are rare in Cushing’s
tricky. The primary treatment modalities for LCH include local excision of the
disease. Somatostatin receptor agonist Pasireotide is indicated for the treatment of
lesion, corticotherapy, chemotherapy, radiotherapy, and imunnotherapy with anti-
patients with Cushing’s disease for whom surgery is not an option or has failed.
CD1a monoclonal antibodies. The data regarding the treatment of the central
We present a case of pituitary apoplexy in patient with recurrence of Cushing’s
nervous system involvement with LCH are very limited. Cladribine (2-CdA) is a
disease treated with Pasireotide.
promising agent in this setting as previously reported. Cladribine has good
Case
bioavailability in the CNS. A total of six cycles of cladribine monotherapy can be
38 years old female presented with quick weight gain, weakness, irregular
administered with respect to the good profile of toxicity in this indication.
menstruation, hirsutism, hypertension, newly diagnosed diabetes mellitus. High
However, prolonged neutropenia and respiratory infections led to premature
levels of blood cortisol and ACTH were observed. Cortisol was not suppressed
termination of the treatment in our case.
after 1 mg overnight dexamethasone suppression test (DST) and after low-dose
DST. High-dose DST suppressed cortisol secretion. Pituitary macroadenoma with
DOI: 10.1530/endoabs.49.EP837
diameter of 12!9 mm was diagnosed on MRI. Patient underwent transsphenoi-
dal surgery in January, 2012. In 2014 recurrence of Cushing’s disease was
diagnosed and second transsphenoidal surgery was performed in January, 2015.
In November, 2015 recurrent pituitary adenoma with diameter of 15!11 mm was
identified on MRI and hormonal tests confirmed hypercortisolemia with elevated
ACTH again. Therapy with Pasireotide was started in January, 2016. After 9
months of successful use of this medication patient was emergently hospitalized
to the Department of Endocrinology with an episode of an acute headache,
nausea, vomiting. Ptosis of a right eyelid and blurred vision occurred. Head MRI
EP838
demonstrated pituitary apoplexy and tumor spreading around right optical nerve
A rare association of autoimmune diabetes insipidus and hypophysitis
and optic chiasm. Pituitary apoplexy led to hypocortisolemia and need of
with partial pituitary insufficiency
hydrocortisone for several days. Two weeks later normal cortisol levels were
Livia Matei1, Corina Stefaroi1, Simona Mogos1,2 & Dumitru Branisteanu1,2
observed, hydrocortisone discontinued. Further treatment with Pasireotide 0.6 mg
1Endocrinology Clinic, ‘Sf. Spiridon’ Clinical Emergency Hospital, Iasi,
b.i.d. was continued. 4 months after pituitary apoplexy and further treatment with
Romania;2Department of Endocrinology, University of Medicine and
Pasireotide, ptosis and blurred vision regressed, eucortisolemia was achieved.
Pharmacy “Gr. T. Popa”, Iasi, Romania.
Conclusion
To our knowledge we report the first case of pituitary apoplexy in patient with
Cushing’s disease treated with Pasireotide. This complication might be related to
We present the case of a 40 year old man presenting at first consultation an
Pasireotide effect on tumorogenesis mechanisms.
‘idiopathic’ fast-onset and severe polyuro-polydipsic syndrome
(diuresis of
10 l/24 hours, with urine osmolality of less than 50 mOsm/kg and urine gravity
DOI: 10.1530/endoabs.49.EP839
lower than 1001). Clinical examination showed pallor and decreased pilosity at an
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP840
EP842
Hemodialysis patient with metastatic renal cell carcinoma to the
A hypopituitarism case diagnosed after sphenoid sinus mucocele
pituitary stalk presenting as hypopituitarism: an autopsy case
operation
Hisashi Sugano1, Riku Ino1, Yuko Dehara2 & Yoshinori Tuchiyama2
Betul Ekiz-Bilir1, Bulent Bilir2, Aysel Oz3, Halide Gunes-Ciftci4,
1Department of Diabetes and Endocrinology, Kochi Health Sciences Center,
Neslihan Soysal-Atile1 & Gulsah Elbuken5
Kochi, Japan;2Department of Clinical Nephrology, Kochi Health Sciences
1Endocrinology and Metabolic Diseases Division, Tekirdag State Hospital,
Center, Kochi, Japan.
Tekirdag, Turkey;2Internal Medicine Department, Medical Faulty, Namik
Kemal University, Tekirdag, Turkey;3Radiology Department, Tekirdag
State Hospital, Tekirdag, Turkey;4Department of Otolaryngology and Head
Introduction
and Neck Surgery, Tekirdag State Hospital, Tekirdag, Turkey;5Internal
Pituitary metastases occur in 1% to 4% of cancer patients in autopsy studies. The
Medicine Department, Endocrinology and Metabolic Diseases Division,
most frequent primary tumors are breast and lung tumors. Renal cell carcinoma
Medical Faculty, Namik Kemal University, Tekirdag, Turkey.
(RCC) is a rare cause of pituitary metastases, with only 25 previously reported
cases.
Case report
Introduction
A 77-year-old-man was admitted to our hospital because of acute progression of
Mucoceles-mucus containing benign cysts of paranasal sinuses- are common with
chronic renal failure presenting with appetite and weight loss in August 2014. He
an incidence of 1% but involvement of sphenoid sinus is much less common. In
underwent hemodialysis. His fasting blood glucose was low without any
this case report, we reported a patient presented with hypopituitarism after
symptoms. In 1998, he had undergone left nephrectomy and adrenalectomy,
sphenoid mucocele drainage operation.
and was diagnosed with a clear cell RCC. In 2001, lung metastasis was diagnosed
Case report
and he was treated with interferon therapy, which led to remission. In 2009, lung
A 59- year-old woman was admitted to our endocrinology out-patient clinics with
metastasis was observed again, but he declined treatment. He had hyperprolacti-
a complaint of fatigue over the past 2 months. One month prior to admission, she
nemia and hypopituitarism; levels of PRL: 292.8 ng/ml, free T4: 0.56 ng/ml,
had been internalized for about 10 days in our hospital’s infectious diseases
TSH: 0.953 mIU/ml, cortisol:
2.0 mg/ml, ACTH: 5.4 pg/ml, IGF1: 42 ng/ml.
clinics for fever of unknown origin. After extensive medical investigation, a
Magnetic resonance imaging revealed a 7!8!9 mm mass with a pituitary stalk
sphenoid sinus mucocele and pansinusitis had been diagnosed. An operation for
that compressed the optic chiasm without visual disturbance. Dynamic tests
drainage of the mucocele with endonasal surgical approach had been performed
showed hyporesponses of cortisol, LH, FSH, TSH, and GH. We considered pan-
and she had been externalized for follow-up with an attention card indicating that
hypopituitarism due to pituitary stalk metastasis from RCC but could not diagnose
her nasal cavity was in direct contiguity with the optic nerve. Three weeks after
it histologically. Diabetes insipidus was not recognized, probably owing to renal
the operation, she admitted to our clinics. The physical examination revealed that
failure. Hormone replacement was started with hydrocortisone and L-thyroxine;
her arterial blood pressure was 90/50 mmHg, heart rate was 108 bpm, respiratory,
his hypoglycemia and anorexia improved. In September
2015, he died of
abdominal, cardiac examinations were normal. Her skin was pale and minimal
pneumonia. The autopsy showed that the clear cell RCC had spread to the thyroid
pitting edema was detected. In her repeated laboratory examination, serum
gland, right lung, and pancreas in addition to the pituitary stalk.
cortisol levels were found to be less than
1 mg/dl. Coexisting secondary
Conclusion
hypothyroidism and GH deficiency were detected. The magnetic resonance
We reported a case of a hemodialysis patient presenting with a symptomatic
imaging of the pituitary region was revealed no tissue corresponding to the
pituitary metastasis from RCC. It is difficult to distinguish symptoms of
adenohypophysis. Following adequate replacement therapy with methyl-
hypopituitarism from nonspecific symptoms in a hemodialysis patient. In this
prednisolone and levo-thyroxine, her fatigue relieved. GH replacement therapy
case, we diagnosed an extremely rare pituitary stalk metastasis by autopsy.
was refused by the patient for its administration difficulty.
DOI: 10.1530/endoabs.49.EP840
Conclusion
For mucoceles involving sphenoid sinus, pre-operative and post-operative
endocrinological evaluation is essential.
DOI: 10.1530/endoabs.49.EP842
EP841
Effect of the addition of lanreotide autogel to the treatment of an
aggressive prolactinoma - a case report
Lucio Vilar1,2, Clarice Vilar2, José Luciano Albuquerque1,
Patricia Gadelha1, Ana Carolina Thé1, Erik Trovão1, Izabela Cardoso1,
EP843
Thaíse Cardoso1 & Ruy Lyra1
1Division of Endocrinology, Hospital das Clinicas, Federal University of
Coexistence of acromegaly and rheumatoid arthritis: presentation of
Pernambuco, Recife (Pernambuco), Brazil;2Endocrine Research Center of
three cases
Pernambuco, Recife (Pernambuco), Brazil.
Reyhan Ersoy1, Nagihan Bestepe2, Sevgul Faki1, Cuneyt Bilginer1,
Didem Ozdemir1, Sukran Erten3 & Bekir Cakir1
1Department of Endocrinology and Metabolism, School of Medicine,
Case report
Ankara Yildirim Beyazıt University, Ankara, Turkey;2Department of
A giant prolactinoma
(sizeZ5.2!4.1!3.2 cm; PRLZ6 400 ng/mL) was
Endocrinology and Metabolism, Ankara Ataturk Education and Research
diagnosed in an amenorrheic 19-year old girl who presented to the emergency
Hospital, Ankara, Turkey;3Department of Rheumatology, School of
room complaining of headaches and bilateral decrease in visual acuity for
Medicine, Ankara Yildirim Beyazıt University, Ankara, Turkey.
10 days. The patient was started on cabergoline (CAB) in progressive doses up to
3 mg/week. PRL levels decreased from 6 400 to 4 600 ng/dl within 60 days, with
improvement of visual complaints and visual fields defects. The dose was
Introduction
subsequently increased up to 6 mg/week over the next 6 months but PRL did not
Musculoskeletal system is widely affected in acromegalic patients which might
normalize (1 840 ng/dl) and amenorrhea persisted. A new pituitary MRI was
cause difficulties in the diagnosis and treatment of inflammatory rheumatological
performed revealed a w50% tumor reduction. Six months later, worsening of
diseases. Here, we report coexistent rheumatoid arthritis
(RA) in three
visual fields and a 20% increase in tumor volume were detected, whereas PRL
acromegalic patients presenting with continuing joint and back pain although
levels increased to 2 270 ng/ml. A transsphenoidal surgery (TSS) was therefore
acromegalic state was in remission.
undertaken (Ki-67 expressionZ8%), which led to a w30% reduction of tumor
Case 1
volume whereas PRL levels decreased from 2 270 to 1 210 ng/dl within 4 months.
A 64 years old female patient with acromegaly and macroadenoma had undergone
CAB was restarted but PRL did not normalize (520 ng/dl), despite the use of
transsphenoidal surgery 11 years ago and radiosurgery 7 years ago because of
doses up to 4 mg/week (maximal tolerated dose) for 6 months, and amenorrhea
clinical and laboratory evidence of disease. The patient got into remission 3 years
persisted. Lanreotide autogel
(120 mg every 28 days) was added to CAB
after radiosurgery. Because she had morning stiffness and symmetrical pain and
(4 mg/week). The combined treatment was well tolerated and lead to decrease of
swelling in interphalangeal joints, she was consultated with rheumatology and
PRL levels to 91 ng/ml (NR: 2.8-29.2) within 8 months, as well as to resumption
diagnosed as seronegative RA. Her complaints improved dramatically at the
of a regular menstrual cycle.Moreover, the combination of CABClanreotide
second month of methotrexate, prednisolone and indomethacin treatment.
autogel enabled further tumor shrinkage but invasion of both cavernous sinuses
Case 2
persisted. CAB dose could be subsequently reduced to 3 mg/week.
A 62 years old female had undergone transsphenoidal surgery for acromegaly 12
years ago. She had been treated with conventional radiotherapy and radiosurgery
DOI: 10.1530/endoabs.49.EP841
4 and 10 years after diagnosis, respectively because remission could not be
achieved by medical treatment which had been stopped about a year after
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
radiosurgery. She had symmetrical pain, swelling and deformities in inter-
Introduction
phalangeal and metacarpal joints. Seronegative RA was diagnosed and
Cyclic Cushing’s syndrome is a rare disorder, characterized by repeated episodes
methotrexate and prednisolone were started.
of cortisol excess interspersed by periods of normal cortisol secretion ranging
Case 3
from days to years. It remains a difficult diagnostic challenge in endocrinology,
Acromegaly had been detected 13 years ago in a 57 years old female. Because she
we report a case.
had refused surgery, she had been treated with conventional radiotherapy and cure
A case report
had been achieved in a year. She complained morning stiffness, back pain and
The patient was 41 years old woman, she presented in 2012 a period of
pain and swelling in hand joints. She was diagnosed to have seropositive RA and
symptomatic hypercortisolism. Urinary free cortisol was elevated to 113 mg/24,
treated with methotrexate, sulfosalazine and indomethasine.
Low-dose dexamethasone testing was negative, ACTH was elevated to
Conclusion
20.2 pmol/l, the high-dose dexamethasone suppression test was positive, a
Symptoms related with RA might be confused with musculoskeletal symptoms
pituitary MRI and a thoraco pancreatic scanner were normal; These finding led us
seen in acromegaly. Detailed rheumatological physical examination and
to an ACTH-dependent Cushing’s syndrome. The patient was revaluated 5
immunological evaluation might be helpful to display concomitant rheumatolo-
months later and she was clinically and biochemically better. Six months later she
gical disease in acromegalic patients with ongoing musculoskeletal complaints
presented relapsed symptoms and a biochemical recurrence of hypercortisilosm
despite achievement of treatment targets.
(high urinary cortisol:
125.7 mg/24
and negative Low-dose dexamethasone
DOI: 10.1530/endoabs.49.EP843
testing). In 2015 the patient presented a sudden tumor syndrome, pituitary MRI
revealed an intrasellar arachnoidocele that was in favour of the apoplexy of an
adrenocorticotropic pytuitary adenoma. The patient was revaluated 9 months later
and she was clinically better, The Urinary free cortisol was normal (20 mg/24).
Discussion
Cyclic Cushing’s syndrome is characterized by rhythmic fluctuations in
EP844
glucocorticoid production, both clinical and biochemical spontaneous remissions
Case of TSH secreating pituitary adenoma (TSHOMA) where course
may occur in patients with this disorder. Our patient presented two periods of
was modified by coexistant autoimmune hypothyroidism
normal glucocorticoid production and two periods of hypercortisolism. Causes of
Ameya Joshi1, Rajesh Ghagre2, Premlata Varthakavi3, Pradeep Dalwadi3 &
cyclic Cushing’s syndrome are multiple dominated by pituitary adenoma. The
Nikhil Bhagwat3
biological and radiological investigations in this case and therfore the subsequent
1Bhaktivedanta Hospital and Research Institute, Mira Road, Thane,
evolution enabled a diagnosis of a Cushing’s syndrome spontaneously regressive
Maharashtra, India;2Ashtavinayak Hospital, Borivali, Mumbai,
by the apoplexy of pytiutary adrenocorticotropic adenoma. Clinicians should be
Maharashtra, India;3Topiwala National Medical College and BYL Nair
aware that hypercortisolism may occur periodically and the duration of the
Charitable Hospital, Mumbai Central, Mumbai, India.
periods of normal and abnormal cortisol secretion can vary significantly, so the
correct diagnosis can be a challenge in clinical practice.
DOI: 10.1530/endoabs.49.EP845
Introduction
TSHOMAs are rare pituitary tumors with prevalence of 1-2 cases per million.
We present a case of of TSHoma where the course was complicated by the
coexistence of autoimmune hypothyroidism.
Case
41 year old male presented with fatigue, lethargy and palpitations. On screening
was found to have raised t3 - 216.30 ng/dl (N-70-204 ng/dl), t4 - 12.10 mg/dl(N-
4.2-11.6 mg/dl) and TSH - 27.55 uIU/ml (0.2-5.7 uIU/ml). Further evaluation
revealed raised free t3 (FT3), free t4 (FT4) and TSH (column 1, Table 1), raised
anti thyroid peroxidase antibodies and negative TSH receptor antibody, normal
cortisol - 10.8 mg/dl (N-5-25), testosterone - 769.73 ng/dl (N-275-900), prolactin
EP846
- 18.89 ng/ml (5-25), IGF1 - 124 ng/ml (64-210) levels. Thyroid function of first
Breast cancer and newly discovered non-secretor pituitary mass- as risk
degree relations was normal. SHBG - 78.20 nmol/l (N-11.2-78.1) and alpha
of metastases?
subunit levels - 3.8 ng/ml (0.1-0.5) were raised. TSH concentration significantly
Ana Valea1, Iulia Oprisor2, Mara Carsote3, Dan Dumitru Pop4,
reduced 5 hours after single octride dose as well as after three doses of 100 mg
Andra Morar5, Cristina Ghervan1 & Carmen Emanuela Georgescu1
octride over 24 h. MRI confirmed presence of pituitary macroadenoma 2.4!
1I.Hatieganu UMPh & Clinical County Hospital, Cluj-Napoca, Romania;
1.2!1.2 cm abutting the chiasma (visual fields normal). Patient was subjected to
2Clinical County Hospital, Cluj-Napoca, Romania;3C.Davila UMPh &
transsphenoidal surgery. The adenoma immunostained positive for TSH, was also
I.Parhon National Institute of Endocrinology, Bucharest, Romania;
positive for p53 with MIB index 3-5%. Patient FT3, FT4 and TSH was low 2
4Oncology Institute, Cluj-Napoca, Romania;5Clinical Hospital of Infectious
weeks post surgery and 25 mg thyroxine was started. Follow up report at 6 weeks
Diseases, Cluj-Napoca, Romania.
showed low FT3, FT4 and raised TSH levels after which thyroxine was stepped
up. Patient did not need any other hormone replacement.
Introduction
Even if breast cancer is rare cause of pituitary metastases, the diagnosis of a
pituitary adenoma, shortly after surgery for breast cancer, raises suspicion of a
Table 1 Serial free t3 free t4 and TSH levels.
possible secondary determinations.
Material and method
After 3
Post
This is a case report revealing the medical history and endocrine profile of a
After
doses of
Post
Post
surgery
female with breast cancer and pituitary macroadenoma.
5 h of
100 mg
surgery
surgery
12
Baseline octride
octride
2 weeks
6 weeks
weeks
Case data
A 64-year old non-smoking female (with menopause at age of 52), who had
Free t3
4.86
1.19
1.1
2.7
undergone treatment for breast cancer (diagnosed at the age of 60), with left
(1.7-3.7 pg/ml)
radical mastectomy pT2N0M0 L0 V0 Pn0 R0, followed by adjuvant radiation
Free
1.83
0.53
0.62
1.12
treatment and aromatase inhibitor hormonal treatment, was admitted for
t4 (0.7-1.8 ng/ml)
TSH
25.5
13.8
7.6
0.1
54
3.82
headache, dizziness, diplopia, and narrowed visual field. Pituitary MRI performed
(0.2-5.7 uIU/ml)
pointed a 40/26/36 mm-sized mass of oval shape, with intra and extra-sellar
expansion. Endocrine evaluation indicated low levels of serum gonadotropins
(FSH of 10.5 U/l, normal: 30-150 U/L and LH of 1.6 U/l, normal of 8.2-41 U/l),
DOI: 10.1530/endoabs.49.EP844
low FT4 levels (free thyroxine of 0.61 ng/dl, normal: 0.89-1.76 ng/dl), normal
levels of morning plasma cortisol
(of
19.8 mg/dl, normal:
5-25 mg/dl), and
moderate increase of prolactin (24.4 ng/ml, normal:1.3-20 ng/mL). Thyroxine
substitution therapy was initiated and followed by transsphenoidal adenomect-
omy. Histopathology revealed a mixed pituitary adenoma. Assessement
EP845
performed three month after surgery highlighted persistent hyperprolactinemia
(of 22.9 ng/ml), central hypogonadism (FSH of 10.1 U/l, LH of 2.6 U/l), normal
Cyclic Cushing’s syndrome: a diagnostic challenge
FT4 levels (of 0.95 ng/dl), and persistent pituitary mass (of 36/21/30 mm) on
Elmghari Ghizlane, Elbahi Meryam, Rafii Sana & Elansari Nawal
MRI. The patient will be further followed-up by a multidisciplinary team
Faculty of Medicine and Pharmacy, Marrakech, Morocco.
regarding endocrine and oncologic profile.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
46), basal cortisol: 3.4 mg/dl (n:5-29), growth hormone: 2.25 ng/ml and IGF1:
This case emphasizes that diagnosis of pituitary macroadenoma can be difficult
440 ng/ml (n:70-212). Hypophyseal-thyroid and hypophyseal-gonadal axis were
when occurs in the context of a pre-existing breast cancer. Intensive follow-up is
normal. GH levels measured 30-60-90 and 120 min after oral 75 g glucose
necessary for specific treatment.
tolerance test were
2.16,
1.65,
1.5
and 1.8, respectively. The patient was
DOI: 10.1530/endoabs.49.EP846
diagnosed with acromegaly and intramuscular octreotide 20 mg/month, pre-
dnisolone 5 mg in the morning and 2.5 mg in the evening were initiated before
hypophyseal surgery. Left upper lobectomy of the left lung was performed and
pathologic examination of surgical material revealed squamous cell carcinoma.
VinorelbineCcisplatin chemotherapy was initiated and the patient was scheduled
for hypophyseal surgery.
EP847
DOI: 10.1530/endoabs.49.EP848
Meningoencephalitis as the first clinical sign of a pituitary macro
adenoma: a case report
Ghizlane Elmghari, Ilham Bouizammarne & Nawal Elansari
Department of Endocrinology, Diabetes and Metabolic Diseases CHU
Mohamed VI, Marrakesh, Morocco.
Introduction
The classical revealing manifestations of a pituitary adenoma are represented by
EP849
the combination of a tumor syndrome and endocrine syndrome. The occurrence of
meningoencephalitis as a mode of revelation of a macroadenoma is exceptional.
Case
Abstract withdrawn.
Mr. M.O, 36 years old, with no significant medical history, brutally presented
severe headaches, vomiting, behavioral disorder with fever and bilateral
decreased visual acuity. On examination, the patient was conscious, febrile to
39.8
with nuchal rigidity. At presentation: leukocytosis at
18 000/m3, a
C-reactive protein at 69 mg/l. The head CT scan showed bilateral areas of hypo
density with Intra-and suprasellar invasive lesional process. The magnetic
resonance imaging showed a pituitary macroadenoma 30!32 mm invading the
sphenoid sinus, the right cavernous sinus and elevating the optic chiasm. The
cerebrospinal fluid analysis showed a lymphocytic liquid with elevated protein
and normal glucose level. Culture was negative as well as herpes simplex virus
EP850
PCR. The biological analysis of endocrine hormones balance objectived a pan
Temozolomide alone or in combination with bevacizumab and
hypopanpituitarisme insufficiency. The patient received ceftriaxone, acyclovir,
capecitabine in the treatment of atypical pituitary adenomas - own
replacement therapy and was scheduled for surgery.
experience
Discussion
Maria Kurowska, Joanna Malicka & Jerzy Tarach
Meningoencephalitis is a rare presentation as first manifestation of macro-
Department of Endocrinology, Medical University, Lublin, Poland.
adenoma. In literature, only three cases of Meningoencephalitis were reported as
Introduction
revealing macroadenomas. We illustrate this observation through an unusual and
Atypical pituitary adenomas are tumors refractory to conventional therapy and
serious form of revelation of a macroadenoma.
characterized by a tendency to rapid progression and high recurrence rate. The
DOI: 10.1530/endoabs.49.EP847
aim of the study was to summarize our experience in treatment of atypical
pituitary adenomas with temozolomide (TMZ).
Material
5 patients (3F;2M) aged 44-58 (mean 52.4G5.4) years treated in 2013-2016. We
analyzed the results, tolerance and side effects of TMZ.
Results
EP848
In three patients (1F;2M) atypical corticotroph adenomas were diagnosed (two
A rare case with acromegaly: increased hypophyseal FDG uptake in
Nelson’s syndromes, one Crooke’s cells adenoma), in 1F-prolactinoma resistant
PET/CT performed for lung cancer staging
to dopamine agonists and in 1F-type 3 silent adenoma (GHC, PRLC). The
Veysi Asoglu1, Ece Celik2, Mehmet Celik3, Buket Yilmaz Bulbul3,
disease duration ranged 3-23 years (mean 12.4G7.2). Before TMZ implemen-
Yusuf Durmus1, Semra Ayturk2, Funda Ustun4 & Sibel Guldiken3
tation, patients underwent a total of 11 transsphenoidal adenomectomies (1-4),
1Department of Internal Medicine, Medical Faculty, Trakya University,
four craniotomies, two patients - stereotactic X-ray-therapy, 1 - tomotherapy and
Edirne, Turkey;2Department of Chest Diseases, Edirne Sultan 1. Murat
2
- bilateral adrenalectomy. All patients started with TMZ monotherapy
State Hospital, Edirne, Turkey;3Department of Endocrinology and
150 mg/m2 for five consecutive days with 23-days intervals. The number of
Metabolism, Medical Faculty, Trakya University, Edirne, Turkey;
courses ranged from 2 to 13. The total remission, lasting from 45 months was
4Department of Nuclear Medicine, Medical Faculty, Trakya University,
obtained in a patient with Crooke’s adenoma, partial remission in one patient with
Edirne, Turkey.
Nelson’s syndrome, transient stable disease (2-4 months) in two patients (with
Nelson’s syndrome and somatotropinoma). The prolactinoma was refractory to
TMZ. The only side effect was vomiting. In two patients with relapse of Nelson’s
Acromegaly affects 4-6 people in a million and hypophyseal GH releasing
syndrome TMZ was used in combination with bevacizumab (six courses) in 1F
adenoma is the most common cause of the disease. It shows its effects on GH and
and in 1M with capecitabine (CAPTEM - five courses), but in both cases it caused
IGF1. Since they grow rapidly, they are usually diagnosed at the stage of
short-term disease stabilization.
macroadenomas. Heart failure, arthritis, OSAS and DM may develop during
Conclusion
course of the disease. Although the most common accompanying malignancy is
colon cancer, the incidence of malign melanoma, breast, thyroid, gastric and lung
TMZ is the most effective in treatment of atypical corticotroph adenomas as a
single agent and in the first line of treatment, however it is less effective in
cancers is also increased. Increased hypophyseal Fluorine-18 fluorodeoxyglucose
recurrent form of the disease.
uptake is rare on positron emission tomography and computed tomography (FDG-
PET/CT). Since hypophyseal adenomas may give false positive results on
DOI: 10.1530/endoabs.49.EP850
PET/CT, verification should be made by MRI. In this study, we aimed to present a
case with increased FDG uptake in hypophysis and lung on PET/CT. 64-year
male patient was presented with dyspnea and weight loss. Physical examination
revealed prognatia, acral enlargement in hands and feet, dermal thickening and
decreased breath sounds on apikal part of left lung. Chest X-ray and thoracic CT
imagings demonstrated 2 cm sized nodular opacity in the upper lobe of the left
lung. On FDG-PET/CT examination, increased FDG uptake was observed in this
EP851
2 cm sized nodular lesion in the lung and in 3 cm sized hypophyseal region.
Pachydermaperiostosis: a rare syndrome presented with acromegaloid
Hypophyseal MRI was performed and macroadenoma was detected. Ocular
changes
examination revealed hemianopsia. Laboratory examination findings were as
Meliha Melin Uygur1, Izzet Hakki Arikan2, Oguzhan Deyneli1 &
follows: hemoglobin: 12.3 g/dl (13.7-17.5), sodiuum:140 mmol/l (normal: 135-
Dilek Gogas Yavuz1
145), potassium: 4.4 mmol/l, creatinin: 0.73 mg/dl, ACTH: 5 pg/ml (normal: 0-
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Marmara University School of Medicine, Endocrinology and Metabolism
EP853
Disease Department, Istanbul, Turkey;2Marmara University School of
Ocult Cushing syndrome: (adicional) difficulties in hypercortisolism
Medicine, Nephrology Department, Istanbul, Turkey.
approach
Ana Filipa Martins1, João Martin Martins1,2 & Sónia Do Vale1,2
1
Hospital de Santa Maria - Chln, Lisboa, Portugal;2Faculdade de Medicina
Introduction
de Lisboa, Lisboa, Portugal.
Pachydermoperiostosis (PDP) is a rare hereditary syndrome with familial and
idiopathic forms that is characterized by subperiosteal new bone formation with
pain, polyarthritis, cutis vertices grata, seborrhea, hyperhidrosis and digital
Introduction
clubbing. Periostosis and cutaneous thickening along with the absence of any
Cushing syndrome (CS) result from inappropriate exposure to increased non
signs of cardiovascular, pulmonary, hepatic, intestinal and mediastinal diseases
regulated glucocorticoid levels. It remains challenging regarding diagnosis and
causing secondary hypertrophic osteoarthropathy suggest PDP. The incidence of
management. Pituitary ACTH-secreting adenomas account for most of the cases
the disease is unknown. It is manifested mainly by dermatological and
if exogenous and paraneoplasic forms are excluded.
rheumatological symptoms. Rheumatoid arthritis, acromegaly, neurofibromato-
Case report
sis, hypothyroidism must be considered at differential diagnosis.
A 45-year-old women was referred to the endocrine outpatient department
Case report
because of obesity, muscular weakness, high blood pressure (HBP), diabetes
A 21-year-old male presented to the internal medicine department with
mellitus
(DM) and hypercholesterolemia beginning 3 years before. Analytic
polyarthritis and acromegaloid facial features. The patient had clubbing, swelling
evaluation evidenced ACTH- dependent hypercortisolism, with no cortisol
without an inflammation signs at knee joints and wrist; and thickening and folding
suppression after dexametasone 1mg overnight. Low-dose dexametasone (0.5 mg
of the facial skin (cutis verticis gyrata). The patient had hyperhidrosis but didn’t
quid for 48 h) excluded pseudocushing; high dose dexamethasone (2 mg quid for
have enlargement of hand, feet or lingua. Laboratory examination including
48 h) suggested pituitary CS. However no lesion was identified in pituitary RMN
growth hormone assay, thyroid profile, romatoid factor, anti nukleer anticor, anti
and inferior petrous sinus catheterization with simultaneous CRH dynamic testing
CCP, tests for syphilisis, ESR were normal. He did not have family history and
was inconclusive. Treatment with metyrapone 1500 mg/daily normalized 24-h
genetic transmission is ruled out by HPGD gene analysis. There were symmetric
urinary cortisol excretion and morning cortisol levels, but clinical manifestations
subperiostal bone formation at the radiographs of forearms and legs. The
persisted with progressive weight gain, worsened diabetes control, increased
scintigraphy showed a osteoblastic hyperactivation in the distal radius,
blood pressure levels and pathologic rib fractures, despite additional drugs. The
metacarpal bones and tibia. Based on clinical and radiological findings PDP
patient was submitted to bilateral adrenalectomy, which immediately controlled
was diagnosed. We consulted the patient to rheumatology department for arthritis
the disease with no further need for antidiabetic or blood pressure drugs and
and steroid theraphy was started.
significant weight loss.
DOI: 10.1530/endoabs.49.EP851
Discussion
Even when imaging and functional evaluation are diagnostic, CS treatment may
be challenging. Bilateral adrenalectomy is not the first line therapeutic option, but
as in this case correction of hypercortisolism more than apparent normalization of
cortisol levels may require it. Life-long morbidity is expected regarding glico-
and mineralocorticoid reposition, however this is easier to obtain and may be
associated with less co-morbidities than sustained hypercortisolism.
DOI: 10.1530/endoabs.49.EP853
EP852
Temozolomide Treatment in Aggressive Pituitary Adenoma
Pinar Sisman1, Ahmet Bilgehan Sahin2, Ozen Oz Gul3, Soner Cander3,
Erdinc Erturk3 & Canan Ersoy3
1Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,
Turkey;2Uludag University Medical School, Department of Internal
Medicine, Bursa, Turkey;3Uludag University Medical School, Department
of Endocrinology and Metabolism, Bursa, Turkey.
Background
EP854
Aggressive pituitary adenomas (APAs) take place phenotypically between benign
A case of cystic prolactinoma responsed to medical treatment
pituitary adenomas and pituitary carcinomas with systemic metastasis. Frequent
Tulay Omma, Nese Ersoz Gulcelik, Anara Karaca & Isilay Taskaldiran
recurrence and resistance to conventional treatments are characteristic features of
Ankara Training and Research Hospital, Ankara, Altındag˘, Turkey.
APAs in their clinical course. Temozolomide is an alkylating agent that has been
used in the treatment of pituitary carcinomas and APAs since 2006. Herein, we
report a patient who received temozolomide treatment due to APA.
Introduction
Case presentation
Cystic prolactinomas are considered resistant to volume depletion by dopamine
A 57-year-old male patient with complaints of headache and visual impairment
agonists (DAs). Because of the effectiveness and tolerability, dopamine agonists
had been admitted to state hospital in 1991. Laboratory and imaging studies had
(DAs) are the first line therapies in prolactinoma and reduce tumor mass as well as
revealed nonfunctioning invasive pituitary macroadenoma, and he had underwent
prolactin levels in most of all patients. Rathke’s cleft cysts, craniopharyngiomas
transcranial operation. The patient had developed pituitary insufficiency after
and arachnoid cysts are differential diagnoses to keep in mind. DAs resistance or
operation; therefore replacement therapy had been started. Thirty radiotherapy
intolerance, psychiatric disorders associated with dopamine agonist use and
(RT) sessions had been performed due to the lack of complete resection of the
patient preference can be indications for surgical intervention. Large,
mass. Then, he was referred to our department. He was reoperated in 2006 and
predominantly cystic prolactinomas are usually treated surgically and are
2009. In magnetic resonance imaging (MRI) after surgeries, a macroadenoma
presumed to be resistant to volume reduction by DAs. Although optimal
(37!35!30 mm in size) was observed and follow-up was planned because of its
management of cystic prolactinomas are not defined yet, several individual case
size to remain stable. In 2012, MRI revealed that the mass grown in size (50!
reports and case series have suggested that DAs may reduce these lesions. Here
40!38 mm). It filled suprasellar cistern and sphenoidal sinus, and infiltrated
we present a patient with cystic prolactinoma responsed to medical treatment.
cavernous sinuses. After six cycles of temozolomide were given with
30
Case report
conventional RT sessions, minimal reduction in mass size was observed. Six more
A 20-year-old women presented with secondary amenorrhea and spontaneous
cycles of temozolomide was given. After treatment, the mass was measured as
galactorrhea for three months. She has not taken any prolactin-increasing
40!38!28 mm. The patient’s monitoring still continues with stable disease.
medications and was not pregnant. Her biochemical, hematological laboratory
Discussion
tests and hypophysis function tests were normal except prolactin. Her prolactin
In our case, minimal shrinkage and stabilization of the mass size were achieved
level was 133 ng/ml (normal value is 2.7-19.6) and macroprolactin was negative.
after temozolomide treatment. According to the case reports published in the
Pituitary MR scan revealed a 9!7 mm cystic adenoma at the left side of
literature, the effectiveness of temozolomide in APAs is about 55%, although
adenohypophysis. Infundibulum, suprasellar cistern and optic chiasm were intact.
interpretation of efficacy criteria differs in various publications. However, large-
Hence her clinical picture was consistent with prolactinoma, we administered
scale studies are needed to determine the indications, proper doses and duration of
cabergolin 0.25 mg twice a week. After three months of cabergolin therapy her
temozolomide treatment.
prolactin level decreased to
6.5 ng/ml. She had regular menses and no
DOI: 10.1530/endoabs.49.EP852
galactorrhea. After eight months, hypopsis mr scan demonstrated a remarkable
reduction in the tumor size, measured as 6!3.5 mm.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Discussion
Case
In conclusion, it is appropriate to consider dopamine agonist therapy in patients
A 85 years old woman with regulated hypertension admitted with partial loss of
with cystic prolactinomas before considering surgery.
conciousness. She had cachectia and body mass index was 16.7 kg/m2. There was
DOI: 10.1530/endoabs.49.EP854
no acute pathology in cranial imaging. Because electroencephalography revealed
findings compatible with nonconvulsive status epilepticus, levatiresatam was
started. In laboratory examination, she had hypokalemia (2.5 mg/dl) resistant to
i.v. replacement. Her serum cortisol was 126 mg /ml (5-20 mg/ml) and ACTH was
331.7 pg/ml (0-60 pg/ml). Hypophysial MRI showed a 6!3 mm lesion in right
hypopysis. She did not any physical signs of Cushing syndrome. In thoracal CT, a
16 mm solid irregular lesion extending to the parencyma and costal pleura in right
EP855
lung was observed. Abdominal CT revealed a 125 mm heterogenous mass and
A case of pituitary apoplexy in a patient with Cushing’s disease due to
satellite lesions in the liver and hypertrophic adrenal glands. A tru-cut biopsy
corticotroph macroadenoma
from the lesion was reported as metastasis of neuroendocrine tumor. The lesion
Elisabeta Sava1, Bianca Leca1, Anca Sirbu1, Olivia Georgescu1,
was diffusely positive for TTF-1, cytokeratin 7, synaptophysin and chromagranin.
Luminita Cima1, Suzana Florea2 & Simona Fica1
Ki67 proliferation index was 10-15% and primary tumor was suggested to be
1Endocrinology Department, Elias University Hospital, Carol Davila
atypical carcinoid tumor of lung according to the immunohistopathological
University of Medicine and Pharmacy, Bucharest, Romania;2Laboratory
findings. The patient died at the 20th day of intensive care unit due to sepsis.
Department, Elias Hospital, Bucharest, Romania.
Conclusion
Ectopic ACTH syndrome is a rare cause of ACTH dependent Cushing syndrome.
It can be easily included in the differential diagnosis in a patient with classical
Corticotroph macroadenomas are exceptionally found in Cushing’s disease.
signs of Cushing syndrome and without adenoma in hypophysis. However, like
Pituitary apoplexy is a rare endocrine emergency condition caused by either
ours, well-known physical appearance and signs of Cushing syndrome might not
hemorrhage or infarction of the pituitary gland. We report a case of a 56-year-old
be seen in all patients, and the only clinical presentation might be neurocognitive
female diagnosed with type 2 diabetes in 2008. One year after, at the periodical
dysfunctions.
follow up, she presented with uncontrolled diabetes (HbA1cZ12.26%) and
clinical manifestations suggestive for hypercortisolism, therefore insulin therapy
DOI: 10.1530/endoabs.49.EP856
was initiated; hormonal profile revealed baseline cortisolZ26.4 ng/ml, cortisol
level after low-dose dexamethasone suppression testZ21.7 ng/ml, ACTHZ
122 ng/ml, and a 2.4/1.8/2.9 cm pituitary macroadenoma was found. While
waiting for surgery appointment, in January 2010 the patient experienced severe
headache, nausea, vomiting and diplopia. She was admitted to ICU, diagnosed
EP857
with pituitary apoplexy and transferred to neurosurgery department where surgery
Cushing’s disease management through time- a case report
was performed. Clinical improvement of Cushing’s symptoms, diplopia,
Sanja Borozan & Olivera Boskovic
hypertension and diabetes (HbA1cZ6.5% without insulin therapy) was noted.
Clinical centre of Montenegro, Podgorica, Montenegro.
The postoperative pituitary MRI revealed a rest tumor
(7/8 mm); slightly
Cushing’s disease (CD) is a rare disorder caused by an increased secretion of
increased ACTH levels
(70.1 pg/ml) and abnormal
1 mg DXM overnight
adrenocorticotropin hormone (ACTH) from the anterior pituitary gland, usually
suppression test (5.33 ng/ml). She received medical treatment with ketoconazole
as a result of pituitary adenoma. Transsphenoidal tumour resection is the best first
(not tolerated) and cabergoline
(2 mg/week); the clinical manifestation of
line therapy option for these patients but
10-30% of them fail to achieve
hypercotisolism reappeared and diabetes was poorly controlled. Despite
remission and need further treatment modalities to eliminate hypercortisolemia.
medication, ACTH and cortisol secretion remained elevated and pituitary MRI
Long-term outcomes and possible impacts on quality of life in these patients are
scan showed tumor progression. Considering the development of the tumor in
still not well examined. We report a case of a 73-year-old patient who presented in
close proximity of the optic chiasm she was refused for surgery and gamma knife
1982, as 38-year-old women with generalized malaise, facial fullness, increased
radiation therapy, being lost to follow-up for 2 years. In 2016 she was admitted
skin pigmentation, hirsutism, hypertension, hyperglycemia and depression.
with severe hepatic cytolysis (ALTZ766 U/l, ASTZ484 U/l), mild cholestatic
Laboratory evaluation showed elevated serum levels of ACTH and cortisol
syndrome, hypercortisolism and uncontrolled diabetes HbA1cZ9.6%. The
with loss of diurnal variation and no suppression after overnight low-dose
presence of hepatic cytolysis caused postponement of bilateral adrenalectomy.
dexamethasone test. Computerized tomography (CT) scan revealed hypodense
Our patient presented pituitary apoplexy in a corticotroph macroadenoma, with
persistence of Cushing’s disease after surgery and no therapy of hypercortisolism
zone in posterior pituitary and no lesions in adrenal glands. The patient underwent
transsphenoidal surgery which confirmed 5 mm pituitary tumour in posterior lobe
at the moment. Bilateral adrenalectomy is probably the best option, after the
with anterior spreading into normal tissue that inhibited the complete resection.
control of hepatic function.
Histological finding was ACTH
- secreting microadenoma. During the
Keywords: pituitary apoplexy, corticotroph macroadenoma
postoperative course, patient developed diabetes insipidus; depression and high
DOI: 10.1530/endoabs.49.EP855
blood pressure were still present. Serum cortisol level was 832 nmol/l, ACTH
26.3 pmol/l (reference range:1.2-10.2 pmol/l). The patient consented to bilateral
total adrenalectomy in November 1984. which showed adrenal hyperplasia. After
second surgery, the symptoms of CD were diminished and steroid replacement
therapy was started as following treatment. During time, patient developed
hypothyroidism, electrolyte concentrations are kept in balance. ACTH levels
were up to 194 pmol/l (with marked hyperpigmentation localized predominantly
EP856
in face area), cortisolemia up to
579 nmol/l according to which the
Ectopic ACTH syndrome presenting with partial loss of conciousness
Hydrocortisone dose adjustments were made. Recent pituitary magnetic
and nonconvulsive status epilepticus in a patient with no signs of
resonance imaging (MRI) demonstrated no signs for tumour recurrence. After
Cushing syndrome
33 years of therapy, the evaluated quality of life in our patient is not significantly
Eray Onur Mert1, Samet Yaman1, Didem Ozdemir2, Nagihan Bestepe3,
impaired.
Dursun Ali Saglam4, Osman Ersoy5, Reyhan Ersoy2 & Bekir Cakir2
DOI: 10.1530/endoabs.49.EP857
1Ankara Yildirim Beyazit University, School of Medicine, Department of
Internal Medicine, Ankara, Turkey;2Ankara Yildirim Beyazit University,
School of Medicine, Department of Endocrinology and Metabolism,
Ankara, Turkey;3Ankara Ataturk Education and Research Hospital,
Department of Endocrinology and Metabolism, Ankara, Turkey;4Ankara
Ataturk Education and Research Hospital, Department of Internal Medicine,
EP858
Ankara, Turkey;5Ankara Yildirim Beyazit University, School of Medicine,
A case of extrapontine myelinolysis after surgery for a pituitary tumor
Department of Gastroenterology, Ankara, Turkey.
Manuel Cayón-Blanco, M Gloria Baena-Nieto, Rosa Márquez-Pardo,
Rosario López-Valasco, Isabel M Torres-Barea &
Introduction
Lourdes García-García-Doncel
Ectopic adrenocorticotrophic hormone (ACTH) syndrome is associated with
Hospital Jerez de la Frontera, Jerez de la Frontera (Cádiz), Spain.
variable tumor groups most commonly originating from neuroendocrine cells.
Here, we reported a patient considered to have nonconvulsive status epilepticus
Introduction
initially due to neurological symptoms and diagnosed as neuroendocrine tumor
Rapid correction of hyponatremia is known to cause central pontine myelinolysis.
with ectopic ACTH syndrome.
It may concurrently involve other areas of brain as well, referred as extra-pontine
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
myelinolysis (EPM). Isolated EPM however is a very rare occurrence. We present
EP860
a case of EPM where the hyponatremia was secondary to syndrome of
A case of tuberous sclerosis complex associated with non-functioning
inappropriate antidiuretic hormone secretion
(SIADH) after surgery for a
pituitary incidentaloma and moderate hyperprolactinaemia
pituitary macroadenoma.
Zsuzsanna Szanto & Zsuzsa Tanko
Case report
University of Medicine and Pharmacy, Targu Mures, Romania.
A 36-year-old man underwent transsphenoidal surgery for a non-functional 2.4!
2.6!1.8 cm pituitary macroadenoma causing chiasmatic compression. During
the immediate postoperative period, the patient developed polyuria and received
Tuberous sclerosis complex is characterised by non-malignant tumours in the
desmopressin. Six days after surgery, he left the hospital asymptomatic receiving
skin, brain, kidneys, heart, eyes, lung, but sometimes angiomyolipomas may
hydrocortisone. Diuresis volume was normal and desmopressin was not necessary
develop in the adrenals, ovaries, thyroid, and rarely neuroendocrine tumours in
anymore. On the 8th postoperative day, his level of consciousness decreased and
the pancreas, pituitary gland, parathyroids. The case of a 46-years-old female
suffered from seizure requiring intubation. Blood examination revealed severe
patient suffering of tuberous sclerosis and endocrine disturbances is presented.
hyponatremia (serum sodium level of 108 mEq/l) and 1 day later serum sodium
She is known with temporal lobe epilepsy since early childhood, and anxious
increased rapidly to
135 mEq/l. On the 16th postoperative day, orotracheal
depressive disorder with obsessive elements since young adulthood, currently
intubation was discontinued but the patient was unable to communicate. Physical
receiving carbamazepine, sulpiride and fluvoxamine. At 41 years of age she was
examination revealed global hyperreflexia, clonus, dysarthria and gait disturb-
diagnosed with bilateral scleroatrophic kidneys, stage 2 chronic renal disease,
ance. Head MRI on the 18th postoperative day demonstrated intense high-signal
hypocalcemia, and endocrine investigations were recommended. The diagnosis of
bilateral lesions in corpus striatum on FLAIR and DWI, and extrapontine
tuberous sclerosis was based on four major (facial angiofibroma, periungual
myelinolysis was diagnosed. The patient’s symptoms improved gradually after
fibroma, Shagreen patches, cardiac rhabdomyoma) and one minor criteria
rehabilitation and antispasticity treatment. It was suggested that the changes in
(confetti skin lesions). Endocrine investigations and follow-up started from 2012.
serum sodium levels after pituitary surgery were due to SIADH due to
Low serum calcium level (total Ca: 8.32 mmol/l, normal: 9-11, ionic Ca:
degeneration of nerve terminals in the posterior pituitary.
0.92 mmol/l, normal: 1.1-1.6) with high intact parathyroid hormone value (iPTH:
Conclusions
133 pg/ml, normal: 15-67) showed a secondary hypoparathyroidism. Alfacalci-
Incidence of hyponatraemia following pituitary surgery is reported between 3 and
dol and calcium therapy have normalized iPTH (47.8 pg/ml) and calcium levels
25%. The delay in onset of SIADH can lead to practical problems for
(2.34 mmol/l, normal: 2.1-2.56). In 2015, at 44-years of age amenorrhoea-
neurosurgical units where there is very early discharge following pituitary
galactorrhoea syndrome developed due to hyperprolactinaemia (139.9 ng/ml,
surgery. As pituitary surgery may trigger changes in serum sodium leading to
normal:
5-26). Polyethylene glycol treatment showed the presence of
myelinolysis, this possibility should always be borne in mind when treating such
macroprolactin and a moderate genuine hyperprolactinaemia, which was
patients.
explained by the use of antidopaminergic therapy.
5 mg/day bromocriptine
DOI: 10.1530/endoabs.49.EP858
normalized menstrual disturbancies, but psychiatric symptoms worsened,
therefore we reduced the dose to 2.5 mg/day (PRL: 40.75 ng/ml). In 2015 cranial
and abdominal MRI were performed. None of the typical lesions of tuberous
sclerosis were observed, but a 4 mm pituitary microadenoma was detected, which
was interpreted as a non-functioning pituitary incidentaloma. In the literature a
few cases of GH, ACTH- or PRL-secreting pituitary adenomas, and one non-
functioning adenoma were reported.
DOI: 10.1530/endoabs.49.EP860
EP859
Hypopituitarism caused by an intrasellar meningioma: case report
Stavroula Gavriilidou1, Constantinos Belis1, Kalliopi Xydiari1,
EP861
Aikaterini Afentoulidi1, Vasilios Athanasiou1, Sofia Malaktari-
Patient with empty sella and clinical features of acromegaly
Skarantavou1, Symeon Tournis2 & Christos Savvidis1
Dimitra Pappa1, Pinelopi Thoda1, Andreas Rizoulis1, Ioannis Gountios1,
1Department of Endocrinology, Hippocratio General Hospital of Athens,
Eftihia Kapsalaki2 & Alexandra Bargiota1
Athens, Greece;2Laboratory for Research of the Musculoskeletal System
1Department of Endocrinology and Metabolic diseases, University Hospital
“Th. Garofalidis”, Medical School, University of Athens, KAT Hospital,
of Thessaly, Larissa, Greece;2Department of Radiology, University
Athens, Greece.
Hospital of Thessaly, Larissa, Greece.
Meningioma is a common, usually benign, tumor of the brain and the spinal cord
Introduction
that originates from any dura surface. Such lesion accounts for 10 to 15% of
Acromegaly is a systematic disease with charecteristic clinical features, which is
nonadenomatous sellar masses. Purely intrasellar meningiomas are relatively rare
due to GH hypersecretion mainly from pituitary adenomas and in rare cases it can
and can mimic a nonfunctioning adenoma. A 33-year-old man with a history of
be due to ectopic GHRH and GH hypersecretion. Sometimes localizing the source
1.5 year fatigue, anemia and erectile dysfunction referred to our department. The
of hypersecretion is difficult. Here we present a case of a woman with acromegalic
laboratory data revealed low levels of ACTH, Cortisol, FSH, LH and
phenotype and empty sella.
Testosterone, while TSH, FT4, IGF-1, PRL, KC and NaC levels were normal.
Presentation
Pituitary MRI demonstrated the presence of an intrasellar mass measuring 2.4!
A 47 years old woman referred to our department after recent onset of high blood
2.4!1.7 cm in diameter. The suprasellar extension was causing displacement of
pressure, headache and dizziness and a head MRI which revealed an empty sella.
the optic nerves and the chiasm. There were foci of low signal intensity consistent
Clinically she had acromegalic features and acromegaly was confirmed
with areas of calcification or hemorrhage. Formal visual field testing resulted
biochemically (IGF-1 941.1 ng/ml and basic GH 5.41 mg/l and after OGTT
normal. The patient received replacement therapy with hydrocortisone and
3.36 mg/l). A pituitary MRI confirmed the empty sella with no obvious pituitary
testosterone and referred to a Neurosurgeon. Few days before surgery the patient
tissue present. In order to localize the source of the GH hypersecretion further
complained of polyuria and polydipsia and desmopressin was prescribed. The
biochemical and imaging tests were performed
(plasma chromogranin and
mass couldn’t be totally resected through transsphenoidal approach due to its hard
calcitonin, 24 hour urine metanephrines and nonmetanephrines, head and neck
fibrous tissue. The histological report showed Grade I psammomatous
111
CT, abdomen CT,
In-Octreotide scanning) and all were negative.
meningioma. The postoperative MRI revealed residual tumor measuring 1.8!
Determination of IR-GHRH though was indicative of pituitary hypersecretion.
1.8!1.6 cm in diameter. A debulking surgery followed and the postoperative
Octreotide LAR 40 mg failed to result in biochemical control of the disease and
blood tests demonstrated panhypopitutarism with low levels of ACTH, Cortisol,
Pegvisomant (10 mg/day) was added. Eleven months later biochemical control
FSH, LH, Testosterone, TSH, FT4, PRL and IGF-1. Thyroxine replacement
was achieved (normal for her age IGF-1 and GH ! 1 mg/l), but a pituitary MRI at
therapy was added. Meningiomas of the pituitary fossa represent approximately 5
that time revealed an 9!4.4!6 mm adenoma.
to 10% of intracranial meningiomas. They commonly cause visual dysfunction
Conclusions
and infrequently hormonal insufficiency. In our case the patient presented with
Pegvisomant, a GH antagonist, used as monotherapy or in combination for
hypopituitarism caused by the meningioma, but no visual disturbances. To our
treating acromegaly is very effective in controling the disease, but growth of the
knowledge this is the first case that an intrasellar psammomatous meningioma
pituitary adenomas is being described in rare cases. Although when combined
causes pituitary insufficiency of both the anterior and posterior lobe with normal
with somatostatin analog this risk is lower, in our case revealed the adenoma.
visual fields.
DOI: 10.1530/endoabs.49.EP861
DOI: 10.1530/endoabs.49.EP859
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP862
Conclusions
Lymphocytic hypophysitis is an uncommon cause of hypopituitarism which can
Esthesioneuroblastoma causing ectopic ACTH Syndrome
present symptoms long time after the diagnosis. Due to the inflammatory changes,
Cristina Lorenzo González, Estefanía González Melo, Elena Márquez Mesa,
the patient could present headache and other local symptoms despite the absence
Pilar Olvera Márquez, María Teresa Herrera Arranz, Bruno Francisco
of compression of nearby structures. In this case, if the patient does not respond to
García Bray, Yolanda Zambrano Huerta & Enrique Palacio Abizanda
high doses of steroids, surgery is mandatory.
Hospital Universitario Nuestra Sen˜ ora de la Candelaria, Santa Cruz de
Tenerife, Spain.
DOI: 10.1530/endoabs.49.EP863
Introduction
Esthesioneuroblastoma is an uncommon malignant neoplasm with an average
5-year survival rate of about
45%. Ectopic ACTH syndrome due to
esthesioneuroblastoma is extremely rare and there have been very few cases
reported.
EP864
Case report
Title: IgG4 related hypophysitis
A 54-year-old woman was admitted to our hospital with symptoms of leg edema
Pinelopi Thoda, Dimitra Pappa, Anastasia-Konstantina Sakali,
and general fatigue of one month’s duration. Physical examination showed moon
Eleni Georgiou, Ioannis Gountios & Alexandra Bargiota
facies and edema on her lower extremities bilaterally but no other cushingoid
Department of Endocrinology and Metabolic Diseases, University of
features. Laboratory examination revealed a severe hypokalaemia (1, 99 mmol/l)
Thessaly, Larissa, Greece.
and endocrine tests revealed a marked elevation of plasma ACTH (1123 pg/ml)
and cortisol levels (cortisol in serum 110, 1 mcg/dl and 24-hour urinary cortisol
296, 7 mcg). Dexametasone suppression tests both with 1 and 8 mg were non-
Introduction
suppressible. These physical and endocrine findings were consistent with the
IgG4
Related Hypophysitis
(IgG4-RH) is a newly recognized form of
diagnosis of ACTH-dependent Cushing’s syndrome: ectopic Vs secondary to
hypophysitis. It usually appears as part of IgG4-Related Disease (IgG4-RD),
pituitary macroadenoma. Computed tomography
(CT) scans of the chest,
an immune mediated disease, with manifestations in many organs. Isolated
abdomen and pelvis were normal except for hyperplastic adrenal glands. A
hypophysitis without other IgG4-RD manifestations is rare.
pituitary magnetic resonance image (MRI) showed a normal pituitary; however,
Presentation
there was a large and aggressive mass centred in both nostrils. The mass extended
A 64 years old female referred to our department for further investigation of a
into the frontal sinus and ethmoidal cells. Otolaryngology department was
9 month history of fatigue, muscle weakness, recurrent episodes of right temporal
consulted and a biopsy of the lesion was performed. The pathologic study of the
headaches, anorexia and weight loss and a month’s history of diplopia and right
biopsy confirmed the diagnosis of esthesioneuroblastoma. Therapy with
eyelid ptosis. Past medical history was unremarkable. On clinical examination
ketoconazole 1000 mg daily was initiated preoperatively. Three weeks later the
there was marked proximal muscle weakness, right eyelid ptosis, diplopia, but
patient underwent a combined frontal craniotomy and endoscopic transnasal
visual fields were normal. Laboratory evaluation revealed hypopituitarism of the
approach. Adjuvant postoperative radiation treatment was performed without
anterior pituitary lobe. Magnetic resonance imaging (MRI) showed a thickened
complications. The patient’s symptoms completely resolved and the ACTH and
pituitary stalk and an enlarged heterogenous pituitary gland with expansion to the
cortisol levels returned to normal values.
right cavernous sinus. IgG4 levels were elevated (192 mg/dl, normal values:
Conclusions
8-140 mg/dl). Based on these findings the diagnosis of IgG4-RH was made. The
Cushing’s syndrome due to olfactory neuroblastoma may have satisfactory
patient was commenced on prednisolone 40 mg/day and thyroxine. A remarkable
prognostic and control of symptoms with combined therapy consisting of surgery
clinical improvement was observed within the first forthnight. Three months later
and radiation. We herein present a patient with a 3 year disease free survival after
she had no diplopia, no muscle weakness and repeated MRI of her pituitary gland
successful treatment.
showed great improvement of the previous picture. IgG4 levels were reevaluated
DOI: 10.1530/endoabs.49.EP862
and were found to be reduced.
Conclusion
Isolated IgG4-RH is a rare entity. IgG4 levels should be obtained in cases
suggestive of hypophysitis. Corticosteroid treatment greatly improves the clinical
picture.
DOI: 10.1530/endoabs.49.EP864
EP863
Lymphocytic hypophysitis which underwent surgery despite the
absence of compression of nearby structures. A case report
Javier González1, Alberto Díez2, Alma Prieto2 & Marta Fernández2
1Hospital Virgen de la Luz, Cuenca, Spain;2Hospital Del Bierzo, Leon,
Spain.
EP865
Pituitary apoplexy as the first manifestation of silent somatotropinoma
Introduction
Ewa Obel1, Marcin Lewicki1, Magdalena Urbanczuk1,3, Agata Smolen2,
Lymphocytic hypophysitis is a strange cause of hypopituitarism which can
Beata Matyjaszek-Matuszek1 & Jerzy Tarach1
represent a difficult diagnostic and therapeutic challenge.
1Department of Endocrinology, Medical University, Lublin, Poland;
Objectives and methods
2Department of Epidemiology and Clinical Research Methodology, Medical
Describe the diagnosis, evolution and treatment of a case of lymphocytic
University, Lublin, Poland;3Department of Clinical Pathomorphology,
hypophysitis in a patient who began with hypopituitarism and a year after the
Medical, Lublin, Poland.
diagnosis had local symptoms. We reviewed the medical history of the patient
from the moment the patient contacted with us to the months after the patient went
surgery. It has been collected clinical, laboratory and radiological data during this
Introduction
period.
Pituitary apoplexy is a rare endocrine disorder which can occur due to
Results
haemorrhage into pituitary gland. It is often associated with the presence of
This 51-year-old man presented with low TSH (0,122), low ft4 values (0.45) and
pituitary adenoma, uncommonly being the first clinical manifestation of an
hypogonadotropic hypogonadism without any other pituitary alterations. His
underlying tumour. It can cause hypopituitarism and diabetes insipidus. Pituitary
visual examination was normal. The MRI demonstrated a 15.5!10!8.5 sellar
adenomas are classified by their secretion properties as functional and clinically
lesion, thickening in the pituitary stalk
(6 mm), loss of differentiation
non-functioning, the latter, however, can exhibit positive immunostaining for
(hyperintensity) of the neurohypophysis and heterogeneous parenchyma of the
pituitary cell types in histologic examination and are thus classified as ‘silent
adenohypophysis. Because of the absence of symptoms in the patient, we
adenomas’.
corrected the deficits and we followed up. At 3 months after diagnosis the patient
Case study
developed adrenal insufficiency so we corrected this new deficit. At 1 year after
A 37-year-old male patient was admitted to the Department of Neurosurgery with
diagnosis the patient presented with severe headache and Tolosa-Hunt syndrome,
complaints of strong persistent headache with accompanying temporal visual
so we began treatment with high dose of dexamethasone. The patient had initial
fields narrowing. Pituitary tumour apoplexy was diagnosed after the imaging
improvement but relapsed after decreasing dexamethasone, so the patient was
revealed a pituitary tumor 25 mm in diameter with features of haemorrhage.
treated with trans-sphenoidal surgery with a total removal of the lesion. The
Preoperative assessment revealed gonadotropin deficiency with low concen-
patient remains asymptomatic on pituitary replacement therapy.
trations of prolactin. After undergoing transsphenoidal resection of pituitary
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
macroadenoma, hormonal evaluation unveiled additional deficiencies in the form
Observation
of secondary adrenal and thyroid insufficiency with accompanying diabetes
A 36-year-old lady (Gravida 3 Parity 2 Live Birth 2), presented to our outpatient
insipidus. At that point, the patient was transferred to the Department of
clinic on May 2007 forsuspicion of acromegaly. Clinical examination revealed
Endocrinology of Medical University of Lublin for further evaluation. The
acromegalic features. Hormonal profile revealed elevated human growth hormone
replacement therapy with hydrocortisone, levothyroxine, testosterone and
(HGH) 47.3 mUI/l and insulin-like growth factor 1 (IGF-1) 576 ng/ml (normal
desmopressin was introduced, stabilizing and improving the patient’s condition.
109-358 ng/ml), her serum prolactin PRL was also mildly elevated 76.7 ng/ml
During the follow-up no restoration of pituitary secretion function in any axis was
Follicle-stimulating hormone
(FSH), luteinizing hormone
(LH), Thyroid
observed. Histologic examination of the tumour sample displayed a larger size
stimulating hormone (TSH) and Free Thyroxine (FT4) were within normal
than previously assumed (50 mm in the largest diameter), positive immunostain-
range. Cortisol level during hypoglycaemia insulin test was 73 and 107 mg/l.
ing for GH (diffuse) and PRL (sparse) allowing to classify the tumour as silent
Magnetic resonance imaging of the pituitary gland revealed: Left postero-lateral
subtype
3 adenoma. Clinical and laboratory evaluation did not reveal any
intra-pituitary expansive lesion measuring 17!11 mm with extension to the
acromegalic features; decreased prolactin levels persisted.
sphenoid sinus. Final diagnosis was: Pituitary macro-adenoma on GH, with
Conclusions
Hyperprolactinemia and Secondary adrenal insufficiency. She underwent
Pituitary apoplexy and/or hypogonadrotropic hypogonadism can be the first
endoscopic transnasaltranssphenoidal radical excision of the tumor on Mars
symptom of pituitary macroadenoma. Clinically non-functioning adenomas may
2009. Magnetic resonance imaging of the pituitary gland after surgery revealed:
immunostain positively for more than one pituitary hormone determining their
Absence of evidence of adenomatous residue. On June 2010, patient present in 3rd
classification as silent subtype 3 adenomas.
trimester of the pregnancy. Ophthalmological examination, hormonal profile and
DOI: 10.1530/endoabs.49.EP865
Oral glucose tolerance test (OGTT) of 75 gr glucose were without anomaly. She
then went on to deliver a full-term baby girl by caesarean section in August 2010.
Discussion
Pregnancy in a patient with acromegaly is very unusual, as the enlarging pituitary
adenoma suppresses gonadotropin secretion rendering the patient amenorrheic
and infertile. Up to 30% of HGH-secreting pituitary adenomas also secrete
prolactin and this adds to the problem.Although pregnancy is unusual in
acromegaly, it is by no means rare.
EP866
DOI: 10.1530/endoabs.49.EP867
Unprogrammed pregnancy in women with active Acromegaly: a case
report
Inés Luque-Fernández, Mónica Olivar-Azuara, Ofelia Llamazares-Iglesias
& Almudena Vicente
Endocrinology Division, Virgen de la Salud Hospital, Toledo, Spain.
Introduction
Reports of pregnancy occurring in acromegalic patients are uncommon.
Nevertheless, it appears that women are usually able to carry their pregnancy
to full term
Case
EP868
39 year old woman referred to endocrinology for secondary amenorrhea and
Clinical case report: MEN-1 syndrome with coincident AIP gen
hyperprolactinemia (PRL 55.54 mg/dl). As she mentioned typical symptoms of
mutation and MEN-1 gen deletion
Acromegaly, we extended the study, finding high levels of IGF1 and a pituitary
Inmaculada Gonzalez-Molero1, Juan Antonio García Arnés2, Josep Oriola3,
macroadenoma (25!16 mm) in MRI. Presurgical treatment with Octreotide was
Stella Gonzalez Romero1, Maria Cruz Almaraz1, Silvia Maraver4,
started
(120 mg/28 days) and complete transsphenoidal surgical resection of
Gabriel Olveira1 & Francisco Tinahones1,4
GH/PRL secreting pituitary adenoma was performed. 6 months later, as IGF1
1Hospital REgional de Málaga, Málaga, Spain;2Medicine Faculty, Malaga
levels and GH during oGTT remained high, and no biochemical remission was
University, Málaga, Spain;3Hospital Clinic, BArcelona, Spain;4Hospital
achieved, treatment with octreotide and cabergoline was restarted. 13 months
Virgen de la Victoria, Málaga, Spain.
later, she got unexpectedly pregnant and pharmacological treatment was
withdrawn as soon as pregnancy was diagnosed (7-9 weeks). Patient was
clinically and biochemically evaluated throughout pregnancy with at least one
We present the clinical case of a family with an initial diagnosis of AIP syndrome
visit per trimester. In spite of medical treatment withdrawal, IGF significantly
with AIP mutation and a secondary diagnosis of MEN syndrome associated
decreased compared to preconceptional values. Normal fetal growth and
because of a large MEN-1 gen deletion. A male patient 16 years old was evaluated
development was observed, with no maternal complications (gestational diabetes
because of delayed growth and pubertal development. He had headaches, nausea
or gravid hypertension) and no congenital malformations in the newborn. After
and vomits since seven years old. MRI showed: Large pituitary mass of 47.6!
delivery IGF1 increased to pregestational levels. During the postpartum period,
22!47.2 mm that erode the floor of the sella, extending into the left prepontine
there was no problem for breastfeeding until medical treatment was restarted.
cistern and surrounding the carotid. After some months with high dosis of
Discussion
cabergoline there were not response so surgical treatment was decided. Four
Several reports conclude that GH-supressive treatment can be safely withdrawn
months after surgery MRI showed again a mass of 30!20!30 mm, remained
after conception in most women with acromegaly. In this case, withdrawal of
hipopituitarism and hyperprolactinemia. Family history: The mother consulted
octreotide and cabergoline was safe for obstetrical and fetal outcomes with an
with gynecologist in
2004 because of menstrual disturbances and bilateral
uneventful course of pregnancy and delivery, with a helthy newborn.
galactorrhea. Pituitary macroadenoma without invasion of surrounding structures
was diagnosed. During the follow up the mass had the same volume and Pituitary
DOI: 10.1530/endoabs.49.EP866
axis were normal. Results of the Genetic study of AIP geneheterozygous mutation
in exon 6: 974G O A (p.Arg325Gln.The mother and the brother, had the same
mutation while the rest of the family does not carry it. An MRI and hormonal
analysis were performed in the brother and initially were normal, but last MRI
showed a pituitary microadenoma. Two years ago hypercalcemia appeared in a
routine analysis of the mother. We confirmed hyperparathyroidism and an image
suggestive of adenoma was confirmed in the imaging tests. A parathyroidectomy
was performed. In both sons calcium and iPTH are rising slightly in progressive
analytics. After this, we requested abdominal CT and gastrointestinal and
EP867
pancreatic hormones to rule out a possible association of neuroendocrine tumor.
The results were normal in the two children, but in the mother we discovered a
Acromegaly and pregnancy: case report
pancreatic polypeptide elevation and a 8 cm mass in pancreatic body and tail. The
Maria Khatib
genetic study of MEN gen with MLPA (multiplex ligation dependent probe
Rabta University Hospital, Tunis, Tunisia.
amplification) revealed the following result: heterozygous deletion corresponding
to exon 1- 11(chr11 positions:64571868-64578482).To our knowledge, this is the
Introduction
first case of a family with the two genetics disorders (AIP and MEN-1) matching
Pregnancy in patients with acromegaly is a rare and challenging medical situation.
and resulting in MEN-1 syndrome.
Here in, we report a patient with acromegaly who presented to us in the
DOI: 10.1530/endoabs.49.EP868
3rdtrimester of pregnancy after endoscopic transnasaltranssphenoidal radical
excision of the tumor.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP869
and natremia of 124 mEq/l. Hyponatraemia was very resistant to treatment
despite hypertonic saline replacements, hence desmopressin was suspended. On
Coexistence of thyrotropinoma and chronic autoimmune thyroiditis, a
next day urine spot analysis showed that natriuresis was 63 mEq/l with serum
diagnostic challenge
sodium 132 mEq/l. This was interpreted as CSW and control was achieved with
Izaskun Olaizola, Nerea Egan˜a, Ismene Bilbao, Maite Perez de Ciriza,
aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/tid. Two
María Luisa Antun˜ano, Estela Elías, Cristina García, Maite Aranburu,
days after, Na levels were normalized and desmopressin was restarted.
Alfredo Yoldi & Miguel María Goena
Hypertonic saline dose was gradually decreased and switched to sodium chloride
Hospital Universitario Donostia, Donostia/San Sebastián, Gipuzkoa, Spain.
tablets. He was discharged on fludrocortisone 0.1 mg/bid, oral sodium chloride
16 g/day, oral desmopressin 0.1 mg/bid, hydrocortisone 20 mg/day, levothyrox-
Introduction
ine 100 mg/id. Two months later he was only on hydrocortisone, desmopressin
TSHomas are rare TSH producing tumors, whereas chronic autoimmune
and levothyroxine.
thyroiditis is a frequent condition. Patients with TSHoma are characterized by
Conclusion
increased circulating levels of peripheral thyroid hormones, but when a chronic
We presented a rare case of a patient with DI and CSWS successfully treated.
autoimmune thyroiditis is associated, they may be normal or low, making the
Hyponatremia in a DI patient may erroneously be interpreted as inadequate DI
diagnosis challenging.
control leading to therapeutic errors. Thus, all clinical and analytical data should
Case report
be evaluated together for an early and proper diagnosis.
A 55 year-old woman, with previous medical history of obesity and impaired
DOI: 10.1530/endoabs.49.EP870
fasting glucose, was diagnosed of primary autoimmune subclinical hypothyroid-
ism, with fT4 1.01 ng/dl (0.85-1.75), TSH 9.45 mUI/l (0.3-4.2) and positive anti-
thyroid peroxidase antibodies. Levothyroxine treatment was started, but despite
increasing doses with fT4 values over the normal range, normalization of TSH
could not be achieved, therefore, she was sent to the Endocrinologist. She was
under levothyroxine 150 mg/day, with fT4 1.87 ng/dl, fT3 4.2 pg/ml (2.0-4.4),
EP871
TSH 54.56 mUI/l. She complained of asthenia and nervousness, with no other
Adipsic diabetes insipidus - a diagnostic and therapeutic challenge
relevant symptoms. On suspicion of resistance to thyroid hormones and the
Daniela Magalhães1,2, César Esteves1,2, Maria Manuel Costa1,2,
asthenia, levothyroxine dose was increased to 175 mg/day, with subsequent blood
Pedro Rodrigues3 & Davide Carvalho1,2
test: fT4
1.93 ng/dl, fT3
4.3 pg/ml, TSH 40.90 mUI/l, free-a-subunit
370.8
1Department of Endocrinology, Diabetes and Metabolism of Centro
mUI/mL (!1.3). Pituitary magnetic resonance imaging showed a big infiltrating
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, Porto,
tumor mass at the pituitary region. The rest of pituitary function was normal. She
Portugal;3Department of Internal Medicine of Centro Hospitalar de São
presented worsening visual impairment. Levothyroxine treatment was withdrawn,
João, Porto, Portugal.
with fT4 0.92 ng/dl, fT3 3 pg/ml and TSH 413 mUI/l. Surgery was performed
with a partial exeresis. Diagnosis of pituitary adenoma was confirmed, visual
Introduction
impairment improved, and TSH and free-a-subunit concentrations fell down to
In diabetes insipidus (DI) the serum sodium is often in the high normal range,
49.2 mUI/l and 220.8 mUI/ml. Treatment with somatostatin analogues has been
required to provide the ongoing stimulation of thirst to replace the urinary losses.
started.
Marked hypernatremia can occur if a central lesion impairs both ADH release and
Conclusions
thirst.
TSHomas can be misdiagnosed if they coexist with chronic autoimmune
Case report
thyroiditis. Normal peripheral thyroid hormones may cause us to not think of
A 57-year-old woman presented with dysuria, polyuria and fever. She was
TSHoma as a cause, therefore, if increasing doses of thyroid hormone therapy do
medicated with ciprofloxacin, however, she maintained symptoms, accompanied
not achieve to normalize TSH, we always have to exclude a thyrotropinoma.
in the next day by nausea, vomiting and notion of decreased urine output.
DOI: 10.1530/endoabs.49.EP869
Analytical study revealed a normal blood count, urea 116 mg/dl and Cr increased
from
0.87
to
3.85 mg/dl, hypernatremia
155 mEq/l and CRP
41.8 mg/dl.
Urinalysis was normal. Renal ultrasound and abdominal CT did not show
alterations. Her past medical history was significant for diabetes mellitus treated
with metformin 850 mg/bid, arterial hypertension under losartan 25 mg/id and
spironolactone 25 mg/id and dyslipidemia under pravastatinCfenofibrate 40C
160 mg/id. She had a history of hypernatremia known for 1-year that resulted in
EP870
two hospital admissions. We found records of a plasma osmolality (POsm) of
Central diabetes insipidus and cerebral salt wasting syndrome: a
348 mOsm/kg and a urine osmolality
(UOsm) of
947 mOsm/kg. When
challenging coexistence
questioned, she reported polyuria and nocturia, without polydipsia. In the present
Maria Manuel Costa1,2, Cesar Esteves1,3, José Luis Castedo1,
admission, POsm and UOsm were 320 and 118 mOsm/kg, respectively. As there
Josué Pereira2,4 & Davide Carvalho1,3
was a record of UOsm incompatible with the diagnosis of DI, the patient
1Department of Endocrinology, Diabetes and Metabolism of Centro
performed a brief dehydration test, during which UOsm was stable below
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of
350 mOsm/kg and there was no urine output following desmopressin
Porto, Porto, Portugal;3Instituto de Investiga
¸a˜o e Inovação da Saúde da
administration. She performed a therapeutical trial with desmopressin that
Universidade do Porto, Porto, Portugal;4Department of Neurosurgery of
resulted in increased UOsmO9% and corresponding reduction of POsm. Basal
Centro Hospitalar de São João, Porto, Portugal.
pituitary function was normal. Pituitary MRI showed a reduced pituitary gland
and thinning of pituitary stalk lower half suggesting the existence of an arachnoid
cyst.
Introduction
Conclusion
Combined central diabetes insipidus (DI) and cerebral salt wasting syndrome
In patients with free access to water, hypernatremia should be exceptional since
(CSW) is a rare clinical finding. However, when this happens, mortality is high
intact thirst mechanism is a powerful defense against hyperosmolality. We report
due to delayed diagnosis and/or inadequate treatment.
a case of severe hypernatremia caused by partial DI with hypodipsia.
Case report
DOI: 10.1530/endoabs.49.EP871
42-year-old man referred to neurosurgery due to a non functional pituitary
macroadenoma with bitemporal hemianopsia. He underwent partial ressection of
the tumour on July 2nd 2015. On the following day of surgery he presented
poliuria with sodium (Na) 149 mEq/l, plasma osmolality (pOsm) 301 mOsm/kg
and urine osmolality
(uOsm) 293 mOsm/kg. He started nasal desmopressin
0.05 mg/day with good response. He was already on dexamethasone 4mg and
EP872
levothyroxine 75 mg due to hypopituitarism. On july 9th he became confused.
Endosalpingiosis - re-thinking risk tumours in acromegaly
Cerebral CT was performed with no significant changes. His natremia dropped to
Daniela Magalhães1,2, Rita Bettencourt-Silva1,2, Patrícia Leit
˜o3,
128 mEq/l, with development of poliuria despite maintenance of desmopressin
Paulo Morgado4, Conceição Souto-Moura5 & Davide Carvalho1,2
doses. Hemoglobin and hematocrit rose from 9.1 g/l to 11.6 g/l and 27.5-32.5,
1Department of Endocrinology, Diabetes and Metabolism of Centro
respectively. Thyroid function was normal and the patient was on hydrocortisone
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicina, Porto,
30 mg/day. At 1200 h he initiated 150 mg/hydrocortisone infusion, but Na did not
Portugal;3Department of Radiology of Centro Hospitalar de São Jo
˜o,
increased. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg,
Porto, Portugal;4Department of Interventional Radiology of Centro
respectively. At
1600 h hydrocortisone was increased and hypertonic saline
Hospitalar de São Joa˜o, Porto, Portugal;5Department of Pathological
replacements started. At 1800 h he was dehydrated with poliuria and vomiting
Anatomy of Centro Hospitalar de São João, Porto, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
Endocrine Tumours and Neoplasia
There is circumstantial evidence supporting a role of growth hormone and insulin-
EP874
like growth factor
1
in the development and progression of tumors.
Insulinoma in MEN type 1 mistaken as temporal lobe epilepsy
Endosalpingiosis is characterized by the presence of non-neoplastic fallopion
Norhaliza Mohd Ali
tube-like epithelium in ectopic anatomical locations.
Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia.
Case report
A 45-year-old woman presented with a constant moderate to intense perianal pain
limiting basic daily life activities. She also complained about pain at right
Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant
posterior superior iliac spine area that worsened with body movements. There was
disease characterized by pancreatic, parathyroid, and anterior pituitary tumours.
no history of trauma and inspection of the area and rectal examination were
Hypercalcaemia due to parathyroid tumours is usually the first manifestation.
normal. Her past medical history was significant for acromegaly diagnosed 4-year
Pancreatic islet tumours occur less frequently, among them gastrinomas and
earlier and confirmed by anatomopathological analysis of a pituitary macro-
insulinomas are the most prevalent. Insulinomas can be difficult to diagnose. It
adenoma removed by transsphenoidal surgery. She had history of hyperplastic
was not uncommon for patients to have been misdiagnosed with psychiatric
polyposis of the rectum but further investigation with colonoscopy showed no
illnesses or seizure disorders before insulinoma was recognized. We presented a
apparent mucosal lesions. Pelvic CT revealed a poorly delimitated nodular soft
patient who was diagnosed to have temporal epilepsy, which later turned out to be
tissues densification in the right ischiorectal fossa of indeterminate nature. Pelvic
an insulinoma in MEN-1. A
23-yr-old male presented with an auditory
MRI showed a spiculated soft tissue mass involving the lateral planes of the
hallucination of a voice asking him to kill his mother. He has had seizure for a
levator ani muscle and the internal obturator muscle, conditioning obliteration of
year, and was being treated as temporal lobe epilepsy
(TLE) with two
the fat planes around the sciatic nerve. Given the surgical risks inherent to
antiepileptics. Asymptomatic hypoglycaemia was noted during his follow up
resection of the lesion, CT-guided biopsy was performed and the histological
for TLE; but did not trigger further investigation. He has been having recurrent
examination was compatible with endosalpingiosis. Since the benign nature of the
hypoglycaemia during admission and remains asymptomatic even though his
lesion, medical treatment with an oral contraceptive was chosen.
blood glucose went down as low as 1.8 mmol/l. Fasting C-peptide level taken
Conclusions
during hypoglycaemia was inappropriately normal i.e.
947 pmol/l
(298-
Acromegaly appears to be associated with an increased risk of benign and
1324 pmol/l). MRI pancreas revealed a mass at the head and uncinate of
malignant tumors. This case reports an unusual association between acromegaly
pancreas; measuring
2.86!3.2!2.9 cm. H e was also diagnosed to have
and endosalpingiosis. Surveillance of signs and symptoms in acromegalic patients
hypercalcaemia secondary to primary hyperparathyroidism. Neck US showed the
as well as adequate screening for possible comorbidities is crucial to allow timely
presence of a probable right inferior parathyroid adenoma. He has bilateral renal
diagnosis, clinical differential diagnosis and appropriate treatment of future
calculi; with left proximal ureteric calculus causing moderate hydronephrosis and
lesions.
hydroureter requiring stenting. A final diagnosis of MEN-1 with Insulinoma and
DOI: 10.1530/endoabs.49.EP872
primary hyperparathyroidism was made. He underwent Whipple’s procedure
instead of enucleation of the insulinoma as the tumor is adjacent to the pancreatic
duct and major vessels. A total parathyroidectomy and implantatation of the left
parathyroid was also performed, together with prophylactic thymectomy. He
remains euglycaemic following the surgery. Insulinoma can pose a diagnostic
challenge even to an experience clinician. Misdiagnosis of insulinoma as
psychiatric illness and seizure is common; and might lead to disastrous
consequences. This is unfortunate as insulinoma is curable after surgery. This
case highlights the importance of considering insulinoma in patients presenting
with seizures or psychosis.
DOI: 10.1530/endoabs.49.EP874
Developmental Endocrinology
EP873
Can dehydroepiandrosterone-sulphate be a new diagnostic parameter
in male patients with idiopathic hypogonadotropic hypogonadism?
Kenan Cadirci1, Ayse Carlioglu1 & Senay Durmaz2
1Erzurum Regional and Educational Hospital, Erzurum, Turkey;2Kırıkkale
University, Kırıkkale, Turkey.
DHEA and its sulphate derivative DHEA-sulphate (DHEA-s) are major androgen
EP875
hormones of adrenal origin. The purpose of this study was to investigate DHEA-s
Pregnancy in multiple endocrine neoplasia type 1: a case report
levels in male patients with idiopathic hypogonadotropic hypogonadism (IHH)
Gordana Pemovska1, Sasha Jovanovska Mishevska1 & Tatjana Proseva2
and to determine whether DHEA-s levels are a useful marker in the diagnosis of
1University Clinc of Endocrinology, Diabetes and Metabolic Disorders,
hypogonadotropic hypogonadism. 91 subjects, 31 male patients diagnosed with
Skopje, Macedonia;2Clinical Hospital, Stip, Macedonia.
IHH (mean age 19.7G2.6 years) and 60 healthy males (mean age 20.7G2.6
years) as a control group, were included in the study. The patients in the IHH
group were selected from subjects who had not yet started treatment for
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrinopathy
hypogonadism and who had no additional disease, while the healthy control group
characterized by tumours of the parathyroid glands, adenohypophyseal and
consisted entirely of individuals presenting to the clinic for routine check-ups.
pancreatic tumours. We present a case of a young, 24 years old female patient
Both groups’ FSH, LH, total and free testosterone, ACTH, cortisol and DHEA-s
with a positive familial background for MEN1 (on the fathers’ side of the family).
levels were investigated. Mean DHEA-s levels were 133.4G56.5 mg/dl in the
She is one of two sisters with determined heterozigocity of the MEN 1 gene (Exon
IHH group and 433.3G160.3 mg/dl in the control group. The difference was
2, codon 111). At the age of 12, insulinoma of the head of the pancreas was
statistically significant (PZ0.000). Total testosterone levels in the patient and
diagnosed in our patient, with dimensions
2!2.5 cm. She underwent two
control groups were 28.0G26.3 nmol/l and 568.1G288.0 nmol/l, respectively
operations in order to remove the insulinoma, with consecutive pancreatojeju-
(PZ0.000), free testosterone levels were 9.7G14.3 pg/ml and 18.0G9.0 pg/ml
nostomia and duodenojejunostomia. In the same period, adenohypophyseal
(PZ0.006). The differences were statistically significant. Low DHEA-s levels in
prolactinoma measuring 8 mm was diagnosed and Cabregoline therapy was
patients with IHH were determined to be independent of age, cortisol and ACTH
initiated. One year before she got pregnant, primary hyperparathyroidism was
at multivariate logistic regression analysis. ROC analysis showed that DHEA-s
diagnosed and hypoparathyroidectomy was counselled, but the patient did not
%38.2 mg/dl supports a diagnosis of IHH with 100% specificity and 100%
decide to do the operation. The possible maternal and foetal complications of
sensitivity. DHEA-s is as useful and predictive marker as total testosterone, which
hyperparathyroidism were pointed out to the patient, but she decided to keep the
is used in the diagnosis of patients with IHH. DHEA-s levels were significantly
pregnancy. The PTH values are above 100 pg/ml (ref. values 15-65 pg/ml) with
lower in patients diagnosed with IHH compared to the control group, and we
increased values of total and iodised calcium (1.5-1.65 mmol/l). The patient is
conclude that DHEA-s may be a predictive marker capable of use in the diagnosis
currently in the seventh lunar month of the pregnancy, with reported normal foetal
of IHH.
development by the gynaecologist, and delivery is planned for the 36th week of
pregnancy.
DOI: 10.1530/endoabs.49.EP873
DOI: 10.1530/endoabs.49.EP875
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP876
considered as first line treatment in patients who failed to surgery or who are not
candidates to surgical treatment. The goal of this initial dosage is to reach GH
The giant who could not stop growing
levels below 1.0 ng/ml and insuline like factor type 1 (IGF1) levels within range
Debra Maxine Gordon
for age and gender. The objective of this study is to determine the percentage of
Wits Donald Gordon Medical Centre, Johannesburg, South Africa.
patients that attain goals for GH and IGF1 after 3-6 doses of Octreoride LAR.
Methods
Introduction
We included patients with acromegaly diagnosis within our centre, between the
The presentation of a patient with Gigantism, gynaecomastia and increasing
years 1995 and 2015 that received a minimum of three applications of Octreotide
height suggests underlying Hypogonadotrophic Hypogonadism. Aetiologies such
LAR before obtaining new levels of GH and IGF1 to determine response to
as a pituitary hamartoma is unlikely.
treatment. We included patients that received surgical treatment before institution
Case study
of Octreotide and those who had contraindications to surgery and had to initiate
A 39 year old male presents with a 20 year history of increasing height, shoe size,
Octreotide as part of initial treatment.
headaches, sweatiness and gynaecomastia for the past 10 years. He was 2.08 m
Results
tall with features in keeping with Acromegaly. He had normal secondary sexual
A total of 34 patients were included, with an average of five applications of
characteristics and Tanner stage 3 gynaecomastia. Acromegaly was confirmed.
Octreotide LAR before evaluation, 67% had surgical treatment, 68% were male,
His bone age was 17 years. He had hypogonadotrophic hypogonadism. Pituitary
with an age average of 47 years, 20% had diabetes, and 38% had systemic
MRI showed an enlarged, partially empty sella turcica and a hypothalamic
hypertension. Initial GH levels were 8.19 ng/ml in average and with an average
hamartoma. He received testosterone cypionate, oestrafem and a somatostatin
tumour diameter of 15 mm. In all patients a decrease in GH and IGF1 levels was
analogue. He improved clinically but his gynaecomastia had worsened. He was
observed (3.65 ng/ml in average), but only 15% attained GH and IGF1 levels
referred for a mastectomy.
goals, 50% continued with active disease and the rest had a discordant pattern.
Discussion
Among patients that received surgical treatment prior to Octreotide LAR only 8%
Acromegaly/Gigantism are uncommon disorders. tumors ususally arise de-novo
attained goals, 52% remained active. Of the patients who did not receive surgery
and secrete GH. Occasionally, there is a family history and an Aryl hydrocarbon
27% attained goals and 46% remained active.
mutation
(FIPA) or Multiple Endocrine Neoplasia should be considered.
Conclusion
Hypothalamic Hamartomas are rare causes of GNRH secretion, but usually
Despite a decrease in GH and IGF1 levels in all patients after Octreotide LAR
present in childhood. This patient’s presentation suggests that the onset of
treatment only 15% attained goals. Patients who did not received surgery had
Acromegaly was in late teenage years, and therefore unlikely to be due to the
better results than patients who received it. This initial mode of treatment is not
Hypothalamic Hamartoma. The enlarged, partially empty sella turcica, suggests
enough to control disease so over 70% of patients will need higher doses of
possible auto-infarction of a prior macroadenoma.
Octreotide LAR and perhaps association with other drugs.
DOI: 10.1530/endoabs.49.EP876
DOI: 10.1530/endoabs.49.EP878
EP877
Intrasellar malignant haemangiopericytoma: a rare case
Tahir Omer, Rahat Tauni, Mark Gurnell & Olympia Kolouri
Cambridge University Hospitals, Cambridge, UK.
EP879
Pasireotide: an effective treatment for resistant acromegaly
We report a case of malignant hemangiopericytoma in sellar region in a 73-year-
Wickrama Kankanamge Maheshi Gihani Amarawardena1,2,
old lady who initially presented with symptomatic hyponatraemia. She was found
Kamani Dhanushka Liyanarachchi1,2, John David Charles Newell-Price1,2,
to have hypocortisolism on short synacthen test. She was treated with
Richard John Martin Ross1 & Miguel Debono2
hydrocortisone and was found to have secondary hypothyroidism. Her
1Department of Oncology and Metabolism, University of Sheffield,
gonadotropin levels were commensurate with menopause, prolactin levels were
Sheffield, UK;2Department of Endocrinology, Royal Hallamshire Hospital,
normal and there was no suggestion of diabetes insipidus. Initial pituitary
Sheffield, UK.
magnetic resonance imaging (MRI) was normal. Ten months after the initial
presentation, she developed bi-temporal visual field deficits, and repeat imaging
revealed a large sellar mass compressing the optic chiasm. She underwent
The granulation pattern of somatotroph adenoma is well known to be associated
emergency endoscopic endonasal resection. Histopathology was consistent with
with differing clinical and biochemical characteristics and it has been shown that
malignancy haemangiopericytoma (WHO Grade III). She had residual tumour on
sparsely granulated tumors respond poorly to commonly used somatostatin
repeat imaging and underwent intensity modulation radiotherapy allowing high
analogs. We report a challenging case of acromegaly with a sparsely granulated
precision delivery of radiation to the tumour avoiding nearby structures. Her
tumor, resistant to multiple modalities of treatment given over several years and
repeat MRI seven months after surgery suggests stable appearances, and she is on
ultimately achieving biochemical control with pasireotide. A 26-year-old lady
thyroxine, hydrocortisone and desmopressin replacement. Haemangiopericyto-
presented with classical features of acromegaly. She had no family history of
mas are rare mesenchymal tumours arising from pericytes of the capillaries and
pituitary tumors or hypercalcaemia. An OGTT confirmed acromegaly, IGF-1 was
can happen anywhere in the body. Sellar and parasellar malignant haemangioper-
1710 mg/l and mean growth hormone (GH) was O600 mU/l, indicating high
icytomas are exceedingly rare with only a few cases reported worldwide. They
disease burden. In addition, there was secondary hypogonadism, marginally
can present with mass effects like headache or visual symptoms or symptoms of
elevated prolactin and hypothyroidism. MRI scan showed a
4 cm pituitary
hypopituitarism. They often mimic pituitary adenomas on imaging. There are no
macroadenoma with suprasellar extension and right side cavernous sinus
guidelines available for the optimal management of these tumours as they are
invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed
rare. They are very aggressive tumours that tend to recur and metastasize, even
moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for
after complete resection, therefore postoperative radiotherapy is essential.
GH. Postoperative investigations showed uncontrolled disease (IGF1-1474 mg/L,
DOI: 10.1530/endoabs.49.EP877
mean GH-228 mU/l) and residual tumor in the cavernous sinus. She received
external beam fractionated radiation. Over the years she received octreotide LAR
(up to 30 mg), lanreotide (up to 120 mg) 2 weekly, cabergoline, pegvisomant and
stereotactic radiosurgery to no avail. Only pegvisomant resulted in some disease
control; however this had to be stopped due to abnormal liver functions. Fifteen
years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a
Growth Hormone IGF Axis - Basic
month, her IGF-1 dropped and has remained within the normal range for age
EP878
(103-310 mg/l). Pasireotide was well tolerated and the patient’s symptoms
improved significantly. Somatostatin receptor subtyping revealed a positivity
Initial response to octreotide LAR in Mexican patients with acromegaly
score of two for both SST5 and SST2a subtypes.
Arturo Pen˜a Velarde & Alma Vergara López
Conclusion
Centro Medico Nacional 20 de Noviembre, México, Mexico.
Tumours that poorly respond to first generation SST, especially sparsely
granulated somatotroph adenomas, can respond to pasireotide and treatment
Introduction
should be considered early in the management of resistant tumours.
In Mexico there is scant literature about medical management and its response in
DOI: 10.1530/endoabs.49.EP879
patients with acromegaly. Octreotide LAR at a dosage of 20 mg weekly is
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP880
Research Centre for Endocrinology, Moscow, RussiaZ0.785). The Duncan post-
hoc test demonstrated significantly lower values of decorin in patients with
The disorder of secretion of somatotropic hormone in women with the
acromegaly compared to patients with Cushing’s disease and healthy controls: (1)
polycystic ovaries syndrome (PCOS) by comparison to patients with the
5015.38 pg/ml (95% CI 4855.71-5175.06), (2) 4469.89 pg/ml (95% CI 4285.85-
non-functional pituitary adenomas (NFPA)
4653.94), (3) 4841.29 pg/ml (95% CI 4633.86-5048.71) (The National Research
Yulduz Urmanova1,2 & Mushtary Saidnazirkhanova1,2
Centre for Endocrinology, Moscow, Russia!0.001). This finding was confirmed
1Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan;2Center of
by performance of Student’s t-test in pairs for groups (1) and (2) (The National
Endocrinology, Tashkent, Uzbekistan.
Research Centre for Endocrinology, Moscow, Russia!0.001) and groups (2) and
(3)
(The National Research Centre for Endocrinology, Moscow, RussiaZ0.008).
Tashkent Pediatric Medical Institute, department of endocrinology, department
Significant negative moderate correlation was demonstrated between decorin and
of dietology, Center of the Scientific and Clinical Study of Endocrinology,
IGF-1 values - rZK0.413 (The National Research Centre for Endocrinology,
department of neuroendocrinoloy, Ministry of Health of the Republic of
Moscow, Russia!0.001). There was also a weak negative correlation of very
Uzbekistan. Republic of Uzbekistan, 100125, Tashkent, Mirzo Ulugbek str. 56.
low significance between decorin and myostatin - rZK0.111 (The National
The aim to study the disorder of secretion of growth hormone for women with
Research Centre for Endocrinology, Moscow, RussiaZ0.425).
PCOS by comparison to patients with NFPA.
Conclusion
Material and methods
The serum decorin levels tend to be reduced in subjects with acromegaly. At the
Under our supervision in the department of neuroendocrinology of the Center of
same time, the levels of myostatin don’t depend significantly on decorin values.
Endocrinology of PH Ministry of RUz ambulatory in a period from September
DOI: 10.1530/endoabs.49.EP881
2015 for December, to 2016, 15 adult patients of fertil age were observed with
PCOS and 15 - with NFPA. Middle age of patients to make 25.5 and 28.9
accordingly. The remoteness of disease hesitated in limits from 7 months to
9 years.
Results
EP882
It was set that in both groups there were neuroendocrine violations peculiar to
each of pathologies. So, in a 1 group of patients with PCOS such violations, as
Could statin modify molecular phenotype of pituitary growth
obesity, met most often, strium, acanthosis, acne, hyperandrogenemiya.
hormone-secreting tumors?
hyperpolymenorheya, and in the second is secondary amenorrheya, hyperpro-
María Rosa Alhambra Expósito1,2, Paloma Moreno Moreno1,2, Concepción
lactinemiya, pahhypopituitarism. In both groups there was anovulation, and also
Mun˜ oz Jiménez2, María Ángeles Galvez Moreno1 & Raúl Luque Huertas2
decline of secretion of STH, IGF-1. In addition, in the group of patients with
1Hospital Universitario Reina Sofía, Córdoba, Spain;2IMIBIC, Córdoba,
NFPA the most for certain mionectic basale levels of trope hormones of
Spain.
hypophysis were educed - STH, LH, FSH on a background hyperprolactinemiya
and normal values of IGF-1, while for patients with PCOS the decline of STH,
Background
LH, FSH, was marked on a background hyperandrogenemiya and declines of
Acromegaly is the consequence of excessive growth hormone (GH) secretion,
IGF-1.Thus, it is set that in the group of patients with PCOS the most reliable
usually produced by a pituitary adenoma. In the last years, statins have been
decline of basale levels of IGF-1 was educed, while the deficit of STH met rarer.
implicated in the response to treatment of patients with acromegaly. Although this
Conclusions
fact is not very clear.
The secretions of STH and IGF- 1 educed in our research of violation confirm
Objective
these literatures that for patients with PCOS the decline of levels of STH and IGF-
To analyze whether pretreatment with statins modifies the adenoma molecular
1 takes place on a background hyperinsulinemiya and hyperandrogenemiya that
phenotype of the acromegalic patients and how this changes could help to
requires further research.
influence the response to treatment.
DOI: 10.1530/endoabs.49.EP880
Material and methods
Observational study including patients with acromegaly, diagnosed at the
Endocrinology and Nutrition Unit of the Hospital Reina Sofía from 2007 to
2012, in which surgery, radiology and molecular phenotyping of the adenoma was
carried out.
Results
22 patients were included (38G15 years old; 65% women). Three patients meet
EP881
cure criteria. These who take statins have lower prolactin levels
(9.33G
2.77 mg/dl) than those who do not (54.30G52.31, P 0.005). There were no
The levels of decorin in patients with Cushing’s disease and acromegaly
differences about molecular phenotype between two groups, it shown in Table 1.
Timur Tsoriev, Zhanna Belaya, Lyudmila Rozhinskaya, Alexandr Ilyin,
Patients meet cure criteria had taken more statins that those who had not (P 0.048).
Larisa Nikankina, Galina Mel’nichenko & Ivan Dedov
Conclusion
The National Research Centre for Endocrinology, Moscow, Russia.
Overall, our results indicate that there is a significant correlation between stantin
pre-surgical treatment and the disease cure. However, there is not correlation
Decorin is myokine expressed and released in response to muscle contractions. It
between use of statin and molecular phenotype.
induces growth and hypertrophy of skeletal muscles in different ways including
myostatin inhibition. It is still not clear whether decorin takes part in development
of muscle atrophy in endocrine pathologies.
Table 1
Objective
To evaluate decorin levels in patients with endogenous hypercortisolism and GH
Statin
oversecretion.
Materials and methods
Yes
No
P
Three groups were involved in our study: 1) patients with Cushing’s disease
GH
91.56G72.49
213.90G515.02
O0.05
(nZ29), 2) patients with acromegaly (nZ25) and 3) healthy controls (nZ20).
Prolactine
0.99G1.31
44.18G132.25
O0.05
24-h urine free cortisol (24-hUFC) (immunochemiluminescent assay, Vitros ECi)
Sst1
0.000042G0.000046
0.00279G0.0056
O0.05
and evening salivary cortisol (electrochemiluminescent assay, Cobas e601) were
Sst2
0.0055G0.0067
3.3070G13.1979
O0.05
measured in patients with Cushing’s disease, and IGF-1 (immunochemilumines-
Sst3
0.00067G0.00048
0.0047G0.01146
O0.05
cent assay, Liaison) was evaluated in patients with acromegaly. Serum decorin
Sst5
0.0099G0.00789
0.07180G0.2312
O0.05
levels were measured by enzyme immunoassay Human Decorin ELISA kit
DR1
0.0042G0.0036
0.0296G0.0561
O0.05
SK00641-01, serum myostatin values were also determined (Myostatin ELISA kit
DR2T (2L)
0.0740G0.1185
0.179G0.056
O0.05
Immundiagnostik AG).
(0.018G0.019)
(0.119G0.329)
Results
One-way ANOVA was performed for all patients and controls. There were not
found any differences among the groups in sex (PZ0.959), age (The National
DOI: 10.1530/endoabs.49.EP882
Research Centre for Endocrinology, Moscow, RussiaZ0.180) and BMI (The
National Research Centre for Endocrinology, Moscow, RussiaZ0.270). No
differences were found in myostatin levels among the groups (The National
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP883
have an AE that led to study medication discontinuation and 5.5% to a dose
reduction. The most frequently reported all causality AEs were arthralgia (4.6%),
A surprising and dramatic neuroendocrine-immune phenotype of mice
headache (3.6%), influenza (2.8%) and depression (2.8%), whereas for TRAEs
deficient in Growth Hormone-Releasing Hormone (GHRH)
these were arthralgia (2.6%) and peripheral edema (1.8%). The most frequently
Khalil Farhat1, Gwennaelle Bodart1, Chantal Renard1, Christophe Desmet2,
reported SAE was pituitary tumor recurrence, all causality (nZ320/15 809, 2.0%)
Michel Moutschen3, Frédéric Baron4, Yves Beguin4, Roberto Salvatori5,
and TR (nZ154/15 809, 1%). The reported occurrence of death was highest for
Henri Matens1 & Vincent Geenen1
general disorders and neoplasms (benign, malignant and unspecified) in 148 and
1GIGA-I3-Immunoendocrinology, University of Liege, Liege, Belgium;
146 patients, respectively.
2GIGA-I3-Cellular and Molecular Immunology, University of Liege, Liege,
Conclusion
Belgium;3GIGA-I3-Immunology and Infectious Diseases, University of
The results of this large study of GHRT in adult/adolescent patients with GHD
Liege, Liege, Belgium;4GIGA-I3-Hematology, University of Liege, Liege,
complement data from clinical trials and confirm the favorable safety profile of
Belgium;5Division of endocrinology Diabetes and metabolis, John hokins
GHRT.
University, Baltimore, Maryland, USA.
DOI: 10.1530/endoabs.49.EP884
In the framework of close interactions between the immune and neuroendocrine
systems, Growth Hormone (GH) has been proposed to exert significant effects on
the immune system, but there is not yet a consensus about GH immunomodu-
latory properties. These studies investigated the immune and anti-infectious
response of dwarf GhrhK/K mice presenting a severe deficiency of the
GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell
EP885
responses of GhrhK/K mice were not severely affected but a constant B-cell
Effect of GH treatment on coagulation and fibrinolysis parameters in
lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious
prepubertal children with growth hormone deficiency
responses of GhrhK/K mice toward Streptococcus pneumonia, a B-dependent
Feneli Karachaliou1, Helen Pergadou2, Anastasia Dettoraki2,
pathogen, GhrhK/K mice were unable to trigger production of specific IgM and
Evangelia Boudouvi1, Maria Kafetzi3, Aspasia Fotinou2, Helen Platokouki2
IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with
& Vassiliki Papaevangelou1
either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These
1Pediatric Endocrinology Unit, 3rd Department of Pediatrics, University
vaccines both include the serotype 1 (our S. pneumoniae strain) and provide
General Hospital Attikon, Athens, Greece;2Haemophilia Center -
an effective protection in mice. A short GH supplementation to GhrhK/K mice
Haemostasis and Thrombosis Unit, Aghia Sophia Children’s Hospital,
(1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to
Athens, Greece;3Biochemistry-Hormonology Department, P and A
Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct
Kyriakou Children’s Hospital, Athens, Greece.
impacts upon spenic areas. Furthermore, after intranasal instillation of a non-
lethal dose (defined by the full clearance by WT C57BL/6 mice after 24 h) of
serotype 1 S. pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This
Background
was proved by a marked time-dependent increase in pulmonary bacterial, a
Increased fibrinogen levels have been reported in prepubertal children and
septicemia already 24 h after infection and a survival limit of 72 h. We also
adolescents with growth hormone deficiency (GHD), which were reduced after
observed a dramatic decrease in lung B- and T-cell populations and an increase in
rhGH treatment. rhGH treatment has also been shown to exert a beneficial effect
proportion of inflammatory macrophages. By contrast, WT and heterozygote
on the amount of aPAI-1 in children with GHD. Aim of the study was to evaluate
mice completely cleared S. pneumoniae infection after 24 h. In conclusion, our
whether prepubertal GH deficient (GHD) children showed any impairment in
data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays
coagulation- and fibrinolysis-related parameters and the effect of GH therapy on
an important and unsuspected role in defense against S. pneumoniae.
these parameters.
DOI: 10.1530/endoabs.49.EP883
Patients and methods
Fifteen prepubertal children (ten girls and five boys) of a mean (S.D.) age of 9.8
(0.4) yrs with GH deficiency were included in this hospital based prospective
study. Serum levels of PT, APTT, fibrinogen, VII, VIII, AT, PC, D-dimers, Plg,
and PAI-1 were measured before and after 6-12 months of GH treatment.
Results
At baseline all studied parameters were within normal ranges. A significant
EP884
increase in PT values was noted after a mean (S.D.) interval of 9.3 (0.4) months of
treatment: 12.46 (0.2)sec vs 12.1(0.15)sec, PZ0.045. A significant decrease in
Safety of growth hormone replacement therapy (GHRT) in adult
PAI-1 levels (3.04 (0.1) U/ml vs 2.28 (0.3) U/ml, PZ0.018) was noted at the same
patients with GH deficiency: data from kims
time. No significant changes in the rest of parameters were found during the study
Cecilia Camacho-Hubner1, Peter Jonsson3, Ferah Aydin3, Natasa Rajicic1,
period.
Jose Cara1, Roger Abs2 & Judith Hey-Hadavi1
Conclusion
1Endocrine Care, Pfizer Inc, New York, New York, USA;2Antwerp Centre
GH replacement therapy for 6-12 months led to a significant increase in PT
for Endocrinology, Antwerp, Belgium;3Endocrine Care, Pfizer Health AB,
values, while fibrinogen levels did not change. Moreover, GH treatment reduced
Sollentuna, Sweden.
PAI-1 levels in GHD children, suggesting a beneficial effect of GH treatment on
possible risk of future atherothrombosis. Further evaluation of the clinical
Background
significance of these changes is needed.
The efficacy of recombinant human growth hormone replacement therapy
DOI: 10.1530/endoabs.49.EP885
(GHRT) has been demonstrated, in part, through clinical trials conducted
worldwide. KIMS (Pfizer International Metabolic Database), established in 1994
and active until 2012, includes treatment outcome data and real world safety from
15 809 patients from 31 countries.
Objective
The main objective of this analysis was to evaluate the long-term safety of
patients with hypopituitarism or with Idiopathic GH deficiency receiving GHRT
EP886
in adult life.
Nodular thyroid disease in acromegaly: cohort of 69 patients at a single
Study design
institution
This open label, international, multi-center study enrolled adult and adolescents
Cristina Álvarez-Escolá, Diego Meneses González, Óscar
with hypopituitarism and GH deficiency. Patients were treated according to the
Moreno Domínguez & Lucrecia Herranz de la Morena
standard of care of their physicians. A total of 15 809 patients (94.4% Caucasian,
University Hospital La Paz, Madrid, Spain.
50.5% males, 22.2% childhood-onset) were enrolled, with a mean age (S.D.) of
43.9 yr (15.3) at time of enrollment; the mean duration of follow-up was 5.3 yrs
and 83 128 patient-years. Safety outcomes included all reported causality adverse
Materials and methods
events (AEs), treatment related (TR) and serious AEs (SAEs), including neoplasm
The aims were to evaluate the frequency of nodular thyroid disease (NTD) in
incidence.
acromegalic patients and to correlate clinical and metabolic features with disease
Results
activity and other. We conducted a cross-sectional study including retrospectively
8093
(51.2%) patients were reported to have 27118 AEs, of which 16.6% TR, and
69 acromegalic patients attending to an University Hospital in Madrid, Spain
3998
(25.3%) patients were reported to have 7154 SAEs. 12.2% were reported to
between 1980 and 2016. Mean age was 63 (32-92) years, 63.8% of patients were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
female. Mean age at diagnosis of acromegaly was 48 (11-78) years, time between
isolated STD (10.3G3.5y). Except from TS, male gender was more frequent at all
initial symptoms and diagnosis was 24 (0-240) months, 50 patients (72.5%) had a
diagnosis. Were associated with oncologic disease nZ182/1968(9.2%):
macroadenoma and 23 (33.8%) were cured after transsphenoidal resection,
nZ97/182(53%) had primary tumours of CNS and nZ66/182(36%) due to
among the other medical treatment or radiotherapy was necessary for attaining
hemato-oncologic disease (leukemia/lymphoma).
disease control. Thyroid function was normal in 42 patients (60.9%), 22 (31.9%)
Conclusions
had hypothyroidism
(15
primary, seven secondary) and
5
(7.2%) had
Somatotropin supported treatment in our country has evolved along time, with
hyperthyroidism. NTD were observed in 56 patients (81.2%) and 10 (14.5%)
new approved indications after 2010. The most frequent diagnosis remains
had diffuse goitre. Thyroid volume was
16.1
(4.7-272.7) ml. Fine-needle
isolated somatropin deficiency with a high age at submission witch probably
aspiration biopsy (FNAB) was performed in 17 patients. Suspicious or malignant
compromises the final stature. We must have more support for deficient
cytology was detected in 23.5% of the FNABs specimens, all of them (11 patients,
somatropin adult patients.
15.9%) underwent thyroidectomy. Pathology revealed nodular goitre in six and
DOI: 10.1530/endoabs.49.EP887
thyroid carcinoma in five patients (7.2%). Other cancers detected were colorectal,
breast, prostate and gastric in 4 (5.8%), 2 (2.9%), 2 (2.9%) and 1 (1.4%) patients,
respectively. Patients with NTD (nZ56) showed similar age, duration of disease,
thyroid volume, concentrations of GH/IGF-1 at diagnosis and IGF-1 at last
follow-up compared with the group of patients without NTD
(nZ13).
Considering only patients with NTD, thyroid volume was not correlated with
age, estimated acromegaly duration, time between the first symptoms to
diagnosis, fT4, TSH, GH/IGF-1 at diagnosis or IGF-1 at last follow-up. Thyroid
volume was not different whether acromegaly was active or not (17.5 vs 14.3 mm).
Male Reproduction
Conclusions
EP888
Thyroid structural abnormalities are frequent in patients with acromegaly,
Delayed puberty revealing an uncommon genetic disease: about one
therefore routine physical examination and thyroid ultrasound are recommended
case
in all of them. Thyroid cancer was the most common neoplasia in our study,
El Ansari Nawal & Sara Askaoui
which is similar to other reports.
Service of Endocrinology Diabetes and Metabolic Diseases, Marrakech,
DOI: 10.1530/endoabs.49.EP886
Morocco.
Contexte
Kallmann syndrome is a rare genetic disease which can affect both men and
women. It combines hypogonadotropic hypogonadism which characterised by a
failure to start or to fully complete puberty naturally; olfactory disorders such
hyposmia or anosmia, impaired color vision, deafness, unilateral or bilateral renal
EP887
aplasia and midline anomalies.
Somatropin treatment Supported by NHS: characterization of
Objective
submitted patients - 2006 to 2016
We report a case of this rare syndrome, responsible of delayed puberty view of
Margarida Bastos1,2, Alice Mirante1,2, Caldas Afonso1,3,
infertility.
Carlos Vasconcelos1,4, Conceição Bacelar1,3, Conceição Pereira1,5,
Patient - intervention
Lurdes Lopes1,6, Marcelo Fonseca1,7, Joana Serra-Caetano2,
A patient of 23 years, from a non consanguineous marriage, consultant for
Miguel Patrício1,2, Cesar Marques Esteves1,11, Florbela Ferreira1,8,
delayed puberty with a Tanner stage to P2G2, without cryptorchidism or
Graciete Braganc¸a1,9, Luísa Raimundo1,10, Lurdes Matos1,6,
hyposmia.
Lurdes Sampaio1,8, Manuel Fontoura1,11 & Teresa Borges1,3
Intervention
1Comissa˜o Nacional para a Normalização da Hormona de Crescimento
We realized a hormonal exploration, with a morphological exploration of
(CNNHC), Portugal, Portugal;2Endocrinology and Pediatric Endocrinology
hypothalamic-pituitary region.
Departments of: CH Universitário de Coimbra, Coimbra, Portugal;
Main outcome measure
3CH Porto, Porto, Portugal;4CH Lisboa Ocidental, Lisboa, Portugal;
We have suspected this diagnosis through severe hypogonadism (absence of
5Oncology Portuguese Institute Francisco Gentil, Lisboa, Portugal;
developpement of secondary sex characteristics). The definitive diagnosis relies
6CH Lisboa Central, Lisboa, Portugal;7Unidade ULSM, Matosinhos,
on the detection of the genetic anomaly, not available to our level, hormonal
Portugal;8CH Lisboa Norte, Lisboa, Portugal;9H Fernando Fonseca,
explorations, olfactometry, abnormalities on MRI Kallmann syndrome.
Amadora, Portugal;10CH Garcia de Horta, Almada, Portugal;
Result
11CH S. João, Porto, Portugal;12L. Biostatistics and MI and IBILI, FMC,
Hormonal exploration showed hypogonadotropic hypogonadism. MRI is in favor
U Coimbra, Coimbra, Portugal.
of a predominant Hypoplastic right olfactory tract and the olfactory grooves, with
a normal rod.
Introduction
Conclusion
In our country somatropin treatment is supported by the National Health Service.
Kallmann syndrome is a rare disease, responsible of severe hypogonadism, the
A National Committee (CNNHC) rules and analysis the submission papers of
diagnosis is based on characteristic abnormalities of the olfactory bulbs on MRI.
patients with: isolated/multiple somatotropin deficiency (STD), short stature in:
With the correct diagnosis and treatment, fertility can be achieved in many cases
renal chronic disease (DRC), small for gestational age (SGA), Turner syndrome
and the risk of osteoporosis reduced.
(TS) and Prader Willi syndrome (PWS). In adults only isolated somatropin
DOI: 10.1530/endoabs.49.EP888
deficiency diagnosed in childhood.
Aims
To analyze the characteristics of patients submitted to the CNNHC from 2006 to
2016.
Methods
Retrospective study of cases submitted to CNNHC for somatotropin (2006-2016).
Data collected: demographic, submission date, diagnosis and committee’s
Neuroendocrinology
decision. Statistic analysis by SPSS21 (P!0.05).
EP889
Results
Empagliflozin increases urinary volume output in healthy volunteers
Total submissions nZ1968 corresponding to 1909 children/six adults; Males
with artificial SIADH - a placebo-controlled double blind crossover
(59.5%) and Females
(40.5%). Mainly coming from Pediatric centres
study
(nZ1573/80.3%). Submissions increased along time, with a minimum of 87 in
Julie Refardt1, Bettina Winzeler1, Fabian Meienberg1, Deborah Vogt2 &
2007 and a maximum of 252 in 2011. Were approved a total of nZ1412 (72%)
Mirjam Christ-Crain1
cases: at first submission nZ1243 (63.4%) and after reevaluation nZ169 (8.6%).
1Department Endocrinology University Hospital Basel, Basel, Switzerland;
Not approved nZ535 (27.2%). Diagnostic prevalence: somatotropin deficiency
2Clinical Trial Unit University Hospital Basel, Basel, Switzerland.
nZ1233 (62.9%): isolated nZ1067(54.4%) and multiple nZ166(8.5%); SGA
nZ324(16.5%), TS nZ177(9%); RCD nZ122(6.2%) and PWS nZ53(2.7%).
Somatotropin deficiency remained the most frequent diagnosis along the years.
Introduction
Age at submission: DRC were submitted earlier (6.4G4.2y), followed by SGA
The Syndrome of inappropriate antidiuresis (SIADH) is the predominant cause of
(7.9G3.0y), TS (8.5G3.6y), PWS (9.4G4.0y), multiple STD (9.7G5.1y) and
hyponatremia and its therapy options are unsatisfying. SGLT2-inhibitors have
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
become a valuable treatment option for type 2 diabetes by increasing glucose
EP891
excretion in the urine with concomitant osmotic diuresis. We therefore
Clinical features and natural history of clinically non-functioning
hypothesized that SGLT2-inhibitors could be a novel treatment option for
pituitary incidentalomas
SIADH.
Pedro Iglesias1, Karina Arcano1, Vanessa Trivin˜o2, Paula García-Sancho3,
Material and methods
Juan José Díez1, Fernando Cordido2 & Carles Villabona3
We included 14 healthy volunteers in this prospective placebo controlled
1Department of Endocrinology, Hospital Universitario Ramón y Cajal,
crossover study. To induce SIADH, participants were concomitantly administered
Madrid, Spain;2Department of Endocrinology, Hospital Universitario A
desmopressin i.v. and hydrated. After the initial oral volume load and
Coru
˜ a, A Corun˜a, Spain;3Department of Endocrinology, Hospital
administration of desmopressin, a single dose of the study drug empagliflozin
Universitario Bellvitge, Barcelona, Spain.
25 mg or placebo was given in random order. The main outcomes were total
urinary volume excretion, glucosuria and the area under the curve (AUC) of the
serum sodium concentration. The outcome measures were obtained 2-8 hours
Objetive
after administration of the study drug.
To assess the clinical features of incidental clinically non-functioning pituitary
Results
adenoma (NFPA) and to analyze its natural history.
Fourteen participants (64% males), BMI 23.1 kg/m2 (G2.4), age 28.6 years (G9),
Methods
with similar serum sodium levels on both study days (empagliflozin 140 mmol/l
A multicenter retrospective study in patients with NFPA followed-up from 1992
(G1.5) vs placebo 140 mmol/l (G1.3)) completed the study. Empagliflozin lead
to 2015 was performed.
to significantly increased urinary volume excretion
(579.3 ml G194.8
vs
Results
367.3 ml G158.8; PZ0.001) due to glucosuria
(74.18 mmol G22.3
vs
Fifty-seven patients were studied (29 women (50.9%); age 55.8G16.7 years.
0.12 mmol G0.04; P!0.001). There was no difference in the AUC of the
43.9% were older than 60 years, 40.3% belonged to the age group of 40-60 years
serum sodium concentration under Empagliflozin compared to Placebo
and 15.8% were younger than 40 years. Most patients (nZ55, 96.5%) were
(Difference of AUC 0.2, CI -7.38; 6.98, PZ0.96).
diagnosed by magnetic resonance imaging
(MRI).
71.9%
(nZ41) were
Conclusion
macroadenomas; 2 of them (3.5%) were giant adenomas (S4 cm). Patients
In healthy volunteers with artificially induced SIADH, empagliflozin increased
with macroadenomas were older than those with microadenomas (59.5G16.7 vs
volume excretion due to osmotic diuresis. Most probably due to the short
46.4G18.1 years, PZ0.007). Microadenomas were more common in women
treatment duration serum sodium levels remained unchanged. Additional studies
(41.3
vs
14.3%, PZ0.023). About half of them
(nZ28; 49.1%) showed
in real live setting are needed to further examine the possible role of empagliflozin
suprasellar extension; of these, 19 (33.3%) were accompanied by chiasmatic
as a new treatment option for SIADH.
compression. Invasion of the cavernous sinuses was present in 28.1% (nZ16).
DOI: 10.1530/endoabs.49.EP889
Hypopituitarism was present in
14
(24.6%) patients. Twenty-four patients
(42.1%) underwent surgery. Twenty-six non-operated patients were evaluated
after a median follow-up of 15.5 months (interquartile range, 5.7-32.7). No
significant changes were found in the maximum tumor diameter at the end of
follow-up (1.2G0.6 vs 1.2G0.7 cm; NS). The majority of NFPAs evaluated
(nZ23, 88.5%) did not show any changes in size. In two cases (7.7%) tumor size
decreased and in one patient (3.8%) increased.
Conclusion
Incidental NFPA is diagnosed by MRI preferably from the 5th decade of life
without sex predilection. Most of them are macroadenomas, more commonly
diagnosed in men and at an older age, compared to microadenomas. The
EP890
suprasellar extension with chiasmatic compression and hypopituitarism are
frequent at diagnosis. Most of the non-operated NFPAs remain with stable tumor
Metformin increases pressure pain threshold in lean PCOS women
size over time, being growth an unusual event.
Marta Kialka1, Tomasz Milewicz1, Krystyna Sztefko2, Iwona Rogatko2
& Renata Majewska3
DOI: 10.1530/endoabs.49.EP891
1Department of Gynecological Endocrinology, Medical College, Jagiello-
nian University, Cracow, Poland;2Department of Clinical Biochemistry,
Medical College, Jagiellonian University, Cracow, Poland;3Department of
Epidemiology, Chair of Epidemiology and Preventive Medicine, Medical
College, Jagiellonian University, Cracow, Poland.
EP892
Background
Despite the strong preclinical rationale, there are only very few data considered
Pituitary stalk lesions - experience of single center
Mirjana Doknic1,2, Sandra Pekic1,2, Dragana Miljic1,2, Marko Stojanovic1,2
the utility of metformin, as a potential pain therapeutic in humans. The aim of this
& Milan Petakov1,2
study was to determine, the association between metformin therapy and pressure
1Department Neuroendocrinology, Clinic for Endocrinology, Diabetes
pain threshold (PPT) in lean polycystic ovary syndrome (PCOS) women. We
Mellitus and Metabolic Diseases, Clinical Center Serbia, Belgrade, Serbia;
hypothesized that metformin therapy in lean PCOS women increases pressure
2Schoole of Medicine, University of Belgrade, Belgrade, Serbia.
pain threshold.
Materials and methods
Twenty-seven lean PCOS women with free androgen index (FAI) phenotype O 5
Introduction
and 18 lean healthy controls were enrolled to the study. Fifteen of PCOS women
Lesions of the pituitary stalk (PSL) are a challenging diagnostic problem for
were randomly assigned to be treated with metformin
1500 mg daily for
clinicians. Because of the critical location and role of the pituitary stalk, mass
6 months. PPT and plasma b-endorphins levels were measured in all women at the
lesions in this area are not often biopsied, and the diagnosis may be based on
beginning of the study and after 6 months observation.
clinical evaluation and imaging. Due to biopsy risk, about 40% PSL diagnosis are
Results
‘probable’ or ‘unknown’.The main clinical symptoms of PSL are visual field
We observed increase in pressure pain threshold values measured on deltoid and
defect, DI and hypopituitarism.
trapezius muscle in PCOS with metformin group after 6 months metformin
Aim
administration,
(4.81G0.88 kg/cm2, P!0.001 on deltoid muscle and 5.71G
To evaluate etiology, clinical manifestations and MRI in patients (pts) with PSL
1.16 kg/cm2 on trapezius muscle). We did not observe any significant changes in
who were seen at our department over 10 years.
PPT values in PCOS without treatment group and controls. We did not observe
Patients
any significant changes in serum b- endorphin levels in any studied groups during
We selected 20 pts (11 females) with abnormal pituitary stalk visualized on MRI.
6 months observation.
The mean age at diagnosis was 38.3 years G10.2 (range, 8-67 years).
Conclusion
Results
We conclude that metformin therapy increases pressure pain threshold in PCOS
Neoplastic lesions were diagnosed in 7 pts (35%): germinoma, pituicytoma,
lean women, without affecting b- endorphin plasma concentration. Our results
craniopharyngeoma, non-Langerhans hystiocytosis, pituitary adenoma, Rathke
may suggest the potential role of metformin in pain therapy. We propose that
cyst and simple cyst one each. Distant metastatic tumors in pituitary stalk were
larger, randomized studies, on metformin impact on pain perception should be
confirmed in 3 pts (15%). Inflammatory lesion were noticed in 4 pts (20%):
performed.
2 lymphocytic infundibuloneurohypophysitis and
2 tuberculosis. Congenital
DOI: 10.1530/endoabs.49.EP890
anomalies were noticed in 2 pts (10%). Four patients (20%) with PSL were of
unclear etiology. Tissue biopsy samples from the pituitary stalk itself were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
obtained in eight patients. Six pts have suffered from diabetes insipidus. Growth
suppressed after intracerebroventricular (i.c.v.) injection of STM-II and ATM-4
hormone deficiency was the most common hormone deficiency (15 pts, 75%),
upon hyperosmotic shock, suggesting that this heteromer has an essential role in
followed by secondary hypogonadism in 12 pts (60%) and ACTH and TSH
mediating water drinking behaviour on hyperosmotic stress. However, in vivo role
deficiency in 8 pts (40%) each. Complete hypopituitarism was noticed in 8 pts
of SCTR/AT1aR in central osmoregulatory centre is yet to be elucidated.
(40%). Nine pts had visual field defect.
Vasopressin (Vp) is one of the key components to access osmoregulation because
Conclusion
of the physiological link between Vp release and drinking behaviour, meanwhile,
The risks associated with obtaining histological samples from the pituitary stalk,
ANGII and SCT are potent in stimulating Vp release, hence it is a spate of interest
even in the group presented, the diagnosis was frequently based on other clinical
to understand whether SCTR/AT1aR heteromer regulate osmoregulation via Vp
findings and serial MR imaging. For the most challenging pituitary stalk lesions,
release pathway. In this study, we demonstrated that SCTR/AT1aR heteromer is
an individualized approach, guided by clinical expertise, remains the best
involved in the regulation of Vp release and expression, as well as the central
strategy.
neural involvement in PVN. Upon SCT/ANGII-stimulation, plasma Vp release
DOI: 10.1530/endoabs.49.EP892
was largely reduced (47.64% decrease) and Vp expression in PVN is significantly
dropped (64.08% decrease) 15 mins after i.c.v injection of STM-II or ATM-4.
This finding supports the hypothesis of SCTR/AT1aR in mediating water balance,
and also provides concrete basis in demonstrating the in vivo role of a GPCR
heteromer.
DOI: 10.1530/endoabs.49.EP894
EP893
First pediatric case of successfully treated Cushing’s disease in Armenia
Gayane Bayburdyan, Lusine Arakelyan & Yelena Aghajanova
Yerevan State Medical University, Yerevan, Armenia.
EP895
Introduction
The hyponatremia in neurosurgical patients
Cushing’s disease
(CD) is the most common albeit rare in paediatric and
Liudmila Astaf’eva, Maxim Kutin, Yuliya Sidneva & Pavel Kalinin
adolescent population form of ACTH-dependent Cushing’s syndrome, with
Burdenko Neurosurgical Institute, Moscow, Russia.
potentially serious morbidity. Thus, it presents diagnostic and therapeutic
challenges for the clinician. Early diagnosis and treatment of Cushing’s disease is
vital for long-term outcome. Paediatric pituitary-dependent Cushing’s disease,
Background
caused by an ACTH-secreting corticotroph adenoma, accounts for 75-80% of
Hyponatremia is a relatively frequent and serious complication developed in
Cushing’s syndrome and is almost always caused by a pituitary microadenoma.
patients with different neurosurgical pathology. The aim of the study was to
Case report
identify the frequency of occurrence of hyponatremia in neurosurgical patients.
14 yo girl presented to endocrine clinic with severe headaches, increased blood
Materials and methods
pressure
(BP) up to 140/100 mmHg, wide reddish-purple abdominal striae,
A retrospective analysis included 39479 patients operated in the Institute of
amenorrhea and weight gain up to 20 kg during last year. She was unsuccessfully
Neurosurgery from January 2008 to December 2014.
managed by a gynecologist with oral contraceptives for 8 months. In endocrine
Results
clinic patient was examined according to Endocrine Society guidelines with
785 patients (2% of all operated patients): 554 adults and 231 children had
subsequent diagnosis of Cushing’s disease due to ACTH-secreting pituitary
hyponatremia with Na level less than 130 mmol/l. In 63% of cases (497 patients)
microadenoma
(corticotropinoma). Patient underwent surgical removal of
we observed a moderate decrease of Na (125 to 130 mmol/l), in 11% of cases (88
adenoma with gamma knife (GKS) resulting in reversal of symptoms.
patients) the level of Na was less than 120 mmol/l. The mortality rate in patients
Conclusions and follow up
with hyponatremia was 14.3%, what is 10 times faster than that of the rest of
Endocrine parameter normalization after GKS included normal 24-hour urinary
patients without hyponatremia operated during these years. In adults most often
free cortisol (UFC) concentration and normal levels of pituitary and peripheric
hyponatremia developed either after surgical removal of craniopharyngiomas
hormones 4 months. However, posttreatment secondary hypothyroidism was
(11%) or as a result of an acute stroke (22%). In children - after surgery of
diagnosed with TSH of 2.2 IU/ml (0.5-4.0) and FT4 of 12.1 pmol/l (12.0-22.0).
craniopharyngiomas (10%), astrocytomas (7%), ependymomas (24%) and germ
BP was stable at 110/70 mmHg. Regular menstrual function resumed 6 months
cell tumors (10.5%).
after the surgery, and weight loss of 10 kg was documented 10 months after the
DOI: 10.1530/endoabs.49.EP895
surgery. Adenoma size decreased from 0.6 to 0.2 cm in 7 months by MRI. Current
medications comprised of Levothyroxin 75 mcg only. This is the first case of
successful treatment of paediatric Cushing’s disease in Armenia. Although
transsphenoidal neurosurgery is the gold standard therapy of pituitary Cushing’s
disease, GKS seems to be safe and effective way of treatment, however, long-term
follow-up is necessary.
EP896
DOI: 10.1530/endoabs.49.EP893
Bilateral inferior petrosal sinus sampling and the outcome of
transsphenoidal surgery in patients with Cushing’s disease: experience
of a Tertiary Portuguese Hospital
Ana Coelho Gomes1, Lia Lucas Neto2, Francisco Tortosa3, Maria
Raquel Carvalho1, Eduardo Barreiros1, Luís Barreiros1, José Miguéns4 &
Maria Joa˜o Bugalho1
1
Endocrinology, Diabetes and Metabolism Department, Santa Maria
Hospital, Lisbon, Portugal;2Neuroradiology Department, Santa Maria
EP894
Hospital, Lisbon, Portugal;3Pathology Department, Santa Maria Hospital,
SCTR/AT1aR heteromer related osmoregulation in hypothalamus
Lisbon, Portugal;4Neurosurgery Department, Santa Maria Hospital, Lisbon,
Oi Kwan Mak & Billy K.C. Chow
Portugal.
The University of Hong Kong, Hong Kong, Hong Kong.
Introduction
Emerging studies suggest that GPCR oligomerization could confer functional
Bilateral inferior petrosal sinus sampling (BIPSS) is the gold-standard for the
advantages to receptors and even constitute clinical applications. Recent study
differential diagnosis of ACTH-dependent Cushing Syndrome when the pituitary
found that angiotensin II 1a receptors (AT1aR) and secretin receptors (SCTR) can
adenoma on MRI is doubtful or absent. This study aimed to analyze whether
form heteromer and participate in osmoregulation. Studying GPCR dimerization
BIPSS can influence the outcome in patients with Cushing disease (CD).
faces many technical challenges, including selectivity and specificity. Since
Methods
transmembrane (TM) peptides can act as competitors against the interacting
Retrospective, descriptive study. Forty-two patients with CD submitted to
surfaces between two receptors and therefore, it is utilized in this study as a
transsphenoidal surgery (TS) between 2005 and 2016 were divided into two
unique tool to illustrate the specific functions performed by SCTR/AT1aR
groups based on the performance of BIPSS. Different variables were analyzed:
heteromer. STM-II and ATM-4 are discovered as the interacting surfaces of
year of diagnosis, preoperative laboratory tests and pituitary MRI, immediate
SCTR/AT1aR heteromer, in which STM-II can only disrupt heteromer formation,
postoperative laboratory tests, histological findings, postoperative hypopituitar-
while ATM-4 can inhibit both receptor homomer formation. Previous study
ism, presence of permanent diabetes insipidus, follow-up duration and final
shows that hyperosmolality-induced water drinking behaviour in mice is greatly
outcome.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
of the patients, adenomas in 16.8% and CRC in 5%. In total, 27 adenomas and 69
Ten out of forty-two patients with CD were submitted to BIPSS.
HP were detected. The prevalence of CRC, CP and adenoma found in this study
compared to normal population was: 5 vs 1% (PZ0.001); 47.5 vs 32.6%
(PZ0.003) and 16.8 vs 38% (PZ0.001), respectively. Concerning AF, there was
no differences between patients with abnormal and normal colonoscopy.
BIPSS
No BIPSS
p-value
Conclusions
The prevalence of CRC and CP was significantly higher in patients with
Diagnosis Year (%):
0/70/30
9/47/44
0.355
acromegaly. On the contrary, adenoma was significantly less prevalent. No
1995-2000 / 2001-2010 /
association between any of the factors studied and the phenotype CRC/CP was
O2010
observed. To our knowledge, this is one of the largest Portuguese series,
Preoperative sellar MRI
20/0/30/50
66/16/0/6
!0.01
nevertheless results have yet to be validated.
(%): Microadenoma /
DOI: 10.1530/endoabs.49.EP897
Macroadenoma / Indeter-
minate Lesion / No Image
Preoperative Laboratory
100/0
59/13
0.159
Tests (%): Classical /
Non-Classical
Immediate Postoperative
40/40
41/41
1
Laboratory Tests (%):
Criteria for Cure /
EP898
No Criteria for Cure
Acromegaly and malignant neoplasms
Histology (%): Adenoma /
60/10/30
78/3/9
0.462
Vânia Gomes, Eduardo Barreiros, Luís Barreiros, Florbela Ferreira,
Corticotroph Hyperplasia /
Ana Gomes, Ana Filipa Martins, Ana Sofia Osório, Ana Wessling,
Normal tissue
Catarina Silvestre, Dinis Reis, Ema Nobre, Maria Raquel Carvalho,
Postoperative anterior
20/20/20
28/25/44
0.713
Mário Mascarenhas, Sónia do Vale, José Miguéns & Maria João Bugalho
pituitary deficiency (%):
Santa Maria Hospital, Lisbon, Portugal.
Isolated / Multiple / None
Permanent Diabetes
0/100
6/94
0.418
Introduction
Insipidus (%): Yes / No
Acromegaly is a rare disease resulting from pathological oversecretion of growth
Mean Follow-Up (years)
5.7G3.8
6.8G5.1
0.544
hormone (GH) and insulin-like growth factor-1 (IGF-1). The clinical spectrum
(0-11)
(1-21)
includes cardiovascular and respiratory diseases but also increased risk of benign
Final Outcome (%):
70/30
47/50
0.386
Remission / Active Disease
and malignant neoplasms.
Objectives
Evaluate the prevalence of cancer and seek for associated factors in acromegaly.
Note: In some parameters the sum of the partial percentages is not 100%
Methods
because some patients didn’t have that information.
Retrospective study of 94 patients with acromegaly treated in a single tertiary
center from 1985 to 2016. The group with malignant neoplasms was compared
Discussion
with the group without malignancy. Statistical analysis was performed with SPSS
Groups were different in terms of the preoperative imaging. For the other
software, version 20. Statistical significance: P ! 0.05.
variables, no differences were observed. The final outcome, despite the higher
Results
number of macroadenomas in the group without BIPSS was not statistically
63.8% of the patients were female and the mean age at diagnosis was 48.7G12.9
different. Results await further confirmation.
years. Median GH and mean IGF-1 at diagnosis was 9.8 ng/ml (range: 0.61-228)
and 857.4G412.7 ng/ml, respectively. Median diagnostic delay of acromegaly
DOI: 10.1530/endoabs.49.EP896
was 7 years (range: 1-36). Cancer was present in 13 (13.8%) of the 94 patients.
Colon cancer was diagnosed in five patients (5.3%), breast cancer and renal cell
carcinoma each in 3 (3.2%), follicular thyroid cancer, melanoma and endometrial
carcinoma each in 1 (1.1%). In three cases, cancer was found before acromegaly
(breast cancer in 2 and colon cancer in 1). One patient had two malignancies
(thyroid and renal cell carcinoma). The diagnostic delay of acromegaly was
higher in the group with malignant neoplasm
(PZ0.004). There was no
EP897
statistically significant difference between the two groups relative to GH, IGF-1,
The prevalence of colorectal cancer and colon polyps in acromegaly:
age and body mass index at diagnosis and gender.
thirty years’ experience of a tertiary referral center
Conclusions
Vânia Gomes, Luís Barreiros, Eduardo Barreiros, Florbela Ferreira,
Colon cancer was the most prevalent, followed by breast and renal carcinoma.
Ana Gomes, Ana Filipa Martins, Ana Sofia Osório, Ana Wessling,
In the group with malignant neoplasms, diagnostic delay was significantly higher,
Catarina Silvestre, Dinis Reis, Ema Nobre, Maria Raquel Carvalho,
suggesting that prolonged exposure to high GH and IGF-1 levels can be related to
Mário Mascarenhas, Sónia do Vale, José Miguéns & Maria João Bugalho
cancer development. Search for cancer should be a major task in the follow-up of
Santa Maria Hospital, Lisbon, Portugal.
these patients.
DOI: 10.1530/endoabs.49.EP898
Introduction
Several studies suggest a higher risk of colorectal cancer (CRC) and colon polyps
(CP) in acromegaly, however there is still controversy regarding associated
factors (AF) able to contribute for its development. Data on the prevalence of
CRC and CP in Portuguese patients with acromegaly are limited.
Objectives
To assess the prevalence of CRC and CP in acromegalic patients and compare to
EP899
the normal Portuguese population. To determine the relevance of a number of AF
Endogenous Cushing’s syndrome ( clinical and biochemical features in
(growth hormone, insulin-like growth factor-1, body mass index and age at
a large cohort of patients
diagnosis, gender, diagnostic delay and disease duration) for its development.
Lucio Vilar1, Clarice Vilar2, José Luciano Albuquerque2, Erik Trovão1,
Methods
Ana Carolina Thé1, Patricia Gadelha1, Maíra Melo1, Barbara Gomes1,
Retrospective study of 101 acromegalic patients assisted in a tertiary center from
Thaíse Borges1, Izabela Cardoso1 & Ruy Lyra1
1985 to 2016, who underwent at least one colonoscopy. Comparative analysis
1Division of Endocrinology, Hospital das Clinicas, Federal University of
with data from screening studies conducted in the normal Portuguese population.
Pernambuco, Recife (Pernambuco), Brazil;2Endocrine Research Center of
Statistical analysis was performed with SPSS software, version 20. Statistical
Pernambuco, Recife (Pernambuco), Brazil.
significance: P! 0.05.
Results
Of the 101 patients (female: 62.4%; mean age at diagnosis: 49.5G12.8 years),
Patients and methods
47.5% presented abnormal colonoscopy with CP, which were more frequent in
We retrospectively analysed the clinical and biochemical characteristics of a
the left colon. Histological analysis identified hyperplastic polyps (HP) in 29.7%
cohort of 150 patients with endogenous Cushing’s syndrome (CS). Cushing’s
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
disease (CD) accounted for 61.3% of cases (nZ92), ectopic ACTH secretion
Conclusion
(EAS) 7.3% (nZ11), and adrenal diseases 31.3% (nZ47). Among CD cases,
Mild hyponatremia can predate the diagnosis of a malignancy. However, in our
there were 19 macroadenomas (20.6%), a female predominance (60.5%) and a
series of 11/52 patients, in only one was hyponatremia studied. The lack of
median age of 33 years old (range 14-55). Bronchial carcinoid was the most
importance given to the finding of frank hyponatremia, albeit mild, could delay
frequent cause of EAS (nZ7). When biochemical and clinical features were
tumor diagnosis.
compared in cases of CD and EAS, the only significant difference was the higher
DOI: 10.1530/endoabs.49.EP900
frequency of hypocalemia in EAS
(80% vs. 15%; P!0.001). Concerning
screening tests, the sensitivities of overnight
1 mg-DST (cut-off, 1.8 mg/dl
(50 mmol/l)), UFC and late night salivary cortisol (LNSC) were 94%, 90% and
96%, respectively. The combination of two of these tests yielded a sensitivity of
98% ACTH levels were normal (42%) or elevated (58%) among patients with
CD; they were above the normal range in all EAS cases and !10 pg/ml in all
patients with adrenal disorders. Regarding dynamic tests, HDDST had a mean
sensitivity and specificity of
79/55
and
70/100%, respectively, using the
supression cut-offs of O50% and O80%, respectively. The diagnostic accuracy
of CRH test and desmopressin test did not significantly differ (PZ0.28) in the
EP901
distinction between CD and EAS. The combination of HDDST and CRH or
Hyperprolactinemia as a manifestation of hormonally inactive pituitary
desmopressin tests was more accurate than each test alone. The overall diagnostic
adenoma
accuracy of BIPPS was 94%. Pituitary MRI depicted all macroadenomas and 64%
Zamira Khalimova & Mijgona Safarova
of microadenomas. CT scan and/or MRI detected 90% of bronchial carcinoid, as
Center for the Scientific and Clinical Study of Endocrinology, Uzbekistan,
well as all thymic carcinoid.
Tashkent, Uzbekistan.
Conclusion
CD and EAS cannot be accurately be distinguished based only on clinical and
biochemical features. LNSC was the most sensitive screening test for CS.
Aim
The work was initiated to study prolactin levels in hormonally inactive pituitary
DOI: 10.1530/endoabs.49.EP899
adenoma by the size of the tumor.
Material and methods
We examined 85 patients with hormonally inactive pituitary adenomas, 45
women and 40 men among them aged from 18 to 50 years (mean age 44.5G3.85
years). The disease duration from the onset to diagnosis based on the medical
history and MRI ranged from 1 to 15 years.
Results and discussion
Guided by the aim of study we divided the patients into three groups. 26 patients
with the tumor size up to 10 mm were included into the first group. Thirty-three
patients with the tumor size up to 20 mm comprised the second group. Twenty-six
patients with the tumor size 30 and more mm were included into the third group.
EP900
Analysis of hormonal parameters demonstrated correlation between prolactin
Hyponatremia predating the diagnosis of malignancy in oncological/
level and the tumor size. Hyperprolactinemia was registered in 2, 45 and 100% of
hematological patients with SIADH
patients in the first group, second and third groups, respectively. In patients with
Irene Crespo-Hernández1, Martin Cuesta-Hernández1, Alejandro Santiago-
macroadenomas hyperprolactinemia was clinically presented in combination with
Perez1, Emilia Gomez-Hoyos2, Ana Ortola-Buigues2, Paz de Miguel-
hypopituitarism. Among patients of the third group, chiasmal and cephalgic
Novoa1, Joan Chafer-Vilaplana1, Alfonso Calle-Pascual1 &
syndromes, the latter with the oculomotor nerve damage, were the main
Isabelle Runkle1
symptoms; lactorrhea-amenorrhea syndrome came the third.
1Hospital Clínico San Carlos, Madrid, Spain;2Hospital Clínico de
Conclusions
Valladolid, Valladolid, Spain.
Quite frequent sign of hormonally inactive adenoma, hyperprolactinemia upon
formations in chiasmal-sellar area not always can be an outcome of prolactin-
Introduction
secreting adenomas; the fact is to be taken into account in choosing the treatment
Euvolemic hyponatremia
(HN) caused by the Syndrome of Inappropriate
tactics.
Antidiuretic Hormone Secretion (SIADH) can predate a diagnosis of malignancy.
DOI: 10.1530/endoabs.49.EP901
It is thus essential to accurately diagnose the etiology of HN/SIADH when
detected.
Methods
Retrospective, descriptive study of all 52 oncological/hematological malignancy
patients diagnosed with SIADH in our Department between January 2011 and
EP902
December 2016. HN was detected via computerized Primary-care/hospital case
histories, and the computerized laboratory data base. Hyponatremia was
considered to predate detection of malignancy/initiation of diagnostic study
when a serum sodium (SNa) !135 mmol/l was detected 6 months before
Abstract withdrawn.
definitive oncological/hematological diagnosis (PTD). A patient was considered
probably euvolemic (PE) when SNa descent was accompanied by a predominant
pattern of lowering serum urea, creatinine and Uric acid levels, probably
hypovolemic (PH) if urea, creatinine and Uric acid levels rose while not
hypervolemic. SNa in mmol/l.
Results
Males: 32/52(61.5%), mean age:63.4 (S.D.:11)years. Etiology of SIADH: lung
cancer: 18/52(34.6%), gastrointestinal: 6/52 (23.1%), genitourinary: 11/52 (21%),
hematological: 5/52 (9.6%). 11/52 (21%) patients presented HNO 6 months
PTD: median 40 (24-60), median age: 67 (63-76) years, initial SNa: 133 (130-
134). Three patients were PH. Eight were PE, one receiving enalapril, another
EP903
carbamazepine, another thiazide. In 5/8 (62%) PE patients, case histories revealed
no initial cause for HN. HN was present a median of 25 (19-40.5) months PTD,
range: 14-41. Initial SNa: 133 (129.5-133). None presented a low Urine Density.
Abstract withdrawn.
Hyponatremia was persistent, present in 42/50 (84%) tests, with a continuum up
to ectopic-SIADH diagnosis, suggesting that SIADH induced their sustained
hyponatremia. Etiology: lung (epidermoid), endometrial, breast, gastric, prostate.
In only 1/11 (9%) patients was hyponatremia studied PTD, with SIADH workup
responsible for prostate tumor diagnosis.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP904
hyperintensive T2
(22/55,
40%; 12/55,
21.8%;
9/55,
16.4%, respectively).
HypoT1/hypoT2 tumors had the smallest volume.
Study of CHD7 gene in KAL 1-negative patients previously diagnosed
Conclusion
with congenital hypogonadotropic hypogonadism that develop new
In all type of pituitary tumors hypointensive MR-signal (either T1 or T2) was
pituitary deficiencies
associated with infrasellar tumor expansion and smaller tumor volume. In
Beatriz Lecumberri1,2, Francisco Javier Rodríguez2, Óscar Moreno1,
contrast, hyperintesive T2 was associated with suprasellar tumor expansion and
Manuel de Santiago1, Manuel Nistal2,4, Elena Vallespin2,3, Angel Campos2,3
bigger tumor volume. IsoT1/isoT2 tumors were found only in NFA group;
& Karen Heath2,3
hypoT1/hypoT2 tumors were observed only in somatotropinomas so further
1Endocrinology Department, La Paz University Hospital, Madrid, Spain;
investigations should be carried on to prove the diagnostic value of these results.
2IdiPAZ, Madrid, Spain;3INGEMM; La Paz University Hospital, Madrid,
Accurate determination of T1/T2 signal intensity can be used as additional
Spain;4Pathology Department, La Paz University Hospital, Madrid, Spain.
predictors of hormonal and proliferative activity of pituitary tumors.
DOI: 10.1530/endoabs.49.EP905
Introduction
Recent studies suggest that some patients initially diagnosed with congenital
hypogonadotropic hypogonadism
(CHH), may evolve towards a combined
pituitary hormonal deficiency (CPHD). Heterozygous pathogenic CHD7 variants
impair neural cell crest guidance causing CHARGE syndrome and have been
associated with abnormal pituitary development/function/structure and isolated
CHARGE features, including HH. We aimed to genotype CHD7 and phenotype
EP906
thoroughly those adult patients previously diagnosed with CHH that developed
Cholinergic modulation of the hypothalamic-pituitary-adrenal activity
new pituitary deficiencies during the follow-up.
and somatotroph function in smokers and non-smokers
Patients
Jesús Pérez-Luis1,2, Judith López-Fernández1,2, Isabel Mascaren˜o1,2 &
From 20 unrelated KAL 1-negative patients with a past CHH diagnosis followed
Javier Salvador3
in our adult endocrinology clinic during an average of 21.2 years (13-37), we
1Hospital Universitario de Canarias, Tenerife, Spain,2Universidad de La
selected those with new pituitary deficiencies
- 7/20, all males, mean age
Laguna, Tenerife, Spain,3Hospital Universidad de Navarra, Pamplona,
37.2
years
(29-53)
- and studied CHD7
using a targeted NGS panel
Spain.
(HYPOPIT.V1). Markedly low IGF-1 levels were detected in 6/7 (85%) and of
TSH in 4/7 (57.4%).
Results
Introduction and objectives
2/7 patients (28.6%) harboured heterozygous CHD7 rare variants. The variant of
The inhalation of tobacco smoke leads to an acute increase in cortisol, ACTH and
unknown significance NM_017780:exon31:c.G6255T:p.L2085F that suggests
GH concentration, both in chronic smokers as in non-smokers. However, most
pathogenicity but lacks functional sudy, was found in a 53-year-old male, that has
studies have failed to demonstrate differences between both groups in basal levels
a left temporal arachnoid cyst, a pars intermedia cyst, low IGF-1 levels, a
of these hormones in plasma or urine. Additionally, cholinergic pathways have
pigmentary glaucoma treated with iridotomy, aortic elongation and a “Sertoli-
been shown to play an inhibitory role in ACTH secretion in non-smokers. UFC
cell-only syndrome” diagnosis based on testicular biopsy performed at 38 years.
and circulating levels of cortisol, ACTH and GH were evaluated basally and after
Another
37-year-old-male, that was hormonally and surgically treated for
pyridostigmine in smokers and non-smokers.
bilateral cryptorchidism during childhood, and currently shows a partial empty
Subjects and methods
sella, absence of neurohypophysis and low TSH and IGF-1 levels, had the rare
We studied UFC (urinary free cortisol) on 24 h urine samples and the effects of
pathogenic heterozygous variant NM_017780.3:c.8416COG:p.Leu2806Val,
administration of placebo and pyridostigmine on ACTH, cortisol and GH
involved in CHARGE, isolated HH, and in a few CPHD cases with atypical
secretion in 10 young males: five smokers and five non-smokers. In each test,
CHARGE features. Curiously both fathers of these two patients died before 65
placebo or pyridostigmine (120 mg) were given orally in random order on
years of age due to lung diseases (the first being cancer).
different days at 0830. Blood samples were drawn at 0830, 0900 and then every
Conclusions
15 min until 1130. Area under the curve was calculated. Data are expressed as
Our results suggest that CHD7 should be included in the genetic study of CHH
mean G SEM.
patients, especially in those that develop new pituitary deficiencies over time.
Results
DOI: 10.1530/endoabs.49.EP904
Basal levels of UFC, plasma ACTH, and serum GH were not different between
smokers and non-smokers. In contrast, basal serum cortisol was higher in smokers
at 1015 (15.42G1.38 vs 10.29G1.40 mcg/dl) and 1045 (12.96G1.14 vs 8.89G
1.19 mcg/dl). PD raised GH secretion within each group, while it decreased
cortisol at 1015 (15.42G1.38 vs 13.20G1.50 mcg/dl) in smokers and ACTH at
1115
(16.87G1.54 vs 12.49G1.65 pg/ml) in non-smokers.
Conclusions
EP905
Chronic smoking is associated with increased basal serum cortisol and normal
MR-characteristics as predictors of pituitary adenomas hormonal and
UFC, while it is related to a decrease in serum cortisol after pyridostigmine.
proliferal activity
Besides, an inhibitory effect of cholinergic stimulation on ACTH is confirmed in
Yulya Krivosheeva, Alexander Dreval, Evgenia Panteleeva, Galina Stashuk
non-smokers.
& Irena Ilovayskaya
DOI: 10.1530/endoabs.49.EP906
Moscow Regional Research and Clinical Institute, Moscow, Russia.
Introduction
Previous studies demonstrated a relationship between T1- and T2-weighted signal
intensity and tumor growth pattern in pituitary somatotropinomas. The goal of
this retrospective study was to analyze the MRI characteristics of pituitary
macroadenomas with different hormonal activity in newly diagnosed patients.
EP907
Material and methods
Diagnosis, treatment and follow-up of non-functioning pituitary
Pre-treatment T1- and T2-weighted MR-images (Intera Achieva, PHILIPS, 3.0T)
adenomas
of patients with 42 non-functional adenomas (NFA), 18 macroprolactinomas, 55
Ana Barrera-Martín1, Paloma Moreno-Moreno1, María-Rosa Alhambra-
somatotropinomas were analyzed, taking into account the intensity of the signals
Expósito1, Aura-Dulcinea Herrera-Martínez1, Ángel Rebollo-Román1,
produced by the tumors, as well as their dimensions and growth direction. The
Pedro-Blas García-Jurado2 & María-Ángeles Galvez-Moreno1
results were expressed as M? (25%; 75%).
1Endocrinology Service. Hospital Universitario Reina Sofia, Córdoba,
Results
Spain;2Radiology Service. Hospital Universitario Reina Sofia, Córdoba,
In NFA group, majority of patients (30/42, 71%) had isointensive T1-signal in the
Spain.
most common combinations with hyperintensive or isointensive T2 (18/42, 42.9
and 9/42, 21.4%, accordingly). NFA’s volumes did not differ between these
subgroups. In prolactinoma group 15/18 (83.3%) patients showed hyperintense
Introduction
T2 in the most common combination with isointensive T1 (7/18, 38.9%) and
Non-functioning pituitary adenomas
(NFPAs) represent the most common
hypointensive T1
(6/18,
33.3%). IsoT1/hyperT2
prolactinomas had bigger
pituitary tumour. They usually appear in the middle age of life, without
volume compared to hypoT1/hyperT2 ones. In somatotropinoma group 43/55
differences between genders. Mass growth produces the first symptoms so the
(78.2%) patients had hypointensive T1 in combinations with hypo-, iso- or
diagnosis is usually late. Surgery is the first-line treatment with variable success
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(19-83%). The objective of this study is to evaluate the symptoms, diagnosis,
EP909
treatment and final state of patients with NFPAs.
Cholinergic modulation of the hypothalamic-pituitary-adrenal activity
Methods
and somatotroph function in DM-1
Observational retrospective study of patients with NFPAs evaluated between
Jesús Pérez-Luis1,2, Judith López-Fernández1,2, Isabel Mascaren˜o1,2 &
January 2002 and December 2015 at “Hospital Universitario Reina Sofía” in
Javier Salvador3
Córdoba. Results were analysed with SPSS 18.0.
1Hospital Universitario de Canarias, Tenerife, Spain;2Universidad de La
Results
Laguna, Tenerife, Spain;3Hospital Universidad de Navarra, Pamplona,
34 patients, 50% women. Mean age: 56.2G11.9 years old. Mean follow-up: 5.2G
Spain.
3.9 years (range: 1-14 years). Symptomatology: 38.2% campimetric alterations,
35.3% headache and 11.8% symptoms derived from hormonal deficits. 29.4%
incidental diagnosis in magnetic resonance imaging. Mean diameter of tumour:
Introductions
30.2G11.4 mm. 64.7% extrasellar growth, 55.9% chiasmal compression, 23.5%
Alterations of the somatotrophic and hypothalamic-pituitary-adrenal (HPA) axes
grade I of Knosp classification. Initial treatment: 91.2% transsphenoidal surgery
occur frequently in patients with poorly controlled DM-1. These disorders could
(8.8% cabergoline).
64.7% post-surgery complications. Anatomopathological
be related to abnormalities in the cholinergic tone regulating both hormonal axes.
diagnosis: pituitary adenoma, except
1 patient with tissue necrosis;
11.8%
Subjects and Methods
patients had p53 positive; mean Ki-67: 2G2.4%. Only 5 patients were cured after
UFC (urinary free cortisol) on 24 h urine samples and the effects of placebo and
the first surgery (2 patients had recurrence) and 29 had radiological persistence of
pyridostigmine on ACTH, cortisol, GH and glucose circulating levels were
disease. Adjuvant treatment: cabergoline (10 patients), radiotherapy (11 patients),
studied in
16 young males: 10 normal controls and 6 patients with poorly
radiosurgery
(2
patients), second surgery
(10
patients) and third surgery
controlled DM-1 (HbA1c 9.2%) without retinopathy or nephropathy. Placebo or
(2 patients). Finally, 26.5% of patients are cured and 73.5% have persistent
pyridostigmine (120 mg) were given orally on different days at 0830. Blood
disease. Hormonal deficits:
44.1% pre-surgery and
79.4% post-surgery.
samples were drawn at 0830, 0900 and then every 15 min until 1130. Area under
Campimetry improved in all patients.
the curve (AUC) was calculated for the full sampling period and for 1 hour
Conclusions
intervals. Data are expressed as meanGSEM.
i) There are not differences in the prevalence of NFPAs by gender in our series.
Results
ii) The diagnosis was motivated by the symptomatology (predominantly visual);
UFC (47.21G7.29 vs 33.70G2.63 mcg/24 h, P!0.05), and GH and glucose
less frequent incidental diagnosis. iii) Most patients underwent transsphenoidal
levels were higher in diabetics than in controls, whereas ACTH and cortisol levels
surgery, being the success of this first surgery in our series less than the published
were not different. Pyridostigmine did not alter ACTH nor cortisol levels, while it
rates.
raised GH secretion within each group, with the greatest increase in diabetics
DOI: 10.1530/endoabs.49.EP907
(AUC 0-60 min: 149.46G82.34 vs 23.68G12.01 ng/ml/60 min, P!0.05). UFC
was negatively correlated with HbA1c. Basally, GH did not correlate with ACTH
nor cortisol levels.
Conclusions
The higher UFC figures in diabetics suggest some degree of hypercortisolism in
poorly controlled DM-1. Cholinergic activation in diabetics elicits GH
hyperresponse, but does not modify cortisol nor ACTH levels, either in diabetics
or controls. This fact speaks against an altered common mechanism in the
cholinergic system regulating somatotrophic and HPA axes in DM-1, suggesting
EP908
that cholinergic tone is not involved in the raised UFC excretion seen in these
patients.
Decreased prolactin levels in plasma and cerebrospinal fluid in naïve to
treatment patients with multiple sclerosis
DOI: 10.1530/endoabs.49.EP909
Agnieszka Baranowska-Bik1, Dorota Uchman2, Lidia Martynska3,
Malgorzata Kalisz3, Anna Litwiniuk3, Wojciech Bik3,
Boguslawa Baranowska2 & Jan Kochanowski2
1Department of Endocrinology, Centre of Postgraduate Medical Education,
Warsaw, Poland;2Department of Neurology, Medical University of
Warsaw, Warsaw, Poland;3Department of Neuroendocrinology, Centre of
EP910
Postgraduate Medical Education, Warsaw, Portugal.
Increased GH response to GHRH plus pyridostigmine unrelated to
augmented glomerular filtration rate in DM-1
Background
Jesús Pérez-Luis1,2, Judith López-Fernández1,2, Isabel Mascaren˜o1,2 &
Data from the literature has documented a remarkable immune-modulating role of
Javier Salvador3
prolactin. Previous evaluations of prolactin levels in patients with multiple
1Hospital Universitario de Canarias, Tenerife, Spain;2Universidad de La
sclerosis (MS), disease of autoimmune origin, showed conflicting results. Thus, to
Laguna, Tenerife, Spain;3Hospital Universidad de Navarra, Pamplona,
clarify the impact of prolactin on MS pathology we decided to assess prolactin
Spain.
levels in plasma and cerebrospinal fluid in naïve to treatment subjects with newly
diagnosed MS.
Material and methods
Introduction and Objectives
A total number of 83 individuals were included: 41 patients with MS (30
In patients with poorly controlled DM-1, the frequently observed alterations of
females/11 males) and 42 age-matched controls (36 females/6 males). All MS
somatotrophic axis seem to be related to abnormalities in the hypothalamic
subjects were newly diagnosed and they were without any treatment at the time of
cholinergic tone regulating this axis. The effects of cholinergic stimulation on GH
taking the samples of blood and cerebrospinal fluid. Prolactin was determined
responses to GHRH were evaluated in patients with poorly controlled DM-1 and
both in plasma and cerebrospinal fluid, and cytokines (TNF-alpha, IL-6, IL-10)
the relationship of these responses to metabolic control and kidney function tests.
were evaluated in plasma in all subjects.
Subjects and Methods
Results
Microalbuminuria and creatinine clearance (GFR) on 24 h urine samples, and the
Prolactin levels in plasma were found to be markedly lower in MS patient when
effects of GHRH plus placebo and plus pyridostigmine on GH and glucose
compared to those of the controls (7.64G5.99 ng/ml vs 10.12G6.76 ng/ml;
circulating levels were studied in
16 young males: 10 normal controls and
P!0.05). These results correspond with concentration of prolactin measured in
6 patients with poorly controlled DM-1 (HbA1c 9.2%) without retinopathy or
cerebrospinal fluid as in MS individuals prolactin was significantly decreased
nephropathy. On different days, placebo or pyridostigmine (120 mg) were given
(2.84G0.35 ng/ml vs 3.42G0.89 ng/ml; P!0.05). The comparison of cytokines
orally at 0830 and GHRH 50 mcg IV at 0930. Blood samples were drawn at 0830,
levels revealed no differences between the examined groups. A positive
0900 and then every 15 min until 1130. Response parameters were calculated.
correlation between prolactin concentration in plasma and TNF-alpha levels
Data are expressed as meanGSEM.
was found in MS subjects.
Results
Conclusion
GHRH raised GH levels within each group. However, while GH responses were
Decreased levels of prolactin may reflect disturbed pituitary activity as well as
not different between diabetics and controls after GHRH plus placebo, they were
disrupt immunological system regulation at the early stage of multiple sclerosis.
actually higher after GHRH plus pyridostigmine in diabetics (AUC of response of
Acknowledgment
GH: 4085.83G1227.86 vs 1914.46G385.06 ng/ml/120 min, P!0.05). GFR was
The study was supported with CMKP grant no.501-1-31-22-2015.
greater in diabetics, although not significant
(134.85G20.62
vs
110.12G
8.13 ml/min). GH was not correlated with glucose in any of the tests.
DOI: 10.1530/endoabs.49.EP908
Furthermore, HbA1c, microalbuminuria and GFR showed no correlation with
GH in diabetics.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
primary objective of the study is to assess the safety and efficacy of Omnitropew
In this study, the higher GH responses to GHRH plus pyridostigmine in diabetics
in adults treated in routine clinical practice, with particular emphasis placed on
suggest that there is an augmented cholinergic tone in poorly controlled DM-1
the risk of glucose intolerance or diabetes and normalisation of IGF-I levels.
patients. Furthermore, these findings are not related with the higher GFR observed
Results
in diabetics.
As of December 2016, 1121 patients had been enrolled on the study, of whom 586
DOI: 10.1530/endoabs.49.EP910
(52.3%) were pre-treated with another rhGH. Mean (standard deviation [SD])
. In total
patient age is 49.7 (15.3) years, and mean (SD) BMI is 29.4 (6.3) kg/m2
2455 adverse events (AEs) in 665 (59.3%) patients have been reported, with 444
(in 247 [22%] patients) of these regarded as serious. One hundred and thirty-nine
AEs in 80 (7.1%) patients were suspected to be drug-related; these included
general disorders/administration site conditions in 19 patients, nervous system
disorders in 23 patients and musculoskeletal/connective tissue disorders in 24
patients. A total of 26 serious AEs in 17 (1.5%) patients were suspected to be
EP911
related to Omnitropew treatment, including one incidence of diabetes. Of the 188
Increased morbidity associated with the treatment of
patients who discontinued treatment, 47 (25%) did so due to an AE.
craniopharyngioma
Conclusions
Cristina Capatina1,2, Anda Dumitrascu2, Andra Caragheorgheopol2 &
Based on this interim analysis, Omnitropew treatment in adults with GHD is well
Catalina Poiana1,2
tolerated in a real-life clinical practice setting, both in previously treated and
1Carol Davila University of Medicine and Pharmacy, Department of
rhGH-naïve patients. The ongoing PATRO Adults study will provide further data
Endocrinology, Bucharest, Romania;2C.I.Parhon National Institute of
on the diabetogenic potential and overall safety of long-term GH treatment in this
Endocrinology, Bucharest, Romania.
population.
DOI: 10.1530/endoabs.49.EP912
Background
Craniopharyngioma is a rare epithelial tumor of the central nervous system,
affecting both children and adults and associated with significant morbidity.
Objective
To study the posttreatment evolution of craniopharyngioma in children and adults
EP913
in a large mixed cohort.
Clinical case description of family with hereditary pituitary adenoma
Material and Methods
Tatiana Tarasova, Ekaterina Pigarova, Larisa Dzeranova, Anatoly Tulpakov
We performed a retrospective review of craniopharyngioma patients evaluated in
& Ivan Dedov
the National Institute of Endocrinology in Bucharest between 1990 and 2016.
Endocrinology Research Centre, Moscow, Russia.
Results
A total of 82 patients (59 adults, 39.27G15.5 years old; 23 children, 12.96G4.2
years old) with a mean follow-up of 6.85 years were included. All underwent
Introduction
surgery
(57
cases,
69.5% transcranial,
25
cases,
30.48% transsphenoidal
In recent years, more attention is driven to the cause of hereditary forms of
approach,), 34 being operated on more than once. 13 patients (15.85%) were
pituitary adenomas. Although for most cases causal genes are not discovered yet,
irradiated (1 before surgery, the others after). The surgical excision was complete
AIP mutations are the most prevalent.
in 26 cases (31.7%). Surgery led to anosmia (in 7 cases), CSF leak (3 cases),
Materials and Methods
subdural hematoma (2 cases). After surgery 21 cases (25.6%) had cognitive
Case descriptions, high-parallel sequencing using a gene panel (MEN1, CDKN1B,
impairment, 5 (6.09%) had hypothalamic syndrome (diurnal sleepiness, appetite
PRKAR1A, GNAS, AIP, SDHA, SDHB, SDHS, SDHD, PRKCA, CDKN2C,
and memory dysfunction). The endocrine dysfunction was aggravated after
CDKN2A, POU1F1, PTTG2).
treatment in 64 cases (78%), improved in 5 (6%) and stable in 14 cases (17%).
Case description
The evolution of the tumor revealed stable remnant in
29 cases
(35.3%),
Index case - a 59-year-old man with clinical features of acromegaly (the size of
progressively increasing remnant in 23 (28%), recurrence in 2 (3.4%) and cure in
adenomas at baseline 3.9!3.2!3.9 cm, growth 165 cm), secondary diabetes
28 cases (34.14%) during follow-up. There was no significant difference in the
mellitus, multinodular goiter, obesity I grade, arterial hypertension. First clinical
complications rate between children and adults.
symptoms were noted since the age of 30 years. At the age of 51 he underwent
Conclusions
transcranial adenomectomy, then at the age of
58
years
- transnasal
Craniopharyngioma is a tumor frequently necessitating repeated treatments,
adenomectomy. Because of persistent disease activity he was initiated medical
associated with very significant morbidity. The results and complications of
therapy with sandostatin analogs (40 mg of octreotide depo) without hormonal
treatment are similar in adults and children.
control of acromegaly - IGF 497.5 ng/ml (15-250) and GH 80 ng/ml (0-1.2).
DOI: 10.1530/endoabs.49.EP911
MRI after surgery pituitary adenoma with supra-, infra- and parasellar extension.
The patient’s
28-year-old son also has acromegaly
(intrasellar pituitary
macroadenoma at MRI (the size of adenomas 0.7!1.2!0.6 cm), first clinical
symptoms were noted since the age of 27 years, growth 167 cm, without
complication); he was operated transnasally at the age of 28 years without
postoperative remission: GH at OGTT
2.67-2.52-1.95-2.05-2.37 ng/ml, IGF
567.2 ng/ml (60-280). Genetic investigation revealed a mutation in exon 6 of the
EP912
AIP gene pR271W (not previously described, possible pathological).
Conclusion
The PATRO adults study of Omnitrope for the treatment of adult
AIP mutation in our family with hereditary pituitary adenoma is associated with
patients with growth hormone deficiency: latest results
high aggressiveness and resistance to medical therapy with somatostatin analogs.
Paolo Beck-Peccoz1, Charlotte Hoybye2, Robert Murray3, Suat Simsek4,
Markus Zabransky5 & Gunter Stalla6
DOI: 10.1530/endoabs.49.EP913
1Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Cà Granda
Ospedale Maggiore Policlinico, Milan, Italy;2Karolinska University
Hospital, Stockholm, Sweden;3St James’s University Hospital, Leeds, UK;
4Medisch Centrum Alkmaar, Alkmaar, The Netherlands;5Sandoz Inter-
national GmbH, Holzkirchen, Germany;6Max Planck Institute of
Psychiatry, Munich, Germany.
EP914
Molecular and genetic basis of the disease in families with pituitary
adenomas
Introduction
Tatiana Tarasova, Ekaterina Pigarova, Larisa Dzeranova, Anatoly Tulpakov
The ongoing, international, open, longitudinal, non-interventional study, PATRO
& Ivan Dedov
Adults, aims to determine the long-term safety and efficacy of Omnitropew
Endocrinology Research Centre, Moscow, Russia.
(Sandoz), a recombinant human growth hormone (rhGH). Safety data from an
interim analysis are presented here.
Methods
Introduction
Eligible patients are male or female adults who are receiving treatment with
Most of the work on the analysis of molecular genetic defects in pituitary
Omnitropew and who have provided informed consent. Patients treated with
adenomas devoted to the study of 1-2 candidate genes. The high-performance
another rhGH before starting Omnitropew therapy are eligible for inclusion. The
parallel sequencing is more promising.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Materials and Methods
pathways are known for the regulation of apoptosis. Additionally, these two
There were a total of 26 families (58 patients, 36 (62.1%) men and 22 (37.9%)
pathways could activate cAMP-response-element-binding protein (CREB), which
women) with pituitary adenomas secretion of various types. The number of
has been shown to promote cell survival. Therefore, their phosphorylation levels
families with homogenous type was 17 (somatotropinomas 13, prolactinomas 2,
in the cerebellum were compared between Sct-/- and WT mice. The basal levels
corticotropinomas 1, inactive pituitary adenomas 1), with a heterogeneous type -
of phosphor-ERK1/2
(pERK1/2) and phosphor-CREB
(pCREB) showed a
9
(7
of theses families had somatotropinomas/inactive pituitary adenomas,
significant decrease in Sct-/- mice, but not phosphor-AKT
(pAKT). The
2 families had prolactinomas/inactive pituitary adenomas. The number of family
cerebellar slices obtained from Sct-/- displayed a dose-dependent increase of
members with hypertension ranged from 2 to 7.The high-performance parallel
pERK1/2 and pCREB, but not pAKT, in response to graded concentrations of
sequencing was implemented with the gene panel (MEN1, CDKN1B, PRKAR1A,
secretin peptide and the impaired phosphorylation of ERK1/2 and CREB in Sct-/-
GNAS, AIP, SDHA, SDHB, SDHC, SDHD, PRKCA, CDKN2C, CDKN2A,
cerebellar slices was able to be recovered by the treatment of secretin compared
POU1F1, PTTG2).
with WT, suggesting the involvement of ERK1/2 and CREB. Specific inhibitors
Genetic investigation
were applied for further confirmation. Secretin failed to reduce the level of
According to a study in four patients with somatotropinomasidentified mutations
activated Caspase-3 when either ERK1/2 or CREB was inhibited, revealing that
were AIP p.R271W and p.A411GfsX47, one patient was identified with
ERK1/2 and CREB was required for secretin’s neuroprotective function. Our
polymorphisms with unproven value in pathological gene SDHA p.V589V, and
results clearly provide evidence that ERK1/2 and CREB play a role in mediating
one patient with the phenotype of McCune-Albright syndrome had heterozygous
the anti-apoptotic function of secretin.
p.S163P replacement in SDHB gene.
DOI: 10.1530/endoabs.49.EP916
Conclusion
The genetic changes using a multi-gene panel were identified in only 20% of
tested families. New gene candidates are highly needed for familial pituitary
adenomas.
DOI: 10.1530/endoabs.49.EP914
EP917
Predictors of remission after transsphenoidal adenomectomy in patients
with Cushing’s disease
Eugenia Marova, Galina Kolesnicova, Svetlana Arapova, Andrey Grigoriev
& Anasteysa Lapshina
EP915
Endogrinology Research Centre, Moscow, Russia.
Pituitary adenoma with gigantism and TSH-induced hyperthyroidism:
a case report
Abstract
M Gloria Baena-Nieto, Rosa Márquez-Pardo, Manuel Cayón-Blanco,
Cushing’s disease (CD) is the heavy disease of the hypothalamic-pituitary-
Lourdes García-García-Doncel, Rosario López-Velasco & Isabel M Torres-
adrenal axis. The cause of the disease is pituitary adenoma (corticotropinoma).
Barea
Hypersecretion of ACTH by a pituitary adenoma leads to increased secretion of
Hospital de Jerez, Jerez, Cádiz, Spain.
cortisol by the adrenal cortex and the development of total endogenous
hypercortisolism. The gold standard treatment for this disease is surgical removal
Abstract
of corticotropinoma. However, adenomectomy is not effective in all cases and
A 14-yr-old male patient with acromegaly and TSH-induced hyperthyroidism is
approximately 20% of cases after the radical treatment fails to achieve remission
reported. He was referred for hormonal study due to clinical suspicion of
of the disease and then comes the relapse. The aim of our work was to evaluate the
acromegaly. Physical examination showed acromegalic/gigantism features (high
factors influencing the result of adenomectomy in patients with the Cushing’s
stature:
194.5 cm (PO90), such as: abnormal growth of the hands and feet,
disease and identification of recurrence predictors. Materials and methods:
furrowed forehead and pronounced brow ridge). No goiter was found. GH levels
retrospective assessment of clinical and hormonal factors in 84 patients with CD,
were high and were not suppressed after oral glucose (GH: 12.50 ng/ml, GH after
influencing early and long-term results of adenomectomy.
glucose: 6.19 ng/ml; IGF-1: 1391 ng/ml); Serum thyroid hormones levels were
DOI: 10.1530/endoabs.49.EP917
high, although TSH levels were not suppressed (TSH: 0.96 mU/ml, T4: 3.57 ng/dl
T3:
11.06 pg/ml). Antithyroglobin, antimicrosomal autoantibody, and TSH
receptor antibody were negative. Gonadotropines, prolactine and ACTH leves
were normal
(Prolactina:
12.79 ng/dl, LH:
9.37, FSH:
4.56, Testosterona:
760.9 ng/dl, Cortisol:
5.9 mcgr/dl, ACTH: 15.1 pg/ml). A pituitary magnetic
resonance imaging of the pituitary revealed a 7-mm adenoma. He was diagnosed
of acromegaly and hyperthyroidism. Pre-operative treatmen with octreotide was
iniciated and transsphenoidal surgery was performed to remove the pituitary
adenoma. Post-operative serum thyroid hormone and GH levels returned to
EP918
normal, and IGF-1 levels were still elevated (786 ng/ml). Immunohistochemical
Copeptin after arginine infusion for the differential diagnosis of the
staining of the operative specimen showed positive reactions to both TSH and
polyuria-polydipsia syndrome “The CARGO-Study”
GH. Pituitary gigantism is a rare condition caused by growth hormone secreting
Bettina Winzeler, Nicole Nigro, Julie Refardt & Mirjam Christ-Crain
pituitary tumor. Choromophobe adenoma producing either acromegaly and
University Hospital Basel, Basel, Switzerland.
hyperthyroidism have been described in a limited number of cases none of them
on an infant.
Background
DOI: 10.1530/endoabs.49.EP915
The spectrum of polyuria-polydipsia syndrome (PPS) includes diabetes insipidus
(central or nephrogenic) and primary polydipsia. In clinical practice the
differential diagnosis particularly of central diabetes insipidus (cDI) and primary
polydipsia
(PP) is often difficult. The current gold standard
- the water
deprivation test (WDT) with or without vasopressin (AVP) measurements - lacks
reliable diagnostic accuracy. Arginine infusion is known to stimulate various
hormones secreted by the anterior pituitary gland such as growth hormone and
EP916
prolactin. Based on own preliminary data we hypothesized that arginine also
Secretin protects from apoptosis by activation of ERK1/2 and CREB
stimulates AVP mirrored by copeptin, the C-terminal part of the precursor
Lei Wang & Billy Chow
peptide. The aim of this study was to evaluate the diagnostic utility of copeptin
The University of Hong Kong, Hong Kong, Hong Kong.
measurements after arginine infusion in patients with PPS.
Methods
Between 2013 and 2017 patients with polyuria-polydipsia syndrome were
Abstract
included in this prospective study. Patients underwent first a standard water
There are a growing number of studies identifying secretin as a neuroprotective
deprivation test for diagnosis of PP or cDI and second an arginine infusion
factor. Consistently, our previous data showed that neuronal apoptosis
(L-Arginine Hydrochloride 0.5 g/kg body weight i.v. over 30 min). Blood was
considerably increased in the developing cerebellum from secretin knockout
withdrawn at different time points (e.g. 30, 45, 60 min) after arginine infusion for
(Sct-/-) mice. However, the underlying mechanisms remained poorly understood.
copeptin measurements. Additionally, 20 healthy controls underwent arginine
Extracellular signal-regulated protein kinase
(ERK) and AKT signalling
infusion without prior WDT.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
have been reported as immune-related adverse effects. However, nivolumab-
A total of 51 patients (63% female) were enrolled. 28 (55%) patients were
induced hypophysitis has a lower incidence than ipililumab.
diagnosed with PP, 11 (22%) with complete DI and 12 (23%) with partial DI. The
Case report
study was terminated in January 2017. Final results of copeptin levels will be
A 69-years old man with metastatic melanoma started to receive nivolumab. Ten
measured in batch analysis in February 2017 and compared between patients with
weeks after the first cycle of nivolumab he presented hyperthyroidism in blood
complete cDI, partial cDI and PP as well as 20 healthy volunteers. We would be
test. As it was suspected Hashimoto’s thyroiditis none antithyroid drug was
delighted to present the final results of this study at the 19th European Congress of
started. The thyroid scintigraphy and the presence of anti-thyroid peroxidase
Endocrinology.
antibodies confirmed the diagnosis and the thyroid function was monitoring.
Significance
Forty days later, the laboratory findings showed hypothyroidism and levothyr-
If our hypothesis is true, copeptin measurements after arginine infusion are a
oxine was provided. Nivolumab treatment continued to be administered. Three
promising new tool in the differential diagnosis of polyuria-polydipsia syndrome
months later, the patient was admitted because of general weakness and mild
with the advantage of short and safe test protocol.
confusional state. Blood test showed severe hyponatremia (110 mEq/l) with a
DOI: 10.1530/endoabs.49.EP918
decreased plasma osmolarity
(250 mOsm/kg). Adrenal insufficiency was
suspected so a new blood sample was taken in order to determine cortisol
(2.68 mg/dl) and ACTH (! 5 pg/ml) and hydrocortisone treatment was beginning
promptly. The assessment of hypothalamic-pituitary-gonadal axis showed a slight
decrease in testosterone (1.24 ng/ml) with LH and FSH normal levels. Insulinlike
growth factor-1 (IGF-1) was normal, as well as prolactin. Thyroid function was
abnormal because of discontinuation of treatment with levothyroxine: TSH
25.47 mUI/ml, FT4 0.39 ng/dl. Magnetic resonance imaging scan was performed
EP919
and it was reported as mild enlargement of the pituitary gland and the stalk.
Diabetes mellitus in Cushing’ syndrome: a systematic review
Hydrocortisone treatment was continued after the patient was discharged from
Thizá Londero1,2, Ana Marina Moreira1,2, Cristiane Leita˜o1,2,
hospital. Two weeks later, normal sodium levels were showed in biochemical test.
Ticiana Rodrigues1,2 & Mauro Czepielewski1,2
Discussion
1Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil;2Universidade
Monoclonal antibodies used in malignant melanoma as ipililumab or nivolumab
Federal do Rio Grande do Sul, Porto Alegre, Brazil.
could cause several endocrine auntoimmune disorders. Despite hypothyroidism is
a common adverse effect, hypophysitis is a rare finding associated to nivolumab in
Introduction
contrast to ipililumab. Clinicians should suspect this pathology in order to achieve
Diabetes mellitus (DM) is an expected condition in Cushing syndrome (CS) but
a promptly diagnosis.
there are few data about prevalence and factors associated to occurrence of DM in
DOI: 10.1530/endoabs.49.EP920
these patients.
Objective
To determine the main aspects of DM in CS through a systematic review (SR) of
the literature.
Methods
MEDLINE and LILACS were searched for studies published until March, 2016.
Search strategy comprised the terms “Diabetes Mellitus”, “Glucose Intolerance”,
“Hyperglycemia”,
“Cushing Syndrome”,
“Pituitary ACTH hypersecretion”,
“diabete melito”,
“Cushing”. Observational/interventional studies in patients
with endogenous CS with characterization of DM were included. We excluded
case reports, animal models, and studies about exogenous hypercortisolism or
EP921
subclinical CS.
Kallmann syndrome: about eleven clinical cases
Results
Liliana Fonseca, Claúdia Amaral, Jorge Dores, Isabel Palma, Rui Carvalho,
The initial search yielded 726 titles, 58 were full-text reviewed. Of these, 12 were
Helena Cardoso, Joana Vilaverde & Fátima Borges
included in RS. Seven studies (all cross-sectional) accessed DM prevalence. Most
Centro Hospitalar e Universitário do Porto, Porto, Portugal.
patients were women (93.5%) aged 40-50 years, with disease duration between
29 and 180 months. Pituitary, adrenal and ectopic-ACTH were origin of CS in 325
(70.65%), 134 (29%) and 2 (0.5%) patients, respectively. DM prevalence ranged
from 17 to 47%. Four studies evaluated the role of body mass index (BMI) on DM
Idiopathic congenital hypogonadotropic hypogonadism (CHH) is a rare
occurrence, but none of them found a statistically significant difference. Two
reproductive disorder that is primarily caused by a gonadotrophin-realising
studies demonstrated a higher risk of DM in older ages at CS diagnosis. The
hormone (GnRH) deficiency. When CHH is associated with hyposmia or
correlation of DM and severity of hypercortisolism was analysed in four articles
anosmia is designated by Kallmann Syndrome (KS). This syndrome is a
and two of them presented a positive result. The effect of CS remission on DM
genetic disorder with significant genetic heterogeneity that may present as a
cure was accessed by two studies, with discordant results. DM was associated
sporadic or familial case, following autosomal dominant, autosomal
with higher mortality. Three studies (open-label trials) analysed effect of CS drug
recessive, or X - linked recessive modes of inheritance. This work aim is
therapy on glycaemic control. Mifepristone demonstrated a diabetes improvement
to review all KS cases followed in the Endocrinology service. A total of 11
after 6 months, as rosiglitazone after 30-120 days.
cases were evaluated, 10 men and 1 woman. Patients were mainly diagnosed
Conclusion
in late adolescence, between 17 and 18 years old, when sought a doctor for
DM is a frequent CS comorbidity and its occurrence seems to depend on age at
delayed puberty. All cases presented hypogonadotropic hypogonadism and
diagnosis and disease duration. If CS remission leads to DM remission is still
hyposmia or anosmia with MRI olfactory bulb atrophy criteria. No other
uncertain.
changes in the neuroendocrine axis were found. The patients were followed
DOI: 10.1530/endoabs.49.EP919
between 2 and 33 years (mean time 12 years). All had gonadal steroid
hormones treatment (testosterone or estrogens) and had a good secondary
development of the sexual characteristics, Tanner stage IV/V. Three patients
had fertility therapy with gonadotropin and until now only the girl had
clinical improvements. Four cases made a genetic study: two mutations in
KAL1 gene, one in FGFR1, and one in PROK2 were found. The two patients
with KAL1 mutation presented cryptorchidism and one the two also had
unilateral renal agenesis. The patient with FGFR1 mutation also had an
EP920
history of cryptorchidism. The one with recessive mutation for PROK2 only
Thyroiditis and hypophysitis caused by nivolumab
presented anosmia and hypogonadotropic hypogonadism.
Leticia Perez Fernandez, Isabel Azcona Monreal, María Martinez Garcia,
Conclusion
Maria Elena Lopez Alaminos, Pablo Trincado Aznar, Diana Boj Carceller,
The presence of a delayed pubertal development is suspicious of CHH/KS
Diego Alvarez Ballano & Patricia de Diego García
occurrence. In our study, patients with KS presented good clinical results with the
H.U. Miguel Servet, Zaragoza, Spain.
use of gonadal steroid hormones attaining stages IV/V of Tanner. Women appear
to have better fertility responses to therapy than men, although this findings
Introduction
demand further investigation.
Nivolumab is an anti-programmed cell death-1 monoclonal antibody approved for
DOI: 10.1530/endoabs.49.EP921
the treatment of metastatic malignant melanoma. Several endocrine disorders
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Paediatric endocrinology
Methods
Retrospective observational study with analysis of clinical records of children and
EP922
adolescents with GHD under treatment with GH in the period from 2012 to 2016.
Endocrine manifestations of multisystem Langerhans cell histiocytosis
Statistical analyses were performed using SPSS 24.0 for Windows.
Diana Oliveira1, Flavia Napoli2, Enrica Bertelli2, Alessandra Maggioni2,
Results
Sandra Paiva1, Francisco Carrilho1 & Natascia Di Iorgi2
The final sample consisted in 49 patients, 61.2% were male. Mean age at the
1Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital
beginning of therapy was 9.7G4 years (0.13-16.92). Mean height z-score at time
and University Center, Coimbra, Portugal;2Pediatric Clinic, Endocrinology
of diagnosis was K3.16G0.94, corresponding the mean z-score of the target
and Diabetes Unit, IRCCS G Gaslini, University of Genova,
height to K1.24G0.77. The mean delay in bone age was 2.22G1.50 years (0-6.5
Genova, Italy.
years). Two growth hormone stimulation tests (clonidine and L-Dopa) were
performed in 69.4% of the cases. Brain MRI showed changes in 42.9% of the
cases. Of the
49 patients,
55.1% had an idiopathic GHD, 30.6% isolated
Introduction
deficiency and 14.3% had multiple deficiencies. Mean age at the time of diagnosis
Multisystem Langerhans cell histiocytosis
(LCH) is a rare heterogeneous
was 11.16, 8.84 and 6.57 years in the three groups respectively. Mean treatment
disorder caused by accumulation in multiple organs of dendritic cells
duration was 3.92 years (in 14.2% less than 1 year). The z-score variation in the
phenotypically similar to cutaneous Langerhans cells. Pituitary involvement
group of idiopathic GHD was 0.99, 1.50 and 2.53 in the group of isolated and
is present in about 25% of cases, and central diabetes insipidus is the most
multiple deficiencies respectively.
common deficit in that setting. Panhypopituitarism is rare, but hypothalamic-
Discussion
pituitary dysfunction is amongst the most frequent long-term complications of
As previously described, GHD is more prevalent in males. Comparing the three
the disease.
groups, patients with multiple deficiency are diagnosed earlier and have better
Case report
results with the treatment (higher z-score variation).
We describe the case of a child with normal health status until the age of 7. He
developed polyuria and polydipsia, was hospitalised and submitted to a water
DOI: 10.1530/endoabs.49.EP923
deprivation test, considered indicative of psychogenic polydipsia. At 14-years-
old, elevated liver enzymes were attributed to EBV infection. Liver ultrasound
showed hepatomegaly and heterogeneous echotexture. At
16-years-old, he
presented with hypernatremia, delayed puberty and short stature, as well as slowly
progressive dyspnea. Investigation revealed multiple pituitary deficits (hypogo-
nadotrophic hypogonadism, secondary hypothyroidism, secondary adrenal
insufficiency, growth hormone deficit) and central diabetes insipidus. Brain
magnetic resonance imaging showed a hypothalamic mass (17 mm). He was
started on hormonal replacement therapy
(urofollitropin, human chorionic
gonadotropin, levothyroxine, cortisone, desmopressin). LCH was suspected,
Pituitary - Basic
and chest computed tomography revealed multiple cystic pulmonary lesions
suggestive of the diagnosis, later confirmed by pulmonary biopsy. He started
EP924
standard treatment with vinblastine and prednisone, with intermediate response
SSTR2 inhibits GH-secreting pituitary tumoral cells migration and
after 6 weeks. He developed glucocorticoid-induced diabetes and needed multiple
invasion by increasing cofilin phosphorylation
daily injections of insulin.
Erika Peverelli1, Elena Giardino1, Donatella Treppiedi1, Marco Locatelli2,
Conclusions
Andrea G Lania3, Maura Arosio1, Anna Spada1 & Giovanna Mantovani1
This case report illustrates the importance of investigating multiple signs and
1Endocrine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore
symptoms that arise in a multisystem and complex disorder. In this case, the
Policlinico; Department of Clinical Sciences and Community Health,
endocrine consequences of LCH assume a central role. As was the case here,
University of Milan, Milan, Italy;2Neurosurgery Unit, Fondazione IRCCS
central diabetes insipidus can be the first manifestation of the disease, but its
Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;3Endocrine Unit,
diagnosis is not always straightforward. Early diagnosis can prevent or delay
IRCCS Humanitas Clinical Institute, Humanitas University, Rozzano, Italy.
permanent complications associated with multisystem disease; pituitary deficits,
once established, are mostly permanent.
DOI: 10.1530/endoabs.49.EP922
Although generally benign, pituitary tumors frequently present local
invasiveness that strongly reduces neurosurgery success. We recently
demonstrated a role for the actin binding protein cofilin in promoting non
functioning pituitary tumors invasiveness and an inhibitory effect of
dopamine receptor type 2. Somatostatin (SS) receptor type 2 (SSTR2) is
the main target of pharmacological therapy of GH-secreting pituitary
tumors, reducing both GH secretion and cell proliferation, but its effects on
cell invasion have never been investigated. Aims of this study were: i) to
evaluate the effects of SSTR2 agonist on migration and invasion of rat
somatomammotroph GH3 cells and human GH-secreting pituitary tumoral
cells, and ii) to investigate the molecular mechanisms focusing on the role of
cofilin and the cytoskeleton protein FLNA, that directly interacts with
EP923
SSTR2. Our data demonstrated that SSTR2 agonist BIM23120 incubation
Growth hormone deficiency - the experience of one pediatric
significantly reduced migration (31.3%G12.2%, P!0.01) and invasion on
endocrinology unit of a Portuguese hospital in the last 5 years
collagen IV (22%G3.6%, P!0.001) of GH3, these data being replicated in
Jorge Abreu Ferreira, Fábio Barroso, Cristiana Martins, Joana Freitas,
human GH-secreting tumoral cells (14G2.9% and 41.7G11.3% reduction
Helena Cardoso, Maria João Oliveira & Teresa Borges
of cell migration and invasion, respectively, P!0.05). Moreover,
Paediatric Endocrinology Unit - Centro Materno Infantil do Norte - Centro
BIM23120 induced a marked increase of phosphorylated (inactive) cofilin
Hospitalar e Universitário do Porto, Porto, Portugal.
in both GH3 and primary tumoral pituitary cells (about 2.7 and 2.1-fold over
basal, respectively). This effect was completely abolished by specific ROCK
inhibitor Y27632 but not by pertussis toxin, suggesting an involvement of
Introduction
Rho/ROCK/LIMK pathway and excluding a role for inhibitory hetero-
Hypopituitarism is a clinical syndrome of deficiency in growth hormone (GHD)
trimeric G proteins. Co-immunoprecipitation experiments revealed an
production, which can occur isolated or associated with others pituitary defects.
association of SSTR2 with FLNA, cofilin and LIMK1, suggesting a role
GHD has an incidence of 1:4000 to 1:10 000. It may be idiopathic, congenital or
for FLNA as scaffold protein mediating SS effects on cofilin pathway. In
acquired.
conclusion, our data revealed an inhibitory effect of SSTR2 on GH-secreting
Purpose
pituitary tumor cells migration and invasion involving ROCK-dependent
Characterize the paediatric population with GHD followed at the Paediatric
phosphorylation of cofilin.
Endocrinology Unit of our centre and compare the clinical presentation and
DOI: 10.1530/endoabs.49.EP924
treatment response of the patients with an idiopathic form with the ones with
isolated and multiple hormonal deficiencies.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP925
EP927
Anti-proliferative effect of sodium metaarsenite (KML001) on
Ketoconazole induces inhibition of cell viability and apoptosis in an
ACTH-secreting pituitary adenoma cells
ACTH-secreting tumour cell line model
Dong Sun Kim1, Jung Hwan Park1 & Yeon-Ah Sung2
Roberta Patalano1, Claudia Pivonello1, Domenico Solari2,
1Department of Internal Medicine, Hanyang University College of
Francesca Vitulli2, Davide Iacuaniello1, Monica De Leo1,
Medicine, Seoul, Republic of Korea;2Department of Internal Medicine,
Mariarosaria Negri1, Donatella Paola Provvisiero1, Luigi Maria Cavallo2,
Ewha Womans University School of Medicine, Seoul, Republic of Korea.
Paolo Cappabianca2, Annamaria Colpo1 & Rosario Pivonello1
1Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia,
Università Federico II di Napoli, Naples, Italy;2Dipartimento di
Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Sezione di
KML001 is an orally bioavailable and water soluble trivalent arsenic
Neurochirurgia, Università Federico II di Napoli, Naples, Italy.
compound having anti-cancer activity via controlling the numerous
signaling pathways including phosphoinositide 3-kinase (PI3K)/Akt and
extracellular signal-regulated kinase (ERK) signaling pathways. PI3K/Akt
and ERK signaling pathways are overactivated in adrenocorticotropic
Chronic cortisol excess as a consequence of ACTH overproduction from a
hormone (ACTH)-secreting pituitary adenoma. In this study, we evaluated
pituitary tumour is responsible for the development of Cushing’s disease
the effects of KML001 on cell viability, cell cycle, apoptosis, and ACTH
(CD). The first-line treatment for CD is pituitary surgery, but medical
secretion in mouse ACTH-secreting pituitary adenoma cells, AtT-20 cells.
treatment is an alternative second-line approach to control cortisol excess.
KML001 inhibited the cell viability in time-dependent and concentration-
Among pharmacological agents, the adrenal-blocking drug ketoconazole
dependent manners and significantly decreased the ACTH secretion in a
(KT), is able to control cortisol excess in the majority of patients with CD.
concentration-dependent manner. As the treatment time or treatment
During KT treatment, the adrenal block of cortisol production is expected to
concentration increased, KML001 significantly increased the percentage
induce increase in ACTH levels, but conflicting data demonstrated ACTH to
of AtT-20
cells in apoptosis. As the treatment time or treatment
be increased, unchanged or decreased, suggesting a possible direct KT effect
concentration increased, KML001 significantly increased the percentage
on the pituitary tumour. The aim of the current study was to evaluate the
of AtT-20
cells in the G0/G1
phase and significantly decreased the
effects of KT on cell viability and apoptosis in mouse corticotroph tumour
percentage of AtT-20 cells in the S and G2/M phases. The effect of KML001
cell line (AtT20-D16). MTT assay was assessed to evaluate cell viability and
on numerous signaling pathways was determined by western blots. The
to evaluate the induction of cell apoptosis the study of mitochondrial
phosphorylated form of Akt and mammalian target of rapamycin (mTOR)
membrane potential by JC-1 assay and of PARP cleavage by western blot
proteins were decreased in KML001-treated AtT-20 cells. The phosphory-
were performed. KT induced a dose- (from 10-12 M to 6!10-5 M,
lated form of ERK protein was also decreased in KML001-treated AtT-20
concentrations covering KT therapeutic range of 200-1200 mg/daily) and
cells. However, the phosphorylated form of p38 and JNK protein were
time - (from 24 h to 144 h) dependent inhibition of cell viability (82.4%,
increased in KML001-treated AtT-20
cells. Consequently, KML001
P!0.0001 at
6!10-5M, 84.4% P!0.0001 at 4!10-5 M, 81.1%
inhibited cell proliferation in ACTH-secreting pituitary adenoma cells via
P!0.0001 at 2!10-5 M and 34% P!0.01 at 10-5 M after 144 h). KT
inhibition of cell cycle by inhibition of PI3K/Akt and ERK signaling
treatment at 24 and 48 h induced depolarization of mitochondrial membrane
pathways and induction of apoptosis by activation of p38-MAPK and JNK
potential
(108%, P!0.027 at IC50 2.5!10-5 M) followed by PARP
pathways and might reduce ACTH secretion. These results suggest that
cleavage, confirming the activation of apoptosis. In conclusion, these
KML001 could be a candidate for the treatment of persistent or recurrent
preliminary data suggest that KT has a direct effect on pituitary tumour
Cushing’s disease.
significantly reducing cell viability and inducing apoptosis on a corticotroph
DOI: 10.1530/endoabs.49.EP925
tumour cell model, shedding new light on the possible mechanisms by which
KT may control cortisol excess in CD.
DOI: 10.1530/endoabs.49.EP927
EP926
Angiogenesis-related proteins in pituitary adenomas
Ninelia Minaskan Karabid1, Michael Atkinson2 & Natalia Pellegata1
EP928
1Institute of Diabetes and Cancer (HMGU), Munchen, Germany;2Institute
GPR101 orphan receptor: a novel cause of growth hormone
of Radiation Biology (HMGU), Munchen, Germany.
deregulation
Dayana Abboud1, Adrian Daly2, Nadine Dupuis1, Céline Laschet1,
Bernard Pirotte3, Albert Beckers2 & Julien Hanson1,3
1
Laboratory of Molecular Pharmacology, GIGA-Molecular Biology of
Pituitary adenomas are frequent intracranial tumors that often associate with
disease, University of Liege, Liege, Belgium;2Department of Endo-
the hypersecretion of pituitary hormones or may be non-secreting
crinology, CHU of Liege, Domaine Universitaire du Sart-Tilman, Liege,
(nonfunctioning pituitary adenomas, NFPA). Tumors resembling human
Belgium;3Laboratory of Medicinal Chemistry, Centre for Interdisciplinary
NFPAs develop with complete penetrance in rats affected by the multiple
Research on Medicines (CIRM), University of Liege, Liege, Belgium.
endocrine neoplasia syndrome, MENX. This syndrome is caused by a
germline loss of function mutation in p27Kip1. Gene expression array
analysis performed in our group identified a considerable number of genes
deregulated in rat pituitary tumors compared to normal pituitary tissues.
GPR101 is an orphan G-protein coupled receptor with unknown ligand. In
Some of the deregulated transcripts are associated with angiogenesis,
2014, an international study clearly pointed to a strong association between
including vascular endothelial growth factor (Vegf), angiopoietin-1 (Ang-1)
this receptor and the X-linked acrogigantism (X-LAG) syndrome, which
and -2 (Ang-2). VEGF and ANG-2 were found to promote angiogenesis in
begins in childhood and causes the “tallest giants”. The children (carriers of
several tumor types, while ANG-1 inhibits this process and stabilizes mature
the GPR101 duplication on the X chromosome) grow abnormally even
vessels. We analyzed mRNA and protein expression changes of these 3
before they are one year old, secrete phenomenal quantities of growth
genes in the pituitary adenomas of MENX-affected rats and compared the
hormone, and develop pituitary adenomas that do not respond to current
results with similar analyses conducted on the corresponding human tumors.
therapies. The mechanism by which GPR101 contributes to increased
We could show that Ang-1 was down regulated in rat and human NFPAs
growth hormone secretion is currently not known. Nevertheless, the lack of
whereas Ang-2 mRNA was highly expressed in almost all of the rat pituitary
mechanistic insight into the function of GPR101 precludes its validation as a
adenomas and was enhanced in less than the half of the human NFPAs. Vegf
drug target. This lack of knowledge on GPR101 is the consequence of the
mRNA was up-regulated in MENX-rats but not in NFPAs. At the protein
paucity of specific pharmacological/research tools currently available.
level, we have so far set up the immunohistochemical staining for Ang1 and
Therefore, we propose to study GPR101 functions and its role in growth
-2 on both rat and human tumors. We could show that rat pituitary adenomas
hormone regulation. First, we determined the receptor precise cellular
and human NFPAs show reduced cytoplasmic Ang-1 staining compared to
localization and trafficking. We also deciphered its constitutive signalling
adjacent non tumor cells while Ang-2 was more strongly expressed in tumor
pathways by detecting high cAMP levels as well as arrestin recruitment to
areas.
GPR101. We completed our study with an examination of receptor coupling
DOI: 10.1530/endoabs.49.EP926
to other pathways and G proteins. In parallel, we screened small molecule
libraries in order to identify GPR101 specific ligands, to establish the link
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
between GPR101 and X-LAG with a pharmacological approach. Further-
EP931
more, we applied targeted mutagenesis to modulate the receptor constitutive
Whole exome sequencing of two non-secreting pituitary adenoma
activity in order to understand the receptor function at a molecular level.
tumors from the same patient
These GPR101 mutants will help us to understand the role of this receptor in
Vita Rovite1, Raitis Peculis1, Inga Balcere4, Janis Stukens2, Ilze Konrade4,
GH regulation and/or to treat people suffering from pituitary dysfunction.
Andra Valtere4, Jurijs Nazarovs2, Olivija Caune4, Valdis Pirags2,3 &
This information is an absolute prerequisite to link molecular pharmacology
Janis Klovins1
of GPR101 with physiological functions.
1Latvian Biomedical Research and Study Centre, Riga, Latvia;2Pauls
DOI: 10.1530/endoabs.49.EP928
Stradins Clinical University Hospital, Riga, Latvia;3Faculty of Medicine,
University of Latvia, Riga, Latvia;4Riga Eastern Clinical University
Hospital, Riga, Latvia.
Pituitary adenomas (PA) are benign tumors that develop in pituitary gland.
Hormone secreting PA can cause overproduction of pituitary hormones leading to
different systemic endocrine disorders
(acromegaly, Cushing’s disease and
others). Non-secreting PA can promote headaches (stretching of the dural sheath)
and visual field defects (chiasma compression). We managed to obtain resected
EP929
tumor samples from the patient having non-secreting PA, first tumor was resected
Potential role of biguanides and statins in the treatment of pituitary
in 2010, after operation patient had rapid regrowth and second resection was
adenomas
performed in 2012. Patient had two AIP gene variants rs641081 and rs4930199 in
Mari C. Vázquez-Borrego1, Antonio C Fuentes-Fayos1, Alejandro
genomic DNA. Whole exome sequencing of both tumors and genomic DNA from
Ibán˜ez-Costa1, Cristobal Blanco-Acevedo2, Eva Venegas-Moreno3,
white blood cells was carried out using single end sequencing in 3 batches on
María A Gálvez-Moreno4, Alfonso Soto-Moreno3, Justo P. Casta
˜o1 &
IonProton semiconductor sequencing system with average coverage 10x. Data
Raúl M. Luque1
analysis was performed using Galaxy main server
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC); Reina
Variants were annotated using Annovar tool and obtained variants filtered.
Sofia University Hospital (HURS); Department of Cell Biology, Physiology
SNVs were filtered according to following parameters: sequencing depth O10,
and Immunology, University of Cordoba; CIBER Physiopatho, Cordoba,
base Q at SNV position O13, non-synonymous SNV or stop-gain or stop-loss
Spain;2Neurology Service, HURS/IMIBIC, Cordoba, Spain;3Metabolism
SNV, variation represented on both strands. Remaining SNV were manually
and Nutrition Unit, Virgen del Rocío Hospital; Biomedical Institute of
inspected for irregularities using IGV. 9 non-synonymous SNVs were found in
Seville (IBIS), Seville, Spain;4Service of Endocrinology and Nutrition,
both tumors and not in genomic DNA, further 24 additional nonsynonymous
HURS/IMIBIC, Cordoba, Spain.
SNVs were found in the second tumor that were not present in the first. The
detected alterations include ALKBH8, ASB12, CST1, CLMN, PRSS41, ENPP1,
E2F6 and SNVs in other genes, that are described to influence various cell
Pituitary adenomas (PA) comprise a commonly underestimated pathology in
functions, like regulation, signalling and cell cycle. All SNVs still to be validated
terms of incidence and associated morbimortality. To date, somatostatin and
by Sanger sequencing. Our findings indicate that second tumor had increased
dopamine analogs represent the main medical treatment, but an appreciable
number of variations compared to first tumor, that could be caused by regrowth of
subset of patients are resistant or poorly responsive to these drugs. Therefore, the
second tumor from specific cell subpopulation from initial PA. Exome sequencing
search for new approaches to control tumor growth and/or hormone secretion is
helps to discover genetic spectrum of known PA gene alterations and reveals new
crucial. Biguanides such as metformin (MF; commonly used to treat type-2
potential PA causative factors.
diabetes), phenformin
(PF) and buformin
(BF) have been shown to exert
DOI: 10.1530/endoabs.49.EP931
antitumor actions in different tumor types. Likewise, statins (such as atorvastatin
or simvastatin) treatment have been also related to antineoplastic effects in several
tumor types. Accordingly, the aim of this study was to elucidate the direct effect
of biguanides and statins, alone or in combination, on key functional parameters
(i.e. cell viability, hormone secretion, etc.) in human PA cell-cultures [non-
functioning pituitary adenomas (NFPAs; nZ8), corticotropinomas (ACTHomas;
nZ7) and somatotropinomas (GHomas; nZ4)] and/or rodent pituitary cell-lines
(AtT-20 and GH3). The results showed that biguanides and statins clearly
inhibited cell viability in pituitary cell-lines (being PF and simvastatin the most
EP932
effective compounds, respectively), and a similar effect was also observed with
Ubiquitin specific peptidase 8 (USP8) in human corticotroph pituitary
biguanides in all PA-subtypes. Additionally, the co-administration of biguanides
tumors- possible targets and mode of action
and statins did not alter the initial inhibitory actions of these compounds
Isabel Weigand1, Lisanne Knobloch1, Jens T. Vanselow2, Jorg Flitsch3,
separately in cell lines, which might suggest that biguanides and statins exert their
Carmelia M Monoranu4, Wolfgang Saeger5, Christian Hagel5,
effects through common signaling pathways. In addition, biguanides were able to
Sabine Herterich6, Cristina Ronchi1, Andreas Schlosser2,
significantly reduce GH and ACTH secretion in GH3 and AtT-20 cell lines,
Martin Fassnacht1,6, Timo Deutschbein1 & Silviu Sbiera1
respectively. Taken together, our results reveal a clear inhibitory effect of
1Division of Endocrinology and Diabetes, University Hospital Wuerzburg,
biguanides and statins on PA cell viability and, given their demonstrated clinical
Wuerzburg, Germany;2Rudolf Virchow Center for Experimental Biome-
safety, suggest a potential therapeutic role of these compounds for the treatment
dicine, University of Wuerzburg, Wuerzburg, Germany;3Neurosurgery,
of patients with PA.
University Hospital of Hamburg-Eppendorf, Hamburg, Germany;4Institute
Funding
of Pathology, University of Wuerzburg, Wuerzburg, Germany;5Institute of
Junta de Andalucia (CTS-1406, BIO-0139), MINECO (BFU2013-43282-R),
Neuropathology, University Hospital Hamburg-Eppendorf, Hamburg,
CIBERobn and Merck Serono. CIBER is an initiative of Instituto de Salud Carlos
Germany;6Central Laboratory, University Hospital, University of
III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain.
Wuerzburg, Wuerzburg, Germany.
DOI: 10.1530/endoabs.49.EP929
Recently, somatic, heterozygous mutations in the gene encoding the deubiqui-
tinase USP8 have been identified in 30-60% of corticotroph tumors. These
mutations were found to hinder binding of
14-3-3
proteins, increasing its
deubiquitinating activity. One substrate is Epidermal Growth Factor Receptor
(EGFR), USP8 triggering EGFR recycling and increased EGFR signaling.
However, tumors harboring mutations in USP8 are smaller than WT tumors,
EP930
raising the debate if EGFR, as a potent growth factor, is the only substrate of
USP8 in these tumors. We aimed to identify other putative USP8 targets that
might explain the tumorigenesis and increased ACTH secretion of these cells. A
Abstract withdrawn.
literature search revealed several proteins with deregulated expression associated
with corticotroph tumors that might be the result of increased USP8
deubiquitination (such as the transcription factors TR4 and CREB). Candidates
were analyzed by IHC for their expression levels on FFPE tissue (corticotrophs
(nZ54), functionally inactive
(nZ19), somatotrophs (nZ12) adenoma and
normal pituitary glands (nZ5)). We further metabolically labeled, transiently
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
transfected the murine corticotroph cell line AtT-20 with USP8 WT or mutant
prolactinoma patients according to our previous genechip study. In this study, we
plasmids and performed Tandem-Ubiquitin-Binding-Entity
(TUBE)-assays,
demonstrated that PP4C was crucial for D2R expression and PRL secretion in rat
followed by nanoLC-MS/MS analysis to identify changes in poly-ubiquitinated
pituitary MMQ cells.
protein abundance. Of the 10 analyzed proteins by IHC, 4 had an altered
Methods
expression pattern between USP8 WT and mutated tumors, namely p27/kip1
In this study, we used rat pituitary MMQ cells which could secrete abundant
(mean expression: 1G0.8 vs 0.4G0.6 (PZ0.01), HSP90 (mean expression: 1.8G
prolactin and express functional dopamine receptors. RNA interference on PP4C
0.8
vs
0.7G0.8 (PZ0.03), CRHR (mean expression: 0.4G0.5 vs 0.6G0.7
gene was carried out in rat pituitary MMQ cells. The pCDH vector was used as a
(PZ0.2) and PRKACA (mean expression: 0.6G0.8 vs 1.1G0.6 (PZ0.1). TUBE
PP4C overexpression system to assess the functional consequences of PP4C
assays revealed an increased de-ubiquitination of Small Ubiquitin-Like Modifier
overexpression. Total RNA and proteins were extracted from rat pituitary MMQ
3
(SUMO3) in USP8mut transfected cells, suggesting co-occurrence of another
cells after PP4C silencing or overexpression. Q-PCR method was used to detect
post-translational protein modification. In conclusion, these results suggest a
the changes in D2R mRNA levels. And western blotting was used to detect the
much more complicated mechanism of action of the identified mutations in USP8,
changes in D2R protein levels. Enzyme-linked immunosorbent assay (ELISA)
with sumoylation adding another dimension to the regulation of a USP8 mediated
was carried using ELISA kit for rat PRL.
equilibrium between degradation and recycling.
Results
DOI: 10.1530/endoabs.49.EP932
PP4C silencing increased D2R expression and decreased PRL secretion in rat
pituitary MMQ cells. PP4C overexpression reduced D2R expression and
enhanced PRL secretion in rat pituitary MMQ cells.
Conclusion
Our study indicates that PP4C restrains D2R expression and increases PRL
secretion in rat MMQ cells. These findings suggest the potential role of PP4C in
the pathogenesis of prolactinoma.
EP933
DOI: 10.1530/endoabs.49.EP934
Acquired temozolomide resistance in ACTH-secreting pituitary tumour
cells
Ticiana Silva, Peter Van Koetsveld, Fadime Dogan, Richard Feelders &
Leo Hofland
Erasmus MC, Rotterdam, The Netherlands.
Introduction
Temozolomide (TMZ) treatment has been used for aggressive pituitary tumours
with positive results, but has proven ineffective in controlling tumour regrowth in
cases of disease recurrence. TMZ resistance has been linked to the expression of
EP935
O6-methyl-guanine-DNA-methyltransferase
(MGMT) protein and mismatch
HER2, EGFR and PDGF family members as potential prognostic
repair components (MMR). In the present study, we describe the development
markers and their therapeutic implications
of an in vitro model of acquired resistance to TMZ and the mechanisms involved
Ana Silvia Corlan1, Anca Cimpean1, Marius Raica1, Eugen Melnic2 &
in such resistance.
Raluca Amalia Ceausu1
Methods
1Department of Microscopic Morphology/Histology, Angiogenesis
Mouse AtT20 corticotroph pituitary adenoma cells were used. The TMZ
Research Center, University of Medicine and Pharmacy Timisoara,
resistance protocol consisted of three challenges of TMZ using a previously
Timisoara, Russia;2Department of Pathology, Nicolae Testemitanu
determined EC50 (50% of the maximal effect) dose. AtT20 cells treated with
University of Medicine and Pharmacy, Chisinau, Moldova, Chisinau,
challenges of the vehicle dimethyl sulfoxide were used as control.
Republic of Moldova.
Results
The first TMZ challenge already induced a significant increase in EC50 (decreased
sensitivity) in TMZ-challenged cells (17 mM vs control 3 mM, P!0.001). After
Background
9 weeks following the third TMZ challenge, TMZ-challenged cells remained
The role of EGFR, HER2, PDGF-A and the axis PDGF-B/ PDGFR-b in the
resistant (18 mM vs control 2 mM, P!0.001). In control cells, TMZ treatment
pathogenesis of pituitary adenomas and their correlation with the tumoral
caused an accumulation of cells in G2/M phase (P!0.001), while in TMZ-
immunoprofile are poorly understood.
challenged cells no accumulation was observed (PZ0.91). In control cells,
Materials and methods
50 mM of TMZ induced maximum 11-fold stimulation of apoptosis (1132G241%
The study included 92 cases. We used morphological stains, immunohistochem-
vs 100G5%, PZ0.0008), whereas in TMZ-challenged cells a significantly lower
istry and molecular methods to characterize the tumors.
(2.4-fold) increase in apoptosis was observed
(244G55% vs 100G26%,
Results
PZ0.003). The mRNA expression of MGMT was higher and of MMR
33.33% of adenomas showed a positive immunohistochemical reaction for
components (MSH6, MSH2 and PMS2) was lower in TMZ-challenged cells
HER2- with a membranous and cytoplasmatic pattern- the first one prevailing.
compared to control cells (P!0.001).
The restriction of HER-2
expression to the membrane was noticed in the
Conclusion
basophilic cells of basophilic or mixed adenomas. For the acidophilic cells: the
The present study describes an acquired temozolomide resistant cell corticotroph
expression of HER2 was mostly cytoplasmatic with a granular pattern. In pure
pituitary adenoma model. The TMZ resistance is demonstrated by a sustained
adenomas, the only significant correlation with the expression of HER-2 was
increase in TMZ EC50, a lack of cell cycle changes and lower TMZ-induced
shown for prolactinomas. For bihormonal adenomas we obtained a significant
increase in apoptosis. Acquired TMZ resistance is associated with strongly
correlation of HER-2 with the coexpression of GH-PRL, PRL-LH, TSH-FSH,
increased MGMT expression and lowered expression of components of the MMR
TSH-LH. The gene amplification pattern confirmed the expression of HER-2 in
system.
33,3% of adenomas positive for HER-2. For adenomas positive for EGFR, we
obtained a significant correlation with the coexpression of GH-PRL, PRL-TSH
DOI: 10.1530/endoabs.49.EP933
(partial correlation), PRL-ACTH (total correlation). We analyzed the effects of
PDGF-A and PDGF-B on adenoma cells, depending on their immunoprofile. For
each of these 2 factors, 60-80% of tumor cells were immunohistochemically
positive. We obtained data contradictory to the published one: a positive
correlation between PDGF-A and prolactin expression. We confirmed the known
association between PDGF-B and somatotropinomas.
Discussions and conclusions
EP934
We identified a positive correlation between PDGF-B and PDGFR-b expression,
PP4C restrains dopamine D2 receptor expression in rat pituitary
implying a role for this axis in the pathogenesis of pituitary adenomas. The FSH-
MMQ cells
LH association induces the overexpression of HER-2 in pituitary adenomas,
Na Yi & Bin Lu
specifying a unique subtype of adenomas. We noticed the expression of EGFR in
Huashan Hospital, Fudan University, Shanghai, China.
peritumoral macrophages and folliculo-stellate cells, leaving new opportunities
for studying the role of folliculo-stelate cells and the pathogenic role of EGFR in
these tumors.
Objective
Decline in the number of D2 receptor (D2R) is considered as the reason of
DOI: 10.1530/endoabs.49.EP935
resistance to dopamine agonists (DA). PP4R2 gene was observed up-regulated in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP936
pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with
SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1
Carbohydrate metabolism disturbances at different types of acromegaly
patient had microadenoma, and 2 had normal pituitary MRI results.
treatment
Conclusions
Alexandr Dreval’ & Anna Vinogradova
Improved obstetric care and effective interventions for postpartum hemorrhage
Moscow Regional Scientific Research Clinical Institute named after
have limited the prevalence of SS in developed countries. However, in developing
M.F.Vladimirskiy, Moscow, Russia.
countries like Turkey, SS due to postpartum bleeding remains common. Thus,
physician’s awareness of the symptoms of SS is urgently required to avoid the
Purpose
associated morbidity and mortality.
To investigate the carbohydrate metabolism in depend on acromegaly treatment.
Keywords: Hypothalamic amenorrhea, osteoporosis, pituitary gland
Material and methods
DOI: 10.1530/endoabs.49.EP937
23 patients with newly diagnosed acromegaly (NA) were observed. Carbohydrate
metabolism were investigated after somatostatine analogues treatment (SSA) (14
patients) or after surgery (TSA) (9 patients). Groups were comparable on age,
BMI, acromegaly duration. Were researched HbA1c, fasting plasma glucose level
(FPG), indexes of insulin resistance (the HOMA-IR, a Matsuda-index), areas
under the curve of insulin within the first 30 minutes (AUCins30) and from 30 to
120 minute (AUC ins30-120) of the oral glucose tolerance test initially and after
the treatment.
Results
EP938
At NA patients FPG, HbA1c authentically (P!0.05) worsened within 3-6
Prevalence of discordant acromegaly after surgical treatment and its
months of SSA treatment and considerably (P!0.08) improved after TSA. In
clinical implications in a third LEVEL hospital in Latinamerica
3 months of SSA therapy extent of depression of an AUCins30 considerably
Mireya Pérez, Arturo Pen˜a, Carlos Rojas & Alma Vergara
exceeded extent of depression of an AUCins30-120
(in
11 and 2.3 times
Centro Médico 20 de Noviembre, Mexico, Mexico.
respectively (P!0.05)). Whereas in 3 months after TSA extent of depression of
an AUCins30 was comparable to extent of depression of an AUCins30-120 (2.4
times and 3.2 times respectively).
Background
Conclusions
Acromegaly results from excess growth hormone (GH) secretion by a pituitary
The decreasing of hepatic IR and peripheric insulin sensitivity in condition of
adenoma in 95% of the cases. Discordant acromegaly is defined by the elevation
higher level of insulin in compare with patients receiving SSA at most of these
of GH with normal levels of insulin-like growth factor type 1 (IGF-1) or normal
patients leads to normalization of carbohydrate metabolism. The greatest changes
levels of GH associated with an elevation of IGF-1. Its an important situation in
of parameters of carbohydrate metabolism
(Matsuda-index augmentation,
the follow-up period of patients with acromegaly because there is little
depression of the NOMA-IR index, insulin secretion depression) are noted in 3
information about patient treatment, comorbidities and follow-up. The objective
months of SSA therapy, and further remain at the previous level or change
of this study was to describe the prevalence of discordant acromegaly after
slightly. It is recommended to carry out control of a condition of carbohydrate
pituitary surgery, follow changes in GH and IGF-1 patterns over time and explore
metabolism at patients with an acromegaly, first of all, in 3 months both after the
possible correlations with blood pressure and HbA1C.
carried-out surgical treatment, and after the beginning of SSA therapy.
Methods
Keywords: acromegaly; insulin resistance; secretion; insulin; somatostatine
We retrospectively analyzed the prevalence and characteristics of patients who
analogues; carbohydrate metabolism
had an elevated IGF-1 but normal GH or an elevation of GH with normal IGF-1,
DOI: 10.1530/endoabs.49.EP936
in consecutive post-surgical acromegaly cases from the year 2000 to 2015 at our
institution. To define discordant acromegaly in our study hormonal evaluation
was obtained at the 3 months post surgically (GH, and IGF-1). Discordant patients
were categorized into two groups according to the postoperative GH and IGF-1:
high IGF-1 group (normal GH and high IGF-1), high GH group (high GH and
normal IGF-1). We followed discordant patients at 6 and 12 months with GH,
IGF-1, magnetic resonance (only at 6 months), blood pressure and HbA1c.
Pituitary - Clinical
Results
The prevalence of discordant acromegaly was 11.7% (9/77). Of this patient
EP937
population 77.7% (7/9) changed their biochemical pattern after 12 months of
Four decades without diagnosis: Sheehan‘s syndrome, a retrospective
follow-up. Of these, 11.3% (1/9) in the high GH group became inactive, 66.6%
analysis
(6/9) became active (high IGF-1 group), and 22.2% (2/9) remained discordant
Deniz Gokalp1, Gulistan Alpagat2, Alpaslan Kemal Tuzcu1,
(both in the high GH group) and had normal suppression of GH to glucose.
Mithat Bahc¸eci3, Sadiye Tuzcu4, Fatime Yakut5 & Azat Yildirim6
Positive correlations were found between the level of IGF-1 at 6 months with
1Department of Endocrinology, Acibadem Medical University, Istanbul,
systolic blood pressure
(RZ0. 89, PZ0. 001) and diastolic blood pressure
Turkey;2Department of Endocrinology, Dicle University School of
(RZ0.891; PZ0.002). No correlation was found between GH, IGF-1 and HbA1c
Medicine, Diyarbakir, Turkey;3Izmir Ataturk Education and Research
or tumor size.
Hospital, Izmir, Turkey;4Department of Nuclear Medicine, Gazi Yasargil
Conclusions
Education and Research Hospital, Diyarbakir, Turkey;5Department of
Discordant acromegaly in the postsurgical state is a rare entity, with variation in
Radiology, Diyarbakir Memorial Hospital, Diyarbakir, Turkey;6Azad
hormonal patterns at 12-month follow up and a positive correlation with blood
Yildirim Department of Orthopedics, Gazi Yasargil Education and Research
pressure levels. We suggest that this patients need to be carefully followed due to
Hospital, Diyarbakir, Turkey.
the high likelihood of recurrence, particularly if the elevation is of IGF-1 and with
the presence of residual tumor.
Aim
DOI: 10.1530/endoabs.49.EP938
Sheehan‘s syndrome
(SS) remains a frequent cause of hypopituitarism in
undeveloped and developing countries, but due to improvements in obstetric care,
it is rare in developed countries. We aimed to share the results of a retrospective
study analyzing the demographic, clinical, imaging, and hormonal characteristics
of a large group of patients with SS, and also increase awareness of this syndrome
especially in developed countries.
Methods
The medical records of 124 patients with SS patients who were followed up in the
EP939
Endocrinology Department of Dicle University between 1995 and 2015 were
A case of IgG4-related hypophysitis with long-term cyclic evolution
assessed retrospectively.
Iconaru Laura, Baleanu Felicia, Muteganya Raoul & Karmali Rafik
Results
CHU Brugmann, Bruxelles, Belgium.
The mean period of diagnostic delay was 20.37G8.34 years on average. 5.7% of
patients with SS were literate; 62% of patients delivered at home. Anemia was
identified in 64.5% of SS patients. Mean blood sodium levels were 129.8G11.3
Introduction
mEq/L. The mean urine densities were 1013G6.5. Osteoporosis and osteopenia
IgG4-related disease is a newly recognized entity associated with autoimmune
were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to
conditions involving almost every organ system, characterized by elevated serum
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
IgG4 as well as mass like tissue infiltration by IgG4-positive plasma cells.
EP941
Pituitary gland can be involved and can presented as hypophysitis.
Presurgical medical treatment in Cushing’s disease
Case description
Paloma Moreno-Moreno1, Ana Barrera-Martín1, Alejandro Iban˜ ez-Costa2,
We report a case of a 56-year-old man, who has been suffering for the nine last
María Rosa Alhambra-Expósito1, Concepción Mun˜oz-Jiménez1,
years of episodes of fatigue and headaches with spontaneous remission was
María Ángeles Gálvez-Moreno1, Justo P Castan˜ o-Fuentes2 &
admitted to our hospital for headaches, fatigue, myalgia, diplopia and visual
Raúl M Luque-Huertas2
disturbances. The endocrine assessment revealed a complete ante-hypopituitar-
1Management Unit of Clinical Endocrinology and Nutrition, University
ism. Dynamic LHRH and CRH tests revealed a delayed but robust response of
Hospital Reina Sofía, Córdoba, Andalucia, Spain;2Department of Cell
gonadotrophins and corticotrophin. MRI scan showed nodular thickening of the
Biology, Physiology and Immunology, Instituto Maimónides de Investiga-
pituitary and pituitary stalk with minimal compression of the optic chiasm. Other
ción Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía,
pathology than sarcoidosis was suspected and further investigation showed high
CIBER Fisiopatolo, University of Córdoba, Córdoba, Andalucia, Spain.
levels of blood IgG4. All these findings were highly suggestive for a diagnosis of
IgG4-related hypophysitis. Steroids were administered and within 24 hours, the
patient became completely asymptomatic. A month later, thyroid and gonadal
Introduction
function normalized. Cranial MRI scan showed a net decrease in the size of the
The duration of hypercortisolism in Cushing’s disease
(CD) appears to be
pituitary gland compared to the previous examination.
inversely related to the reversibility of complications, which in turn increase
Conclusions
mortality. This makes it necessary to identify medical therapies capable of
We report a case of IgG4-related hypophysitis who responded completely and
normalizing cortisol overproduction before transsphenoidal surgery. The aim of
rapidly to steroids. Intriguingly, according to his pas medical history, he might
this study was to determine if the clinical data of patients with CD before surgery
have presented a cyclical evolution of his disease with periods of spontaneous
allow predicting the presence and/or abundance of somatostatin
(ssts) and
remission. It’s a rare condition but increasingly recognized and should be sought
dopamine (DRs) receptors at the corticotrophic adenoma, in order to start a more
in face of an acute swelling of the pituitary gland and/or its stalk, since its
effective and personalized presurgical medical treatment.
favorable response to steroid therapy should help to avoid unnecessary surgery.
Patients and methods
Keywords: Hypophysitis, IgG4-disease, panhypopituitarism
Retrospective study performed through review of clinical histories and molecular
DOI: 10.1530/endoabs.49.EP939
profile analysis of corticotrophic tumors. We included all patients diagnosed with
CD (2005-2014) treated with transsphenoidal surgery, and whose tumor sample
was analyzed in the Department of Cell Biology, Physiology and Immunology of
the University From Córdoba. The correlation study was performed using
Spearman’s r.
Results
Nine women with CD and molecular profile analysis of corticotrophic tumor. Age
47.33G12 years. A positive correlation was observed between tumor size at
diagnosis and levels of receptor expression sst2 [rZ0.731 (PZ0.04)], sst3 [rZ
0.735
(PZ0.038)], DR2 [rZ0.821 (PZ0.023)], DR4 [rZ0.946 (PZ0.000)]
y DR5 [rZ0.900 (PZ0,037)]. In addition, there was a marked inverse
correlation between ACTH levels at diagnosis and the sst5
receptor
[rZ
K0.767 (PZ0.016)].
Conclusions
EP940
Tumor size at the diagnosis of CD seems to show a direct correlation with the
Duhok/IRAQ acromegaly; one year of experience
levels of expression of sst2 and DR2 receptors, suggesting that in patients with
Bayar Qasim
CD with macroadenoma in the initial study, preoperative treatment with
Unviersity of Duhok/College of Medicine, Duhok, Iraq.
somatostatin analogs and/or dopamine may be helpful. In addition, the inverse
correlation between ACTH levels at diagnosis and sst5 expression questions
whether the specific analogues of this receptor would be useful in the preoperative
Background
treatment of CD.
Acromegaly is a rare hormonal disorder; the prevalence is w60 cases/million
DOI: 10.1530/endoabs.49.EP941
population1, Incidence: 3.3 new cases/million/year1 Mortality rate 2-4 times that
of general population2. It is usually the result of a somatotrope adenoma in more
than 95% of cases.
Aim
By June 2016, we were celebrating one year of experience in acromegaly. It was
first time to open acromegaly service in Duhok city/Kurdistan region/IRAQ. This
review will include all registered patients during this year. Aim of this revision to
give a brief about our patients’ characteristics and how we can plan for future?
Methods
EP942
This is retrospective study involving ten patients, all patients diagnosed by high
Characteristics and 1-year follow-up of patients with profound
IGF1 level followed by GH suppression test and MRI of pituitary gland. Those
hyponatremia due to primary polydipsia - a multicentre prospective
patients underwent transphenoidal resection, diagnosis confirmed by histopathol-
observational study
ogy too.
Clara Sailer1,3, Bettina Winzeler1,3, Nicole Nigro1, Isabelle Suter-Widmer1,
Results
Birsen Arici1, Martina Bally2, Philipp Schuetz2,3, Beat Mueller2,3 &
Our patients characteristics are shown. The median age of presentation was 44.9.
Mirjam Christ-Crain1,3
Headache and acral enlargement was the most common presentation.
1Endocrinology, Diabetology and Metabolism, University Basel, Basel,
Discussion
Switzerland;2Division of Endocrinology, Diabetology and Metabolism,
Most patients with acromegaly are diagnosed with a macroadenoma. This review
Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland;
include ten patients, eight of them were from Duhok including Zaxo and Akre,
3Department of Clinical Research, University Hospital Basel, Basel,
two of them they moved to live in this city, one from the capital Baghdad and
Switzerland.
another patient from syrian refugee. The prevalence of acromegaly in Duhok city
was 8.2 persons/million/year 4, while the incidence was of new cases was
5.3/million/year. This high number of patients reflects the new input for patients
Introduction
to this service as this was not present before June 2015. Eight patients were
Hyponatremia due to excessive fluid intake (i.e. primary polydipsia (PP)) is
operable they prepared by somatostatin analogue followed by surgery.
common. It may culminate in profound hyponatremia - carrying considerable risk
Conclusion and recommendations
of morbidity. However, data on patients with PP leading to hyponatremia is
The two dilemmas we are facing here in Duhok/IRAQ are: First; delayed
largely lacking. Herein, we describe the characteristics of polydipsic patients
diagnosis as reflected by the fact all of our patients are macroadenoma at
hospitalised with profound hyponatremia, and assess one-year outcomes.
presentation, that is why we need to increase awareness about this disease.
Method
Secondly; low compliance for medical treatment: to improve this we need to
In this prospective observational study, we included 23 patients with an episode of
provide free measurement of both GH and IGF1 levels for all patients receiving
profound hyponatremia (%125 mmol/l) due to PP. Patients were classified into
somatostatin analogue treatment.
subgroups: psychogenic polydipsia (PsyP), dipsogenic polydipsia (DiP), and beer
DOI: 10.1530/endoabs.49.EP940
potomania (BP). Symptoms, laboratory findings, and factors contributing to
hyponatremia (co-morbidities, medication, and liquid intake) were assessed. A
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1-year follow-up was performed to evaluate recurrence of hyponatremia,
in these patients. We hypothesized that non-classical cardiovascular risk factors
re-admission rate, and mortality.
such as epicardial fat
(EF), interventricular septum thickness
(IST), carotid
Results
intima-media thickness (CIMT), may be increased in ACRO and contribute to this
Of the 23 patients (median age 56 years [IQR 50-65], 74% female) 7 had PsyP, 8
higher cardiovascular morbidity.
DiP, and 8 BP. Median serum sodium of all patients was 121 mmol/l (IQR 114-
Objective
123), median urine osmolality 167 mmol/l (IQR 105-184), and median copeptin
To evaluate EF, IST, and CIMT in patients with ACRO compared to controls and
3.6 mmol/l
(IQR
1.9-5.5). Psychiatric diagnosis, particularly dependency
identify possible predictors in this non-classical cardiovascular risk factors.
disorder (43%) and depression (35%), were highly prevalent. Factors provoking
Material and methods
hyponatremia were found in all patients (e.g. acute water load, medication, stress).
We studied CIMT, IST, EF in 30 patients with ACRO (16 males, 5 with active
During the follow-up period, 67% of patients were readmitted, 52% of these with
disease) and 30 matched controls (by age, sex and body mass index (BMI)).
re-hyponatremia, and three patients (38%) with BP died.
Results
Conclusion
Both cohorts were identical regarding the presence of cardiovascular risk factors
Patients with PP have a high prevalence of addictive and affective disorders.
(CVRF. The ACRO cohort presented higher EF and IST compared to the control
Given the high recurrence, re-hospitalisation, and mortality rate, careful
group (0.65G0.16 vs 0.43G0.14 cm, PZ0.001 and 11.31G1.17 vs 10.64G
monitoring and long-term follow-up including controls of serum sodium,
1.47 mm, PZ0.035, respectively). The presence of ACRO (ß 0.545, P!0.001;
education and behavioural therapy is needed.
R2 297) was the unique positive predictor of EF, while BMI and hypertension
DOI: 10.1530/endoabs.49.EP942
were positive predictors of IST (ß 0.379, PZ0.006 and ß 0.344, PZ0.013,
respectively, R2 0.298) in a multiple linear regression model.
Conclusions
Patients with ACRO have higher EF and higher IST (influenced by hypertension
and BMI), compared with matched controls despite a similar prevalence of
CVRF. Increased EF and IST could partially contribute to this increased
cardiovascular morbidity and mortality observed in acromegaly.
DOI: 10.1530/endoabs.49.EP944
EP943
Success rates of pituitary surgery in acromegaly - a tertiary centre
experience in Romania
Minodora Betivoiu1, Iulia Soare1, Sorina Martin1,2, Anca Sirbu1,2,
Alice Albu1,2, Carmen Barbu1,2 & Simona Fica1,2
1Endocrinology Department, Elias Hospital, Bucharest, Romania;
2Endocrinology Department, Carol Davila University of Medicine and
EP945
Pharmacy, Bucharest, Romania.
Pituitary insufficiency - etiopathogeny and diagnostic aspects
Corina Crista1 & Georgiana Hotaran2
1
Clinic of Endocrinology, University of Medicine and Pharmacy ‘Victor
Background
Babes’, Timisoara, Romania;2University of Medicine and Pharmacy
Pituitary surgery is the first treatment option for acromegaly. The reported success
‘Victor Babes’, Timisoara, Romania.
of pituitary surgery varies between 75 and 95% for microadenomas and 45 and
68% for macroadenomas. The aim of this study was to report our experience
regarding the remission rate after pituitary surgery in acromegaly patients.
The study group was represented by 155 cases of pituitary insufficiency (age:
Methods
37.21G16.05; F/MZ116/39) hospitalized in the Clinic of Endocrinology
This retrospective study included 70 patients diagnosed with acromegaly in our
Timi¸oara during the period
2006-2014. The cases were classified into
clinic between 2009 and 2016. The criteria used to define remission were random
ethiopatogenic groups, as follows: iatrogenic pituitary insufficiency (23.87%),
GH !1 ng/ml and normalization of IGF1 levels for gender and age.
tumor compression (21.29%), ischemia (14.84%), idiopathic hypogonadotropic
Results
hypogonadism (3.87%), congenital pituitary insufficiency (6.45%), empty sella
11 patients were lost of follow-up after the first diagnostic visit. We analysed 59
(6.45%), functional pituitary insufficiency (23.23%). In majority, the studied
acromegaly patients (33 women and 26 men) with a mean age at diagnosis of
cases presented hypogonadism (95.48%), while hypothyroidism was found in
44.93G13.57 years. Microadenoms were found in 15 (25.4%) and macro-
65.16% patients and
50.32% of the cases presented adrenal insufficiency.
adenomas in 44 (74.6%) patients. 6 (10.2%) patients associated both GH and
Neurological signs caused by the tumoral mass were found in 42.58% cases. The
prolactin hypersecretion. Pituitary surgery was performed in 41 patients of which
ischemic and congenital forms of the pituitary insufficiency associated mostly
9
(21.4%) were cured. Aditional 7 (21.2%) patients were cured after second
panhypopituitarism (100%, respectively 50%), while the iatrogenic form and
surgery and radiotherapy. Radiotherapy was the first treatment in 11 patients of
those caused by tumor compression presented in high percentages partial pituitary
which 3 (27.2%) were cured. Persistent disease after sugery and/or radiotherapy
insufficiency. The comparison of the hormonal parameters
(ethiopatogenic
was treated with somatostatin analogs (26), dopamin agonists (18) and GH
groups) revealed: significant inferior serum levels of testosterone in the
receptor bloacker (6) in mono or combination therapy.
congenital form and empty sella vs tumor compression (P ! 0.05); significant
Conclusions
inferior levels of the serum estradiol (P ! 0.01) in congenital panhypopituitarism
The rate of surgical success in our patients was found to be low (40% for
vs functional secondary hypogonadism; significant inferior levels of the serum
microadenomas, 6.8% for macroadenomas). This could be explained by the fact
TSH (P ! 0.05) in patients with pituitary insufficiency caused ischemia vs tumor
that most patients presented late at the macroadenoma stage.
compression; significant inferior levels of FT4 (P ! 0.05) in empty sella and
DOI: 10.1530/endoabs.49.EP943
ischemic form vs iatrogenic pituitary insufficiency. The applied therapy targeted
the cause of the hypopituitarism and the hormonal substitution.
DOI: 10.1530/endoabs.49.EP945
EP944
Acromegaly and cardiovascular risk
Betina Biagetti1, Anna Aulinas2, Natividad Lopez1, Esther
EP946
García-Fernandez1, Maria José Arnau-Vives1, Andrea Ciudin1,
Gabriel Obiols1, Belen Dalama1 & Jordi Mesa1
1Vall d’Hebron Hospital, Barcelona, Spain;2Hospital Universitari de Vic,
Abstract unavailable.
Barcelona, Spain.
Background
Acromegaly (ACRO) is associated with increased cardiovascular morbidity and
mortality, however, there is no evidence of an increase in ischemic heart disease
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP947
morphological response without biochemical response is uncommon, whereas
MR without BR is relatively frequent, even more than the coexistence of both.
Long-term outcomes of medical therapy in patients with acromegaly:
a retrospective analysis
DOI: 10.1530/endoabs.49.EP948
Iulia Simona Soare1, Minodora Andreea Betivoiu1, Sorina
Carmen Martin1,2, Anca Elena Sirbu1,2, Carmen Gabriela Barbu1,2,
Alice Ioana Albu1,2 & Simona Fica1,2
1Department of Endocrinology, Diabetes and Metabolic Diseases, Elias
Emergency University Hospital, Bucharest, Romania;2University of
EP949
Medicine and Pharmacy ‘Carol Davila’, Bucharest, Romania.
Ocular findings in adult subjects with congenital, lifetime, isolated,
untreated growth hormone deficiency
Background
Augusto C N Faro1, Virginia M Pereira-Gurgel1, Roberto Salvatori2,
Acromegaly is a rare severe disease which, untreated, leads to increased
Viviane C Campos1, Gustavo B Melo3, Francielle T Oliveira1, Alecia
cardiovascular and respiratory morbidity and mortality. Pituitary surgery is the
A Oliveira-Santos1, Carla R P Oliveira1, Francisco A Pereira1,
first-line therapy, and medical treatment (somatostatin receptor ligands SRLs,
Ann Hellstrom4, Luís A Oliveira-Neto1 & Manuel H Aguiar-Oliveira1
dopamine agonists DA, and GH receptor antagonists GHRAs) is indicated for
1Federal University of Sergipe, Aracaju/Sergipe, Brazil;2The Johns
persistent disease. While selected patients are treated with DA and GHRAs, SRLs
Hopkins University School of Medicine, Baltimore, MD, USA;3Hospital de
remain the mainstay of acromegaly therapy.
Olhos de Sergipe, Aracaju/Sergipe, Brazil;4Sahlgrenska Academy,
Objective
The Queen Silvia Children’s Hospital, Goteborg, Sweden.
The aim of this study is to report our results regarding medical therapy in patients
with persistent acromegaly after surgery and/ or radiotherapy.
Ocular function is fundamental for environmental adaptation and survival
Patients and methods
capacity. Growth factors are thought to be necessary to reach a mature eyeball and
We retrospectively reviewed 59 patients (33 women and 26 men), diagnosed with
consequent adequate vision. However, the consequences of the deficiency of
acromegaly, mean age at diagnosis 44.93G13.57 years, managed between 2009
circulating growth hormone (GH) and its effector insulin-like growth factor I
and 2016 in our department. Controlled disease was defined as normal IGF-1 for
(IGF-I) on the physical aspects of the human eye are still debated. A model of
age and sex and random GH!1 ng/ml.
untreated isolated GH deficiency (IGHD) may clarify this issue. The aim of this
Results
study was to assess the physical aspects of the eyeball of adult IGHD individuals
19 patients, cured after surgery or radiotherapy were excluded.
31 patients
who have never received GH therapy. A cross sectional study was carried out at
received medical therapy and 9 were lost during follow up. 26 were treated with
the University Hospital, Federal University of Sergipe, Brazil, including 25 adult
SRLs alone or in combination therapy, 3 received DA alone, one DA and GHRAs
IGHD subjects homozygous for a null mutation (c.57C1GOA) in the GHRH
and one GHRAs alone. SRLs were used as monotherapy in 13 (50%), tritherapy in
receptor gene, and
28
matched controls. All underwent endocrine and
3
(11.5%), in combination with DA in 9 patients (34.6%) and with GHRAs in one
ophthalmological assessment. The main outcome measures were visual acuity,
(3.8%). IGF-1 normalization was achieved in 10 patients (32%), 7 receiving SRLs
intraocular pressure, refractive error, ocular axial length (AL), anterior chamber
(five in monotherapy, one with DA and one in tritherapy), two DA alone and 1
depth, and central corneal thickness (CCT). Despite unmeasurable serum IGF-I,
with GHRAs alone. Random GH!1 ng/ml was achieved in six patients (19.3%)
there was no difference between the groups in visual acuity, intraocular pressure,
(three in monotherapy SRLs, two in association with DA and one on DA alone).
and refractive error. IGHD subjects exhibited lower absolute values of AL
Controlled disease was found in five patients
(16.1%)
(three receiving
(22.5G0.6 vs 23.5G1.0 mm, P! 0.0001), anterior chamber depth (2.98G0.3 vs
monotherapy with SRLs, one with tritherapy and one with GHRAs).
3.26G0.3 mm, PZ0.001) and CCT (539G28 vs 546G28 mm, PZ0.04) than
Conclusion
controls. All values were within their normal ranges. While mean stature in IGHD
In long-term follow-up, almost 40% patients got full control of acromegaly, but
group was
78% of the controls, mean IGHD axial AL was 96%. These
only 20% of them on medical treatment. Medical approach in acromegaly should
observations suggest no relevant consequences of congenital lack of pituitary GH
be individualized, combination therapy could provide additional biochemical
and of circulating IGF-I on physical ocular findings. Autocrine or paracrine
control, but new therapies should be implemented.
growth factors may be more relevant to ocular growth.
DOI: 10.1530/endoabs.49.EP947
DOI: 10.1530/endoabs.49.EP949
EP948
Resistant prolactinomas: Retrospective study of ten cases
EP950
Marta Araujo Castro, Nuria Palacios García, Javier Aller Pardo,
Evaluation of estrogen effects on the anterior pituitary hormones by
Ainhoa Abad López, Virginia Oses Zarate, Laura Mateos Moreno &
using combined pituitary stimulation test (CPFT) in the Korean
Javier Estrada García
postmenopausal women
Puerta de Hierro’s Hospital, Madrid, Spain.
Sung-Woon Kim & Seungjoon Oh
School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
About 10-15% of prolactinomas (P) are resistant to Dopamine agonists (DA). We
analyzed retrospectively ten resistant prolactinomas (RP) treated at our center
Pituitary hormonal status was important for the evaluation of various diseased
between 1995 and 2014, to identify useful variables to predict DA resistance and
state of hypothalamo-pituitary target organ axis as well as tumorous condition.
its different patterns
(biochemical resistance
(BR), morphological resistance
Measurement of growth hormone (GH), adrenocorticotrophic hormone (ACTH)
(MR) or both). BR is defined as the failure to normalize prolactin (PRL) levels
and cortisol during insulin-induced hypoglycaemia were commonly used to
with R 2 mg/week of cabergoline (C) for at least 3 months. MR is considered
assess pituitary condition on hypoglycaemia stress. Sexual axis was evaluated
when at that dose the tumor size is not reduced by at least 50%. The median age
with target organ hormones, i.e. estradiol or testosterone and LHRH stimulated
was
30.6
years and
5
subjects were male. All patients had secondary
luteinizing hormone
(LH) and follicle stimulating hormone
(FSH). TRH
hypogonadism and 1 had TSH and GH deficiency. The median PRL levels
stimulated prolactin
(PRL) and thyroid stimulating hormone(TSH), and
were 548 (127-1000) ng/ml. There were eight macroprolactinomas (MP) and two
simultaneously evaluated with thyroid hormones (free T4 and T3). All these
microprolactinomas (mP), with an average size of 1.78 (0.4-3.5) cm. Seven had
separated axes were evaluated once with combined pituitary stimulation test
suprasellar extension and three invasion of cavernous sinuses. The median dose of
(CPST) by combined use of regular insulin (0.1 unit/kg body weight), 100 to
C used was 3.4 (2-7) mg/week. The median follow-up was 93.2 (26-348) months.
500 mg of TRH (TSH releasing hormone) and 100 mg of LHRH respectively. We
Five patients had MR, 1 BR and 4 patients both. Seven patients (2 mP and 5 MP)
checked out pituitary hormonal status with CPST in normal Korean
underwent transsphenoidal surgery. The indication was BR and MR in 4, BR in 1
postmenopausal women for physiological situation of pituitary function after
and MR in the other 2 patients. The surgical remission was achieved in 3 patients.
naturally shut down of oestrogen. We enrolled total 230 women, who were 30
The remaining 4 patients were treated with DA and one of them also received
adult GHD (growth hormone deficiency), 116 postmenopausal (PMS), 17 PMS on
radiotherapy. All of them achieved remission. In the 3 non-operated patients an
ERT (oestrogen replacement therapy) and
48
regularly menstrual women
adequate hormonal control was achieved, but with tumor persistence. In
(normal). We did find GH response to hypoglycaemia (indirect) was much
conclusion, prevalence of male sex, a size larger than 1 cm and suprasellar
higher than that of GHRH (direct) stimulation. These findings were meant that
extension were higher in our resistant patients than that reported in non-resistant
GHRH-GH axis was more responded to life threatening stress, then mobilized
prolactinomas; thus, these features could predict DA resistence. The
glucose and stabilized human energy system. Peak GH levels after
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
excision led to disease remission. Currently, 15 months postoperatively, the
patient has no complaints, is normokalemic (without potassium supplements) and
normoglycemic on metformin monotherapy.
Conclusion
The case is noteworthy for the atypical clinical presentation, severity of the
hypokalemia and excellent treatment outcome. The authors emphasize the
importance of high clinical suspicion for secondary causes of DM when
investigating patients with new onset diabetes, as diagnosing and treating the
underlying cause may render the diabetes and its complications potentially
curable and preventable respectively.
DOI: 10.1530/endoabs.49.EP951
EP952
Uncomplicated pregnancy in a patient with McCune Albright syndrome
(MAS) and active acromegaly
Terroba Larumbe1, Crespo Soto1, Anacabe Goyogana1, De Luis Roman2,
Urbon Lopez De Linares1, Cuellar Olmedo1, Ventosa Vi
˜a1,
Calleja Baranda1 & Cabezas Garcia1
1
H.U. Rio Hortega, Valladolid, Spain;2H. Clinico Universitario, Valladolid,
Spain.
Introduction
The association of acromegaly and polyostotic fibrous dysplasia is a rare entity
that presents more difficulties in achieving an effective treatment than classical
acromegaly. Pregnancy is infrequent and carries a high risk when acromegaly is
active.
Clínical case
A 27 year old woman surgically treated for facial asymmetry, without café-au-lait
spots or precocious puberty, was evaluated in 1992 after a normal pregnancy. In
the biochemical tests the following was observed: PRL 95 ng/ml (1.2-40), GH
20.9 ng/ml not suppressed during oral glucose overload, IGF-I 943 ng/ml (101-
333), T4 and T3 elevated with suppressed TSH. The rest of the data including
basal hormones did not show significant alterations. Imaging tests showed diffuse
hypoglycaemia stimulation were mild suppressed with ERT than that of PMS
hyperplasia/adenomatosis of the pituitary gland (14 x 20 x 6 mm) with increased
without oestrogen replacement. We will investigate all pituitary hormonal status
left lining and cavernous sinus invasion and findings compatible with fibrous
with future full data processing in Korean postmenopausal women by CFST.
dysplasia affecting numerous bones of the base of the skull and the cranial vault.
In the thyroid scan, a multinodular goiter with calcifications was found. Therapy
DOI: 10.1530/endoabs.49.EP950
with bromocriptine
(BC)
2,5 mg/day and methimazole was initiated, but
acromegaly remained active because the patient refused treatment with
subcutaneous octreotide. In 1996 she had an uncomplicated second pregnancy
and in January 2000 intramuscular Sandostatin LAR 30 mg/month could be
included in the treatment. Magnetic resonance performed after pregnancy showed
a small 5-mm focal image compatible with a microadenoma and a pituitary gland
close to normal. In 2007 Sandostatin was replaced by GH receptor antagonist
Pegvisomant, 20 mg/day subcutaneous because the control objective for IGF-I
EP951
was not achieved. With this therapy the patient, who also received cabergoline
Acute presentation of cushing disease: severe hyperglycemia and
0.5 mg/wk and metimazol 5 mg/d, was asymptomatic and IGF-I, PRL, thyroid
refractory hypokalemia
function, cardiac tests, fundus and campimetry were normal.
Carlos Tavares Bello1,2, Francisco Sousa Santos2, Catia Ferrinhos2,
Discussion
Filipa Alves Serra2,1, Joao Sequeira Duarte2 & Carlos Vasconcelos2
This patient with MAS presented primary hyperthyroidism, hyperprolactinemia
1Hospital de Egas Moniz, Lisbon, Portugal, Portugal;2Hospital das Forcas
and acromegaly with partial response to Sandostatin LAR but complete response
Armadas, Lisbon, Portugal, Portugal.
to pegvisomant. This drug can be especially useful in the management of MAS-
acromegaly for the risks involved in surgery and radiotherapy. Although
uncontrolled acromegaly can complicate pregnancy, especially by increasing
Introduction
the risk of gestational diabetes and hypertension, in this case, pregnancy evolved
Cushing’s syndrome (CS) is a rare disease resulting from prolonged exposure to
without incident.
supraphysiological levels of glucocorticoids. Cushing’s Disease is the most
frequent cause of endogenous CS. This disease has a broad spectrum of clinical
DOI: 10.1530/endoabs.49.EP952
manifestations and is associated with an increased morbi-mortality. Diabetes
Mellitus (DM) and hypokalemic alkalosis affects up to 50 and 10% of CS patients
respectively. Disease onset and severity reflects the magnitude of cortisol excess,
being ectopic ACTH production is the most frequent cause of acute, severe CS.
Cushing disease tends to have a slower onset with gradual appearance of the
EP953
typical phenotype and associated metabolic consequences.
Impact of etiology, age and gender on onset and severity of
Case report
hyponatremia in patients with hypopituitarism
A 62 year old male with a known medical history of obesity and hypertension was
Dragana Miljic1,2, Sandra Pekic1,2, Mirjana Doknic1,2, Marina
admitted to the emergency department with altered mental status, hyperglycemia
Nikolic-Djurovic1,2, Marko Stojanovic1,2, Vera Popovic2 & Milan Petakov1,2
and hypokalemia. Physical examination was remarkable for obesity, moon face,
1Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes
facial plethora and proximal muscle weakness. At admission: plasma glucose was
and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia;
452 mg/dl serum potassium 2.7 mmol/l and arterial pH 7.6. Excessive iv fluids led
2Belgrade University School of Medicine, Belgrade, Serbia.
to congestive heart failure that was treated with standard doses of furosemide.
Diuretics were soon stopped due to severe refractory hypokalemia (1.7 mmol/l)
that after correction required maintenance iv potassium chloride doses of
Hyponatremia can unmask hypopituitarism and secondary adrenal insufficiency
120 mEq/day. Further laboratory (dexamethasone suppression tests 1 and 8 mg
due to potent non-osmotic stimulation of vasopressin release under stressful
and inferior petrosal sinus sampling) and imaging (pituitary macroadenoma)
conditions. Patients and methods: In a retrospective study 25 patients (13f/12m,
investigations confirmed Cushing’s Disease. Endoscopic transphenoidal tumor
age 58.9G18.6 years) with hyponatremia (119.7G10.5 mmol/l) were identified
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
among 260 in-patients treated for hypopituitarism in our department over a
1Endocrinology Service. Hospital La Mancha Centro, Alcázar de San Juan,
decade. Results: Hyponatremia was recorded in 9.6% of our patients. In 84% it
Spain;2Neurology Service. Hospital La Mancha Centro, Alcázar de San
was the key to diagnosis of hypopituitarism. Patients with hyponatremia and non-
Juan, Spain.
functioning pituitary macro adenomas (group 1. NFPA nZ15) were significantly
older (71.47G4.8 years), compared to patients with hyponatremia from other rare
causes of hypopituitarism (group 2. nZ10; age 40.2G15.3 years, P!0.01):
Introduction
congenital (nZ2), Sheehan’s syndrome (nZ2), intracranial aneurysm (nZ2),
A link between Dopamine agonists and development of impulse control disorders
lymphocytic hypophysitis (nZ1), traumatic brain injury (nZ1), surgery and
is well recognized in the field of neurology. A similar finding in endocrine
radiotherapy for astrocytoma
(nZ1), pituitary metastasis from bronchial
patients is emerging.
carcinoma
(nZ1). Male preponderance in patients with NFPA
(10/15
i.e.
Case report
We report the case of a 38-year-old man with pathological addiction to gambling
66.7%) was in contrast to female predominance in patients with other causes of
associated with low dose cabergoline treatment for a mixed growth hormone (GH)
hypopituitarism (8/10 i.e. 80%). Hyponatremia was more severe in group 2
and prolactin (PRL)-secreting pituitary adenoma. At the age of 29 he was
compared to group 1 (113.5G10.9 mmol/l vs. 124.3G8.1 mmol/l, P!0.01).
diagnosed with mixed (GH and PRL) functioning invasive pituitary adenoma.
Conclusion: Hyponatremia is not uncommon in patients with hypopituitarism,
After surgery and radiotherapy he was given medical therapy with somatostatin
especially at presentation. In older patients, NFPA is the most common
analogues and cabergoline. During follow-up somatostatin analogues were
pathology, usually leading to gradual onset of hypopituitarisim and non-specific
withdrawn but he continued cabergoline treatment to control hypersecretion and
symptoms, while acute hyponatremia can occur with pituitary apoplexy. In
the residual tumour. During follow-up the patient reported pathological gambling
younger patients severe acute hyponatremia is more common leading to diagnosis
habits. He had spent a large sum of money and, although he had tried to stop
of unrecognized secondary adrenal insufficiency and hypopituitarism from
gambling many times he was unable to quit. He did not stop his gambling
various causes.
behaviour despite a marital crisis and divorce. He had even been to a centre for
DOI: 10.1530/endoabs.49.EP953
addictive disorders without success. We decided to withdraw cabergoline. His
impulse-control disorder
(ICD) resolved within months after cabergoline
discontinuation. After 6 months, somatomedin C level was in normal range,
PRL level was mildly high with no sexual dysfunction and the tumour had not
grown.
Conclusions
EP954
The gambling episodes diminished after the discontinuation of cabergoline,
providing evidence for a causal relationship. Cabergoline-induced pathological
Changes in pituitary tumour biology and behaviour in FIPA patient
gambling and another ICDs are probably underreported, and physicians should
with GH secreting aggressive pituitary macro adenoma
consider screening for these in patients treated with dopamine agonists. Screening
Dragana Miljic1,2, Sandra Pekic1,2, Mirjana Doknic1,2, Marina
for ICDs should be undertaken in all patients with DA-treated prolactinomas.
Nikolic-Djurovic1,2, Marko Stojanovic1,2, Emilija Manojlovic-Gacic3,2,
Marta Korbonits4, Jaqueline Trouillas5, Alexandre Vasiljevic5,
DOI: 10.1530/endoabs.49.EP955
Vera Popovic2 & Milan Petakov1,2
1Department of Neuroendocrinology, Clinic for Endocrinology, Diabetes
and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia;
2Belgrade University School of Medicine, Belgrade, Serbia;3Institute of
Pathology, Belgrade, Serbia;4Barts and the London School of Medicine,
London, UK;5Institute de pathologie multu-site des HCL, Lyon, France.
EP956
Rare causes of hypopituitarism in adults in a tertiary care institution
40-year-old female patient presented with acromegaly in 2008 (GH 61 (g/L, IGF-
Sandra Pekic Djurdjevic1,2, Mirjana Doknic1,2, Dragana Miljic1,2,
1 774 ng/ml PRL 1500 mU/L). Macro-adenoma invading the right cavernous
Marko Stojanovic1,2, Marina Nikolic Djurovic1,2, Zvezdana Jemuovic1,
sinus was found on MRI and she underwent two pituitary surgeries revealing
Milica Medic Stojanoska3, Vera Popovic2 & Milan Petakov1,2
sparsely granulated GH adenoma with scattered PRL cells, low Ki 67 and
1Clinic for Endocrinology, Diabetes and Diseases of Metabolism, University
negative p53
immuno-staining. Her second cousin was treated for macro
Clinical Center, Belgrade, Serbia;2School of Medicine, University of
prolactinoma. Both patients tested negative for germline mutations in the AIP and
Belgrade, Belgrade, Serbia;3Clinic for Endocrinology, University Novi
menin genes. Treatment with somatostatin analogue and dopamine agonist was
Sad, Novi Sad, Serbia.
initiated. She was well controlled (GH 1.1 (g/L and IGF-1 291 ng/ml) until 2011
(IGF-1 576...608 ng/ml, GH 4.1 (g/L) when she received 20 Gy gamma knife
radio surgery, to the right para-sellar rest and clivus with good response (2012
Objective
IGF-1 235-306 ng/ml). In 2014 she became symptomatic with headache, VI
Hypopituitarism is a rare disease,a pituitary adenoma and is treatment being the
cranial nerve palsy and biochemical deterioration
(GH 5.3 (g/L and IGF 1
most common cause of it. In recent years there is increased reporting of rare
549 ng/ml). In November 2015 she developed VII & VIII cranial nerve palsy and
causes of hypopituitarism acquired in adulthood, such as other sellar and
biochemically deteriorated (GH 13 (g/L and IGF-1 857 ng/ml). MRI disclosed
parasellar masses, brain damage caused by radiation and traumatic brain injury
tumour progression from the right para-sellar to the infra-sellar region infiltrating
(TBI), vascular lesions, infiltrative/immunological/inflammatory diseases and
clivus, sphenoid and temporal bone and posterior cranial fossa with progressive
infectious diseases. Aim of our study was to increase the awareness to these rare
rise in GH 16(g/L and IGF-1 909 ng/ml levels despite treatment with somatostatin
causes of hypopituitarism.
analogue and dopamine agonist. Avid tracer uptake was noted in the pituitary
Patiens and methods
tumour and neck lymph node on the left side on FDG PET CT and SST2
We performed a cross-sectional database study in our population investigating the
scintigraphy. Third surgery using the posterior cranial fossa approach was
etiology of hypopituitarism in 558 patients in a tertiary care institution recorded
performed. Tumour biology revealed sparsely granulated GH adenoma with high
for the last 11 years. We excluded the patients with pituitary adenomas and
proliferative activity Ki
67 17.2%, positive p53 and 2/10 mitoses. Revised
congenital hypopituitarism. Sixty-eight patients
(32
male,
36 female) were
immunohistochemistry revealed recurrent sparsely granulated GH adenoma
included in the study (mean age 37.3G2.0 years, range 16-72 years).
expressing SSTR2 and Pit1 with low proliferation (Ki 67: 0, mitoses: 0) positive
Results
p53 (1%) grade 2a. This case illustrates our AIP negative FIPA patient with
According to the causes of hypopituitarism the patients were divided in several
sparsely granulated GH adenoma and aggressive behaviour refractory to
groups: nonpituitary sellar and parasellar masses in 10 patients (pituicytoma
multimodality treatment during long term follow up.
nZ1, chordoma nZ2, metastasis nZ3, intravascular lymphoma nZ1,
DOI: 10.1530/endoabs.49.EP954
Langerhans cell histiocytosis nZ3), brain damage in 27 patients (TBI in 9
patients and cranial irradiation in 18 patients), vascular causes in 17 patients
(aneurysm nZ1, apoplexy nZ3, Sheehan’s syndrome nZ6, subarachnoid
hemorrhage nZ6, glomangioma nZ1), immunological/infiltrative/inflammatory
disease in 7 patients (primary hypophysitis nZ6, secondary hypophysitis nZ1)
and pituitary infections in 7 patients (viral hypophysitis-hemorrhagic fever with
EP955
renal syndrome, tuberculosis). Growth hormone and ACTH deficiencies were the
Gambling and cabergoline
most common hormonal deficits (57/68, 84%), followed by FSH/LH deficiency
Julia Silva-Fernández1, Francisco Javier Gómez-Alfonso1, Florentino Del
(52/68, 76%), TSH deficiency (49/68, 72%) and ADH deficiency (8/68, 12%).
Val-Zaballos1, Belvís Torres-Arroyo1, Paloma González-Lázaro1, Álvaro
Ten patients (14.7%) had isolated pituitary hormone deficiency, 13 patients
García-Manzanares Vázquez de Agredos1, María López-Iglesias1,
(19.2%) had
2-3
pituitary hormone deficiencies and
4
pituitary hormone
Rafael García-Ruiz2 & Inés Gómez-García1
deficiencies were present in 45 patients (66.1%).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
effects from autoimmunity and disruption of self-tolerance. They include
A high index of suspicion is required for diagnosing rare causes of
colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies
(hypophysitis
hypopituitarism. The symptoms and signs of hypopituitarism are usually
(0-17%), thyroid dysfunction (0-4%) and primary adrenal insufficiency (0.3-
nonspecific and the recognition of these patients remains the challenge.
1.5%). Ipilimumab-associated hypophysitis is a new form of autoimmune
DOI: 10.1530/endoabs.49.EP956
pituitary disease with an average time of
11 weeks after starting therapy,
suggesting a cumulative effect. Patients may present with weakness, headache,
nausea, anorexia, confusion, memory loss, behavior change, hallucinations, visual
impairment, loss of libido, temperature dysregulation, fever, and chills. Hormone
levels show varying degrees of hypopituitarism, and MRI may be normal or
reveal pituitary gland enlargement and thickening of the stalk. Symptoms resolve
EP957
after withdrawal of the drug and starting hormone replacement; however,
Recombinant Human Growth Hormone Treatment in liver transplant
pituitary function may be impaired for considerably longer or even lifelong.
patient. Case report
Conclusion
Corina Galesanu
The increasing use of immune checkpoint inhibitors such as ipilimumab is an
University of Medicine and Pharmacy ‘Grigore T.Popa’, Iasi, Romania.
emerging cause of hypophysitis that generalists, ER physicians, oncologists, and
endocrinologists need to be aware of.
Background
DOI: 10.1530/endoabs.49.EP958
Linear growth is often impaired after successful liver transplantation. Factors that
negatively impacted growth are age, graft function and corticosteroid
immunosuppression. Short-statured prepubertal liver transplant recipients who
do not show sufficient compensatory growth after transplantation benefit from
treatment with recombinant human growth hormone (rhGH).
EP959
Cas report
A case of hypopituitarism caused by hemorrhagic fever with renal
We communicate the results after the first year of rhGH treatment in a child of 12
syndrome
years old, identified with growth failure after a liver transplantation. Liver
Seung Hee Yu & Kiyoung Lee
transplant (live donor- the mother) to 9 years for secondary cirrhosis (biliary
Gachon University Gil Medical Center, Incheon, Republic of Korea.
atresia), malabsorption syndrome, secondary osteoporosis with multiple femoral
fractures on pathological bone. Height Z108 cm (K 5, 92 SDS), and the weight
was Z20 kg (K2, 5 SDS). Bone age Z7 years. Bone mineral density (BMD-
Hemorrhagic fever with renal syndrome (HFRS) is a severe systemic infection
DXA)-whole bodyZ0.718 g/cm2 (low bone mass acquisition). Blood samples for
caused by hantaviruses that included Hantaan, Seoul, Dobrava, Saaremaa, and
baseline growth hormone (GH) secretion, serum insulin-like growth factor (IGF-
Puumala. In Korea, the most common virus is Hantaan. The classical symptoms
I) concentrations serum alkaline phosphatase, alanine aminotransferase,
of HFRS are fever, hemorrhage, hypotension, and renal failure, but the clinical
y-glutamyl transferase, and total bilirubin concentration, serum free T, and
course can be very diverse. Among them, endocrinologic complications, such as
TSH levels were determined every 6 months. He was treated with subcutaneous
hypopituitarism were developed rarely by HFRS. A 49 years-old man admitted
injections of rhGH at 0.35 mg/kg/ wk. for one year. Treatment was begun after 3
our hospital with fever, myalgia and thrombocytopenia. He was diagnosed as
years of x liver transplantation. He was treated for that with tacrolimus and
HFRS caused by Hantaan and clinical manifestations. In oliguric phase of renal
prednisolone. After the first year, rhGH treatment was continued.
failure, abnormalities of thyroid function, fT4
0.35 ng/dl
(0.89-1.78), T3
Results
24.43 ng/dl (60-180) and TSH 0.358 uIU/ml (0.55-4.78), were found and other
After 12 months of treatment, median serum levels IGF-I increased from 86 to
hormone tests were performed for differential diagnosis. The level of basal
231 ng/ml. Height velocity increased from 2 cm/yr. to 10,2 cm/yr. and BMD-
hormones were prolactin 13.77 ng/ml (2.1-17.7), GH 2.10 ng/ml (0-1), IGF1
DXA whole body from 0.718 g/cm2 to 0.997 g/cm2 (C38%); leanCBMC from
112.87 mg/l
(124-310), ACTH
27.8 pg/ml
(10.0-60.0), cortisol
13.82 mg/dl
15735.6 g to 19510.5 g (C24%); fat decreased from 4378 g to 2990.7 (K32%);
(5.27-22.45), LH
3.94 mIU/ml (1.5-9.3), FSH
2.75 mIU/ml (1.4-18.1) and
and total weight increased with 12%. There were no rejection episodes.
testosterone 104.99 ng/dl (241-827). These results indicated secondary hypogo-
Conclusion
nadism and hypothyroidism and no evidence/was seen hypothalamic or other
In our case rhGH treatment was effective in short, non-GH deficient, liver-
pituitary disease by sella MRI. According to this result, partial hypopituitarism by
transplanted child receiving long term glucocorticoid treatment.
HFRS was suspected in the patient. After conservative treatment, manifestations
and laboratory investigation were improved. He was discharged and tested the
DOI: 10.1530/endoabs.49.EP957
basal hormones again at the outpatient clinic. The results were fT4 1.16 ng/dL, T3
110.43 ng/dl, TSH 1.490 uIU/ml, prolactin 8.27 ng/ml, GH 0.41 ng/ml, IGF1
254.24 mg/l, ACTH 30.9 pg/ml, cortisol 10.36 mg/dl, LH 2.83 mIU/ml, FSH
6.54 mIU/ml and testosterone 214.05 ng/dl. The thyroid function was recovered
to normal level spontaneously and the gonadal hormones were still low level.
EP958
Compared with initial hormone level, the pituitary function is recovering
Immune checkpoint inhibitors: an emerging cause of hypophysitis
sequentially. Our experience suggests the important to investigate the
Ali Rizvi & Brooke McAdams
endocrinologic complications of HFRS and to determine whether treatment of
University of South Carolina School of Medicine, Columbia, South
hormone replacement is needed.
Carolina, USA.
DOI: 10.1530/endoabs.49.EP959
Aim
To describe 2 cases of immune-mediated hypophysitis due to the therapeutic use
of Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA4)-blocking antibody.
Case 1
EP960
A 62 year-old male with history of metastatic melanoma was started on
Prevalence and Incidence of pituitary tumors: a nation-wide Popu-
Ipilimumab. After finishing the 4th at 2 months he complained of weakness,
lation-based study using Korean National Health Insurance claims data
fatigue, and fever, prescribed ciprofloxacin and prednisone 20 mg daily, and felt
Kyeonghye Park1,2, Junggyu Choi1, Se Hee Park2, Joo Young Nam1,
better. 2 days later he was hospitalized with weakness, BP 86/65 mmHg and
Sun Ok Song1, Young Duk Song1 & Eun Jig Lee2
temperature 101.7F. TSH was 0.050 uIU/ml, free T4 0.48 ng/dl, and free T3
1National Health Insurance Service Ilsan Hospital, Goyang, Republic of
1.20 pg/ml FSH 1.2 mIU/ml, LH 0.8 mIU/ml, and prolactin 0.3 n/ml (all low). A
Korea;2Yonsei University College of Medicine, Seoul, Republic of Korea.
Cosyntropin Stimulation Test showed the following cortisol levels (in ug/dl):
baseline
2.60,
30 min post-injection
6.30, and
60 min post-injection
7.90.
Pituitary MRI was normal. The clinical picture was consistent with severe,
Purpose
recent-onset panhypopituitarism. The patient was treated with IV fluids, stress-
We conducted this study to determine the prevalence and incidence of pituitary
dose dexamethasone, and levothyroxine, and discharged on hormonal replace-
tumors in South Korea.
ment. He continues to do well on multi-hormonal endocrine replacement therapy.
Methods
Discussion
This is a nationwide population- based retrospective study. We analysed two
Ipilimumab (Yervoy*) is a monoclonal CTLA4 antibody and immune checkpoint
national databases, the Korean National Health Insurance (NHI) claims database
protein-modulator approved for treatment of melanoma, and being studied in
and Rare Intractable Disease
(RID) registration database, which include
lung, prostate, and bladder cancer. Mechanisms of overcoming tumor-induced
information on every patients with pituitary tumor diagnosed through uniform
immune tolerance trigger ‘Immune-related adverse events’ (IRAEs) as side
criteria from 2009 to 2013. Pituitary tumor was defined into three types based on
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
the ICD-code; i) D35.2
(benign pituitary neoplasm), ii) D35.2CE
22.0
Case presentation
(acromegaly) CE24.0 (Cushing disease), or iii) D35.2CE22.0CE24.0CE22.1
A 41-year-old man admitted to our hospital with gluteal and scapular mass. He
(Hyperprolactinemia) &co-entered D35.2.
had a clinical history of acromegaly which had been diagnosed two years ago, and
Results
was treated with trans-sphenoidal surgery. After surgery, although remission was
The prevalence and incidence of pituitary tumors were described based on the
not achieved, he had no doctor visit and control. On physical examination he had
three definitions. By definition i),
25 135 patients had pituitary tumors and
typical acromegalic features and there was palpable mass on right gluteal and
included in the prevalence estimates. The prevalence was 40.8, 31.4 and 50.1 per
scapular region, which was noticed by the patient within the last two months.
105 populations in total, men and women, respectively. During 2011-2013, total
Laboratory examination revealed high levels of GH
(10.8 ng/ml), IGF1
8 234 incident cases were identified and the incidence was 17.3, 13.7 and 21.0 per
(1072 ng/ml). Abdominopelvic CT revealed an
93!68 mm mass on right
105 in total, men and women, respectively. By definition ii), total 25 135 patients
kidney, 100!65 mm on the right gluteal region and 200!80 mm on the right
had pituitary tumors and prevalence was 52.4, 37.5 and 67.1 per 105 populations
scapular region. Thorax CT revealed metastatic noduler lesions on the right lung.
in total, men and women, respectively. For the incidence estimate, 10 359 patients
The diagnosis of metastatic renal clear cell cancer (RCC) was verified with gluteal
were identified and the incidence was 21.6, 15.8 and 27.3 per 105 in total, men and
and scapular biopsies. Pituitary MRI revealed residual makroadenoma (2 cm).
women, respectively. By definition iii), total 30 175 patients had pituitary tumors
Therapy for acromegaly with octreotide LAR was initiated. The patient
and prevalence was 62.9, 38.7 and 86.8 per 105 populations in total, men and
underwent radiation therapy for the tumors of right scapular, gluteal region. At
women, respectively. For the incidence estimate, total 12 544 patients were
the same time patient recieved interferon-alfa therapy for metastatic RCC. After
identified and the incidence was 26.1, 16.3 and 35.9 per 105 in total, men and
three months of treatment, scapular, gluteal mass regressed but renal mass and
women, respectively.
lung metastasis progressed with diffuse plevral effusion on the right side.
Conclusions
Sunitinib treatment was started for the follow up.
This study provides reliable information of the epidemiology of pituitary tumors
Discussion
in Asian population, and may help to manage this disease accordingly within our
Therefore we report a very rare case of acromegaly with RCC. In adition to the
healthcare system.
increased circulating GH/IGF-1 levels, local expression of GHR and IGF-1/IGF-IR
DOI: 10.1530/endoabs.49.EP960
in the tumor tisues may partly contribute to the growth of multiple tumors. Type
1/IGF1R has an influence on renal cells malignant transformation by induction of
cell proliferation, dediferantiation and antiapoptotic effect. The risk of RCC
progression would have been very high had the acromegaly been left untreated.
control of acromegaly is mandatory in acromegalic patients with cancer.
DOI: 10.1530/endoabs.49.EP962
EP961
Prevalence of acromegaly in eight counties of North-East Romania
Laura Feraru1, Carmen Vulpoi1,2, Voichita Mogos1, Corina Galesanu1,2,
Dumitru Branisteanu1,2, Maria-Christina Ungureanu1,2, Letitia Leustean1,2,
Cristina Cristea1, Simona Mogos1,2, Catalin Buzduga1,2, Raluca Balaceanu1
& Cristina Preda1,2
1University Hospital ‘St Spiridon’, Iasi, Romania;2University of Medicine
and Pharmacy ‘Gr. T. Popa’, Iasi, Romania.
EP963
Introduction
The prevalence of acromegaly is estimated to be 6-28/100000 but several studies
Infundibular lesion presenting with central diabetes insipidus and
suggest that acromegaly is underdiagnosed and its prevalence is underestimated.
hypogonadism
Aim
Gulay Simsek Bagir, Filiz Eksi Haydardedeoglu, Okan Bakiner,
To measure the prevalence of clinically relevant acromegaly in a well-defined
Emre Bozkirli & M Eda Ertorer
population using data from 01.04.2004 to 01.11.2016.
Baskent University Faculty of Medicine, Adana, Turkey.
Method
Cross-sectional study performed in 8 counties from the North-East Romania. Data
Introduction
of patients with acromegaly were collected using the INFOWORLD programme
Pituitary stalk lesions fall into three categories: congenital and developmental
and acromegaly diagnosis code E22.0. The number of inhabitants for each county
(rathke cleft cyst, ectopic neurohypophysis), inflammatory and infectious
was in accord with 2011 Census and 2007 Statistical Directory. We identified all
(hypophysitis, sarcoidosis, tuberculosis), and neoplastic
(Langerhans cell
acromegalic patients who were born and resided for each of the eight counties
histiocytosis, germinoma, metastatic tumors). Herein, we report a case with
diagnosed in the Department of Endocrinology from the University Hospital
infundibular lesion presenting with central diabetes insipidus and hypogonadism.
‘St Spiridon’ Iasi, Romania.
Case report
Results
A 27-years old woman was admitted to our clinic with the story of amenorrhea
238
(164 females and 74 males) patients with acromegaly were identified in a
and polydipsia lasting for three years. She was on desmopressin for two years. Her
total population of 4.2 million inhabitants. The prevalence for Iasi County was
physical examination was unremarkable. Hormonal profile was: TSH:
9,94/100000, Suceava County 5.49/100000, Bacau County 4,13, Galati County
0.79 uIU/ml (0.4-4.67), freeT4: 15.49 pmol/l (11.5-22.7), FSH: 2.03 mIU/ml
1,50, Neamt County 3,94, Botosani County 7,17, Vaslui County 7,37/100000 and
(1.2-15.4), LH:
1.02 mIU/ml
(1.24-7.8), Estradiol:
28.7 pg/ml
(30-119),
Vrancea County 3,53/100000.
Prolactin: 35.3 ng/ml (2.8-29.2), early morning cortisol: 15.2 mg/dl (4.3-22.4)
Conclusions
and IGF1:
152 ng/ml
(117-329). Pituitary MRI demonstrated a
7!5 mm
The highest prevalence was identified in 3 counties (Iasi, Vaslui and Botosani).
infundibular mass with suprasellar extension. Diagnostic work-up for infundib-
The explanation of this results may be the more frequent use of diagnostic
ular lesions was performed, including; chest X-ray, computed tomography (CT)
procedures like CT or IRM, the concern of local endocrinologists to identify this
of thorax, purified protein derivated
(PPD) test and measurement of serum
type of pathology. The sex distribution of the selected population was in favour of
angiotensin converting enzyme (ACE) for ruling out granulomatous diseases.
female patients (2F:1M) and was not consistent with 1:1 sex distribution of
Neck ultrasound, bone scintigraphy, skeletal survey, brain CT and measurement
previous studies.
of beta-HCG were performed for ruling out infiudibular neoplastic lesions, Serum
DOI: 10.1530/endoabs.49.EP961
anti-thyroid peroxidase, anti-thyroglobulin antibody were measured. All were
negative. She exhibited no autoimmune background. Serum IgG4 was normal, as
well. In addition to existing desmopression, estrogen-progesteron therapy was
introduced and menses recovered in a few months. Due to rapid radiological
progression at follow-up, methyl prednisolon 1 mg/kg per day was begun for a
possible infundibulohypophysitis. Significant radiological regression was
EP962
observed at the second month of glucocorticoid therapy.
A male patient with acromegaly and metastatic renal cell carcinoma:
Conclusions
lung, gluteal and scapular metastasis
Pituitary stalk lesions have diverse causes and hypophysitis is one of them. In our
Ziynet Alphan Uc1 & Ozgur Demir2
case, histopathological diagnosis was not possible due to critical location of the
1Endocrinology Department, Usak University School of Medicine, Usak,
infundibular lesion. After detailed work-up, a diagnosis of possible infundibu-
Turkey;2Endocrinology Department, Ankara University School of
lohypophysitis was made and ampiric glucocorticoid therapy was introduced and
Medicine, Ankara, Turkey.
resulted in radiological regression.
DOI: 10.1530/endoabs.49.EP963
Acromegaly is a chronic condition associated with an increased risk of cancer.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP964
panhypopituitarism met - at 10 from 18 patients (55,5%%), while in the 1
group of panhypopituitarism not observed. A bytemporal hemianopsia also with
Pregnancy in Cushing’s disease after treatment with surgery and
greater frequency was observed for patients 2 groups - 11 supervisions (61,1%%).
cyber-knife radiosurgery
In addition, secondary amenorrhea met a bowl also for patients 2 groups - 6
G Gonca Oruk1, Ali Olmezoglu2, Melda Apaydin3 & Gonul Guven
¸4
(33,3%%). Such violations, as secondary ?steopeniya, endocrine encephalopathy,
1Department of Endocrinology and Metabolism, Ataturk Training and
delay of physical and sexual development were educed only in 2 groups of
Research Hospital, Katip Celebi University, Izmir, Turkey;2Department of
patients. Thus, the most expressed neuroendocrine and ophthalmology violations
Radiation Oncology, Celal Bayar University, Manisa, Turkey;3Department
met for patients 2 groups. For patients with the giant adenomas of hypophysis the
of Radiology, Ataturk Training and Research Hospital, Katip Celebi
decline of level of STH, FSH is first of all marked, LH (45%%).
University, Izmir, Turkey;4Department of Neurosurgery, Ataturk Training
Conclusions
and Research Hospital, Katip Celebi University, Izmir, Turkey.
From preliminary data of comparative description of sizes of tumour of sellar area
and level of STH a tendency took place to that as far as growth size of tumour of
Women affected by Cushing’s disease (CD) are often infertile due to abnormal
the Turkish saddle the basale level of STH of plasma was below. For a receipt the
follicular development or anovulation. In these patients, first line treatment is
further protracted supervision of data of patients is required of reliable results
pituitary surgery, which is effective in more than
83% of cases with
with an estimation in a dynamics MRI and STH of plasma with realization of
microadenomas, but only in about 35% of those with macroadenomas. When
loading tests, research of IGF1 and estimation of quality of life for questionnaire
surgery do not normalize circulating ACTH and cortisol concentrations, such
of adult growth hormone deficiency (AGDQoL).
drugs, e.g. ketoconazole or metirapone, and radiotherapy are used as adjuvant
DOI: 10.1530/endoabs.49.EP965
treatment. Concerning radiotherapy, more precise and focused approaches of
delivering larger amounts of radiation have been introduced recently in the
management of pituitary tumors. Cyber-knife radiosurgery (CKR) is considered
as a possible treatment for patients affected by unsuccessfully surgically treated
pituitary adenoma or not suitable for surgery. The disadvantages of this technique
seem to be the length of time to the onset of remission, which is known to be at
least of
6 months, and the possible adverse effects. In patients treated with
radiotherapy, however, mild hypercortisolism can persist for a long time and
fertility could not be restored, even when menses have been normalized. We
report here a case of a 37-yr-old female patient with Cushing’s disease (CD) due
to ACTH-secreting 5 mm adenoma on the left side of the pituitary. Because
EP966
complete clinical remission was not obtained by a transsphenoidal surgery in
Gender differences in real-life GH dosing patterns in adults with GH
2010, CKR was performed for to achieve remission in January 2011. Thereafter,
deficiency (AGHD): experience from a Registry in France
treatment with ketoconazole, at the dose of 400 mg daily, normalized serum
Françoise Borson-Chazot1, Evguenia Hacques2, Véronique Pascal-
cortisol and UFC levels, allowing the recovery of regular menses. Because of low
Vigneron3, Sylvie Salenave4 & Béatrice Villette2
FT4 and low TSH and undetectable AbTPO values, L-T4 replacement was
1Hôpital Louis Pradel, Bron, France;2Novo Nordisk, La Défense, France;
started. 5 years after CKR, morning ACTH, cortisol concentrations, 24-h urinary
3Centre Hospitalo-Universitaire Régional, Nancy, France;4Hôpital Bicêtre,
free cortisol (UFC) and cortisol levels after 1-mg dexamethasone (1-mg dex)
Kremlin Bicêtre, France.
administration were normalized. MRI also showed partial shrinkage of the
pituitary tumor. The patient, who had regular menses, became pregnant 60
months after CKR. During pregnancy, plasma ACTH, serum cortisol and UFC
Introduction
levels increased. Fasting glucose levels (FGL), HbA1c and blood pressure were
Usually GHD women require higher GH doses than males, especially those with
normal all throughout pregnancy. Overall, patient’s body weight increase was
exogenous oestrogens (guidelines). This fact was assessed in real-life practice in
13.6 kg. At the 38th week of an uneventful pregnancy, the patient delivered
France.
vaginally a healthy female newborn (length 48 cm, weight 2600 g). The baby and
Methods
the mother did not show any biochemical signs or clinical symptoms of hypo- or
Data were from a Registry in 84 sites treating AGHD (Norditropinw) up to 5
hypercortisolism. In conclusion, pregnancy should be considered at risk in
years. Naïve patients did not receive GH 6 months before inclusion. Statistics
patients with CD, even the patient has normalized cortisol levels. Moreover,
were descriptive.
periodic evaluation of pituitary function is mandatory during gestation, due to the
Results
high risk of hypopituitarism.
328 patients (129 naïve) were included; mean age 49.2 years (G 14.3 S.D.). 180
DOI: 10.1530/endoabs.49.EP964
were females (55%) with 72 (40%) naïve; data missing for 6. 147 (81.7%) women
had a gonadotropic deficiency: 83 (79%) non-naive and 54 (75%) naive treated
with oestrogen therapy. At inclusion the median IGF-1 SDS (Q1;Q3) in naive
population was K2,20 (K3.20;K1.30) and in non-naïve was 0.00 (K1.30;
C1.10). The median starting dose was similar for naive women and men:
0.20 mg/d. After the first year until the end of the follow up (FU) the median dose
for naïve women was higher than for men. The median dose was higher for non-
naive females (Table 1). At the end of the FU, the median IGF1 SDS (Q1; Q3) in
naive population was C0.30 (K0.50;C0.80) and in non-naïve was C0.50
(K0.40;C1.20).
EP965
Table 1 Median GH dose (Q1;Q3) (mg/day)
The clinic-hormonal description of patients with giant pituitary
adenomas
Year
\ naive
_ naive
\ non-naive
_ non-naive
Yulduz Urmanova & Kamola Alimova
Inclusion
0.20
(0.20;0.30)
0.20
(0.20;0.30)
0.40
(0.20;0.60)
0.30
(0.20;0.40)
1Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan;
1
0.40
(0.30;0.50)
0.30
(0.20;0.40)
0.40
(0.30;0.70)
0.35
(0.20;0.50)
2Center of Endocrinology, Taskent, Uzbekistan.
2
0.50
(0.30;0.60)
0.30
(0.20;0.40)
0.40
(0.30;0.60)
0.40
(0.20;0.50)
3
0.50
(0.30;0.70)
0.39
(0.20;0.50)
0.40
(0.30;0.60)
0.30
(0.20;0.50)
4
0.50
(0.40;0.70)
0.37
(0.20;0.50)
0.40
(0.30;0.65)
0.40
(0.20;0.52)
The aim
5
0.60
(0.45;0.80)
0.40
(0.30;0.50)
0.40
(0.30;0.70)
0.30
(0.20;0.52)
To study the results of researches 35 patients with different pituitary tumours of
sellar area, from them men - 17 (48,6%%), women - 18 (51,4%%).
Materials and methods
Conclusion
Depending on sizes there are the adenomas of hypophysis, educed on CT/?RI,
In real life, physicians consider the recommendation of higher GH dose for
patients were up-diffused on two groups: the first group of patients is
AGHD women at steady state, while the starting dose remains similar in both
macroadenomas (from 20 to 30 mm) - 17 (48,6%%), and second group of
genders. Data from this Registry is consistent with the published data from other
patients - giant - (more than 30 mm) - 18 (51,4%%).
observational studies.
Results
It was educed, that in
2
groups of patients most often there was
DOI: 10.1530/endoabs.49.EP966
panhypopituitarism
- at
8
from
18
patients
(44,4%%), post-operating
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP967
EP969
Is there a role of immunohistochemical expression of pituitary
A case with headache and pitosis: pituitary macroadenoma or
hormones and proliferative marker ki-67 on long-term outcome in our
ophtalmoplegic migraine?
acromegalic patients?
Filiz Eksi Haydardedeoglu, Gulay Simsek Bagir, Okan Bakiner,
Mustafa Sahin, Caglar Keskin, Saba Kiremitci, Esra Erden, Asena Canpolat,
Emre Bozkirli & Melek Eda Ertorer
Murat Cinel, Sule Canlar, Ozgur Demir, Sevim Gullu, Rifat Emral,
Baskent University Adana Teaching and Research Center, Adana, Turkey.
Murat Faik Erdogan, Vedia Gedik, Nilgun Baskal & Demet Corapcioglu
Ankara University School of Medicine endocrinology and Metabolic
Case
Diseases Department, Ankara, Turkey.
A 28-year old man was admitted to our hospital with complaints of three days of
severe headache, diplopia and ptosis of the right eye. He had pituitary
Expression of hormones other than GH may affect the prognosis in acromegalic
macroadenoma and had been on cabergolin 0.25 mg/week for the last six
patients. Generally, Ki-67 is a well-known proliferative index used to predict
months. At physical examination, he demonstrated ptosis and inability to move
remission in pituitary adenomas. We aimed to evaluate the relationship of
the right eye medially. Magnetic resonance imaging showed a 13!12 mm
immunohistochemical expression pituitary hormones, ki-67 and remission. Also
pituitary mass with suprasellar extension and hemorrhage. Visual field analysis
we evaluated the role of pre, post-operative clinical and laboratory values,
was abnormal except the lateral movement of the right eye. Laboratory hormonal
pathological characteristics on long-term remission. We included 64 acromegaly
analysis showed mild cortisol deficiency only. According to clinical, radiological
patients that were treated surgically and followed up in our Endocrinology and
and laboratory results, he was diagnosed as non-functional pituitary adenoma
Metabolic Diseases Department. Demographic, clinical, laboratory and imaging
with apoplexy and III.cranial nerve palsy due to increased intrapituitary pressure.
data were collected. We also re-evaluated the immunohistochemistry of all
Intravenous methyl-prednisolone was started and symptoms resolved. One month
pituitary hormones and ki-67 marker from paraffin blocks. We followed 64
after discharge, although he was using methyl prednisolone 4 mg, he was again
patients (38 women, 26 Male; mean age 46.7G11.8) for 61.8 (6-192) months. We
admitted with complaints of nausea, vomiting, hypotension and ptosis. He was
did not found any relationship between remission and multihormonal expression
immediately taken to pituitary surgery via transnasal-transsphenoidal approach.
in our patients. We also did not found a significant relationship between ki-67
His complaints dissolved following the procedure and he was well at discharge.
expression or sex with remission. Early diagnosis age
(PZ0.045), greater
Histopathological analysis of the operation specimen exhibited a pituitary
adenoma diameter
(PZ0.002), low preoperative LH
(PZ0.036) and high
adenoma with necrosis and hemorrhage. On the fifth postoperative day, he was
postoperative IGF1 (P!0.0001) only factors that are significantly related with
re-admitted with diplopia, photophobia, phonophobia, nausea and vomiting.
low rate remission. Preoperative cortisol levels are related to ki-67 index level
Recurrent headache attacks lasting for about one week within the last 6 months
(PZ0.004). Low preoperative LH and high postoperative IGF1 levels and tumor
reminded accompanying ophtalmoplegic migraine. Eighty mg eltriptan and
diameter may be predictive for remission and low cortisol levels may be
parenteral pulse steroid (1000 mg methyl prednisolone/5 days) were started. The
predictive for the high ki-67 index.
patient had no longer experienced an attack.
DOI: 10.1530/endoabs.49.EP967
Conclusion
Pituitary apoplexy and ophtalmoplegic migraine are rare clinical entities.
Ophthalmoplegic migraine has been recognized as a cranial neuralgia and
characterized by repetitive III, IV and / or VI. cranial nerve palsies. If there is
persistent headache and cranial nerve palsies following surgical decompression of
an adenoma with pituitary apoplexy, accompanying ophtalmoplegic migraine
should be kept in mind.
EP968
DOI: 10.1530/endoabs.49.EP969
Investigation of the pituitary functions long-term after the acute CNS
infections
Gamze Cetinkaya1, Aysegul Ulu Kilic2, Zuleyha Karaca1,
Mehmet Doganay2, Z T Yuce2, Kursad Unluhizarci1, Fahrettin Kelestimur1
& Fatih Tanriverdi1
1Erciyes University Medical School Department of Endocrinology, Kayseri,
Turkey;2Erciyes University Medical School Department of Infectious
EP970
Diseases, Kayseri, Turkey.
Somatostatin analogues-induced diabetes mellitus in acromegalic
patients reverts after drug withdrawal: a long-term study
Daniele Cappellani1, Claudio Urbani1, Chiara Sardella1,
Objectives
Giulia Marconcini1, Claudio Marcocci1, Giuseppe Rossi2 &
Acute bacterial or viral CNS infections have been shown to result in
Fausto Bogazzi1
hypopituitarism during the acute phase, and 6-24 months after the event in a
1Department of Clinical and Experimental Medicine - Section of
few studies. However, there are no data in the literature regarding the long term
Endocrinology, University of Pisa, Pisa, Italy;2Epidemiology and
pituitary functions after acute CNS infections. This cross-sectional study was
Biostatistics Unit - Institute of Clinical Physiology, National Research
designed to evaluate the pituitary functions long-term after the acute bacterial or
Council (C.N.R.), Pisa, Italy.
viral CNS infections.
Methods
19 patients with ages 18-65 (mean: 39.53G17.089 years; 11 male patients, eight
Context
patients female) were included in the study. There were seven patients with acute
Therapy with somatostatin analogues (SSAs) may have deleterious effects on
bacterial meningitis, nine patients with acute viral encephalitis, and three cases of
glucose metabolism in patients with acromegaly, often leading to development of
acute meningoencephalitis. Basal pituitary hormone levels were measured and
diabetes mellitus (DM).
glucagon stimulation test was performed 17-92 months (mean 48.47G25.19
Aim of the study
months) after the acute CNS infections. MRI was performed to evaluate the
To evaluate whether DM, which developed during therapy with SSAs, may revert
pituitary gland volume and to rule out any co-incidental pituitary mass.
after drug withdrawal and cure of acromegaly with pituitary adenomectomy.
Results
Design
There were a total of 5 patients out of 19 (26.3%) with hypopituitarism; 3 (15.7%)
Retrospective cohort study, in a tertiary referral center.
with isolated GH deficiency, 1 (5.2%) with isolated FSH-LH deficiency and 1
Patients
(5.2%) with combined FSH-LH and GH deficiency in the study group. Mean
Eighteen acromegalic patients without DM at the diagnosis of acromegaly treated
pituitary volume was substantially lower in patients with hypopituitarism when
with SSAs as a primary therapy, and then cured by pituitary adenomectomy.
compared to the patients without hypopituitarism. But the difference was not
Methods
statistically significant.
Endocrine status and glucose homeostasis were evaluated at diagnosis of
Conclusion
acromegaly and at least every six months during SSAs therapy. At each control
This study clearly demonstrated that high frequency hypopituitarism, GH
patients were classified in one of the following classes: normal glucose tolerance,
deficiency in particular, was still present long term after the acute bacterial or
prediabes, overt diabetes.
viral CNS infections. Therefore, the patients with acute meningitis, meningoen-
Results
cephalitis and/or encephalitis need to be screened at least 4-5 years after the acute
Median follow-up after starting SSAs therapy was 60 months (IQR 53.2-96.2).
event.
During SSAs therapy, all patients had controlled acromegaly defined by normal
DOI: 10.1530/endoabs.49.EP968
serum IGF-1 concentrations for the age. Among the 13 euglycaemic patients at
diagnosis three developed prediabetes and three diabetes, whereas, among the five
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
prediabetic patients at diagnosis two worsened to overt diabetes; three remained
Table 1 Results of basal endocrine and biochemical investigations of
in the prediabetic range (PZ0.04). After cure of acromegaly with pituitary
patient
adenomectomy and subsequent SSAs withdrawal, prediabetes reverted in five out
of six patients, and diabetes in all five patients (in three reverted to euglycaemia,
Parameter (unit)
Value
while in two reverted to prediabetes) (PZ0.01).
Conclusions
Glucose (mg/dl)
87
In acromegalic patients with controlled disease changes of glycaemic status
Na (mmol/l)
137
induced by SSAs are not permanent.
K (mmol/l)
4.5
DOI: 10.1530/endoabs.49.EP970
FT4 (ng/dl)
2.69
TSH (mIU/ml)
4.70
Cortisol (mg/dl)
8.7
Vanillylmandelic acid (mg/24 s)
1.56
Metanephrine (mg/24 s)
168
Normetanephrine (mg/24s)
298
EP971
Table 2 Results during insulin tolerance test
Pituitary metastases of lung cancer presenting with hypopituatrism
Guzin Fidan Yaylalı1, Senay Topsakal1, Serkan De
˘ irmenciog˘ lu2 &
Parameter
Value
Semin Melahat Fenkçi1
1Pamukkale University Medical Faculty Endocrinology Metabolism
Glucose (mg/dl)
45
Depatment, Denizli, Turkey;2Pamukkale University Oncology Department,
Cortisol (ug/dl)
5
Denzili, Turkey.
GH (ng/ml)
0.45
ACTH (pg/ml)
!0.5
Pituitary tumors are the most frequent intracranial neoplasm, affecting 11 000 of
the world wide population. However metastases in this location are rare and
uncommon presentation of systemic malignancy. Although diabetes insipidus
Table 3 Results during ACTH stimulation test
secondary to cancer metastasis to the pituitary gland is a common manifestation,
anterior pituitary failure is rare. We present a K57-year-old man with
Parameter
hypopituitarism secondary to pituatry metastasis from lung cancer.
Case report
Minute
0
30
60
A 57-year-old patient active smoker presented with headache of 1 month. Cranial
Cortisol (mg/dl)
18.6
24
32
MRI revealed multiple subcortical lesions and hypophyseal noduler lesion 13.6
mm in diameter. The computary tomography scan of the Chest, Abdomen and
Pelvis revealed a 23!22 mm rregularly margined mass in mass in the upper left
lobe with mediastinal lymph nodes, liver and right adrenal metastases.
multinodular goiter. On clinical examination; height 153 cm, weight: 67 kg,
Assessment of pituitary function revealed panhypopituitarism; Cortisol:
BMI:29 BP: 120/70 mm/Hg. The other physical examination findings were
3.17 mg/dl, ACTH:11.5 pg/ml free T4
0.64 ng/dl
(normal range
0-97-1.65),
normal. Radiologic findings included: Abdominal MRI: in the right adrenal gland,
thyroid stimulating hormone level of 0.005 mUI/ml (normal range 0.5-4 IU/ml),
20!12 mm and 33!13 mm in left adrenal gland adenomas was detected. The
total testosterone level of
0.025 ng/ml (normal range 2.5-10 ng/ml), follicle
laboratory findings were shown in Table 1. Basal Cortisol levels were detected as
stimulating hormone level of 0.5 IU/ml (normal range 1-8.4 IU/ml), luteinizing
6.6 mg/dl and insulin tolerans test and ACTH stimulation test were performed.
hormon level of 0.1I U/l (normal range 1-10.5 IU/l) and normal urine osmolarity.
(Table 2, Table 3).
Complete blood count showed the following: hemoglobin 13.6 g/dl, white cell
Conclusion
count 12.64 K/ul, and platelet count 322 K/ul Evaluation of serum chemistry
Acth deficiency is rare in elderly patients is a complex disease and many diseases
revealed lactate dehydrogenase
245 IU/l, sodium
129 mmol/l potassium
that mimic. Sometimes patients are diagnosed by chance. When this case was
4.3 mmol/l. A hormone replacement therapy was indicated urgently. Fiberoptic
examined for adrenal adenoma, ACTH deficiency was unexpectedly detected and
bronchoscopy did not show any endobronchial lesion. Histopathologic exami-
replacement therapy was started. The clinic has the patient improved rapidly with
nation of brochoalveolar lavage revealed metastasis of lung adenocarcinoma.
replacement therapy.
Conclusion
Despite the fact that pituitary metastasis are rare, they must be evaluated in the
DOI: 10.1530/endoabs.49.EP972
presence of pituitary involvement. It may be difficult to differentiate symptoms
due to panhypopituitarism from the constitutional symptoms caused by cancer
progression. Considering that the life expectancy is limited for advanced lung
cancer patients, detection and appropriate treatment of hormonal insufficiency are
important to improve their quality of life.
DOI: 10.1530/endoabs.49.EP971
EP973
Clinical, histological, molecular features and outcomes of
craniopharyngiomas: Single centre experience in Toledo, Spain
Almudena Vicente1, Beatriz Moreno2, Mónica Olivar1, Ana Martínez1,
Manuela Mollejo2, Julia Sastre1 & José López1
1
Department of Endocrinology, Complejo Hospitalario de Toledo, Toledo,
EP972
Spain;2Department of Pathology Complejo Hospitalario de Toledo, Toledo,
ACTH deficiency in patient with bilateral adrenal adenomas
Spain.
Semin Melahat Fenkçi, Senay Topsakal & Guzin Fidan Yaylalı
Pamukkale University Endocrinology Department, Denizli, Turkey.
Background
Craniopharyngiomas (CPs) are epithelial tumors that typically arise in the
Introduction
suprasellar region. They are associated with high levels of morbidity related to
ACTH deficiency is a rare disease with non-specific symptoms such as anorexia,
tumour location and/or treatment-related injuries. Recent discoveries have also
fatigue and weight loss. Due to these silent symptoms the disease is easily
led to a better understanding of CP development and potential treatments.
overlooked and may escape detection for a long time, especially in elderly patient.
Objetive
Case
To analyse the clinical, pathological, molecular features and outcomes of patients
67-year-old female patient applied with complaints of fatigue. Bilateral adrenal
with CP.
adenoma was detected during ultrasonographic evaluation and and patient was
Design
consulted to endocrinology clinic Her personal history included osteoporosis and
Retrospective observational study.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
EP975
Clinical records review and re-evaluation of histologic samples from patients who
The use of increasing doses of cabergoline in the management of
underwent surgery of CP in our institution between 1999 and 2016.
cabergoline-resistant prolactinomas
Results
Lucio Vilar1,2, Clarice Vilar2, José Luciano Albuquerque1,
There were 26 patients (53.8% male), mean age at diagnosis 37 years (range 2-
Patricia Gadelha1, Ana Carolina Thé1, Erik Trova˜o1, Thaíse Borges1,
73). Mean follow-up was 86 months (range 3-288). The commonest presenting
Izabela Cardoso1 & Ruy Lyra1
symptoms were: visual alterations 84% (nZ21), headaches 53.8% (nZ14), and
1Division of Endocrinology, Hospital das Clinicas, Federal University of
behaviour disorders 11.4% (nZ3). 92.3% (24/25) of tumours had suprasellar
Pernambuco, Recife (Pernambuco), Brazil;2Endocrine Research Center of
involvement, with cystic component in 80.8% (16/26). Median tumour size was
Pernambuo, Recife (Pernambuco), Brazil.
30.4 mm (12-50). Initial surgical approach was transcranial in 96.2% (nZ25).
Available histological and molecular results were: 72% (nZ18) adamantinoma-
tous CP and 28% (nZ7) papillary CP (PCP). Three PCP harboured BRAF V600E
Introduction
mutation. In these cases, the average number of surgical interventions were higher
Dopamine agonists
(DA) are the ideal treatment for prolactinomas and
(4 vs1.3) and time to recurrence was shorter (34 vs 99 months). Three patients
cabergoline (CAB) is the drug of choice, for being much more effective and
(11.4%) undergone radiation therapy. Last neuroimaging assessment showed
better tolerated than bromocriptine. However,
10-15% of patients with
residual tumour in 50% of patients. At the end of follow-up, panhypopituitarism
prolactinomas are considered to be resistant to CAB, as they dot not achieve
and diabetes insipidus were detected in
72% (18/25) and
75% (18/24)
prolactin (PRL) normalization, while in use of conventional doses of this drug.
respectively. Symptoms related to hypothalamic dysfunction were found in
Objective
76% (19/25). The mortality was 11.5% (nZ3). Causes of death were: initial
To evaluate the effiaccy of increasing doses of CAB in prolactinomas refractory to
surgery related complications (1), multiple recurrent PCP harboured mutation
CAB 3 mg/wk by in order to achieve prolactin (PRL) normalization.
BRAF v600E (1) and cardiovascular disease (1).
Patients and methods
Conclusions
We prospectively evaluated the management of consecutive patients with
In our study, treatment of craniopharyngiomas were associated with high rates of
prolactinomas refractory to CAB 3 mg/wk who were submitted to progressive
tumor persistence and substantial morbidity. Tumours harboured BRAF V600E
increases in CAB dose, as needed and tolerated every 3 months, up to 9 mg/week.
mutation seemed to be associated with poor prognosis.
The patients were recruited over a 12-month period. Exclusion criteria were
DOI: 10.1530/endoabs.49.EP973
previous pituitary surgery or radiotherapy. Echocardiogram evaluation was
performed in each patient every 6 months.
Results
Twenty five patients were included in this study, 20 with macroprolactinomas.
Overall, normalization of PRL levels was achieved in 18 patients (72%): in 3
(12%) with a dose up to 4 mg/wk, in 9 (36%) with 5 mg/wk and in 6 (24%) with
6-7 mg/wk. No patients benefited from doses O7 mg/wk. No significant
echocardio-graphic valve abnormalities were detected.
Conclusion
CAB doses up to 7 mg/wk were well tolerated and enabled PRL normalization in
EP974
18
(72%) patients with prolactinomas resistant to CAB 3 mg/wk. No patients
Cushing’s disease: is there a Continuum from corticotroph hyperplasia
benefited from doses O7 mg/wk.
to adenoma?
DOI: 10.1530/endoabs.49.EP975
Ana Coelho Gomes1, Lia Lucas Neto2, Francisco Tortosa3,
Maria Raquel Carvalho1, Eduardo Barreiros1, Luís Barreiros1,
José Miguéns4 & Maria Joa˜o Bugalho1
1Endocrinology, Diabetes and Metabolism Department, Santa Maria
Hospital, Lisbon, Portugal;2Neuroradiology Department, Santa Maria
Hospital, Lisbon, Portugal;3Pathology Department, Santa Maria Hospital,
EP976
Lisbon, Portugal;4Neurosurgery Department, Santa Maria Hospital, Lisbon,
Long-term efficacy of octreotide LAR in acromegaly patients,
Portugal.
a prospective single centre study with 7 years follow up
1, Azra Burekovic1,2 & Amela Dizdarevic-Bostandzic1,2
Zelija Velija-Asimi
Introduction
1Medical Faculty University of Sarajevo, Sarajevo, Bosnia and
Successful long-term management of patients with Cushing’s disease
(CD)
Herzegovina;2Clinical Centre University of Sarajevo, Sarajevo, Bosnia
remains a challenge. Few studies have analyzed the long-term recurrence rates of
and Herzegovina.
CD after transsphenoidal surgery (TS).
Objectives
Objective
1) to compare the outcome of patients with and without postoperative criteria for
The aim of this single centre prospective open trial was to evaluate the long-term
cure; 2) to compare the outcome of patients with and without a histological
efficacy of octreotide LAR in acromegaly patients.
diagnosis of adenoma.
Methods
Methods
In total of 19 patients with acromegaly diagnosed at Endocrinology Department
Retrospective, descriptive study. Forty-two patients with CD submitted to TS
of Clinical Centre of University in Sarajevo, somatostatin sensitive (ten females
between 2005 and 2016 were included. Variables analyzed: postoperative criteria
and eight males, age range 40-68 years, six patients with microadenoma and 12
for cure, CD remission and recurrence rates, histological findings.
patients with macroadenoma) were treated with octreotide. Follow-up period was
Results
7 years (2009-2016). The concentration of human Growth Hormone (hGH) and
Surgical remission was achieved in thirty-eight patients. The mean follow-up was
insulin-like growth factor-1
(IGF-1) were evaluated every 6 months, while
6.8 years. Sixteen patients recurred. The mean time to recurrence was 4.6 years.
magnetic resonance imaging was taken every year during follow-up period.
Immediate postoperative evaluation was performed in 34 cases; criteria for cure
Results
were observed in seventeen. Patients with clinical recurrence who presented
During the first year of treatment ten patients were included. In the second year, a
postoperative criteria for cure had a mean disease free-time of 7.1 years, opposed
further seven patients were involved. During the last 4 years, five patients were
to 2.2 years in those without biochemical criteria for cure (P-value 0.032). Six
included. During the seventh year of follow-up, the treatment was successful
patients without biochemical criteria for cure after surgery are in remission.
discontinued at four patients, two patients was passed away due to co-morbidities
Histology documented an adenoma in thirty patients; from these, eleven recurred.
and at two another patients’ treatment was cancelled due to cancer; so currently we
Discussion
followed total of
11 patients. One of patient was treated by Gamma Knife
In this study, 42.1% of the patients who achieved remission, after TS, recurred.
radiosurgery and after that developed pituitary deficiency, but he is needed to
This finding emphasizes the need for continued biochemical and clinical follow-
continue with octreotide treatment because of high hGH and IGF-1 level. During
up. On the other hand, some patients without postoperative criteria for cure were
octreotide treatment, significantly reduced GH (50.87G10.56 vs 3,4G0.76 ng/ml,
in remission, at last observation. Thus, suggesting that biochemical criteria for
P!0,005), IGF-1 (777.66G118.40 vs 349G97.54 ng/ml, P!0.005) and adenoma
cure may be achieved at different timings from patient to patient. Evidence for
size (from 9.6 to 8 mm; P!0.05). GH decrease to less than 1 ng/ml was achieved in
recurrence in eleven patients with adenoma suggests that CD may be a continuum,
66% of cases; tumour size decrease was achieved in 49%, while normalization of
in which there is a basal corticotroph hyperplasia likely to evolve to adenoma.
IGF-1 was achieved in 88% of the patients, respectively. At 1-4 years of follow-up,
DOI: 10.1530/endoabs.49.EP974
20% of acromegaly patients had withdrawn treatment, without recurrence. Two
patients on octreotide treatment have uncontrolled acromegaly.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
tolerance test
(OGTT) have been suggested as early predictor of surgical
Octreotide LAR treatment is effective in decrease of GH, IGF-1 and tumour size
remission (Kim 2012). However, the value of this approach remains to be defined.
in well-selected acromegalic patients.
Aim
DOI: 10.1530/endoabs.49.EP976
The purpose of our study is to evaluate the utility of measurement of GH level
during a 2-week postoperative OGTT as a predictor for surgical outcome in
patients with acromegaly.
Materials and methods
Ten patients (five women and five men) with an average age of 47.4G14.8 years
(range 27-71 years) who had underwent total transsphenoidal adenomectomy
performed by one neurosurgeon were included in this study. All patients harbored
macroadenomas, with average size of
18.9G5.2 mm (range
13-29 mm).
Measurement of GH level during OGTT was performed 14 days after surgery.
EP977
The outcome of TSS was evaluated 6 months after surgery by OGTT and
Is there a gender difference in clinically nonfunctional pituitary
measurement of insulin-like growth factor 1 (IGF-1). The biochemical remission
adenomas?
of acromegaly according to the 2010 remission criteria were defined as nadir GH
Iffet Da
˘ delen Duran1, Ne¸e Ersoz Gulc¸elik2, Dilek Berker1 &
level on an OGTT !0.4 mg/l along with age and gender normalized values of
Serdar Guler1
IGF-1.
1Ankara Numune Education and Research Hospital, Department of
Results
Endocrinology and Metabolic Diseases, Ankara, Turkey;2Ankara
Initial basal GH level was 23.7G24.9 mg/l, initial IGF-1 patient /IGF-1ULN ratio
Education and Research Hospital, Department of Endocrinology and
was 2.7G0.6. Six months after surgery the remission of acromegaly was achieved
Metabolic Diseases, Ankara, Turkey.
in five patients (50%) - mean IGF-1 patient/IGF-1ULN - 0.7G0.2, mean nadir
GH level on an OGTT - 0.30C0.09 mg/l. Nadir GH level on an 2-week
postoperative OGTT was less than 1.0 mg/l in all patients with remission of
Introduction
acromegaly. Whereas, all patients with persistence of the disease had nadir GH
Clinically nonfunctioning pituitary adenomas (NFPA) are the most common
levels O1.0 mg/l on an early postoperative OGTT.
pituitary tumor type. They are usually recognized after they cause symptoms
Conclusion
especially when tumor size increases and eventually invades adjacent structures.
Our initial data suggest that nadir growth hormone level on an
2-week
Nevertheless the discovery would also be accidental. In the literature some kind of
postoperative OGTT less than 1.0 mg/l associated with remission of acromegaly
gender difference is reported in NFA’s behavioral results such as pituitary axis
6 months after surgery. Further researches are required to specify long-term
deficits or consequences of surgery however they resulted with controversial
outcomes.
reports. In our study we investigated if there is male/female preponderance in
terms of NFA’s some number of features.
DOI: 10.1530/endoabs.49.EP978
Materials and methods
We retrospectively examined 101 patients diagnosed as NFA biochemically and
radiologically. All patients were questioned for each possible symptom of
pituitary adenoma at diagnosis. Every patient was examined by laboratory
pituitary hormonal tests. Pituitary adenomas were radiographically evaluated by
MRI (dimensions(mm): d1!d2!d3). Microsurgical resection of adenoma was
performed in patients with symptomatic or large and invasive tumors.
Results
101 patients (57 female (56.4%) and 44 male (43.6%)) were assessed in the study.
The age at diagnosis was younger for women than men (40.0 yr vs 51.4 yr,
P:0.000). Tumor size were larger for men (d1: 21.9G2.6 mm vs 9.4G1.4 mm,
EP979
P:0.000). Among the rate of symptoms headache was the most frequent. Blurred
Giant macroprolactinoma in women still exist
vision was more common in men (45.5% vs 26.8%, P:0.06). The frequency of
Laura Dragomir1, Stefan Florian1,2, Ana Valea1,2 & Cristina Ghervan1,2
pituitary hormone deficiency was more common in men (37.0% vs 12.1%). 43
1Emergency County Hospital, Cluj-Napoca, Romania;2University of
(42%) patients have been performed pituitary surgery. Postsurgical hypopituitar-
Medicine and Pharmacy ‘Iuliu Hatieganu’, Cluj-Napoca, Romania.
ism was more commonly seen in female, whereas permanent DI was more
abundant in male, with nonsignificance in both issues (38.5% in female vs. 27.5%
in male, P:0.34; 7.7% in female vs. 13.3% in male, P:0.60; respectively).
Background
Conclusion
Prolactinomas are the most common hormone-secreting pituitary tumors and are a
Sex would be a prognostic parameter in NPA patients in terms of hypopituitarism,
common cause of anovulation and infertility. Giant prolactinomas (0.5-4.4% of
postoperative hypopituitarism and tumor mass. In our study, women were shown
all pituitary tumors) are rare tumors characterized by their large size (O4 cm),
to be diagnosed earlier and men were defined to have larger tumors. Greatly
compressive symptoms and extremely high prolactin secretion (O1000 ng/ml).
would be explained with the mass effect, we determined hypopituitarism was
Men are most commonly affected, with a reported male to female ratio of 9:1.
more common in men. Selectively postsurgical hypopituitarism, however
Case report
nonsignificant, was found more common in female group in our study.
We present the rare case of 53-years-old female, with a history of amenorrhea
DOI: 10.1530/endoabs.49.EP977
from age 35, who was never investigated or treated. In December 2015 she was
admitted in the neurosurgery department for severe headaches and visual
impairment. On clinical examination, left eye mydriasis and left lateral nystagmus
were noted. A head CT showed a pituitary tumor of 55 mm diameter, invading the
sphenoid sinus, both cavernous sinuses, the left orbit and compressing the third
ventricle, with mass effect. The blood tests revealed a very high serum prolactin
of 32625 ng/ml (4-23) and low sexual and gonadotrophic hormones. Given the
clinical and CT aspects, decompressive transcranial surgery was performed,
resulting in rapid improvement of the neurological signs and lowering of the PRL
EP978
levels to 1980 ng/ml. Nasal fistula and transient diabetes insipidus occurred after
The value of early postoperative OGTT as a predictor of surgical
surgery and were cured by sphenoid sinus filling and treatment with
outcome in patients with acromegaly after total transsphenoidal
desmopressin. For the residual prolactin secretion, Cabergoline treatment was
adenomectomy
started (1.5-2 mg/week) which resulted in prolactin suppression and diminuation
Alexandr Tsiberkin, Vladislav Cherebillo, Uliana Tsoy, Anna Dalmatova,
of the tumoral remaint. The restoration of the gonadotrophic secretion resulted in
Lidiya Belousova & Elena Grineva
numerous painful ovarian cysts that were cured by bilateral oophorectomy.
Federal Almazov North-West Medical Research Centre, Saint Petersburg,
Conclusions
Russia.
We present this rare case in order to highlight the importance of the etiological
investigation of secondary amenorrhea in women. The patient almost died
Introduction
because of the mass effect of a benign tumor, easily manageable by medical
Transsphenoidal surgery (TSS) is the treatment of choice for patients with
treatment and suffered multiple complications due to the neglect of her secondary
acromegaly. However, even after radical surgery persistence of acromegaly may
amenorrhea.
remain up to thirty percent by resent studies (Starnoni, 2016). Nadir growth
DOI: 10.1530/endoabs.49.EP979
hormone (GH) level less than 1.0 mg/l on an early postoperative oral glucose
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP980
for nodules bigger than 1 cm or nodules with malignancy criteria. Thyroid fine
needle aspiration biopsy demonstrated undetermined atypia in 27.3%, suspicious
Associated neoplasia in Romanian acromegalic patients
follicular neoplasia in
36.4%, follicular neoplasia in
9.1% and suspicious
Simona Silea1, Simona Galoiu1,2, Anda Dumitrascu1, Dan Niculescu1,2,
malignancy in 27.32% of the subjects. All patients underwent total thyroid-
Ionela Baciu1,2 & Catalina Poiana1,2
ectomy. Pathological examination of thyroid tissue revealed follicular variant
1C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;
papillary thyroid cancer in 5, classic and follicular variant papillary thyroid cancer
2C. Davila University of Medicine and Pharmacy, Bucharest, Romania.
in 3, diffuse sclerosing variant papillary thyroid cancer in 1, solid variant papillary
thyroid cancer in 1 and follicular, classic and clear cell papillary thyroid cancer in
Introduction
one patient. 72.7% of the patients had multifocal disease and 63.7% of the
Acromegaly has various complications that significantly alter patients’ lives, one
subjects had unilateral disease. Lymphovascular invasion and extrathyroidal
of which is developing neoplasia, a subject of high interest in the scientific
extension were present in 9.1 and 18.2% of the subjects, respectively. No distant
community during the last years but without any firm conclusions.
or local metastasis was detected during mean follow-up period of 28.72G16.18
Aim
months.
The main objective of this paper was to verify if Romanian acromegalic patients
Conclusion
are susceptible to developing neoplasia and what types of tumors are associated
Patients with acromegaly should be considered for the presence of thyroid cancer.
with acromegaly. Another purpose of the paper was to identify the risk factors
DOI: 10.1530/endoabs.49.EP981
involved in tumor predisposition.
Methods
This observational, retrospective study considered 336 acromegalic patients (217
of them females, 64.6%) followed from 2001 until 2015 in report to the evolution
of acromegaly and the development of associated diseases, mainly neoplasia.
Results
Acromegalic patients had a higher risk of developing associated neoplasia (40%
EP982
benign and 10% malignant). Activity of the disease was not an important factor
The triglyceride (TG)/HDL Cholesterol (TG/HDL-C) ratio as marker of
(except for the thyroid - 54.84% of the patients had active acromegaly), whereas
adipose tissue dysfunction at patients with acromegaly
initial values of IGF-1 seemed to influence the developing of prostate neoplasia
Oksana Khyzhnyak, Miroslava Mykytyk & Iurii Karachentsev
(mean corrected value 4.58, PZ0.025). Sex has proved to be a factor too: women
Institute of Endocrine Pathology Problems, Kharkiv, Ukraine.
were more prone to developing neoplasia than men (57.14 vs 34.29%), and
especially multiple types of tumors. The most frequently associated types of
neoplasia in our patients were developed in: thyroid (47% women, 20.95% men),
Background and aims
breast (11.93%) and uterus (5.99%)-for women, and colon (9.52%) and prostate
The ratio of TG/ HDL-C can identify cardiometabolic risk and cardiovascular
(6.67%)-for men. The longer the duration of active acromegaly the higher was the
disease. The visceral adiposity index (VAI) is a sex-specific index, in which
risk of developing colonic neoplasia.
measurements of body mass index and waist circumference are combined with
Conclusions
TG and HDL-C concentrations. T? study association between VAI and TG/HDL-
The results suggest that we need to perform a more meticulously screening of
C and the value of TG/HDL-C ratio as a marker of disfunction of visceral
associated tumours in acromegalic patients, not only using ultrasound and
adiposity tissue at patients with acromegaly.
colonoscopy for the thyroid gland and colon, but also mammography as well as
Subjects and methods
PSA level determination. These evaluations should be taken into consideration
Eighty-eight patients (30 men and 58 women; aged 17-75 years) with acromegaly
periodically in all our acromegalic patients, regardless of the evolution of their
were under investigation. Disease activity was evaluated according to the
main disease.
Consensus Conference criteria (2000). Blood samples for GH, IGF-1, TG, HDL-C
DOI: 10.1530/endoabs.49.EP980
and total cholesterol were taken in fasting state. VAI score and normal values
used by M. C. Amato et al., 2011. It was considered the normal VAI in an age-
dependent group to 30 years !2.52, from 31 to 42 years - !2.23, from 43 to 52
years - !1.92, from 53 to 66 years - !1.93 and more than 67 years - !2.00
Taking into account a value VAI, all patients were divided on two groups: with
normal VAI (55.7%) (group 1) and high VAI (44.3%) (group 2). The 10-years-old
general cardiovasculary risk (CVD) was determined by a calculator «General
EP981
CVD Risk Prediction».
Results
Clinical and histopathologic characteristics of thyroid cancer in the
At nonlinear correlation, TG/HDL-C ratio was highly correlated with VAI in both
patients with acromegaly
men (rsZ0.96, PZ0.00001) and women (rsZ0.97, PZ0.00001), that TG/HDL-C
Buket Yilmaz Bulbul1, Mehmet Celik1, Nuray Can2, Semra Ayturk1,
can serve as more adequate criterion of estimation of disfunction of visceral
Ebru Tastekin2, Atakan Sezer3, Funda Ustun4 & Sibel Guldiken1
adiposity tissue at patients with acromegaly. This supposition confirms exposed
1Department of Endocrinology and Metabolism, Medical Faculty, Trakya
by us for patients in a general group positive correlation TG/HDL-C with the level
University, Edirne, Turkey;2Department of Pathology, Medical Faculty,
of GH (rsZ0.38, PZ0.0001). Before TG/HDL-C it was suggested to use for
Trakya University, Edirne, Turkey;3Department of Surgery, Medical
identification of cardiometabolic risk in general population (M. R. Salazar et al.,
Faculty, Trakya University, Edirne, Turkey;4Department of Nuclear
2014). In a group with high VAI 10-years-old CVD risk and MS risk in 1.6 and 1.4
Medicine, Medical Faculty, Trakya University, Edirne, Turkey.
times, according higher, than in a group with normal VAI (OR 1.56, OR 1.42).
Conclusion
Aim
By the equivalent of VAI for the estimation of expressed of disfunction of visceral
There are some studies suggesting that the risk of developing cancers,especially
adiposity tissue at patients with acromegaly can serve also TG/HDL-C ratio.
thyroid cancer, is increased in the patients with acromegaly. The prevalence of
DOI: 10.1530/endoabs.49.EP982
thyroid cancer is 1.2-10.6% among the patients with acromegaly. In this study, we
aimed to evaluate clinical and histopathologic characteristics of thyroid cancer
among the patients with acromegaly.
Method
We retrospectively evaluated the patients with acromegaly who had been
followed-up by our department between the years 2005 and 2016 and diagnosed
EP983
with thyroid cancer.
Anti-proliferative effects of high doses cabergoline in patients with
Results
prolactinoma
9
(81.8%) of 11 subjects were female and 2 (18.2%) patients were male. The mean
Oksana Khyzhnyak, Teona Gogitidze, Miroslava Mykytyk,
age of the patients at the time of acromegaly diagnosis was 41G11years. Among
Iurii Karachentsev, Nadiya Barabash & Katerina Manskaya
subjects who had been followed for 11.45G9.37 years, all except one patient
Institute of Endocrine Pathology Problems, Kharkiv, Ukraine.
were not in remission and were receiving medical treatment. All subjects were
diagnosed with thyroid cancer after the diagnosis of acromegaly and the mean
time until the diagnosis of thyroid cancer was.27G9.23 years. In terms of thyroid
The aim of the study
hormone status, nine subjects were euthyroid and two patients were found to have
To investigate the anti-proliferative effect of cabergoline (CAB) which was used
central hypothyroidism. Thyroid ultrasonographic examination revealed multi-
in different regimes of suppressive therapy during 12 months in patients with
nodular goiter in all patients. Thyroid fine needle aspiration biopsy was performed
prolactinoma (PROL).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Subjects and methods
EP985
It was examined and underwent a 12 month course of treatment by selective
Venous glucose levels, peak GH and peak cortisol during Insulin
dopamine agonist CAB 61 patients with PROL: microadenoma 42, macro&giant
Tolerance Test using 0.15 UNITS/Kg and 0.1 UNITS/Kg body weight
PROL - 19. (52 women/9 men) aged 16-66 years. The total duration of the disease
Phillip Yeoh1, Ashley Grossman2,1, Shern L Chew1, Pierre Bouloux3,1,
ranged from 1 to 60 months, average (12.3G10.1) months. PROL was verified
Bernad Khoo3,1, Paul Carroll4,1, Simon Aylwin5,1 & Stephanie Baldweg6,1
using MRI 1.5T. Pituitary volume was calculated by the Di Chiro-Nelson. Were
1The London Clinic, London, UK;2John Radcliffe Oxford, Oxford, UK;
estimated total and partial secretory activity (PSA) in PROL. PRL blood levels
3Royal Free Medical School, London, UK;4Guys & St Thomas Hospital,
(ng/ml) were determined. Applied two modes of therapy: 1 - the mode of gradual
London, UK;5Kings College Hospital, London, UK;6UCLH Hospitals,
increase of a CAB dose, since 0.5 mg/week with the subsequent control of the
London, UK.
PRL blood level in each 4 weeks and titration CAB dose if necessary (increase in
a week dose by 0.25-0.5 mg); 2 - the mode of high starting doses from
calculation: the quantity of tablets CAB (0.5 mg) corresponded to frequency rate
Insulin Tolerance Test
(ITT) is a procedure commonly done by Endocrine
of increase of the PRL blood level in relation to the upper limit of age norm, but
Specialist Nurse in endocrine department. We look at over 120 ITT results done in
no more than 4 mg (8 tablets) a week. The statistical data analysis was carried out
2 endocrine centres using Insulin Actrapid 0.15 UNITS/kg and 0.10 UNITS/kg
with SPSS version 9.0.
dose plotting the glucose levels at 30, 45 and 60 min. We also look at peak GH
Results
and peak cortisol on each of these groups.
At purpose of high starting doses of CAB after 1 mth of treatment PRL level in
Aims
58.1% of patients decreased to the reference values, including in patients with
We wanted to know how many percentage of patients achieving hypoglycaemia
macroPROL after 1 month at 26.3% of patients had achieved target levels, after 3
below 0.5 mmol/l, 0.5-1.0 mmol/l, 1.1-1.5 mmol/l, 1.6-2.0 mmol/l and above
months - at 84.2%, and by 6 months of treatment - at 100% patients. In all patients
2.0 mmol/l. We also look at percentage of peak GH response achieving over
it was a statistically significant decreasing the pituitary volume after 12 months of
9 microgram/l, between 8-9 microgram/l and below 8 microgram/l. In the peak
treatment (P !0,001), but only in patients who were treated high starting high
cortisol response, we looked at results over 550 nmol/l; 500-550 nmol/l; 450-
dose CAB recorded decrease in the size of adenoma by 50% or more of the basal
500 nmol/l; 400-450 nmol/l and below 400 nmol/l. Within these data, we also
volume: at 9 microPROL and 4 macroPROL.
look at a small groups of results for patients’ using 0.15 UNITS/kg as repeat dose
Conclusions
and repeat ITT using the lower dose to compare if these are difference in these
The most expressed anti-proliferative effect is noted at application of high starting
markers.
doses of CAB. Optimum therapeutic average and cumulative doses of CAB for
Summary
achievement of maximum therapeutic effect at patients with microPROL are
We are unable to draw summary at the moment as well still got 30 data to go
doses of
0.8 mg/week and
33.8 mg/year, respectively; for patients with
through.
macro&giant PROL - 1.3 mg/week and 67.6 mg/year, respectively. At patients
DOI: 10.1530/endoabs.49.EP985
with microPROL the positive therapeutic effect is reached on a smaller
cumulative CAB dose which is associated with a lower risk of complications in
the long term period.
DOI: 10.1530/endoabs.49.EP983
EP986
EP984
Long-term impact of primary medical and surgical therapy on bone
density in men versus women with prolactinomas
Invasive macroprolactinomas and its response to treatment in male
Lukas Andereggen1, Janine Frey2, Robert Andres1, Marwan El-Koussy3,
patients
Jurgen Beck1, Luigi Mariani4 & Emanuel Christ2,4
Alin Abreu, José Hernández, Margarita Velasco, Pablo Triana &
1Neurosurgery, Bern, Switzerland;2Endocrinology, Bern, Switzerland;
Orlando Casta
˜o
3Neuroradiology, Bern, Switzerland;4Neurosurgery, Basel, Switzerland;
1Centro Medico Imbanaco, Cali, Colombia;2Instituto Nacional de
5Endocrinology, Basel, Switzerland.
Endocrinología, La habana, Cuba;3Universidad Libre Seccional, Cali,
Colombia.
Purpose
The prevalence of pathological bone densities in men and women with
Introduction
prolactinomas treated either primary surgically or medically are infrequently
Prolactin-producing pituitary adenomas are the most common pituitary tumors in
reported across large cohorts. In the present study, we aimed at comparing the
clinical practice. In men they are more aggressive and their response to
impact of either therapeutic approach on the bone density in men vs women with
pharmacological treatment is unknown.
prolactinomas.
Objective
Methods
Describe the clinical characteristics and response according to the treatment of a
Retrospective case-note study including all consecutive patients with prolacti-
group of male patients with invasive macroprolactinomas.
nomas in whom osteodensitometry data was available at study entry and long-
Materials and methods
term follow-up (S 12 months). Bone mineral density (BMD) was assessed by
A retrospective descriptive study, a series of cases, in 30 patients, attending two
dual-energy X-ray absorptiometry. Clinical and biochemical characteristics,
pituitary clinics (National Endocrinology Institute in Havana, Cuba and Imbanaco
tumor size, and remission rates were recorded.
Cali Colombia Medical Center) between 2002 and 2012. Results Between the two
Results
types of treatment were compared and measures of central tendency and test of
Hundred patients (40 men, 60 women) met inclusion criteria. At baseline, men
Student or Kruskal Wallis were used.
had a significantly higher prevalence of pathological BMD than women (28 vs
Results
2%, P!0.001). Primary medical therapy was considered in 47, first-line surgery
The mean age was 44G13.8 years; the disease duration was 5.2G4.1 years; 96%
in 53 patients. Median follow-up time was 79 months (range 12-408 months).
of the patients presented headache, followed by hypopituitarism (80%). The
Long-term PRL values significantly decreased in both cohorts, regardless of the
median prolactin value at admission was 487 ng/ml. 53% required surgery plus
primary treatment. There was a persisted need for dopamine (DA)-agonists in
dopaminergic agonists; in this group there was a decrease in prolactin levels of
75% men compared to 42% women (PZ0.001). The prevalence of pathological
86% at 6 months and 96% at 12 months; in the dopaminergic agonist group, there
BMD in men remained significantly higher than in women (37 vs 7%, P!0.001),
was a 71% decrease at 6 months and 95% at 12 months. Surgical patients had the
independent of the primary treatment strategy.
mayor Tumor size reduction 11.4 mm compared with 8.3 mm, however a year
Conclusions
there were no difference between the groups.
The prevalence of pathological BMD in men remains significantly higher than in
Conclusion
women, independent of the primary treatment strategy. While osteoporosis
Surgical treatment plus dopaminergic agonist showed no differences with medical
prevention and treatment is mainly focusing on women, awareness of the bone
treatment in reducing prolactin values during the first year of treatment regardless
loss in men with prolactinomas should not be underestimated.
of tumor size.
DOI: 10.1530/endoabs.49.EP986
DOI: 10.1530/endoabs.49.EP984
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP987
EP989
Stenosis of the external auditory canal in an acromegalic patient: a
Preoperative HDDST in the prognosis of CD remission after
novel complication
transshenoidal endoscopic surgery
Hee Kyung Kim, Jee Hee Yoon, Yun Ah Jeong & Ho-Cheol Kang
Gussaova Natalya, Tsoy Ulyana, Cherebillo Vladislav, Dalmatova Anna,
Department of internal Medicine, Chonnam National University Medical
Belousova Lidiya, Mitrofanova Lyubov & Grineva Elena
School, Gwangju, Republic of Korea.
Federal Almazov North-West Medical Research Centre, Saint-Petersburg,
Russia.
Acromegaly is associated with a range of comorbidities, including cardiovascular
disease, diabetes, hypertension and sleep apnea. Bony overgrowth and soft tissue
Purpose
thickening not only cause typical external features of acromegaly, but also
Transsphenoidal endoscopic surgery
(TSS) is the first-line treatment for
debilitating musculoskeletal aches. Recently, a few papers reported auditory
Cushing’s disease (CD). Persistence and recurrence of hypercortisolism after
complications of acromegaly, but there has been no report on narrowing of the
TSS considered important problem. In this case search for CD remission
external auditory canal as a complication of acromegaly. A
58-year-old
predictors is actual.
acromegalic patient complained of fullness of both ears. He had transsphenoidal
Aim
surgery for GH-secreting pituitary adenoma 17 years ago. Somatostatin analogue
To study the role of preoperative oral high-dose dexamethasone suppression test
therapy was discontinued 2 years earlier, because nadir GH after oral glucose
(HDDST) in the prognosis of CD remission after TSS.
loading and IGF-1 level were normal. On laboratory exam, random GH was
Materials and methods
0.82 ng/ml, and IGF-1 264.74 ng/ml (reference range, 71-263). On otolaryngo-
60 patients with Cushing’s disease (nine men, 51 women, mean age 41 years
logic examination, both auricles were very hard and immobile, and orifices of
(15-73) who had underwent TSS were included. HDDST was performed in all
external auditory canals (EAC) showed slit-like openings. In left ear, eardrum
cases before the TSS. Postoperative examination was done one and two years
examination was impossible due to severe stenosis of EAC. On temporal bone
after surgery. Remission criteria were: secondary adrenal insufficiency (the need
CT, both ears showed thickening of tympanic membranes and evidence of chronic
for glucocorticoid replacement) or combination of normal midnight serum
otitis media with severe soft tissue thickening of left EAC. Pure tone audiometry
cortisol level, normal 24 h urine free cortisol (UFC) excretion and serum cortisol
documented mild hearing loss in left ear. The patient declined any further
suppression less than
50 nmol/l in
1-mg dexamethasone test. The optimal
evaluation and therapeutic intervention. Ear complications of acromegaly has not
threshold value of serum cortisol suppression in the HDDST for prediction of
received much attention so far. We report a case of ECA stenosis developed in an
CD remission after TSS was calculated by ROC-analysis.
acromegalic patient, as a novel complication of acromegaly.
Results
DOI: 10.1530/endoabs.49.EP987
One year after surgery CD remission was confirmed in 39 patients, whereas in
21 patients hypercortisolism persisted, after two years - in 36 and 24 patients,
respectively. The optimal threshold value of serum cortisol suppression in the
HDDST for prediction of CD remission in one year after TSS was 72%. Test’s
sensitivity and specificity were 82% and 84%, respectively. The probability of
wrong prediction was 17% (PZ0.0001).Two years after TS optimal threshold
value of serum cortisol suppression remained 72%, with sensitivity and specificity
86% and 80%,the probability of wrong prediction was 16% (PZ0.001).
Conclusion
According to our data serum cortisol suppression more than 72% in HDDST may
be used as a prognostic criterion for CD remission after TSS.
DOI: 10.1530/endoabs.49.EP989
EP988
Is Pegvisomant correct choice for acromegaly patient with dilated
cardiyomypathy?
Murat Cinel, Caglar Keskin, Rifat Emral & Demet Corapcioglu
Endocrinology and Metabolism Department, Ankara University Faculty of
Medicine, Ankara, Turkey.
Objectives
Acromegaly may arise with several clinical presentations and cardiac
involvement is the most important factor affecting the course of the disease.
Case
EP990
A 32-years old man admitted to hospital complaining with shortness of breath.
Somatostatin analogs in the treatment of acromegaly: single centre
After initial evaluation he was diagnosed as ‘cardiac failure’. Cardiac evaluation
experience
revealed that he had ‘dilated cardiomyopathy’ with ejection fraction (EF) of 20%,
Agne Abraitiene1,2, Aiste Aleknaite1,2 & Gintare Zelnyte2
global hypokinesia without valvular disease and coronary angiography was
1Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania;
detected as normal. After immediate cardiac treatment he was consultated to
2Vilnius University Medical Faculty, Vilnius, Lithuania.
endocrinology because of hyperglycemia. When the patient evaluated for
hyperglycemia, physical examination findings consistant with acromegaly. He
Introduction
was diagnosed as acromegaly with high IGF-1 and GH level and 19 mm
The purpose of this study was to evaluate effectiveness of somatostatin analog
macroadenoma in pituitary MRI. Because of heart failure, surgery was delayed
(SSA) treatment in patients with acromegaly.
and medical therapy was initiated. After 6 months of therapy with high dose
Methods
somatostatin analogue treatment, his cardiac status did not show any
The study involved retrospective data collection from charts of 29 patients with
improvement and we decided transnasal transsphenoidal adenomectomy. After
acromegaly who received medical therapy at Vilnius University Hospital
surgery he was not in remission and somatostatin analogues were initiated again.
Santariskiu klinikos in 2016.
At the 6 months of additional therapy, IGF-1 and GH level were not in normal
Results
range. We decided to add pegvisomant to therapy. At the
2nd week of
Patient population consisted of 10 males (34.5%) and 19 females (65.5%), mean
combination therapy, he developed severe cardiac failure with EF 10% and
age 58G26 years. Primary SSA therapy was administered in 13 (44.8%) patients
therapy was discontinued. After cessation of pegvisomant, his symptoms revealed
who refused or had contraindications to surgical treatment. Secondary medical
minimally.
therapy was applied in 16 (55.2%) of patients with recurrent disease after
Conclusion
transsphenoidal surgery.
28 patients received SSA treatment
(6
of them in
As we know cardiac problems are the first leading cause of death in acromegaly.
combination with a dopamine agonist (DA)), 18 patients recieved high-dose SSA
Cardiac involvement may appear any of the followings; hypertension, valvular
treatment
(Sandostatin LAR 40 mg or Somatuline Autogel 120 mg every 4
heart diseases, arrhythmias, hypertrophic cardiomyopathy and dilated cardiomyo-
weeks). Based on GH and IGF-1 results, control and partial control was achieved
pathy. Most of the patients treated with pegvisomant show decreased cardiac
in 16 (57.1%) and 8 (28.6%) patients receiving SSA treatment (GDA). 4 (14.3%)
muscle mass in hypertrophic cardiomyopathic patients. There is no data about
medically treated patients remained uncontrolled. High-dose SSA treatment
pegvisomant use in acromegalic patients with dilated cardiomyopathy. Should we
failed to achieve disease control in 4 (22.2%) of patients. Disease control and
use it cautially in dilated cardiomyopathic patients?
partial control was attained in 5 (38.5%) and 5 (38.5%) of patients with primary
DOI: 10.1530/endoabs.49.EP988
SSA treatment and in 12 (75%) and 3 (18.8%) of patients with SSA treatment
after transsphenoidal surgery. We found higher mean IGF-1 level in primary SSA
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
treatment group as compared to secondary SSA treatment patients (455G56 mg/l
EP993
vs 307G40 mg/l, PZ0.04)
Conclusions
SSA treatment (GDA) results in disease control in 57.1% of patients with
Abstract withdrawn.
acromegaly. High-dose SSA treatment failed to achieve disease control in 22.2%
of patients. SSAs are more effective when applied after transsphenoidal surgery as
disease control is achieved in greater percentage of patients and mean IGF-1 level
is lower when compared to patients who refused or had contraindications to
surgical treatment.
DOI: 10.1530/endoabs.49.EP990
EP994
A eight successful pregnancies in six Algerian women with acromegaly:
EP991
a monocenter study of Pierre and Marie Curie center.
Biochemical normalization in acromegaly after 79 months’ treatment
Safia Mimouni
with Pasireotide: case report
Pierre and Marie Curie Center, Algiers, Algeria.
Chiara Bima1, Sabrina Chiloiro1, Donato Iacovazzo2,
Tommaso Tartaglione3, Maria Elena Bracaccia1, Antonella Giampietro1,
Introduction
Antonio Bianchi1 & Laura De Marinis1
Acromegaly usually results from GH hypersecretion elaborated by somatotrop
1Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;
adenoma. The occurrence of a pregnancy in an acromegaly is an infrequent event,
2Centre for Endocrinology, Barts and The London School of Medicine,
but better described in recent years. It could be aggravate GH secretion and tumor
Queen Mary University of London, London, UK;3Department of
volume.
Radiology, Catholic University of the Sacred Heart, Rome, Italy.
Objective
Describe eight pregnancies including twin pregnancy in six acromegalics patients
Pasireotide, a multireceptor-targeted somatostatin analogue, was approved for the
hospitalized in the endocrinology department of the Pierre and Marie Curie center
treatment of acromegaly, after being studied in two large, randomised, multi-
in Algiers.
center clinical trials. We reported the history of a 76 years old man affected by
Materials and method
acromegaly, treated with Pasireotide long acting release (LAR) as first line
Materials: Eight pregnancies; their mean Age was 35.5 years.meanwhile of
therapy. Acromegaly was diagnosed in 2009, as the result of endocrinological
diagnosis: MRI revealed: macro adenoma (nZ7) and microadenoma (nZ1); The
investigation suggested by altered facial appearance and macroglossia. Hormonal
Visual Field was normal, Hypopituitarism was observed in 1 case and thyrotoxic
assays demonstrated high levels of IGF1 (584 ng/ml) and GH (8.7 ng/ml), without
insufficiency in er 1 case. No diabetes mellitus or hypertension were noted.
any suppression of GH at oral glucose tolerance test. Patient consequently
Patients underwent surgery
(nZ5), surgery and radiotherapy
(nZ1). The
underwent brain magnetic resonance (MRI), with the finding of a 7 mm expansive
pregnancies were spontaneous in all cases.
formation of the right half adenohypophysis, suggestive for pituitary micro-
Method: Diagnosis of acromegaly: HGPO/GH; GH/IGF1,magnetic RM imagin-
adenoma. Patient, in November 2009, was enrolled in CSOM230C2305 study and
ing pituitary and Visual Field were performed before conception and at T1, T2,
was treated with Pasireotide LAR at blided dosage, with biochemical control of
T3 of the pregnancy and in the postpartum. We have searched Diabetes Mellitus,
disease and progressive reduction of the pituitary adenoma volume. In May 2016,
gravid hypertension, the Childbirth Incidents, and we examinated Newborns.
following the onset of dyspnea, dysphagia and dysphonia, patient was diagnosed
Results
with anti-MuSK-positive myasthenia gravis, treated with apheresis and steroid
Eight pregnancies resulted in nine healthy babies. Gestational diabetes occurred
therapy, currently in good control. In this period, in according to the detection of
in Three cases and regresses in the postpartum in two cases; No Gravid
very low level of IGF1
and in consideration of concomitant diagnosis of
hypertension. The IGF1 and GH concentrations did not change significantly
myasthenia gravis, therapy with Pasireotide LAR was discontinued and patient
during pregnancy and in the postpartum. Growth adenoma was noticed in two
continued follow-up. The last brain MRI, performed in May 2016, documented
cases but without defect in any visual field. Fetal malformations were not
the stability in size and morphology of the known pituitary microadenoma. Eight
observed, birth weight was normal.
months later, in January 2017, patient is actually in remission, with IGF1 in the
Conclusion
normal reference range for age and gender (196 ng/ml) and GH !2.5 ng/ml
Acromegaly remains a rare cause of infertility. Pregnancy in women with active
(0.5 ng/ml). This clinical case shows the efficacy of Pasireotide in gaining
acromegaly or uncontrolled acromegaly may be associated with an increases risk
biochemical control of acromegaly, factor that is primarily implicated in the
of gestational and gravid hypertension. Pregnancy is occasionally associated with
reduction of disease morbidity and mortality.
an enlargement of adenoma.All these data must be confirmed by prospective
DOI: 10.1530/endoabs.49.EP991
studies.
DOI: 10.1530/endoabs.49.EP994
EP995
EP992
Abstract withdrawn.
Abstract withdrawn.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP996
19.9 pg/ml; C10 min: IPS: 123.9 pg/ml and OIPS: 10.9 pg/ml; C15 min: IPS:
16.2 pg/ml and OIPS: 12.2 pg/ml).
Sheehan syndrome presenting 21 years later as severe heart failure
Conclusion
Ana Gonçalves Ferreira, Sofia Alegria, Maria Carlos Cordeiro &
The localization of the catheters into the inferior petrosal sinus allow to achieve a
Jorge Portugal
higher diagnostic central/peripheral ACTH gradient as compared to other catheter
Hospital Garcia de Orta, Almada, Portugal.
localization.
DOI: 10.1530/endoabs.49.EP997
Introduction
Sheehan syndrome (SS) is caused by postpartum necrosis of the pituitary gland,
associated with significant haemorrhage during or after delivery. It is rare in
developed countries, but still frequent in underdeveloped ones. We present a rare
presentation of this syndrome.
Clinical case
A 48 years old black woman presented at the emergency department for long term
fatigue and dyspnea that worsened a few days before. Her physical examination
revealed muffled heart sounds, decreased breath sounds inferiorly and bilaterally,
a puffy face and dry skin. Also, she had a slurred speech and hoarseness. No other
EP998
significant findings. No relevant past medical history, except for a complication in
Ipilimumab-induced hypophysitis
her second pregnancy (at 17 years), with a significant internal haemorrhage at
Silvia María Maraver Selfa1, María Molina Vega1,
term and an emergency caesarean section (stillborn). No subsequent lactation.
Inmaculada González Molero2, Isabel Mancha Doblas1 &
Amenorrhea since then. Blood tests: Hb 9.3 g/dl
(microcytic, hypochromic
Francisco Tinahones Madue
˜o1,2
anaemia); LDH 1778UI/; CK 6793UI/L; AST 401UI/L; ALT 168UI/L; AF
1Universitary Hospital Virgen de la Victoriatoria, Malaga, Spain;2Malaga
366UI/L; total cholesterol 366 mg/dl; LDL 293 mg/dl; triglycerides 218 mg/dl.
Regional Universitary Hospital, Malaga, Spain.
Arterial blood gas analysis: hypoxemia and slight hypercapnia. Chest x-ray:
bilateral pleural effusion and cardiomegaly. Abdominal ultrasound: cholelithiasis.
EKG: low QRS voltage. Echocardiogram: severe bilateral ventricular systolic
Hypophysitis are a heterogeneous group of inflammatory lesions affecting the
dysfunction raised filling pressures on the left, enlarged atriums and pericardial
hypophysis. Have been described hypophysitis secondary to administration of
effusion. Heart coronarography: no evidence of coronary artery obstruction. Her
immunomodulatory drugs such as interferon and anti-cytotoxic T lymphocyte
thyroid function tests were suggestive of central hypothyroidism
(TSH
antigen-4
antibodies
(CTLA-4). Ipilimumab is an anti-CTLA-4
human
0.70 mU/L; FT4 !0.24). Pituitary functions test reaveled panhypopituitarism
monoclonal antibody that blocks the union between CTLA-4 and B7 receptor
(FSH 4.1 UI/L; LH 2.6 UI/L; Estrogen!10 pg/ml; Testosterone !10 ng/dl;
on antigen-presenting cells causing an antitumoral effect and increasing the
prolactin 0.8 ng/ml, IGF1). ACTH was not reliable because the patient had been
production of autoantibodies. Hypophysitis has been described in 17% of patients
started on corticosteroids before L-thyroxine. Sellar MRI showed an empty sella.
treated with this drug and usually appears before the fourth dose. Clinical
Given her medical history in this clinical setting we believe a SS, left undiagnosed
presentation is similar to other causes of hypophysitis.
for 21 years, caused the panhypopituitarism.
Case report
Conclusion
44 years old man. Medical history: ocular melanoma with hepatic metastases 12
This case is illustrative of a rare presentation of SS, with severe heart failure and
years after surgery. After the 3rd cycle of treatment with intravenous Ipilimumab
low prolactin levels (unusually found).
(3 mg/kg per 3 weeks), the patient began with intense headache. Cranial MRI
showed an increased hypophysis so a morphofunctional study of hypophysis was
DOI: 10.1530/endoabs.49.EP996
performed. Laboratory evaluation: fasting blood glucose 76 mg/dl, creatinine
0.77 mg/dl, sodium 135 mg/dl, aspartate transaminase (AST) 80 UI/l, alanine
transaminase (ALT) 311 UI/l, gamma-glutamyltransferase (GGT) 776 UI/l, TSH
0,04 mUI/ml, free T4
0.65 ng/dl, serum cortisol
(0800 h)
14 mg/dl, ACTH
19 pg/dl, prolactin 8.83 ng/ml, FSH 11.97 mUI/ml, LH 3.23 mUI/ml, testosterone
1.2 ng/ml, GH 0.77 ng/ml, IGF-1 83.4 ng/ml (94-252). Pituitary MRI with
contrast: glandular thickening with extension to cavernous sinus and irregular
contrast enhancement. After the diagnosis of Ipilimumab-induced hypophysitis
with gonadal and thyroid axis deficiency associated, Ipilimumab was stopped.
EP997
The patient began levothyroxine replacement therapy and treatment with
prednisone 60 mg/day, with a progressive dose decrease during a month until
Localization of the catheters during Bilateral sampling of the inferior
get the correct replacement dose.
petrosal sinuses can impact diagnostic power?
Conclusion
Sabrina Chiloiro1, Alessandro Pedicelli2, Iacopo Valente2,
The use of new immunomodulatory drugs makes necessary to identify and define
Tommaso Tartaglione2, Antonio Bianchi1, Antonella Giampietro1,
this hypophysitis cause and set out protocols with the oncologists to avoid undue
Chiara Bima1, Liverana Lauretti3, Carmelo Anile3, Alfredo Pontecorvi1
delay in its diagnosis and treatment.
& Laura De Marinis1
1Pituitary Unit, Catholic University of the Sacred Heart, Rome, Italy;
DOI: 10.1530/endoabs.49.EP998
2Department of Radiology, Catholic University of the Sacred Heart, Rome,
Italy;3Department of Neurosurgery, Catholic University of the Sacred
Heart, Rome, Italy.
Introduction
Bilateral sampling of the inferior petrosal sinuses (IPSS) is considerate actually
the best diagnostic test for Cushing.
Patients and methods
We retrospectively reviewed our series of patients undergone IPSS for Cushing
disease and we compared the difference between central and peripheral ACTH
EP999
gradient in basal condition and after CRH stimulation in cases of localization of
Somatostatin Analogue Treatment of a Persistant TSH-Secreting
the tip of the catheters inside the inferior petrosal sinus or at the confluence of the
Adenoma: a report of case
inferior petrosal sinus into the internal jugular vein. All the pituitary contrasted
İlknur Ozturk Unsal, Erman Cakal, Mahmut Apaydın, Melia Karakose,
Magnetic Resonance was blinded reviewed by two dedicated neuro-radiologist.
Bekir Ucan & Mustafa Ozbek
Results
Saglik Bilimleri Universty Diskapi Yildirim Beyazit Traning and Research
A total of 10 patients achieved an IPSS with CRH stimulation suggestive for
Hospital, Ankara, Turkey.
Cushing syndrome. Four patients had a MR visible pituitary adenomas. In any
cases, infiltration of the para-sellar region was detected. At each time point of the
CRH-test during IPSS (basal, C3, C5, C10, C15 min), central/peripheral
Introduction
ACTH gradient was higher in cases of localization of catheters inside the inferior
Thyrotropinomas are usually considered when the TSH level is inappropriately
petrol sinus (IPS) as compared to cases of localization of catheters outside (OIPS)
elevated or normal in a hyperthyroid patient with increased serum T4 levels,
the inferior petrosal sinus (respectively basal IPS: 9.3 pg/ml and OIPS: 3.8 pg/ml;
regardless of the presence of visible tumor on imaging. The prevalence of these
C3 min: IPS: 68.9 pg/ml and OIPS: 27.8 pg/ml; C5 min: 35.5 pg/ml and OIPS:
adenomas, which account for 0.5-3% of all pituitary tumors has been estimated to
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
be around one case per million. Most thyrotroph adenomas are large and invasive
EP1001
at diagnosis, and present with signs and symptoms of an expanding mass,
A case of pituitary apoplexy. a acute medical emergency and restitutio
including temporal visual field defects. Here, we report a patient treated with
ad integrum
somatostatin analogue with pituitary macroadenoma and hyperthyroidism.
Pilar Rodriguez, Maria Lainez, Maria Jose Lopez, Eloisa Roldan &
Case reports
Isabel Rebollo
A 64-year-old female patient, who had undergone surgical procedure in 2014 for
Complejo Hospitalario Huelva, Huelva, Spain.
solitary fibrous tumor in the left parietal region, applied to be checked because of
enlarged hypophysis gland documented via cranial MRI performed during
follow-up visits. Laboratory findings revealed high levels of fT3 (8.56 pg/ml) and
A 50-year-old woman with no history of interest who was admitted in hospital for
fT4 (2.1 ng/ml) with TSH (6.32 UI/ml) higher than its normal limit. On the MRI
progressive headache 2 weeks of evolution refractory to treatment that was
of the hypophysis, a 22!18!14 mm lesion consistent with macroadenoma,
accompanied by emetic syndrome and paresthesias in face and arms. A CT scan
which was heterogeneously contrasted after IV Gad injection, was detected in the
of the skull (urgency) was performed which was normal. Neurology improves
mid-left half of the pituitary gland. The lesion exceeds the lateral inter-carotid line
with analgesia and steroids, presenting mild drowsiness and mild hyponatremia
in the left aspect and surrounds the left ICA higher than 240 degree. Other
(121 mEq/l). A cerebral MRI was performed, showing a right subacute
hormones of the anterior hypophysis were within the normal range. SHBG was
hemorrhagic adenoma of 1 cm that protrudes into the suprasellar cisterna without
153.9
(30-100 nmol/l) and alpha subunit was 3.9 (0-1.6 IU/l), which were high.
compressing the optic chiasm and extending slightly to the right cavernous sinus.
There was no response to TRH stimulation test. Methimazole was commenced at
Subsequently it begins with severe headache and vomiting, aiming hemiparesis of
a dose of 20 mg and transnasal transsphenoidal pituitary adenomectomy was
predominance crural initially improving with hydrocortisone until it presents
performed. Somatostatin analogue (Octreotid LAR 10 mg/28 day) therapy was
convulsive crisis with prolonged decrease of consciousness and loss of control of
started for the patient, who had residual adenoma (20!15 mm) and in whom
sphincters, with difficult handling of ions. Urinary skull CT scan is performed
euthyroidism could not be achieved. Methimazole was interrupted in the 9th
with images compatible with mild diffuse cerebral edema, so that it enters the ICU
month of somatostatin analogue treatment and determining that the size of
with low level of consciousness and agitation with anisocoria and analytically it is
adenoma is 10!9!8 mm.
objectively a plasma sodium of 108 mEq/l, remaining in this service five days.
Conclusion
Campimetry was performed by the Ophthalmology Service that was normal and
Most thyrotrophs express variable number of somatostatin receptors (SSTR),
consulted the Neurosurgery Service together with Endocrinology was decided
particularly SSTR2 and SSTR5. Somatostatin analogues could be considered in
conservative management, ruling out endonasal transsphenoidal decompression.
the treatment of persistent disease following the surgical procedure performed for
No precipitating factors have been identified. Once stabilized, the patient was
TSH-secreting adenomas.
switched to hydrocortisone 100 mg/8 h, Hypothesis Polyuria clinic and suspicion
DOI: 10.1530/endoabs.49.EP999
of partial DI progressing favorably after being discharged after 44 days of
treatment with hydrocortisone and replacement desmopressin. Since then and
after more than three years of the onset of the picture is followed by the
Endocrinology Service, discarding other hormonal deficits. At present, five years
later, there is no neuro-endocrine symptomatology, with adrenal axis recovery
without substitute treatment and in treatment with desmopressin 100 mg with
withdrawal approach, in joint follow-up with skull MRI study and hypophysis
without alterations, normal. To conclude the interest of this case based on the
literature and the entity we describe as a potentially serious acute pituitary stroke
with vital risk and that is resolved satisfactorily with conservative treatment
EP1000
minimizing sequelae and restitution ad integrum, with autoimmune and
Spindle cell oncocytoma of adenohypophysis: report of a rare pituitary
differencial diagnois without evidence of underlying causes and satisfactory
tumor
evolution with conservative management.
Carlos Marques Pontinha, Manuela Mafra, Luís Cerqueira,
DOI: 10.1530/endoabs.49.EP1001
Amets Sagarribay, Fernando Fonseca & Ana Agapito
Centro Hospitalar Lisboa Central, Lisbon, Portugal.
Introduction
Pituitary adenomas represent 95% of all sellar masses. Spindle cell oncocytoma
(SCO), a rare histopathological entity (0.4% of all sellar tumours), clinically
presents as a non-functional pituitary adenoma. According to WHO
2016
Classification of Tumours of the CNS it is a Grade l tumour, but prognosis
remains uncertain since recurrence is frequently seen among the few cases
reported.
EP1002
Clinical case
Resistant microprolactinoma with partial empty sella
A 59 year-old man presented with progressive fatigue, loss of libido and visual
Sevgul Faki, Sefika Burcak Polat, Cevdet Aydin, Reyhan Ersoy
blurring for 5-years. He had pale and hairless skin and on visual field assessment a
& Bekir Cakir
bitemporal hemianopsia was diagnosed. Hormonal evaluation confirmed low
Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit
testosterone and gonadotrophins as well as central hypothyroidism and
University, School of Medicine, Ankara, Turkey.
hypocortisolism. PRL and IGF1 levels were normal. MRI scan revealed a T1
and T2 isointense 29!17!17 mm sellar mass with suprasselar extension causing
optic chiasm compression. Transsphenoidal surgery removed a grossly bleeding
Introduction
tumour. Histopathological examination revealed a neoplasm composed of
Prolactinomas are the most common hormonally active pituitary tumors that
interlacing fascicles of spindle cells with eosinophilic and oncocytic cytoplasm.
account for 40-60% of all pituitary adenomas and are usually successfully treated
Tumour cells had moderate nuclear atypia and 2 mitotic figures per 10 HPF
with dopamine agonists. Surgery or radiotherapy is reserved for drug
(Ki67/MIB-1 Proliferation Index 2-5%) were identified. The immunohistochem-
intolerance/resistance or in neuro-ophthalmological emergencies. We present a
istry profile was Vimentin/S100/GFAP/EMA/Synaptophysin positive. The final
patient with refractory microprolactinoma with empty sella treated by
diagnosis was SCO. Visual acuity and Goldmann perimetry improved
transsphenoidal surgery.
significantly, but hypopituitarism persisted. MRI scan, 3 months after surgery,
Case
showed a contrast enhanced 9!6!11 mm solid intrassellar mass - normal
42-year-old female patient admitted with a 14 years history of prolactinoma being
pituitary tissue or residual tumour? Reassessment is scheduled in the next
treated with dopamine agonists for ten years. At the end of the tenth year, the
3 months.
tumor was resistant to high dose cabergoline (4 mg/week). Magnetic resonance
Commentary
imaging
(MRI) revealed a partial empty sella with
6.5!3.5 mm pituitary
An apparent total resection of a SCO was obtained. However, prognosis is
adenoma. She underwent transsphenoidal surgery. Histopathologically, a
difficult to predict due to the short time of follow-up. Presence of cytological
pituitary adenoma with rare mitotic figures, Ki-67 index of 2%, no expression
atypia and mitosis in this case and knowledge of frequent recurrence rates obeys
of p53 and no other features of atypia was identified. Immunohistochemistry
to a stringent follow-up. The histogenesis of SCO remains unsolved. According to
showed expression of prolactin by majority of the cells. Postoperative MRI
the latest genetic data, SCO and granular cell tumour of the sellar region
demonstrated empty sella (height of the gland was 2 mm) and no residual mass.
(GCTSR) may be variants of another rare tumour, the pituicytoma.
After operation, cabergoline was restarted because of high prolactin levels and
DOI: 10.1530/endoabs.49.EP1000
amenorrhea. Despite a substantial increase in dosage there was no clinical
improvement in amenorrhea and galactorrhea and there was not any biochemical
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
response. Her other anterior pituitary hormones were normal while serum
unremarkable. Initial investigations were consistent with SIADH
(sodium:
prolactin was 255 ng/ml (4.79-25.3 ng/ml) in her last visit.
109 mmol/l, serum osmolality: 243 mOsm/kg, urine Na: 59 mmol/l and urine
Conclusion
osmolality: 191 mOsm/kg). Urea, creatinine and random glucose were normal.
A minority of patients, ranging from 10-20% in different series does not achieve
CT Head showed pituitary enlargement with sellar expansion. Pituitary profile
normoprolactinemia and/or tumor shrinkage despite treatment with high doses of
showed high prolactin: 8305 mIU/ml, low IGF-1: 78.1 mg/l and low testosterone:
dopamine agonists. Those tumors are usually macroadenomas with cavernous
3.83 nmol/l with normal LH and FSH. Thyroid function was normal with intact
sinus invasion and rarely microadenomas. Resistance can be documented by
pituitary-adrenal axis
(normal Glucagon and ACTH stimulation tests). MRI
demonstrating the absence or poor expression of D2 receptors on the membrane
pituitary confirmed macroadenoma with heterogeneous solid-cystic mass (2.0!
surface of tumor cells, or abnormalities at a postreceptor level. However,
1.9!1.5 cm) with deviation of pituitary stalk. He was treated with Cabergoline
molecular biology studies cannot be routinely performed in our center. Exchange
0.5 mg per week and few days of fluid restriction with improvement of sodium
of cabergoline with bromocriptine was successful in few cases in the literature.
level to 137 mmol/l and prolactin to 61 mIU/l after 2 weeks. Over 5 months
DOI: 10.1530/endoabs.49.EP1002
follow up; he remained asymptomatic with normal sodium and prolactin on
Cabergoline. Hypogonadisim has resolved and IGF-1 has normalized. Repeat
MRI 4 months after discharge showed significant reduction in macroadenoma size
to 1.4!1.3!0.7 cm with pituitary stalk being in midline.
Discussion
Hyponataemia complicating pituitary macroadenomas is usually related to
secondary hypoadrenalism. However, the presence of SIADH with intact
pituitary-adrenal axis in such cases is very rare with only seven cases reported
in literature (six non-functioning macroadenomas and one macroprolactinoma).
The mechanism of AVP release in these cases is not fully understood, but is
EP1003
thought to be related to local mechanical stress on the AVP neurons axonal
Acromegaly: clinical experience and determinants of remission
terminal and dislocation of pituitary stalk and neurohypophysis by pituitary
Ayten Eraydin1, Ersin Akarsu1, Zeynel A Sayiner1, Mesut Ozkaya1,
tumor.
Ibrahim Erkutlu2, Suzan Tabur1 & Mustafa Araz1
Conclusion
1Department of Endocrinology and Metabolism, Faculty of Medicine,
We hereby report the second case of SIADH secondary to macroprolactinoma
University of Gaziantep, Gaziantep, Turkey;2Department of Neurosurgery,
with normal pituitary-adrenal axis. Pituitary macroadenomas should be
Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
considered in differential diagnosis of SIADH even in context of preserved
Introduction
pituitary-adrenal axis.
Acromegaly is a chronical and rare disease which is accompanied by excessive
DOI: 10.1530/endoabs.49.EP1004
growth hormone (GH) secreting hypohysis tumor. In this study we presented
acromegaly patients’ datas who admitted to our center between the years 1998-
2016. We discussed patients’ charecteristics and we aimed to investigate the
determinants which is effecting the remission rate of the patients’.
Method
70 acromegaly patients datas were analyzed retrospectively in our center. We
evaluated patients’ clinical, laboratory, imaging and treatment modalities
informations. The parameters accepted as remission criteria are as follows:
1) Basal GH!2.5 mg/l,
2) Having GH!1 mg/l level after glucose-growth
hormone supression test, 3) Having normal IGF-1 (insulin-like growth factor-1)
level in accordance with age and gender.
EP1005
Results
Clinical characterization and comparison of patients with hipophysary
57.1% of the patients were female. Mean age was 44G12. Mean age was 38G12
tumors and primary empty sella
when the diagnosis established. 97.1% of the patients had typical acromegaly
Alin Abreu, María Eugenia Casanova & Orlando Casta
˜o
symptoms. Other findings are: headache (77.1%), sweating (58.6%), vision defect
Universidad Libre Seccional, Cali, Colombia.
(15.7%), galactorrhea (10%), impotence (10%). Preop GH and IGF-1 levels were
18.3G15.8 mg/l,
954G349 mg/l respectively.
87.1% of the patients had
macroadenoma and % 61.4 of the patients had cavernous sinus invasion. Eight
Introduction
of the patients had drug therapy, 62 of them had surgery as first line therapy. 29%
Non-functioning pituitary tumors and primary empty sella are a common
of the patients’ pathology reports revealed that GH-Prolactin positive staining.
pathology within the differential diagnosis of pituitary masses. The mani-
Somatostatine analogues were administered to 64.5% of the patients after surgery.
festations will depend on the size of the tumor and the compression of adjacent
On the 3th month follow up remission rate was 53.5%, on the 12th month
structures being the most frequent neurological symptoms. Clinically the two
remisson rate was 65%, on the late period of the follow up remisson rate was
entities are very similar and no clinical tools are known to be able to help the
77.1%. There was statistically significant difference between preop GH levels,
differential diagnosis.
adenoma size, cavernous sinus invasion, ki67 proliferation index and remission
Objective
rate (P!0.05).
Perform a clinical and comparative characterization between patients with non-
Conclusion
functioning pituitary tumors and primary empty sella.
We concluded that high preop GH levels, adenoma size, cavernous sinus invasion,
Materials and methods
high ki67 proliferation index were the determinants of the poor outcome. Besides
A retrospective cohort study conducted in a highly complex center of the city of
surgeon experience should take into consideration for better outcome.
Cali, Colombia between January 2002 and December 2014.
DOI: 10.1530/endoabs.49.EP1003
Results
A total of
141 cases were found, 32% had a microadenoma, 30% had a
macroadenoma and 38% had a primary empty sella. 61% of the patients with non-
functioning pituitary tumors were women, as well as 51% of the cases of primary
empty sella. The largest number of patients with pituitary tumors were between 20
and 40 years old while in primary empty sella was between 40 and 59 years.
Headache was reported in 88% of cases, followed by visual disturbances in 59%
and galactorrhea in
41% of cases. As expected, the non-functioning
macroadenomas were those with the highest prolactin value with mean of
50 ng/ml. 97% of nonfunctioning microadenomas reported headache being more
frequent than in cases of macroadenomas and primary empty sella, this suggests
EP1004
the presence of an additional tension component.
A rare case of macroprolactinoma presenting with SIADH
Conclusion
Khaled Dukhan & Khaled Ashawesh
Nonfunctioning pituitary tumors and the primary empty sella are frequent entities
Hamad Medical Corporation, Doha, Qatar.
within the pituitary masses. The clinical distinction of these entities is quite
difficult and requires the accomplishment of an adequate clinical history,
adequate interpretation of hormonal and imaging studies.
Case
DOI: 10.1530/endoabs.49.EP1005
A 52-year-old gentleman was admitted with dizziness and collapse. Past medical
history revealed dyslipidemia treated with statin. Physical examination was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1006
Results
During follow-up (median 7.5 years - 2135.94 person years), 47 patients died,
Prolactinomas in men: retrospective analysis
versus 33 expected from general population, corresponding to a SMR of 1.39
Teresa Rego, Carolina Neves, Ana Margarida Palha, Luisa Cortez,
(95% CI 1.02-1.84). Females had a doubled mortality ratio: SMR 2.13 (95%CI
Fernando Fonseca & Ana Agapito
1.30-3.29. 254 patients (69.8%) were operated and 87 patients (23.9%) were
Department of Endocrinology, Centro Hospitalar Lisboa Central, Lisbon,
irradiated. After pituitary surgery and/or radiotherapy, pituitary tumour remnant
Portugal.
diameter decreased with 35.62G37.35% (range 0-100%). Only 24 (6.6%) of
patients were cured after radical therapy (no remnant). Cox-regression analysis
Introdution
demonstrated that age at diagnosis and pituitary tumour diameter at last
Prolactinomas in men are rare and the majority are macroadenomas. Some studies
evaluation remained independent predictor factors correlated to mortality (hazard
suggest that these tumors in men have higher proliferative activity and
ratio HR 1.07 (95%CI 1.046-1.101, P!0.001 and respectively HR 1.02 (95% CI
aggressiveness indicating gender-specific differences in biological behavior.
1.046-1.101, PZ0.018)), whereas pituitary surgery or radiotherapy, pituitary
Dopamine agonists (DA) are considered first-line therapy.
failure had no impact.
Material/methods
Conclusions
Retrospective analysis of male patients diagnosed with prolactinoma between
In our patients with pituitary NFA mortality is still increased, especially in
2005 and 2016. Age at presentation, clinical, hormonal and image data were
women, influenced independently by the age at diagnosis and residual pituitary
collected. Mode and responses to therapy were analysed.
tumour diameter. A greater extent of tumour removal may increase survival.
Results
DOI: 10.1530/endoabs.49.EP1007
Twenty two patients with median age at diagnosis of 50.8 years were observed.
Sexual dysfunction was the main complaint (59.1%), followed by headaches
(50%) and visual disturbances (36.4%). Imagiology revealed macroadenoma in
95% of the cases (19% giant). At the time of diagnosis mean value of prolactin
(PRL) was 3.662 ng/ml (min 177 ng/ml, max 23.200 ng/ml). Hypogonadism was
present in 54.5%. Fourteen patients (63.6%) were treated with DA as the only
therapy and eight patients (36.4%) with DA and neurosurgery. From the latter
three presented pituitary apoplexy, four were misdiagnosed as non-functioning
adenoma and onepresented cerebrospinal fluid rhinorrhea. None of these patients
were cured after surgery and all received medical therapy. At the last visit
EP1008
normalization of PRL level were observed in 59.1% of the patients (71.4% treated
Autoimmune hypophysitis with isolated corticotroph cell destruction
with AD as only therapy) and 77.8% of the remaining presented a PRL level less
due to Pembrolizumab treatment in a female patient with metastatic
than 2X upper limit of normal. Reversal of hypogonadism occurred in 66.7%.
melanoma
Previous and after therapy MRI findings were available in
12 patients. A
Emmanouil Vasileiou1, Charalampos Tsentidis2, Andreas Bampilis2,
reduction R50% in tumor maximum diameter was achieved in 8 patients. The
Vasiliki Ntova2, Grigoria Betsi2 & Georgia Kassi2
mean follow-up was 5.4 years.
1Private Practitioner, Samos Island, Greece;2Department of Endocrinology,
Commments
Metabolism and Diabetes, Nikaia General Hospital ‘Ag. Panteleimon’,
Our data confirms that prolactinomas in men are usually symptomatic
Athens, Greece.
macroadenomas. Although DA were efficient in reducing tumor size and
normalizing PRL, surgery was performed as first-line therapy in four patients due
to misdiagnosis and possibly late referral to our department. The correct diagnosis
Introduction
is crucial for successful treatment and avoidance of unnecessary surgery.
Pembrolizumab is a programmed death receptor-1(PD-1)-blocking antibody, used
in a variety of advanced malignant tumors with promising results, although
DOI: 10.1530/endoabs.49.EP1006
adverse events are not rare.
Case report
We present the case of an adult female, with negative personal and family history
of autoimmune diseases, who developed malignant superficial melanoma of right
wrist 6 years ago. She was initially treated with surgical resection (lesion and
ipsilateral axillary lymphadenectomy) and high dose interferon treatment and
re-operated due to multiple regional right in transit and left axillary lymph node
metastases. Melanoma was positive for B-Raf mutation and the patient received
Vemurafenib for 3.5 years and then Ipilimumab for four months (lung metastasis).
During that period she developed subclinical hypothyroidism, treated with
thyroxin. She finally received treatment with Pembrolizumab
(multiple
mediastinal and right axillary lymph node metastases) with gradual tumor
EP1007
recession within 4 months. She developed acute pancreatitis, without diabetes
Residual tumour diameter may influence reduced survival in females
mellitus, treated conservatively. Two months after full melanoma recession she
with nonfunctioning pituitary macroadenomas
developed fatigue, anorexia and diplopia for a few days without significant
Simona Galoiu1,2, Iulia Burcea1, Simona Silea1, Oana Voicu1,
findings in brain MRI. A 5-month period followed with exacerbations and
Ionela Baciu1,2, Anda Dumitrascu2, Andra Caragheorgheopol2 &
remissions of somnolence, cognitive dysfunction, anorexia, and weight loss and
Catalina Poiana1,2
finally developed hypotension and hypoglycemia. After a low morning cortisol
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
(4 mg/dl) measurement, she received full hydrocortisone replacement therapy
2C.I. Parhon National Institute of Endocrinology, Bucharest, Romania.
with complete symptoms remission. Thyroxin dose was increased and vitiligo
was developed during that period. There were no significant findings in
hypophysis MRI and melanoma restaging showed complete disease remission.
Objective
Hormonal profile (2nd menstrual cycle day) showed: PRL 12 ng/ml (1.9-25), LH
Patients with pituitary macroadenomas and concomitant hypopituitarism have a
1.2 mIU/ml (1.1-11.6), FSH 2.6 mIU/ml (0.7-11.1), E2 461 pg/ml (13-166),
reduced life expectancy due to various comorbidities.
SHBG 103 nmol/l (18-114), GH 0.93 ng/ml (0.06-5), IGF-1 195 ng/ml (94-252),
Aim
ACTH 1 pg/ml (7-50) while SST for cortisol was 1, 3 and 3 mg/dl at 0, 30, 60 min
To investigate mortality in patients with non-functioning pituitary adenomas
respectively.
(NFAs) and independent prognostic factors influencing survival.
Conclusion
Design
Pembrolizumab completely controlled metastatic melanoma in our patient
Retrospective cohort study in a tertiary neuroendocrine university department.
through immune stimulation. Hypophysitis with isolated corticotroph cell
Methods
destruction was developed as an adverse event. If confirmed in other cases
A total of 364 patients (177F/187M) evaluated for a macroNFA between 2001 and
Pembrolizumab could be used in treatment of refractory Cushing’s disease.
2016 were studied. PAMCOMP computation program was used to calculate
standardized mortality ratio (SMR). Cox regression analysis revealed indepen-
DOI: 10.1530/endoabs.49.EP1008
dent factors associated with mortality.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1009
(72.2%), dyslipidemia (10.2%), sleep apnoea (71.8%), and 17.7% had history of
CVD. In the HTN group, the mean age at diagnosis of acromegaly was 48 years
Aggressive pituitary tumors: a tertiary center experience
(S.D. 12.7) and the mean age at the start of PEGV (Baseline) was 56 years (S.D.
Adriana Lages1, Isabel Paiva1, Leonor Gomes1,2, Patrícia Oliveira1,
12.1) vs 36.3 years (S.D.11.7) and 43 years (S.D. 12.7) for non-HTN group. Time
Francisco Belo1, Diana Oliveira1, Diana Martins1, Mara Ventura1,
from diagnosis to PEGV treatment was 8.4 years (S.D. 8.5) vs 6.5(S.D. 7.2) in HTN
Nelson Cunha1 & Francisco Carrilho1
and non-HTN group respectively. At baseline systolic BP(SBP) was 138.3 and
1Coimbra Hospital and University Center, Coimbra, Portugal;2Faculty of
diastolic BP(DBP) 85 mmHg. Follow up at year 5 showed SBP 134.5 and DBP
Medicine University of Coimbra, Coimbra, Portugal.
82.5 mmHg. Average IGF-1 level at baseline was 488.9 and 218 ng/ml at year 5.
Conclusions
Background
HTN is a common comorbidity in acromegaly. Patients with HTN tend to be older
Pituitary adenomas
(PA) are common intracranial tumors that are mainly
at diagnosis and start of PEGV and have multiple CV risk factors. With PEGV
considered benign. A small group of patients exhibit clinically aggressive
treatment, blood pressure levels remain stable over time.
behavior sometimes unrelated to the histopathological or radiological features.
DOI: 10.1530/endoabs.49.EP1010
Methods
Twelve patients were selected harboring a PA with clinical features of
aggressiveness. All the patients underwent pre and postoperative endocrinolo-
gic/neuroradiologic evaluation.
Results
10/12 patients were male, mean age at diagnosis 38.1 years (range 12-58) and
mean follow-up 14.3 years (range 5-28; died 3/12). In 9/12 cases, the first
manifestation was visual impairment (visual field loss, reduction in visual acuity
and/or cranial nerve palsies). All the patients had invasive pituitary macro-
EP1011
adenomas with expansion into surrounding anatomical structures (11 cavernous
Assessment of macroprolactin through post-PEG monomeric prolactin
sinus; 7 sphenoid sinus; 7 bone invasion). The 12 patients underwent a total of 52
measurement and comparison with gel fitration chromatography in
surgical procedures
(median
4; range
3-6). Apparently total removal was
hyperprolactinemic samples
achieved in 8/12 patients at the first surgical procedure. Regarding histological
Antonio Ribeiro-Oliveira Jr & Maria do Carmo D Gontijo
subtype: 5 gonadotrophinomas; 2 null-cell adenomas; 2 corticotrophinomas; 1
Federal University of Minas Gerais, Belo Horizonte, Brazil.
thyrotrophinoma; 1 prolactinoma and 1 plurihormonal adenoma (GH/ACTH).
Proliferation markers as ki67 O3% was identified in 4; O2mitoses/10 HPF in 3
and p53 IHC expression in 4/12 cases. Six patients underwent radiation therapy
Macroprolactin interference is a common problem in the interpretation of
(RT) postoperatively (5 conventional external RT; 1 stereotactic radiosurgery).
immunoassays for prolactin. Identifying macroprolactinemia can prevent
Medical therapy was tried in 4/12 patients: 3 with dopamine agonists; 1 with
errors in diagnosis and subsequent delivery of treatment to patients. The
somatostatin analog (pasireotide); 2 with steroidogenesis inhibitors (ketoconazole
search for macroprolactin through polyethylene glycol (PEG) precipitation
and metyrapone). Possible metastatic pulmonary disease was identified only in
followed by percentage recovery is the most common used method in
one case; the patient died of tumor progression 10-years after the diagnosis.
clinical laboratories. This study aimed to evaluate the implementation of
Conclusion
macroprolactin assessment in hyperprolactinemic samples, with the
Aggressive pituitary tumors constitute a challenging but not completely defined
interpretation of the results based on validated post-PEG monomeric
entity. We found an elevated number of surgical procedures by patient and
prolactin reference range. It also aimed to verify whether post-PEG
smaller proportion of RT/medical treated patients compared with literature,
monomeric prolactin measurements could match the results obtained
however, with similar outcomes. Adverse results in treatment are possibly related
through Gel filtration chromatography (GFC). Samples from 40 healthy
to difficulty in early detection of this patients’ subgroup that must be treated with a
subjects were utilized for the validation of the post-PEG monomeric
multimodal approach.
prolactin reference range, according to predetermined data quality. The
DOI: 10.1530/endoabs.49.EP1009
macroprolactin assessment by PEG precipitation was then performed on 112
hyperprolactinemic samples
(96
women), and results obtained by
percentage of post-PEG prolactin recovery were compared with post-PEG
monomeric prolactin concentrations. Twenty-five out of the 112 hyperpro-
lactinemic samples were randomly selected for evaluation through GFC for
further comparisons. Assessment of post-PEG monomeric prolactin
concentration with an appropriate validated reference range showed greater
specificity than the conventional criterion of percentage of post-PEG
prolactin recovery, as it identified samples with both excess macroprolactin
EP1010
and monomeric bioactive prolactin, and also reduced the rate of
Hypertension, acromegaly and pegvisomant treatment: Experience
indeterminate results. Furthermore, most of the results obtained in samples
from ACROSTUDY
analyzed by GFC were in agreement with results obtained by post-PEG
Greisa Vila1, Arrt Jan vanderLely2, Sebastian Neggers2, Anton Luger1,
monomeric prolactin measurement. The assessment of macroprolactin
Susan Webb3, Beverly Biller4, Peter Jonsson5 & Judith Hey-Hadavi6
through a validated post-PEG monomeric prolactin reference range should
1Medical University of Vienna, Vienna, Austria;2Erasmus University
be adopted as it outperformed the current utilized criterion.
Medical Centre, Rotterdam, The Netherlands;3Universitat Autonoma de
DOI: 10.1530/endoabs.49.EP1011
Barcelona, Barcelona, Spain;4Massachusetts General Hospital, Boston,
Massachusetts, USA;5Pfizer ACROSTUDY Endocrine Care, Sollentuna,
Sweden;6Pfizer Endocrine Care, New York, USA.
Introduction
Hypertension (HTN) is a major cardiovascular (CV) risk factor and independent
predictor of the increased mortality in patients with acromegaly. Surgical cure of
acromegaly is associated with improvement in blood pressure
(BP) levels,
however little is known on the effect of pegvisomant (PEGV) treatment on HTN.
EP1012
Methods/design
Sheehan syndrome: Sequential hormone failure and late diagnosis
ACROSTUDY is an open-label, international, prospective, non-interventional
Cristiana Costa1, Ana Filipa Martins1, Alexandra Araujo1 &
study monitoring the long-term safety of PEGV. After informed consent, study
Sonia do Vale1,2
patients were enrolled on an ongoing basis. Data were analysed to identify the
1Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital
clinical characteristics and evolution of HTN in patients with acromegaly treated
Center, Lisbon, Portugal;2Endocrinology Department, Lisbon Medical
with PEGV.
School, Lisbon, Portugal.
Results
As of May 31, 2016, data from 2090 patients (15 countries) were available. At
ACROSTUDY start, 1038 patients (49.7%, 51% male) had diagnosed HTN
Introduction
(96.4% were on anti-HTN medications). Most HTN patients were Caucasian
Postpartum infarction of the anterior pituitary, known as Sheehan’s syndrome, is a
(95%) and 75.8% was treated with PEGV before ACROSTUDY start. Modifiable
rare cause of hypopituitarism. In many cases, the hormones deficiency is
CV risk factors that were reported besides HTN were BMI O25 (87.2%), diabetes
sequential which implies late diagnoses.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Case Report 1
EP1014
A 51-year-old woman was observed because her mother had medullary thyroid
Renal prognosis of diabetic patients with and without central diabetes
carcinoma. She had no evidence of endocrine neoplasia. Nevertheless, she was
insipidus
experiencing fatigue, hair loss and dry skin for several months. Her history
Junichi Yatabe1, Midori Yatabe1, Tetsuya Babazono2, Yasuko Uchigata2 &
included a postpartum haemorrhage at 22 with blood transfusion requirement. She
Atsuhiro Ichihara1
was unable to breastfeed and mentioned oligomenorrheic cycles after that and
1Tokyo Women’s Medical University, Endocrinology and Hypertension,
took two years to get pregnant again. Menopause was at 43. Physical examination
Tokyo, Japan;2Tokyo Women’s Medical University, Diabetes Center,
was unrevealing. Baseline endocrine evaluation revealed low gonadotrophines,
Tokyo, Japan.
IGF-1 and fT4 with inappropriate normal tyrotrophin, PRL of 2.5 ng/ml and
morning cortisol of 8.7 mcg/dl with ACTH of 15.3 pg/ml. A multiple pituitary
stimulation test confirmed the deficiency of all anterior pituitary hormones except
Background
the pituitary-adrenal axis. Levothyroxine reposition was prescribed.
It has been suggested that higher arginine vasopressin (AVP) concentration may
Case report 2
be associated with greater eGFR decline in diabetic patients not using inhibitors
A 78-years-old woman was referred to the endocrinology outpatient department
of the renin-angiotensin system (Diabetologia 2013). If excessive AVP action is
after hospital admission due to hypotension, hyponatremia (113 mmol/l) and
detrimental to renal prognosis, then diabetic patients with central diabetes
rhabdomyolysis that improved with corticotherapy. She reported asthenia,
insipidus (CDI) may have relatively preserved renal function. Therefore, we
weakness, myalgias and anorexia that worsened progressively 2 years before
aimed to compare long-term renal prognosis of diabetic patients with and without
admission. Her third pregnancy occurred at the age of 28, with severe blood loss
CDI.
at delivery, inability to breastfeed, oligomenorrheic cycles after that and
Methods
menopause at 36. Endocrine evaluation confirmed a panhypopituitarism and the
We retrospectively identified 39 diabetic patients with CDI followed up at our
CT scan showed an empty sella turcica. She became asymptomatic with
university hospital for more than 4 years. Propensity matching for baseline age,
hydrocortisone and levothyroxine reposition.
sex, BMI, HbA1c, eGFR, SBP, DBP, urinary protein, and length of observation
Conclusion
was performed to select 39 control diabetic patients without CDI in the same
These cases represent two very late diagnosis of Sheehan’s syndrome.
hospital.
Appropriate obstetric/gynaecologic history and clinical suspicion are required
Results
to avoid late manifestations of the disease, namely an adrenal crisis, because the
Baseline demographics of the CDI group were as follows: age 45.6 years, 41%
pituitary-adrenal axis is usually the last one failing. Timely treatment may
female, BMI 27.2, HbA1c 7.0%, eGFR 90.4 ml/min/1.73 m2, blood pressure
dramatically improve quality of life of these patients, who may experience
122/79 mmHg and observation of 1862 days (mean values). There was no
hypopituitarism for long years before diagnosis.
significant difference in eGFR at the end of observation period (Control: 86.3G
DOI: 10.1530/endoabs.49.EP1012
28.1 vs CDI: 85.8G33.7 ml/min/1.73 m2) or the slope of eGFR (Control: K0.9G
/year) between groups. On the other
3.6 vs CDI: K1.1G10.7 ml/min/1.73 m2
hand, eGFR variability (standard deviation) was significantly greater in the CDI
group
(Control:
7.9G5.1
vs CDI:
18.3G13.3 ml/min/1.73 m2, P!10K5).
Considering that excessive fluctuations in eGFR are damaging to the kidney in
general, CDI patients may exhibit milder decline in eGFR when eGFR variability
and other factors, such as the use of renin-angiotensin system inhibitors, are
matched between groups.
Conclusion
A simple analysis of long-term eGFR revealed no significant difference between
EP1013
diabetic patients with and without CDI. Nevertheless, confounding factors, such
Multimodal treatment in pituitary carcinoma arising from a
as greater eGFR variability in CDI patients, may have weakened the relationship
ACTH-expressing pituitary macroadenoma with an unexpected
between AVP action and decline in renal function.
long-term survival
DOI: 10.1530/endoabs.49.EP1014
Cesar Boguszewski, Felipe Schwambach, Karina Manosso &
Sthefanie Pallone
SEMPR (Endocrine Division), Department of Internal Medicine,
Federal University of Parana, Curitiba, Brazil.
Pituitary carcinoma (PC) is defined by the presence of pituitary tumor that is
either not contiguous with the primary sellar tumor and/or has metastasized
to distant sites. It is very rare and associated with poor prognosis, with
a median survival of 12 months when systemic metastases are present, and
EP1015
30 months when metastases are confined to the central nervous system.
Osilodrostat maintains normalized urinary free cortisol levels in a
A 20 years-old man was first diagnosed with a nonfunctioning pituitary
majority of patients with Cushing’s disease: Long-term results from an
macroadenoma in 1981 and submitted to transsphenoidal surgery (TSS).
extension to the LINC-2 study
Histology showed ACTH positive tumor, p53 negative and Ki-67 1%. Three
Jacques Young1, Betul Hatipogulu2, Mark E Molitch3, Xavier Bertagna4,
years later a recurrence was detected and a new TSS followed by
Nathalie Barbier5, Nicholas Sauter6, Beverly M K Biller7 &
conventional radiotherapy
(Rxt) was performed. Hormone replacement
Rosario Pivonello8
therapy (HRT) was initiated for TSH, ACTH and FSH/LH deficiencies. In
1Department of Endocrinology, Hôpital Bicêtre, Université Paris-Sud,
2000, at age 39, he complained of prolonged nasal obstruction. Imaging
Assistance Publique Hôpitaux de Paris, Paris, France;2Endocrinology and
showed a giant invasive sellar tumor with extension to suprasellar region,
Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA;3Division of
cavernous sinus, and nasopharynx; multiple extra-axial lesions in the
Endocrinology, Metabolism, and Molecular Medicine, Northwestern
posterior fossa suggesting meningeal secondary implants and a large mass in
University, Chicago, IL, USA;4Department of Endocrinology, Centre de
the cervical-thoraco-lumbar spine. Histology of the resected giant adenoma
Référence des Maladies Rares de la Surrénale, Hôpital Cochin, Faculté de
and the spinal lesion confirmed an ACTH-expressing PC with a high
Médecine Paris Descartes, Université Paris 5, Paris, France;5Novartis
proliferative index. Fractionated stereotactic Rxt was performed. Cabergo-
Pharma AG, Basel, Switzerland;6Novartis Pharmaceuticals Corporation,
line and pasireotide were prescribed, but discontinued after some months
East Hanover, NJ, USA;7Neuroendocrine Clinical Center, Massachusetts
due to side effects. Tumor regrowth occurred in 2009 when surgery was
General Hospital, Boston, MA, USA;8Dipartimento di Medicina Clinica e
repeated for removal of the main tumor followed by Rxt directed to
Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli,
cerebellar lesions, and again in
2015, when a microsurgery guided by
Naples, Italy.
localization systems and electrophysiological monitoring was carried out.
Temozolomide was prescribed but patient refused the use. Currently, at age
55, he is doing well, working, and maintaining a stable clinical condition
Background
under HRT. Latency time from the diagnosis of pituitary adenoma to PC was
In the
22-week LINC-2
study, osilodrostat
(LCI699), a potent oral
11b-
19 years, and his survival of 16 years after diagnosis of PC has no parallel in
hydroxylase inhibitor, normalized urinary free cortisol (UFC) levels in 15 of 19
the literature to date.
patients with Cushing’s disease (CD). The most common AEs were nausea,
diarrhea, asthenia, and adrenal insufficiency (nZ6 each). Here, we report the
DOI: 10.1530/endoabs.49.EP1013
31-month efficacy and safety results from LINC-2 extension.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Methods
EP1017
Patients receiving clinical benefit at week
22 could enter two consecutive
Evaluation of upper gastrointestinal system in acromegaly
extensions and continue on the same dose of osilodrostat; dose adjustments were
Pinar Sisman1, Murat Pekgoz2, Mete Sisman3, Soner Cander4,
allowed. Response rate: proportion of patients with UFC%ULN (controlled) or
Ozen Oz Gul4, Erdinc Erturk4 & Canan Ersoy4
UFCOULN but R50% decrease from baseline (partially controlled). The
1Harakani State Hospital, Endocrinology and Metabolism Clinic, Kars,
maximum safety follow-up from core baseline was 40.3 months.
Turkey;2Sirnak State Hospital, Gastroenterology Clinic, Sirnak, Turkey;
Results
3Muradiye State Hospital, Surgery Clinic, Bursa, Turkey;4Uludag
Sixteen patients entered the extension, 12 remained on treatment at month 31.
University Medical School, Department of Endocrinology and Metabolism,
Three patients discontinued during extensions (AEs, nZ2; consent withdrawal,
Bursa, Turkey.
nZ1). One patient decided not to continue on to extension-2. The response rate at
month 31 was 100% (controlled, 14 (87.5%); partially controlled, 2 (12.5%))
when missing values were imputed using the last available measurements and
Background
56.3% without imputation ((controlled, 8 (50.0%); partially controlled, 1 (6.3%)).
Because of prolong exposure to elevated endogenous growth hormone (GH) and
No patient had escape from response (UFCOULN at R2 consecutive visits on
insulin-like growth factor (IGF-1) levels in acromegaly, it is resulted in multipl
maximum tolerated dose after initial UFC normalization) during the extension.
comorbidities such as somatic growth, hypertension, diabetes and sleep apnea.
Mean (S.D.) changes in clinical signs of CD from baseline to month 31 (nZ11)
Systemic complications caused by acromegaly include gastrointestinal (GIS)
were: SBP (mmHg), K3.4 (18.5); DBP (mmHg), K5.4 (9.9); weight (kg), K4.5
involvement. In our study it was planned to evaluate the upper GIS findings by
(5.7); and BMI (kg/m2), K1.8 (2.3). The most common clinical AEs were
using endoscopic and ultrasonographic methods in acromegaly patients.
diarrhea, hypocortisolism-related AEs
(nZ6 each), headache, asthenia, and
Subjects and methods
nausea (nZ5 each). Mean (S.D.) plasma ACTH (pmol/l; normal, 1.8-9.2) at
Thirty-nine acromegaly patients who had attended to our center for the last
baseline (nZ15), week 22 (nZ15) and month 31 (nZ10) were 20.0 (10.4), 80.5
6 months were recruited to the study. Upper GIS endoscopies and abdominal
(145.5), and 54.0 (35.1), respectively.
ultrasonography were performed to all patients.
Conclusion
Results
In the majority of patients with CD, osilodrostat maintained normal UFC levels
Of the patient included in the study, 23 were male and 16 were female. The mean
for O2.5 years with a long-term safety profile similar to that after 22 weeks; no
age of the patients was 51.4G11.0 years. The mean duration of acromegaly was
new safety signals emerged. Two phase 3 studies are ongoing to further evaluate
104.3G88.6 months. Upper GIS endoscopy was performed in 39 patients and
osilodrostat in patients with CD.
hiatal hernia, esophagitis and gastritis, duodenitis or gastric ulser were found in
DOI: 10.1530/endoabs.49.EP1015
3
(%7.6), 2 (%1.7) and 31 (%79.4) patients, respectively. In the pathologic
evaluation of gastric antrum biopies, intestinal metaplasia was detected in
12
(%30.7) patients and helicobacter pylori was positive in 13 (%33.3) patients.
Abdominal ultrasonographic evaluation revealed cholelithiasis findings in
15
(%38.6) patients.
Discussion
As a result of our study, there was no statistically significant difference between
age also sex and hiatal hernia, esophagitis, gastroduodenitis, ulcer development in
acromegaly patients. Preoperative GH elevation did not affect the development of
hiatal hernia, whereas preoperative IGF-1 elevation significantly increased hiatal
EP1016
hernia development. The incidence of developing cholelithiasis was statistically
Acromegaly: assessing the clinical outcome through a 10-year
significantly higher in patients with advanced age, long disease duration and no
experience at a tertiary care hospital in Pakistan
postoperative biochemical control. Limitations of our study are the lack of a
Shehla Tabassum & Najmul Islam
control group and the low number of patients. There is a need for controlled
Aga Khan University, Karachi, Pakistan.
studies involving more patients in acromegaly patients.
DOI: 10.1530/endoabs.49.EP1017
Background
Acromegaly is due to excess Growth hormone (GH) production, usually as result
of pituitary adenoma. The diagnosis is often preceded by around 5 years of active
but unrecognized disease. Clinical expression of the disease in each patient
depend on the levels of GH and Insulin-like Growth Factor-1 (IGF-1), age, tumor
size, and the delay in diagnosis. Successful remission after Trans-sphenoidal
surgery (TSS) is reported to be found in 52.5% of cases in the developed
countries.
EP1018
Objectives
Disposition index in active acromegaly: A pilot study
This study was designed primarily for the evaluation of diagnostic characteristics
Dan Alexandru Niculescu1,2, Roxana Dusceac1,2,
of acromegaly and establishment of its management outcomes over a span of
Andra Caragheorgheopol2, Nicoleta Popescu2 & Catalina Poiana1,2
10 years at a tertiary care hospital in Pakistan.
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
Methods
2C. I. Parhon Institute of Endocrinology, Bucharest, Romania.
It was a Descriptive cohort study. Total
53 patients with biochemical and
radiological diagnosis of Acromegaly were included in study between October,
2005 to September, 2015. Patients’ medical record files were reviewed and data
Background
recorded.
Active acromegaly is characterized by decreased insulin sensitivity
(ISen).
Results
However, insulin secretion (ISec) may not increase satisfactorily to compensate
Of the 53 subjects, with mean age of 39.68G14.35 years, 33 (62.3%) were male
for the low ISen.
while 20 (37.7%) were female.The patients presented at a mean duration of
Aim
5.90G4.12 years after onset of symptoms. The most frequent complaint was
To assess ISen and ISec and to calculate disposition index
(DI) using an
somatic growth features in the form of enlarged hands and feet noted by 51
intravenous glucose tolerance test (IVGTT) in patients with active acromegaly.
(96.2%) pts. Overall, 50 (94.3%) patients underwent TSS for removal of pituitary
Methods
adenoma while 3 (5.7%) patients refused to opt surgical option. Only 3 (6%)
Twelve patients (7 men, 5 women) with active acromegaly and 2 normal subjects
patients achieved biochemical and radiological remission after 6 months of
(2 men) underwent a standard IVGTT with a glucose dose of 0.3 g/kg of body
surgery. Among 47 patients with persistent disease after TSS, 26 (55.3%) were
weight. Eight patients had normal glucose tolerance (NGT) and 4 had impaired
treated with radiosurgery/radiotherapy, 12 (25.5%) underwent repeat TSS and
glucose tolerance (IGT). None were on medication for acromegaly of glucose
9
(19.1%) opted for medical treatment, mostly with Cabergoline.
intolerance. ISen was calculated as the slope of the glucose curve between 10 and
Conclusion
75 min (the rate of glucose disappearance) divided by the area under the insulin
TSS is followed by the documentation of a high rate (94%) of failure to achieve
curve between 0 and 75 min. ISec was calculated as the acute insulin response, the
remission and majority of patients have to opt radiotherapy/repeat TSS for the
delta area under the insulin curve between 2 and 10 min after glucose infusion.
persistent disease. With the continuously improving surgical skills, we expect that
DI was calculated as ISen times ISec.
the figures attaining remission after primary TSS will rise in the decades to come.
Results
Keywords: Acromegaly, Characteristics, Management Outcome
Subjects with NGT (8 patients with acromegaly and 2 normal subjects) had a
DOI: 10.1530/endoabs.49.EP1016
significantly higher DI than patients with IGT (801 (632, 1762) vs. 172 (98, 247);
P!0.001). Inside the IGT group there were both patients with extremely low ISen
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
(0.02
L!100 000/pmol!min) and unsatisfactorily increase in ISec
(3862
study (CSOM230CIC05) will provide real-world evidence on the efficacy and
pmol!min/l) and patients with nearly normal ISen (1.09 L!100 000/pmol!
safety of the multi-targeted SSA long-acting pasireotide in uncontrolled
min) but very low ISec (244 pmol!min/l).
acromegaly patients.
Conclusion
Methods
Both insulin sensitivity and insulin secretion contribute to glucose intolerance in
This non-interventional study will analyze efficacy and safety data in acromegaly
acromegaly. DI clearly differentiate glucose intolerant patients from glucose
patients (R18 years) already treated (for R6 months) with monthly pasireotide
tolerant ones.
(retrospective dataset) or about to be treated (prospective dataset). About 200
DOI: 10.1530/endoabs.49.EP1018
prospective patients (2-year follow-up) and 50 retrospective patients are expected
to be enrolled. Outcome measures will include biomarkers (GH and IGF-1),
pituitary imaging, symptom- and quality of life (QoL) scores. The primary
objective is to document treatment efficacy within the prospective data subset; the
endpoint will be the proportion of patients who achieve IGF-1 !1 upper limit of
normal (ULN) and GH !1 mg/l after 6 months. Secondary endpoints will include
the proportion of patients at
6
months
(retrospective) or within
2
years
(prospective) who achieve IGF-1 !1 or !1.3 ULN and GH !1 or 2.5 mg/l,
EP1019
change in tumor size, signs and symptoms, QoL and incidence of hyperglycemia.
In well-controlled patients with acromegaly, glucose homeostasis
Safety assessments will include adverse events, hematology, clinical chemistry
correlates with the level of disease control rather than with the type of
and physical examinations. Interim analyses will be performed once at least 50
treatment
retrospective patients have been exposed to 6 months of treatment and 100
Charlotte Verroken, Bruno Lapauw & Guy T’Sjoen
prospective patients have been treated for at least
6 months, respectively.
Department of Endocrinology, Ghent University Hospital, Ghent, Belgium.
Descriptive statistics, as well as, absolute and relative frequencies will be
reported.
Objective
Conclusion
Acromegaly is often accompanied by abnormalities in glucose and lipid
ACRONIS will provide European real-world data to increase our understanding
metabolism, which tend to ameliorate upon treatment. However, few studies
of the long-term efficacy and safety of pasireotide in uncontrolled acromegaly.
have investigated whether glucose homeostasis and lipid profiles are differently
DOI: 10.1530/endoabs.49.EP1020
affected by different treatment regimens. This study aimed to compare glucose
homeostasis and lipid profiles in patients with acromegaly who are well-
controlled after surgery or under stable treatment with long-acting somatostatin
analogs (SSA) either in monotherapy or in combination with pegvisomant.
Methods
Cross-sectional study in 21 patients with a diagnosis of acromegaly (aged 59.1G
EP1021
10.9 years, 10 males), who were controlled (i.e. serum IGF-1 levels under sex-
Thyrotropin secreting microadenoma - case report of a patient with
and age-specific thresholds) after surgery (SUR; nZ5) or under treatment with
goiter
SSA (SSA; nZ10) or SSA C pegvisomant (COMBI; nZ6). Glucose, insulin,
Sónia do Vale1,2, Ana Filipa Martins1, Dolores López-Presa3,
total cholesterol, HDL-C and LDL-C were measured from fasting serum samples.
Cristiana Costa1 & José Miguéns4
Triglycerides were measured during a mixed-meal tolerance test
(MMTT).
1Endocrinology Department, Santa Maria Hospital, North Lisbon Hospital
Insulin resistance was evaluated using the homeostasis model assessment of
Center, Lisbon, Portugal;2Endocrinology Department, Lisbon Medical
insulin resistance (HOMA-IR); insulin sensitivity was evaluated by hyperinsu-
School, Lisbon, Portugal;3Pathology Department, Santa Maria Hospital,
linemic-euglycemic clamp.
North Lisbon Hospital Center, Lisbon, Portugal;4Neurosurgery
Results
Department, Santa Maria Hospital, North Lisbon Hospital Center, Lisbon,
IGF-1 levels tended to be lower in SUR (138.4G54.4 ng/ml) as compared to SSA
Portugal.
(194.5G16.3 ng/ml) or COMBI (173.3G52.3 ng/ml) (PZ0.056). After adjust-
ment for age and BMI, between-group differences were observed for HbA1c
(PZ0.048), fasting glucose (PZ0.022), and HDL-C (PZ0.015), with lower
Introduction
levels in SUR as compared to SSA or COMBI. No differences were observed in
The prevalence of pituitary thyrotropin secreting tumors (TSH-omas) is 1-2 cases
fasting insulin, cholesterol, LDL-C, HOMA-IR, glucose disposal rate during
per million inhabitants, most of them being macroadenomas. The differential
clamp, or triglyceride levels during MMTT. Independently of the treatment
diagnosis may be challenging, especially for microadenomas.
regimen, IGF-1 levels correlated positively with fasting glucose and insulin levels
Case Report
(ßZ0.52 and ßZ0.57, both PZ0.010), with HOMA-IR (ßZ0.66, PZ0.003), and
A 50-year-old male was observed at the endocrinology department with
inversely with glucose disposal rate (ßZK0.60, PZ0.006).
multinodular goiter. He noticed progressive neck enlargement over the previous
Conclusion
months but denied other complaints. There was no family history of thyroid
In patients with acromegaly who are controlled after surgery or under stable
pathology. He presented hot sudorific hands and a large nodular goiter.
medical therapy, indices of glucose homeostasis correlate with circulating IGF-1
Laboratory evaluation revealed a predominantly high T3 with non-suppressed
levels, independently of the treatment regimen.
TSH (TSH 1.73 mU/ml (Reference range - RR: 0.55-4.78), T3-2.08 ng/ml (RR:
DOI: 10.1530/endoabs.49.EP1019
0.60-1.81), T4-11.7 mg/dl (RR:4.5-10.9), FT3-7.74 pg/ml (RR: 2.3-4.2), FT4-
1.93 ng/dl (RR: 0.8-1.76)). The sonography showed an enlarged thyroid gland
with bilateral nodules of 37, 50 and 70 mm. Additional evaluation revealed
negative anti-thyroid antibodies, high total testosterone and SHBG, chromogranin
A, alpha-subunit of glycoproteic hormones
(aGS) and aGS/TSH ratio, but
otherwise normal pituitary function and no evidence of other endocrine neoplasia.
There was no TSH or aGS response to TRH administration and the MRI revealed
EP1020
a 6 mm pituitary lesion. Thyroid nodules cytology was benign. A TSH-oma was
admitted and long-acting octreotide administered, with normalization of thyroid
European observational study of long-acting pasireotide for
function and subsequent trans-sphenoidal tumor resection. Pathological analysis
uncontrolled acromegaly: ACRONIS study design and rationale
revealed an adenoma with positive TSH immunohistochemistry. Over the next
Andrea Giustina1, Gesine Enderle2, Daniela Mesenka3, Debolina Mondal4
months, there was TSH suppression and secondary hypothyroidism, during which
& Christof Schofl5
levothyroxine was administered, and subsequent recovery of normal thyroid
1Cattedra di Endocrinologia, Universita’ Vita e Salute San Raffaele, Milan,
function. Slight reduction of the goiter was observed.
Italy;2Novartis Farma S.p.A, Origgio, Italy;3Novartis s.r.o., Prague, Czech
Discussion
Republic;4Novartis Healthcare Pvt. Ltd., Hyderabad, India;5Centre of
Distinguishing pituitary TSH-omas from thyroid hormone resistances may be
Endocrinology and Metabolism, Obstmarkt 1, 96047 Bamberg, Germany.
challenging, but it is important for correct therapeutic options and avoid
endocrine and neurological complications. Baseline thyroid function and
Introduction
sonography do not adequately distinguish both entities, but the absent family
Acromegaly is a rare, serious disease caused by the presence of a pituitary
history, high SHBG, aGS and aGS/TSH ratio, blunt TSH and aGS response to
adenoma secreting an excessive amount of growth hormone (GH), which leads to
TRH, and FT3/FT4 normalization with long-acting octreotide, together with a
a consequent increase in circulating insulin-like growth factor-1 (IGF-1) levels,
small but existent pituitary adenoma, prompted a microthyrotropinoma diagnosis.
and excessive skeletal growth and soft tissue enlargement. It is usually managed
DOI: 10.1530/endoabs.49.EP1021
by surgery and/or treatment with somatostatin analogs (SSA). The ACRONIS
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1022
technique (TFS vs TSS P!0.05), but not in age, pituitary function or number
of interventions.
Non-functioning pituitary adenoma; improved endocrine outcomes
Conclusion
with increasing surgical experience: The Manchester Cohort
It is important to identify those patients in risk of developing permanent DI, which
Sumithra Giritharan1, Tara Kearney1 & Kanna Gnanalingham2
in our case were those with bigger tumors that required TFS.
1Department of Endocrinology, Salford Royal NHS Foundation Trust,
Salford, UK;2Department of Neurosurgery, Salford Royal NHS Foundation
DOI: 10.1530/endoabs.49.EP1023
Trust, Salford, UK.
Case notes of 150 consecutive patients (58% male) who underwent pituitary
surgery by a single surgeon for non-functioning pituitary adenoma and
endocrine follow up at our centre between July 2005 and February 2015
were reviewed. All patients underwent endoscopic transsphenoidal surgery
as the first approach. Post-operative pituitary function was assessed by
measurement of baseline pituitary hormonal profile and a glucagon
EP1024
stimulation test to assess ACTH and GH axis. Mean age at surgery was
Etiology and some clinical characteristics of hypopituitarism over the
61 years (range
23-87 years). Pre-operatively,
63.3% of patients had
years of follow up
evidence of hypopituitarism and vision was affected in 58% of patients.
Milica Medic Stojanoska1,2, Bojan Vukovic1,2, Ivana Bajkin1,2,
Post-operatively, hypopituitarism was detected in 70% of patients. New
Tijana Icin1,2, Andrijana Milankov1,2, Jovanka Novakovic Paro1,2,
hormone deficiency developed in 25.3% of patients. Post-operative vision
Jovana Prodanovic1,2 & Nikola Curic1,3
improved 46.6% of the total cohort and remained static in 47.3% of patients.
1Clinical center of Vojvodina, Clinic for Endocrinology, Diabetes and
During this time period, 10% of patients underwent further surgery and 28%
Metabolic Dieseases, Novi Sad, Serbia;2Medical Faculty University of
of patients were referred for radiotherapy. To assess if increasing surgical
Novi Sad, Novi Sad, Serbia;3Clinical Center of Vojvodina, Center for
experience affected patient outcomes, data was assessed in two time periods;
Laboratory Medicine, Novi Sad, Serbia.
patients undergoing surgery in the early years between 2005 and 2010
(nZ67) and patients undergoing surgery in the latter years between 2011
and 2015 (nZ83). There was no significant difference between pre-op
hypopituitarism between these groups however, there was a statistically
The data of etiology and clinical characteristics of hypopituitarism in
significant difference in terms of post-operatively hypopituitarism, with a
different countries differes. The aim of the study is to investigate etiology
lower number of patients in the latter group experiencing post-operative
and some clinical characteristics of patients with hypopituitarism that were
hormone deficiency (79.1% vs 62.7%, PZ0.033). Furthermore, there was a
treated in the Clinical center of Vojvodina. The study was conducted as a
statistically significant difference in terms of pre-operative visual status,
retrospective study. There were 32 males and 28 female patients. Mean age
with more patients in the latter group without any visual compromise (28.4%
was 52.2G17.5 years. Data was analized before and after substitution of
vs 51.8%, PZ0.008). There was no significant difference in terms of post-
hypopituitarism. Patients were treated with levothyroxine, hydrocortisone,
operative visual outcomes. In conclusion, data from our cohort demonstrates
sexual steroids, growth hormone and with desmopresine depending on the
improved endocrine outcome with increasing surgical experience over time.
type deficiency. At the time of the diagnosis, mean age was 40.2G18.7 and
It also highlights change in clinical practice in our centre with more patients
the average period of treatment was 15.9G11.4 years. The most common
undergoing surgery prior to the development of visual symptoms.
causes of hypopituitarism were pituitary macroadenomas
(53.3%) and
craniopharyngeomas (21.7%). Partial hypopituitarism with deficiency in
DOI: 10.1530/endoabs.49.EP1022
two or more functions was diagnosed in 64.4% subjects and panhypopitui-
tarism in 28.8%, deficiency of one function in 6,8%. Average body mass
index after the treatment was 27.8G6.5 kg/m2. Blood pressure was in
normal range and without changes during the treatment. High levels of total
cholesterol and LDLcholesterol before the treatment showed statistically
significant decrease during the treatment (6.29G1.57 vs 5.32G1.38 mmol/l;
P%0.009 and 4.12G1.45 vs. 3.20G1.11 mmol/l; P%0.005 respectly).
Levels of HDLcholesterol and triglycerides were not changed significantly
EP1023
during the treatment. Crosslaps was decreased non-significantly and bone
Polyuria and diabetes insipidus after surgery for pituitary tumors
mineral density showed absence of osteopenia and osteoporosis during
Nerea Egan˜a Zunzunegui, Ismene Bilbao Garay, Cristina García Delgado,
treatment. Correlation analysis showed statistically significant negative
Izaskun Olaizola Iregui, Maite Perez de Ciriza Cordeu, Maria Luisa
correlation between LDL cholesterol and levothyroxine (rZK0.341). 10%
Antun˜ ano Lopez, Maite Aramburu Calafell, Nicolas Sampron,
of subjects had a cardiovascular event. One subject died because of sepsis.
Alfredo Yoldi Arrieta & Miguel Maria Goena Iglesias
We concluded that hypopituitarism in our region is commonest in the middle
Hospital Universitario Donostia, San Sebastian, Guipuzcoa, Spain.
aged population, the main cause being pituitary macroadenomas.
Cardiovascular risk factors of untreated hypopituitarism are reversible and
cardiovascular events are rare.
Introduction
DOI: 10.1530/endoabs.49.EP1024
Central diabetes insipidus (DI) is a common complication after pituitary surgery,
but is transient in the majority of patients. The aim of our study is to determine the
incidence and course of DI in the postoperative period and to characterize the
factors associated with this disease.
Methods
We performed a retrospective study of 44 patients (50% females) with a mean age
of 54 years (24-83), treated with transsphenoidal (TSS) or transfrontal surgery
(TFS) between January 2013 and December 2016. 26 were nonfuntioning
adenoma, 7 somatotrophinoma, 6 corticotrophinoma, 2 gonadotrophinoma, 1
tirotrophinoma, 1 Rathke’s cyst and 1 craniopharyngeoma. 93.2% underwent TSS
EP1025
(72% endoscopic) and 6.8% (3 patients) TSF. 18% were reinterventions. We
A novel DICER1 gene mutation in a 10-month-old boy presenting with
consider polyuria if diuresis is O200ml/h for 3 consecutive hours and DI if the
ACTH-secreting pituitary blastoma and lung cystic dysplasia
natremia is O145 mEq/l so that the patient is candidate for subcutaneous
Alexey Kalinin1, Natalia Strebkova1, Anatoly Tiulpakov1,
desmopresine.
Eugene Vasiliev1, Vasily Petrov1, Anna Kolodkina1, Maria Kareva1,
Results
Nadezhda Mazerkina2 & Valentina Peterkova1
25 patients (56%) developed polyuria during early postoperative, 11 (25%)
1Endocrinology Research Centre, Moscow, Russia;2Scientific Research
transient DI between 1 and 5th day and 10 (22%) SiADH between 3 and 10th day.
Neurosurgery Institute, Moscow, Russia.
15% of these patients presented 2 phases DiCSiADH, none of them 3 phases. DI
was permanent in only 3 patients (6.8%), all after TFS. There was no difference
comparing the DI group vs no DI in tumor size, pituitary function and surgery
technique. However, we found differences between transient and permanent DI
Hypercortisolism due to Cushing disease is an extremely rare condition in
groups in tumor size
(53!36!42 vs 18!16!15 P!0.05) and surgery
children under one year of age. We present a case of a 10-month-old boy
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
with lung cystic dysplasia and pituitary blastoma (ACTH-secreting). The
Klinikum der Universitat Munchen, Medizinische Klinik und Poliklinik IV,
disease manifested with symptoms of hydrothorax due to cystic dysplasia of
Munchen, Germany.
the right lung’s upper lobe. Surgical resection of the affected area has been
carried out. Symptoms of endogenous hypercortisolism appeared soon after
Introduction
lung surgery. Cushing disease due to pituitary macroadenoma has been
Acromegaly is characterized by chronic growth hormone (GH) excess and leads
diagnosed. Pituitary adenoma was surgically removed; pituitary blastoma
to numerous changes in bodily functions and comorbidity. We compared
with isolated ACTH-secretion was revealed by immunohistochemistry.
potassium homeostasis in patients with acromegaly to hypertensive controls.
A combination of lung cystic dysplasia and pituitary blastoma was
Methods
suspicious for a DICER1 gene defect. p.C199X mutation in DICER1 gene
We prospectively assessed serum potassium, urinary potassium excretion,
was found. He has been followed up for four years after the pituitary surgery.
aldosterone and renin, acid-base balance as well as glomerular filtration rate
The patient has been receiving replacement therapy with hydrocortisone,
according to the CKD-EPI formula in 71 patients with acromegaly (37 male, 34
levothyroxine and growth hormone. No other DICER1-related conditions
female; age 59G14 years) and 70 hypertensive age and gender matched patients
were detected during the last follow-up visit. The same mutation was found
(HP) in whom secondary hypertension was ruled out (37m, 33f; 59G14 year). Of
in the mother, who had a history of euthyroid multinodular goiter.
the acromegaly patients, 23 had active disease (AD) and 48 were biochemically
Conclusion
controlled (BC).
Combination of lung cystic dysplasia and ACTH- secreting macroadenoma
Results
should prompt to DICER1 gene analysis. We have shown the variable clinical
Serum potassium levels were more elevated in patients with acromegaly (4.2 vs
phenotype in DICER1 mutation carriers within a family.
4.0 mmol/l, PZ0.008). Urinary excretion of potassium was also elevated in
DOI: 10.1530/endoabs.49.EP1025
patients with acromegaly as compared to hypertensive controls
(53.3
vs
35.3 mmol/l, P!0.001; 69.3 vs 52.9 mmol/g Creatinine, PZ0.004). Analysis
of variance in potassium excretion showed highly significant differences between
AD, BC and HP (P!0.001). Post-hoc comparison revealed higher excretion in
AD (66.3 mmol/l) as compared to BC
(47.1 mmol/l, PZ0.003) and HP
(35.3 mmol/l, P!0.001; BC vs HP PZ0.012). Mean arterial pressure was
higher in hypertensive patients (110 vs 104 mmHg, PZ0.009). There were no
statistically significant differences in GFR (PZ0.618), BMI (PZ0.549), sodium
EP1026
levels (PZ0.589), antihypertensive medications used (9 groups of antihyperten-
Pituitary insufficiency following traumatic thoracic injury in adolescent
sive drug classes; 0.117!P!1.0), aldosterone (PZ0.41) and renin (PZ0.161).
male patient-case study
Discussion
Aleksandra Gilis-Januszewska, Malgorzata Wilusz, Renata Turek-Jabrocka,
We observe higher serum potassium levels in patients with acromegaly compared
Jacek Pantoflinski, Malgorzata Trofimiuk-Muldner, Lukasz Kluczynski,
to patients with hypertension. Still, urinary excretion of potassium is also
Alicja Hubalewska-Dydejczyk & Dorota Pach
significantly higher despite comparable characteristics of both patient groups.
The University Hospital in Krakow, Krakow, Poland.
Higher intramuscular potassium levels have previously been shown in
acromegaly. Further research is warranted to elucidate potassium homeostasis
in acromegaly.
DOI: 10.1530/endoabs.49.EP1027
Traumatic thoracic injuries in children and adolescents are rare, but could be
connected with others traumas, often with traumatic brain injury (TBI).
Based on data in the current literature, approximately 15-20% of TBI
patients develop chronic hypopituitarism. Growth hormone
(GH) and
ACTH deficiency are the most common, followed by gonadotropins and
thyroid-stimulating hormone. The greatest challenge associated with
endocrine complications in individuals with polytrauma injury is early
recognition of these subtle problems. We present a case report of a 24-years-
old male. In 2007 (when he was 15-years-old) the patient underwent a traffic
accident, thoracic injury (hemothorax, dissection of the descending part of
EP1028
the aorta, aortic stent-graft implantation to the left subclavian artery) and
Russian hypothalamic and pituitary tumors registry (OGGO) data
concussion. During post traumatic period he had transient polydipsia and
analysis: acromegaly
polyuria. In
2013 gonadal axis deficiency was confirmed. Testosterone
Alexander Lutsenko, Elena Przhiyalkovskaya, Ekaterina Pigarova,
replacement therapy was started. During current investigation low growth
Zhanna Belaya, Liudmila Rozhinskaya & Irina Stanoevich
hormone level (GH) and insulin-like growth factor 1 (IGF-1) level were
Endocrinology Research Centre, Moscow, Russia.
found to be low. Patient’s hight is 160 cm, mothers 158 cm, fathers 182 cm.
Mid Parental Height (MPH)Z173.5 cm. An insulin tolerance test (ITT) was
performed. There was’t an adequate GH response-the insufficiency of
Objective
somatotropic axis was confirmed. There were no others hormonal
To analyze registry data on patients with acromegaly.
abnormalities. Further examinations e.g. NMR of the pituitary, genetic
Materials and methods
examination and DEXA are performed.
Russian hypothalamic and pituitary tumors registry database (on-line platform),
Conclusions
which contains data on 3719 patients with acromegaly.
Physical signs such as lack of progression through puberty, with decrease in
Results
testicular volume and libido, short stature and history of after trauma transient
According to the database, highest prevalence of acromegaly per
100 000
diabetes incipidus could suggest the presence of unrecognised hypopituitarism.
inhabitants is registered in: Penza region (7.3), Kirov region (7.3), Krasnoyarsk
Careful investigation and monitoring is necessary to unmask and treat such
region
(6.2). Most common clinical presentations in registered acromegalic
hormone deficiencies in the transition phase.
patients were: headaches (72%) maxillofacial changes (68%), arthralgias (48%)
excessive sweating (39%). Information about tumor size was available in 1543
DOI: 10.1530/endoabs.49.EP1026
patients: by the time of diagnosis, 516 (33.4%) had pituitary microadenomas and
1027
(66.6%) had macroadenomas. 59.5% of registered patients were prescribed
medical therapy: 65.9 and 34.1% were treated with somatostatin receptor ligands
(SRL) and dopamine agonists respectively. 29.9% of patients were primarily
treated surgically and remaining 10.6% underwent radiotherapy. Remission is
registered in 22% cases, 23% of patients have only partial disease control, 41%
have an active disease and 14% of records have no data regarding disease state.
Conclusions
Russian hypothalamic-pituitary tumors registry is a promising instrument for
EP1027
epidemiologic and clinical data acquisition. Data suggest that multimodal
treatment approach is essential to achieve higher remission rates in patients with
Potassium homeostasis in patients with acromegaly in comparison with
acromegaly.
hypertensive patients
Sylvère Stormann, Katharina Schilbach, Christine Pichl, Robert P Kosilek,
DOI: 10.1530/endoabs.49.EP1028
Hans-Joachim Anders & Jochen Schopohl
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1029
diameter of 15.9(11) vs 12.05(4.95) mm, respectively. After 6 months of SSA
therapy there was 51.2% decrease in IGF1 levels in No-Ha vs 72.3% in Ha. Six of
Adherence to hormone replacement therapy in patients with
the No-Ha had surgery and four of the Ha. The hormonal response in No-Ha was
hyp-opituitarism using the Morisky 4-item scale: results of a pilot,
complete in the 50% and partial in 20% of patients vs 83% and 17% in Ha,
prospective, cross-sectional study
respectively. O20% of tumour shrinkage occurred in 40% of the No-Ha vs 66%
Cesar Boguszewski, Simone Abe, Bruna Barbosa, Claudia Biondo,
of the Ha.
Debora Takito, Kamila Santos, Sayuri Hayashi & Victor Amarilla
Conclusions
SEMPR (Endocrine Division), Department of Internal Medicine,
Our results show the effectiveness of the pre-operative treatment with SSA in the
Federal University of Parana, Curitiba, Brazil.
acromegaly, in terms of hormonal but also anti-tumoral effects. T2-signal
intensity at diagnosis it’s a good prognostic marker of the effectiveness of SSA
Objective
therapy and it’s correlated with the tumour size-invasion and hormone levels at
To investigate adherence to hormone replacement therapy (HRT) in patients with
diagnosis.
hypopituitarism in a tertiary center outpatient clinic.
DOI: 10.1530/endoabs.49.EP1030
Patients and methods
Prospective, cross-sectional study of patients with hypopituitarism on HRT for at
least two pituitary deficiencies (independent of diabetes insipidus). Medication
adherence was assessed using a validated Portuguese version of four-item
Morisky scale, in which participants were asked to indicate the extent to which
they agreed with each of 4 statements (two related to unintentional and two with
intentional nonadherence) by rating on a 4-point scale (strongly agree, agree,
disagree, strongly disagree). Patients were categorized as nonadherent if they
indicated agreement (ie, reported either ‘strongly agree’ or ‘agree’) to either item
EP1031
of the subscale. Potential co-variables associated with adherence were tested.
Results
Ninety consecutive patients completed the survey, but five were excluded because
Abstract withdrawn.
they were on HRT with a single hormone. Of the remaining 85 patients (47 men,
age 48G16 year), 31 were on HRT with two hormones, 32 with three, 18 with
four and
4 with five. Levothyroxine, glucocorticoids, sex steroids, growth
hormone and desmopressin were prescribed to 81, 66, 64, 8 and 21 patients,
respectively. Mean number of prescribed medications (excluding HRT) per
patient was 3.1 (S.D. 2.4; range 0-9). The etiology of the hypopituitarism was non-
functioning pituitary tumors
(nZ19), functioning pituitary tumors
(nZ17),
craniopharyngeomas (nZ13), other tumors (nZ3), congenital (nZ14), vascular
(nZ13), trauma (nZ2), and idiopathic (nZ4). Fifty-six (65.9%) patients reported
unintentional nonadherence, while only
9
(10.6%) reported intentional
nonadherence. Complete adherence was reported by 29.4% of the patients,
while 5.9% showed both unintentional and intentional nonadherence. There were
no associations of adherence to gender, age, number of pituitary deficiencies and
EP1032
prescribed medications.
Conclusion
Does cyproterone acetate therapy contribute to the observed elevation
Self-reported unintentional nonadherence to HRT is a common finding in patients
in serum prolactin levels in trans women?
receiving HRT for hypopituitarism.
Justine Defreyne1, Nienke Nota2, Cecilia Perreira3, Schreiner Thomas4,
Fisher Alessandra Daphne5 & T’Sjoen Guy1,6
DOI: 10.1530/endoabs.49.EP1029
1Department of Endocrinology, Ghent University Hospital, Ghent, Belgium;
2Department of Endocrinology, Department of Internal Medicine, VU,
University Medical Center, Amsterdam, The Netherlands;3Department of
Endocrinology and Metabolism, San Juan de Dios Hospital, Santiago, Chile;
4
Department of Endocrinology, Oslo University Hospital, Oslo, Norway;
5Sexual Medicine and Andrology Unit, Department of Experimental,
Clinical and Biomedical Sciences, University of Florence, Florence, Italy;
EP1030
6Center for Sexology and Gender, Ghent University Hospital, Ghent,
Hormone and tumor responses to primary or pre-operative therapy
Belgium.
with somatostatin analogs in acromegaly and the relation with
T2-weighted MRI signal
Maria Picallo, Rogelio Garcia Centeno, Aurelio Lopez Guerra, Yoko
Objective
Lucia Olmedilla, Maria Arnoriaga, Maria Requena, Javier Agreda,
Hormonal treatment in trans women (MtF transgender persons) in Europe usually
Victor Andia, Marcel Sambo, Susana Monereo, Maria Angeles Velez,
consists of estrogens and anti-androgens, e.g. cyproterone acetate (CPA). After
Bettina Weber & Jose Atencia
initiation of cross-sex hormone therapy, an elevation in serum prolactin levels is
Gregorio Maran˜ on Hospital, Madrid, Spain.
frequently observed in trans women, which was previously attributed to estrogen
agents. This analysis evaluates whether CPA contributes to the elevation of
prolactin in trans women receiving cross-sex hormones.
Objective
Design
Study of the efficacy of SSA in the biochemical and tumour control and the
This study is part of the European Network for the Investigation of Gender
relation between the T2-weighted MRI signal intensity and the response to SSA.
Incongruence (ENIGI). Belgian data were selected for this substudy. Trans
Material and methods
women that initiated cross-sex hormone treatment (which consists of oral CPA
16 patients with GH-secreting pituitary adenomas (7_/9\) that received primary
50 mg in combination with estrogen substitution in Belgium) and underwent
or pre-operative treatment with SSA. We classified them according to baseline
orchiectomy were prospectively evaluated. Post-surgery estrogen was reinitiated
T2-weighted MRI sequences as Hypo-intense
(Ha) and No-Hypo-intense
in unchanged dose.
adenomas (no-Ha). Results expressed like media (S.D.).
Methods
Results
Sex steroids, gonadotropins and prolactin were compared at baseline, pre and post
Median age at diagnosis was 50.6 (18.5) years. 10 patients (9 macroademonas)
surgery (patients receiving orchiectomy) and after 12 and 18 months of cross-sex
had pre-operative therapy with SSA during 18.58 (26.9) months, with 47.2%
hormone therapy (patients not receiving orchiectomy).
decrease in IGF1 levels and 24.5% of tumour shrinkage. After neurosurgery three
Results
patients required medication for hormonal control. Only one patient had
Data was collected of 107 trans women, with a mean age of 31.5 years. After
postsurgical complications (hypopituitarism). Six patients (two macroadenomas)
1 year of cross-sex hormone therapy, there was an increase in serum prolactin
received exclusively medical treatment during 59.77(64.5) months. They showed
levels in all patients (9.65 mg/l), with a decrease after 18 months (14.10 mg/l) and
56.8% of reduction in IGF1 levels and 49% of tumour shrinkage. In the last
after orchiectomy (10.17 mg/l). However, serum prolactin levels post orchiectomy
consultation, 4 achieved hormonal control and two needed dose adjustment. From
were significantly lower than serum prolactin levels after 18 months of CPA
the whole group, ten were no-Ha and 6 Ha, showing at diagnosis: GH 20.13(16.5)
therapy, whereas there was no difference in serum estrogen levels between both
vs
14.75(19.8) mg/l, IGF1
973.5(474) vs
703.7(243.5) mg/l and a maximum
groups.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
Conclusions
The observed elevation of serum prolactin levels in trans women is likely caused
The results of this study suggest that fetal exposure to cabergoline through early
by CPA (independent of estrogen therapy), as prolactin levels return to normal
pregnancy does not induce any increase in the risk of miscarriage or fetal
after CPA discontinuation, independent of serum estrogen levels.
malformation. According the results of the study in patients with hyperprolacti-
DOI: 10.1530/endoabs.49.EP1032
nemia risk of gestational diabetes mellitus is higher than in the population that
require further investigations.
DOI: 10.1530/endoabs.49.EP1034
EP1033
A rapidly resolving prolactinoma with cabergoline treatment
Goknur Yorulmaz1, Aysen Akalin1 & Esra Akcan2
EP1035
1Division of Endocrinology, Eskisehir Osmangazi University School of
Clinical and hormonal characteristics of patients with different types
Medicine, Eskisekir, Turkey;2Radiology Department, Eskisehir State
hypophysitis: a single-center experience
Hospital, Eskisehir, Turkey.
Narin Nasiroglu Imga1, Ali Erdem Yildirim2, Ozden Ozdemir Baser1 &
Dilek Berker1
1
Department of Endocrinology and Metabolism, Ankara Numune Education
Introduction
and Research Hospital, Ankara, Turkey;2Department of Neurosurgery,
Prolactinomas are the most common pituitary tumors. Macroadenomas are rarely
Ankara Numune Education and Research Hospital, Ankara, Turkey.
seen. Dopamine agonists such bromocriptin and cabergoline are the preferred
treatments for prolactinomas. Herein, we report a patient with macroadenoma
whose adenoma has resolved rapidly with cabergoline treatment.
Background
Case
The inflammation of the pituitary gland known as hypophysitis. It is a rare disease
A 49 year old male patient evaluated for weakness and headache. After detection
accounting for approximately 0.24-0.88% of all pituitary diseases. Main forms of
of central hypothyroidism he was referred to our department. His prolactin level
hypophysitis are histologically classified as lymphocytic, granulomatous, IgG4
was more than
1925 ng/ml. His laboratory tests were concordant with
related and xanthomatous. We aim to present ourpatients of hypophysitis with
panhypopituitarism. Replacement therapy was initiated. A macroadenom with a
clinical,laboratoryand radiological features.
size of 28 mm was detected in pituiter MRI. Cabergolin treatment (3 mg/week)
Methods
was initiated. The size of the adenoma was decreased to 16 mm in the 3rd month
We retrospectively reviewed our database of 1293 patients diagnosed with
of the therapy. In the 6th month of the treatment the size of the adenoma regressed
pituitary diseases between 2010 and 2017. Demographical data, clinical features,
to 5 mm.
endocrinological dysfunction, magnetic resonance imaging findings, treatment
Conclusion
courses and follow-up periods were evaluated. Primary hypophysitis diagnosis
Prolactinomas are tumors with a good response to medical treatment. A rapid
was made by the exclusion of secondary causes of hypophysitis, consequently
response was detected in our patient but there is data about cabergolin resistance.
twelve patients with hypophysitis were identified.
So, a close follow up is required in patients with prolactinomas.
Results
DOI: 10.1530/endoabs.49.EP1033
The frequency of hypophysitis was found 0.93% in all cases of pituitary disease.
Twelve patients (nine females and three males); ages ranged between 17 and 61
years were evaluated. The characteristic features of our patients tend to be female
predominance and young population. Diagnosis of hypophysitis was made after
pituitary biopsy in 4 patients and in 8 patients after pituitary operation due to
adenoma. Headache (63%) and visual problems (18%) were the most frequent
nonendocrine symptoms. Anterior pituitary hormone deficiencies (63.7%) and/or
diabetes insipidus (16.7%) were seen amongpatients.According to histopatholo-
gical forms, 4 had lymphocytic, 6 had granulomatous and 1 had xanthogranu-
EP1034
lomatous types of hypophtsitis.
Pregnancy outcome in women with prolactinomas exposed to dopamine
Conclusion
agonists at early stages of gestation
Hypophysitis should be considered in the differential diagnosis of sellar masses.
Svetlana Vorotnikova, Darya Skuridina, Larisa Dzeranova,
It can mimic pituitary adenomas in radiological and endocrinological aspects.The
Ekaterina Pigarova & Zhanna Belaya
different patterns of anterior pituitary hormone deficiencies and diabetes insipidus
Endocrinology Research Centre, Moscow, Russia.
may be seen in the course of disease.
DOI: 10.1530/endoabs.49.EP1035
Introduction
Medical therapy with dopamine agonists is the best treatment for prolactinomas of
any size or invasiveness and restores ovulatory cycles in 80-90% of patients.
Cabergoline currently suggested nearly exclusively rather than other dopamine
agonists due to its excellent tolerability and long half-life. That is why the
question of safety using of this drug during pregnancy and embryo-fetal
development is actual.
EP1036
Aim
Comparative study of different methods for monomeric prolactin
The aim of the study is to assess the risk of pregnancy and fetal pathology in
determination in patients with hyperprolactinemia
patients with prolactin-secreting tumors treated with cabergoline at early stages of
Svetlana Vorotnikova, Larisa Dzeranova, Ekaterina Pigarova,
gestation.
Aleksandr Il’in, Nataliya Popova, Marina Vershinina, Olga Sukhanova,
Materials and methods
Nataliya Kadrina, Larisa Shibina & Ivan Dedov
The study included 24 patients from 24 to 38 years old with prolactin-secreting
Endocrinology Research Centre, Moscow, Russia.
tumors, who become pregnant during therapy with cabergoline
(Dostinex).
A retrospective analysis of the outcomes of 33 pregnancies based on available
medical records and questioning of the patients.
Introduction
Results
Prolactin exists in various forms including the monomeric biologically active
Of the 33 pregnancies 26 resulted in births (78.8%), in one patient a spontaneous
form (23 kDa) and a higher molecular weight form, bound most commonly to
miscarriage was registered at 7 weeks (3.0%), six women required medical
IgG, known as macroprolactin (O100 kDa). Macroprolactin lacks biological
abortions due to the non-developing pregnancy on terms from 4 to 7 weeks
activity but can interfere in standard prolactin immunoassays and is one of the
(18.2%). In
6% of cases (two pregnant) gestational diabetes mellitus was
causes of false-positive results. In Russian Federation the most common method
diagnosed. The average gestational age was 39.8 weeks (36-41 weeks). Preterm
for macroprolactin determination is PEG precipitation test.
delivery occurred in four women (15.3%). In total 27 children were born (in one
Aim
case - twins), 26 (96.3%) of them were healthy at the time of the birth. The growth
The aim of the study was an evaluation of the monomeric prolactin level
and development of the children did not differ from their peers in the general
measured by two methods: immunochemiluminescent (Cobas 6000) with manual
population.
PEG precipitation and immunofluorescent method (Brahms Cryptor).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Materials and methods
Objective
We had conducted a retrospective analysis of 41 samples of patients with
To evaluate the presence of glucose metabolism abnormalities and their impact on
hyperprolactinemia (3 of them were males). The mean age was 32G2.1 years.
IGF-1 levels in patients with acromegaly.
Prolactin was measured by the immune chemiluminescent
(after PEG
Methods
precipitation) and immunofluorescent methods.
Ninety-three acromegalic patients (52 male/41 female) were included in this
Results
study who were seperated into three groups as normal glucose tolerance (NGT),
The mean values found by immune chemiluminescent method with manual PEG
prediabetes and diabetes mellitus (DM). Insulin resistance (IR) was calculated
precipitation were 460.0 [334.0;807.2] mU/l, by immunofluorescent - 432,4
with homeostasis model assessment (HOMA). HOMA-IR O2.5 or %2.5 were
[338.8;700.0] mU/l. The number of patients with intrareference prolactin levels
defined as insulin resistant or noninsulin resistant groups, respectively. We
was 41% (17) for the first method and 48.8% (20) for the second one. At the same
compared the groups in terms of many factors that may be associated with glucose
time, six patients with equivocal results received by immune chemiluminescent
metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were
method and PEG precipitation had normal prolactin levels by immunofluorescent
used for impact of glucose metabolism abnormalities on IGF-1 levels.
method. The phenomenon of macroprolactinemia without elevated level of
Results
monomeric prolactin was registered in 24.4% (10) of patients. In one person of
Frequencies of NGT, prediabetes and DM were 25% (nZ23), 41% (nZ38) and
this group with clinical features of hyperprolactinemia, the increased hormone
34% (nZ32), respectively. Patients with DM were significantly older and with an
levels was revealed by Cryptor analyzer.
increased frequency of hypertension than NGT and prediabetes groups
Conclusion
(P!0.001, PZ0.01, respectively). IGF-1% ULN/GH ratio was significantly
Measurements of prolactin levels by the immunofluorescent method is useful for
lower in prediabetes group than in NGT group (PZ0.04). Similarly IGF-1%
correct diagnosis in patients with equivocal results received by immune
ULN/GH ratio was significantly lower in insulin resistant group than in
chemiluminescent method with PEG precipitation.
noninsulin resistant group (PZ0.04). Baseline and suppressed GH levels were
DOI: 10.1530/endoabs.49.EP1036
significantly higher in insulin resistant group than in noninsulin resistant group
(PZ0.024, P!0.001, respectively).
Conclusion
IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism
disorders and IGF-1 levels might be inappropriately lower in acromegalic patients
with IR or prediabetes. We suggest that IGF-1 levels should be re-evaluated after
the improvement of IR or glycemic regulation for the successful management of
EP1037
patients with acromegaly.
Pituitary Stalk Hemangioblastoma: a case report and review of the
DOI: 10.1530/endoabs.49.EP1038
literature
David Barbosa, Carolina Faria, Ana Sofia Osório, Ema Nobre &
Maria João Bugalho
Diabetes and Metabolism Department, CHLN - Hospital de Santa Maria,
Endocrinology, Lisbon, Portugal.
EP1039
Introduction
Monthly pasireotide provides clinical benefit over 12 months in patients
Hemangioblastomas (HBL) in the pituitary stalk are extremely rare. Most
with Cushing’s disease
pituitary stalk HBL reported in the literature were associated with von Hippel-
Rosario Pivonello1, Marcello Bronstein2, Jochen Schopohl3,
Lindau (VHL) disease.
Tuncay Delibasi4, Ariel Barkan5, Nori Suzaki6, Libuse Tauchmanova7,
Case report
Pritam Gupta8, Stefan Petersenn9 & André Lacroix10
We report the case of a 34-year-old female patient with VHL disease diagnosed at
1Università Federico II di Napoli, Naples, Italy;2University of São Paulo
the age of 18 with multiple complications (bilateral retinal and cerebellum HBL,
Medical School, Sa˜o Paulo, Brazil;3Medizinische Klinik IV, University of
renal cell carcinoma). Brain magnetic resonance imaging (MRI) demonstrated an
Munich, Munich, Germany;4Hacettepe University, Ankara, Turkey;
hypointense suprasellar mass measuring 9!8!9 mm with marked homogenous
5University of Michigan, Ann Arbor, MI, USA;6Nagoya Medical Center,
contrast enhancement after gadolinium administration, originating from the
National Hospital Organization, Nagoya, Japan;7Novartis Pharma AG,
pituitary stalk, suggesting a pituitary stalk HBL. The initial hormonal workup was
Basel, Switzerland;8Novartis Healthcare Pvt Ltd, Hyderabad, India;
normal. A visual field defect evaluation was not feasible due to severely low
bilateral visual acuity. During the 4-year follow-up, a slight increase in the mass
9ENDOC Center for Endocrine Tumors, Hamburg, Germany;10Centre
hospitalier de l’Université de Montréal, Montreal, Canada.
volume and prolactin level was observed; depending on the clinical, radiological
and laboratory evolution, a future surgical approach cannot be disregarded.
Review of the literature
Introduction
The previously reported cases of HBL in the pituitary stalk were analyzed.
A monthly, long-acting formulation of pasireotide normalized or reduced mean
Seventeen cases have been reported, the majority (fourteen) being associated with
urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a
VHL disease and the remaining considered to be sporadic. Ten patients had no
multicentre, double-blind, Phase III study. The effects of long-acting pasireotide
visual symptoms or hormonal dysfunction, and therefore were kept on
on signs and symptoms of CD are reported here.
observation. A total of six patients were operated. Of the six surgical cases,
Methods
four patients developed panhypopituitarism, and two patients had visual field
Patients with persistent/recurrent (nZ123) or de novo (non-surgical candidates;
disturbances preoperatively with partial recovery after surgery. None of the
nZ27) CD and mUFCR1.5-5xULN were randomized to monthly pasireotide
patients were treated with radiotherapy.
10 mg (nZ74) or 30 mg (nZ76). Dose could be up-titrated (10-30 mg/30-
Conclusion
40 mg) at month (M) 4 if mUFCO1.5xULN and/or at M7, M9, or M12 if
To our knowledge, this is the 18th case of HBL in the pituitary stalk. According to
mUFCO1.0xULN. Primary endpoint was mUFC%ULN at M7, regardless of
our review, pituitary stalk HBL often remain asymptomatic and do not require
dose titration. Signs/symptoms of CD were evaluated at regular intervals. All data
treatment. Surgery can be reserved until associated signs or symptoms occur.
shown are mean (95%CI).
DOI: 10.1530/endoabs.49.EP1037
Results
mUFC reduction was accompanied by substantial clinical improvements. Mean
changes (95%CI) in clinical signs to M12 in the 10mg and 30mg groups included:
weight, K3.4 kg (K4.8,K2.0) and K6.5 kg (K8.3,K4.7); BMI, K1.3 kg/m2
(K1.8,K0.8) and K2.6 kg/m2 (K3.3,K1.9); waist circumference, K4.5 cm
(K7.2,K1.8) and K6.2 cm
(K8.7,K3.6); health-related QoL score,
6.4
(1.3,11.6) and
7.0
(3.0,10.9). Clinically relevant decreases in systolic
EP1038
(K5.0 mmHg (K8.8,K1.3)) and diastolic (K3.1 mmHg (K5.7,K0.5)) BP
were reported in the
30 mg group; downward trends were also seen with
Impact of glucose metabolism disorders on IGF-1 levels in patients with
pasireotide
10 mg (systolic BP: K4.6 mmHg
(K9.9,0.7); diastolic BP:
acromegaly
K3.4 mmHg (K7.3,0.4)). A significant (P!0.0001) relationship was found
Sema Ciftci Dogansen, Gulsah Yenidunya Yalin, Seher Tanrikulu &
between change in mUFC and systolic/diastolic BP, after adjusting for
Sema Yarman
antihypertensive medication. Changes in other clinical parameters occurred
Division of Endocrinology and Metabolism, Department of Internal
irrespective of whether patients achieved mUFC%ULN at M7. The safety profile
Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul,
of long-acting pasireotide was similar to that of twice-daily pasireotide.
Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
patients complained of fatigue and lethargy; however five patients presented
Reductions in mUFC levels during 12 months’ long-acting pasireotide treatment
with hyponatraemia.
10 of the 19 patients had autoimmune illnesses;
were accompanied by improvements in clinical signs of CD. Long-acting
hypothyroidism was the most common autoimmune disease with eight
pasireotide is an effective treatment option for patients with CD, with a
patients suffering primary hypothyroidism. CRH stimulation testing was
convenient monthly administration schedule.
available in 6 of the 19 patients, five of these patients had a rise in ACTH
DOI: 10.1530/endoabs.49.EP1039
with CRH administration, indicating possible hypothalamic involvement.
Two patients had complete recovery of their HPA axis when repeat testing
was performed. IIAD is a rare, poorly defined disorder that typically presents
with insidious symptoms but can present with severe hyponatraemia. It is
associated with autoimmune diseases, in particular primary hypothyroidism.
Two patients in this case series had complete recovery of their HPA axis,
therefore repeat testing should be performed at intervals.
EP1040
DOI: 10.1530/endoabs.49.EP1041
Radiological study of clinically non-functioning pituitary
macroadenomas: a single institutional experience
Cristina Moreno, Miguel Paja, Aitzol Lizarraga, Eider Etxeberria,
Cristina Arrizabalaga, Estíbaliz Ugarte, Ana Izuzquiza, Fernando Go
˜i,
Natalia Iglesias & Laura Calles
Endocrinology Unit-Basurto University Hospital, Bilbao, Spain.
EP1042
Autonomic impairment in idiopathic diabetes insipidus
Introduction
Mattia Barbot1, Filippo Ceccato1, Marialuisa Zilio1, Nora Albiger1,
When facing with non-functioning pituitary macroadenomas
(NFPMA),
Marco Boscaro1, Franca Bilora2 & Carla Scaroni1
radiological invasion is determinant to surgical approach, apart from histological
1Endocrinology Unit, Department of Medicine, DIMED, Padova, Italy;
biomarkers of pituitary tumor aggressiveness (Ki-67; p53 and mitotic index).
2Vascular Medicine Unit, Department of Cardiovascular Sciences, Padova,
Invasive tumors usually need additional surgery and/or radiotherapy. There are no
Italy.
much studies describing epidemiological data on aggressive pituitary tumors in
clinical practice. We provide information regarding the radiological findings of
NFPMA in a single tertiary center during 17 years.
Introduction
Material and methods
Since DI was reported to be associated to increase mortality, the aim of this study
We evaluate retrospectively MR imaging of NFPMA diagnosed between 1999
is to evaluate the presence of autonomic dysfunction (AD) in patients with DI.
and 2016 in our Hospital. Evaluation includes infrasellar invasion, Knosp’s
Methods
classification in both cavernous sinus, measure in three dimensions, contact with
We enrolled 12 patients (six females) with central idiopathic DI and 12 controls,
quiasm, and intensity of signal in T2.
matched for age, sex and common cardiovascular risk factors, who were
Results
evaluated using the tilt, lying-to-standing, hand grip, deep breath, Valsalva
From 48 cases, we selected 41 with valuable presurgical MRI. 15 men and 26
maneuver and Stroop tests.
women, mean age 61 years (24-83). Infrasellar invasion ocurred in 19 (46.34%),
Results
Knosp III or IV in 21 of 82 cavernous sinus (25.6%). 3 patients (7.3%) presented
The tilt test showed a significant more pronounced decrease in both systolic
invasion of three areas. Mean craneocaudal diameter was 29.65 mm (8-52),
(K20.7G18 vs K1.92G7 mmHg, PZ0.0009) and diastolic blood pressure
transversal 21.5 mm (11-43) and anteroposterior 19.14 mm (11-51), with 80.5%
(K10.5G14.3 vs K1.5G5.5 mmHg, PZ0.02) in patients than in controls.
displacing optic quiasm. 22% were giant adenomas (O40 mm) and T2 secuences
Furthermore three patients with DI had to suspend the test because of the onset of
hiperintense, suggesting scarcely granulated tumour, was present in 19.5%.
syncope. The lying-to-standing test indicated a marked reduction in blood
Conclusions
pressure in patients with DI too (1.047G0.137 vs 1.533G0.144, PZ0.0001).
In our series, 56% of NFPMA had criteria of radiological invasión, infrasellar or
Similar results were find in Valsalva (ratio,
1.033G0.193 vs 1.431G0.109,
cavernous sinus invasion. This finding remarks the complex management of these
PZ0.00001) and deep breath tests (1.075G0.112 vs 1.33G0.083, PZ0.00002).
neoplasm and the need of a multimodal approach.
Discussion
DOI: 10.1530/endoabs.49.EP1040
All the principal autonomic tests performed were concordant, indicating that
patients with central DI have an impaired autonomic nervous system function
despite normal hydroelectrolytic balance under desmopressin therapy. This
impairment may reflect both a damage in the autonomic system and the absence
of the vasoactive effect of AVP on vascular smooth muscle which acts as a rescue
mechanism in case of rapid drop in blood pressure. Patients with central DI should
be educated on how to prevent orthostatic hypotension.
EP1041
DOI: 10.1530/endoabs.49.EP1042
Idiopathic isolated acquired ACTH deficiency- a case series from the
Irish National Pituitary Network
Anne marie Hannon1, Diarmuid Smith1, Mark Sherlock2, Steven Hunter3 &
Chris Thompson4
1Department of Endocrinology and Diabetes, Beaumont Hospital, Dublin 9,
Ireland;2Department of Endocrinology and Diabetes, Adelaide and Meath
Hospital, Tallaght, Dublin, Ireland;3Department of Endocrinology and
EP1043
Diabetes, Royal Victoria Hospital, Belfast, UK;4Department of Endo-
Salivary and serum cortisol levels by liquid chromatography tandem
crinology and Diabetes, Cork University Hospital, Cork, Ireland.
mass spectrometry after standard dose ACTH test in the diagnosis of
central hypopituitarism
Valentina Morelli1, Elisa Polledri2, Rosa Mercadante2, Beatrice Sonzogni1,
Giovanna Mantovani1, Serena Palmieri1, Elena Malchiodi1, Elisa Verrua1,
Idiopathic Isolated ATCH deficiency (IIAD) is a rare cause of secondary
Anna Maria Barbieri1, Emanuele Ferrante3, Maura Arosio1,
adrenal insufficiency characterised by ACTH deficiency with otherwise
Silvia Fustinoni2 & Iacopo Chiodini1
intact pituitary function. Our objective was to describe the presentation, the
1Unit of Endocrinology and Metabolic Disease, Fondazione IRCCS Cà
autoimmune associations and diagnostic findings observed in IIAD. We
Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;
present a case series of 19 cases of idiopathic Isolated ACTH deficiency
2Department of Clinical Sciences and Community Health, University of
which were identified from the National Pituitary Register in Ireland.
Milano, Milan, Italy;3Unit of Internal Medicine 1, ASST Santi Paolo e
A chart and biochemical review was performed to identify the presentation,
Carlo, San Carlo Borromeo Hospital, Milan, Italy.
clinical features, diagnostic criteria and associated diseases of people with
IIAD. All patients had normal pituitary MRI imaging, (one patient refused,
however he had a normal CT brain) and other causes for ACTH deficiency
Objective
such as medication or traumatic brain injury were excluded. 19 patients were
The diagnosis of central hypoadrenalism (HPAI) is a major clinical challenge.
identified as meeting criteria (15 women and 4 men). The age at presentation
The gold standard procedure remains insuline tolerance test
(ITT). Liquid
ranged from 21 to 88 years, with a median age of 52 years. The majority of
chromatography tandem mass spectrometry (LC-MS/MS) is considered the best
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
procedure for the evaluation of cortisol levels. This study aimed to evaluate cut-
use to diagnose eucortisolism and avoid unnecessary replacement HC treatment
offs of serum (TM-SeC) and salivary cortisol (SaC) by LC-MS/MS and serum
in this patients.
cortisol by ECLIA assay (E-SeC) after Standard dose ACTH test (SDCT) in
DOI: 10.1530/endoabs.49.EP1044
diagnosing HPAI.
Design
In this study we performed SDCT in 52 consecutive patients (F/M, 33/19, age
42.9G13 yrs) referred to our Center to evaluate at specific time points E-SeC,
TM-SeC and SaC. In the same group of patients we also evaluated E-SeC after
ITT, to diagnose HPAI (using a cut off!500 nmol/l).
Results
HPAI was diagnosed in 8 out of 52 patients (five patients operated on for a
pituitary macroadenoma, and
3 with a pituitary microadenoma). Using the
EP1045
diagnosis of HPAI made by ITT as reference test, we found that after SDCT an
Nivolumab and pembrolizumab induced hypophysitis
E-SeCO348 nmol/l at 0-min, O671 nmol/l at 30-min or O756 nmol/l at 60-min
Marleen Vosjan-Noeverman, Rob van den Brom, Geke Hospers,
excluded HPAI, whereas an E-SeC !155 nmol/l at 0-min, !436 nmol/l at
Jeroen Hiltermann & Gerrit van den Berg
30-min or !527 nmol/l at 60-min confirmed HPAI. By using LC-MS/MS we
University Medical Center Groningen, Groningen, The Netherlands.
found that after SDCT a TM-SeC O378 nmol/l at 0-min, O1012 nmol/l at
30-min or O1021 nmol/l at
60-min excluded HPAI, whereas a TM-SeC
Introduction
!149 nmol/l at 0-min, !334 nmol/l at 30-min or !351 nmol/l at 60-min
Immune checkpoint blockade in cancer treatment causes frequent adverse events
confirmed HPAI. Similarly by LC-MS/MS we found that after SDCT a SaC
of auto-immune etiology. Ipilimumab
(anti-CTLA-4
antibody) causes a
O7.4 nmol/l at 0-min, O15.8 nmol/l at 30-min or O23.3 nmol/l at 60 min
hypophysitis in up to
10% of patients. In contrast, during treatment with
excluded HPAI, whereas a SaC!1.7 nmol/l at 0-min, ! 4.7;nmol/l at 30-min or
nivolumab and pembrolizumab (both anti-PD-1 antibodies), hypophysitis is rare
!7.3 nmol/l at 60-min confirmed HPAI.
(!1%).
Conclusions
Results
We can conclude that even evaluating TM-SeC and SaC, after SDCT there is
In the past year, we identified 4 cases of hypophysitis in patients treated with anti-
large gray area of indeterminate results.
PD-1 therapy (incidence 1% out of a total group of 395 patients). Two patients
DOI: 10.1530/endoabs.49.EP1043
(male aged 78, female aged 58) were treated with nivolumab for non-small cell
lung cancer and
2
patients
(male aged
61, female aged
69) received
pembrolizumab for metastatic melanoma. After 8-12 cycli, all patients developed
fatique, two patients developed edema and 1 patient developed nausea and a
blurry vision. There was no period of transient headache as typically found in
hypophysitis caused by ipilimumab. Laboratory examination revealed the
diagnosis. Brain magnetic resonance imaging showed a normal pituitary gland
in all patients. At diagnosis, pituitary failure was present for the thyroid and
adrenal axis in 2 and 3 patients, respectively. One patient developed failure of the
pituitary-gonadal axis.
EP1044
Discussion
Risk and diagnosis of hypocortisolism after transsphenoidal surgery for
In contrast to hypophysitis after ipilimumab treatment, anti-PD-1
induced
sellar tumors
hypophysitis seems characterized by an insidious clinical course, without typical
Milagros Sierra1, David Males1, Laura Perez-Olivares1, Ana Maria Casta
˜ o-
symptoms or associated MRI abnormalities. In contrast, the pattern of endocrine
León2, Jose Fernández2, Igor Paredes2, Alicia Serraclara1 &
failure of the adrenal axis is immediately life threatening. Given the sharp
Maria Calatayud1
increase in the number of patients treated with immune checkpoint inhibitors,
112 de Octubre University Hospital Endocrinology and Nutrition
more patients with this rare side effect are expected. Therefore, it is necessary to
Department, Madrid, Spain;212 de Octubre University Hospital Neurosur-
screen for central hypocortisolism and hypothyroidism and be aware of the
gery Department, Madrid, Spain.
possibility of a varied clinical presentation.
DOI: 10.1530/endoabs.49.EP1045
Introduction
Transsphenoidal surgery (TS) is used for pituitary and suprasellar tumors. It has a
risk of damaging the pituitary axis and developing hypocortisolism, a potential
life threating risk.
Objetive
Incidence of hypocortisolism after TS, postsurgery cortisol (PSC) levels that
EP1046
predict hypocortisolism and potential risk factors for hypocortisolism after TS.
Heterogeneity of the patient pathway for adult growth hormone
Methods
deficiency: Perspectives from a CEE Endocrinologists expert panel
Prospective study in patients who underwent TS in
2016. Glucocorticoid
Ilan Shimon9, Corin Badiu1, Artur Bossowski2, Mirjana Doknic3,
replacement (GR) began in surgery with hydrocortisone (HC) 100 mg tid. We
Iveta Dzivite-Krisane4, Václav Hána5, Jana Kollerova6, Emil Natchev
defined hypocortisolism as PSC!10 mcg/dl (discharged with HC 20 mg/day),
Natchev7, Marija Pfeifer8, Nikolette Sz
˜cs10, Juliana Hey-Hadavi11 &
possible hypocortisolism as PSC 10-20 mg/dl (discharged with HC 10 mg/day)
Roy Gomez12
and eucortisolism as PSC O20 mcg/dl 3 days after TS. Definitive eucortisolism
1University of Medicine and Pharmacy, Bucharest, Romania;2Klinika
was defined as Cortisol O18 mcg/dl after 100 mcg ACTH stimulation or basal
Pediatrii,, Endokrynologii, Diabetologii z Pododdzialem Kardiologii,
cortisol O20 mcg/dl 5 weeks after TS.
Poland;3Klinicki Centar Srbije, Beograd, Serbia;4Bernu kliniska
Results
universitates slimnica, Riga, Latvia;5Charles University, Prague, Czech
Twenty-three (12 females) patients underwent TS, mean age 52 years (22-85):
Republic;6Univerzitna Nemocnica Bratislava, Bratislava, Slovakia;
56%nonfunctioning adenomas,
20%GH adenomas, 4%arachnoid cyst and
7Clinical Center of Endocrinology and Gerontology, Medical University,
8%craniopharyngioma. Preoperative features: tumor’s mean diameter: 25 mm
Sofia, Bulgaria;8University Medical Centre, Ljubljana, Slovenia;9Rabin
(5-65), involvement of cavernous sinuses (KNOSP gradeR2) 60%. Five patients
Medical Center, Petah Tiqva, Israel;10Semmelweis University, Budapest,
present preoperative hypocortisolism. Pituitary-adrenal axis (PAA) assessment:
Hungary;11Pfizer, New York City, USA;12Pfizer Innovative Health,
After TS 9 patients were diagnosed of hypocortisolism, 13 of possible hypoC and
Brussels, Belgium.
1
of eucortisolism. Five week after TS:
8
were diagnosis of definitive
hypocortisolism and 15 of definitive eucortisolism. Mean PSC was 13.5 mcg/dl
(2.28-22.5) in definitive eucortisolism patients and 8.75 mcg/dl (1.2-14.35) in
Introduction
definitive hypocortisolism. 75% with definitive hypocortisolism patients had PSC
Effective identification, diagnosis and management of growth hormone (GH)
!12 mcg/dl. In patients with definitive hypocortisolism:
60% presented
deficiency in adults are crucial for treating endocrinologists to provide the best in
preoperative hypocortisolism,
30% preoperatory GH deficit, 60% cavernous
patient care. As such, it is important that we share our experiences to understand
sinuses involvement, with KNOSP grade O2 and 50% were O30 mm.
challenges and obstacles to enhance the patient journey. The objective of this
Conclusions
project was to start identifying these challenges and obstacles.
Hypocortisolism after TS is a mayor complication; large and invasive tumors
Methods and findings
have more risk to develop postsurgery pituitary hypofunction. Three days PSC
In November 2016, an expert panel of 10 endocrinologists from across 10 Central
can predict development of definitive hypocortisolism, PSC R15 mcg/dl may be
and Eastern European (CEE) countries met to discuss their standard of care and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
journey taken by adult GH-deficient
(AGHD) patients in their respective
24 h, and a MRI scan, in order to objectivate the diagnosis. Initial cooperation was
countries. Prior to the meeting the experts were asked to summarize in a
present. The anamnesis revealed diabetes insipidus diagnosed at age 30, treated
systematic way, the standard of care available for AGHD patients in their
with desmopressin spray 10 mcg two times a day, in the morning, and diabetes
countries and share this with their peers. The meeting was chaired by one of the
mellitus type II from age 60, treated with 4 shots of fast insulin, 42 U/day. Clinical
experts and each participant had adequate time to present their perspective
examination revealed signs of mild dehydration. Lab tests highlighted mild
followed by discussion. It was uncovered that there was a substantial degree of
hyperglycemia of
142 mg/dl and hyponatremia of
129 mol/l. Glycated
diversity in the management AGHD patient pathway across CEE. The main
haemoglobin was 7.3%. Plasmatic osmolarity was 272.3 mOsm. The patient
variations included: initial entry to the healthcare system and referral journey;
was uncooperative to stoping or changing the schedule of desmopressin treatment,
tests required to confirm diagnosis; availability of programmes to manage patients
so she was discharged with natremia of 139 mmol/l. Recent medical history
during transition to adulthood; limitations of who prescribes GH therapy,
showed a recent emergency admission with similar clinical and biochemical
medication re-imbursement by national healthcare services and, the frequency of
futures. Moreover, it was proved that the patient had many ER admissions in
follow-up visits and monitoring of patients. Although most countries represented
Bucharest’s hospitals, with same situation. In this respect, the diagnosis of diabetes
relied on international society-led, published guidelines, few countries have
insipidus itself can be put under question, complicated by the psihogenic adherence
developed national guidelines for patient management.
to desmopressin treatment of the patient. Frequent clinical manifestations of
Conclusion
hyponatremia due tu desmopressin abuse in our patient is highlighting not only the
This expert panel recognizes a high degree of diversity in the patient pathway
complexity of psihogenic association to organic abuse, but also the need for
across CEE. Sharing of local experiences with other colleagues may help in
cooperation between practitioners across EU.
understanding areas of high heterogeneity as well as facilitating the sharing of
DOI: 10.1530/endoabs.49.EP1048
best practice. Further work will be needed to identify differences in practice
patterns and AGHD patient management among other regions in the world.
DOI: 10.1530/endoabs.49.EP1046
EP1047
EP1049
Considerable delays to achieve adequate control in treating patients
Aggressive pituitary tumours: a multicenter study
with acromegaly
Ana Palha1, Leonor Gomes2, João Sequeira Duarte3, Concei
¸a˜o Marques3,
Marinella Tzanela, Olga Karapanou, Christianna Giatra, Efstathia Botoula,
Cláudia Amaral4, Ana Amado4, Fátima Borges4, Isabel Ribeiro4,
Elisabeth Tiaka, Lambraki Anastasia & Stylianos Tsagarakis
Eduardo Barreiros5, Luis Barreiros5, José Miguéns5, Maria João Bugalho5,
Department of Endocrinology and Diabetes, Evangelismos Hospital,
Adriana Lages2, Isabel Paiva2, Olinda Marques6, Rui Almeida6,
Athens, Greece.
Teresa Martins7, Luisa Cortez1, Ana Agapito1 & Fernando Fonseca1
1Centro Hospitalar Lisboa Central, Lisbon, Portugal;2Centro Hospitalar
Universitário Coimbra, Coimbra, Portugal;3Centro Hospitalar Lisboa
Ocidental, Lisbon, Portugal;4Centro Hospitalar Porto, Oporto, Portugal;
Acromegaly is a rare disease that leads to considerable morbidity and
5Centro Hospitalar Lisboa Norte, Lisbon, Portugal;6Hospital de Braga,
mortality, both reversible by adequate control of the disease. However,
Braga, Portugal;7Instituto Português de Oncologia de Coimbra, Coimbra,
patients that could be adequately controlled confront delays in achieving
Portugal.
treatment targets. The aim of the present study was to estimate the time to
disease control after diagnosis and the reason leading to control delays.
We retrospectively studied 119 acromegalic patients (aged 46.4G12.5; 71
Introduction
females). Following appropriate treatment modalities all achieved IGF-1
Pituitary tumours are considered benign, however some exhibit an aggressive
levels within normal limits for age (43 pts had GH !1.0 ng/ml, and 76 pts
behavior. Defining a timely treatment is challenging due to absence of accurate
had GH !2.5 ng/ml). Acromegaly was adequately controlled within 0-6
prognostic predictors.
months in 19 patients (15.9%), within 6-12 in 14 (11.8%), and within 12-24
Objective
in 21 (17.6%). In 65 patients (54.6%) disease control was achieved after 24
To evaluate radiological and histopathological features of aggressive pituitary
months (25-412, median 103 months). Earlier controlled patients were older
tumours.
(50G11.9 vs 43.5G12.3, PZ0.00434), and underwent surgery sooner after
Methods
the diagnosis (8.0G6.8 vs 19.8G30.9 months PZ0.0324). When under
Multicenter and retrospective study. Criteria for aggressiveness were: invasion to
medical treatment, the main reasons for delay control were the late referral
sphenoid and/or cavernous sinus; growth progression after treatment (surger-
and initiation of medical therapy
(5.4G5.0
vs
124.6G117.1 months,
y/medical/radiotherapy); early recurrence (%12 months). Atypical features were
PZ0.0138), and the time elapsed to modify dosage and/or implementing
Ki-67O3%, p53 positivity, mitoses O2/10xHPF or brain/spinal/systemic
alternative treatment options (4.4G3.7 vs 16.1G11.1 months, PZ0.0138).
metastases.
Tumor size or extension, GH and IGF-1 had no impact to time to control.
Results
According to our audit a substantial proportion of patients remain
Forty-five patients
(28
men) were collected from seven tertiary endocrine
uncontrolled for several months despite the efficacy of available therapeutic
departments. Age at diagnosis was 41.2G12.2 years. In 35.6% of patients first
modalities in these patients. The main reason seems to be the delay to cease
symptoms occurred before 35 years. Symptoms related to tumour expansion,
early surgical intervention or to adjust the medical treatment options.
hypersecretion and deficiency of hormones were the first manifestations in 73.6,
DOI: 10.1530/endoabs.49.EP1047
13.2 and 13.2% of patients, respectively. Our cohort comprised nonfunctioning
adenomas (64.4%), somatotropinomas (9.0%), corticotropinoma (13.3%) and
prolactinomas (13.3%). All were macroadenomas and 82.2% showed radiological
signs of invasion. Of the 44 operated patients, 56.8% required three or more
surgeries. Complementary radiotherapy was used in 66.7% of patients, medical
therapy in 42.2% of patients, two of these with temozolomide. Histopathology
EP1048
was obtained in 42 patients. Imunohistochemichal staining was GH positive in
Hyponatremia - the other face of diabetes insipidus complications
9.5%; PRL 14.3%; ACTH 11.9%, TSH 2.4%, FSH/LH 19%; plurihormonal
Madalina Bucur & Carmen Barbu
14.3%; nonsecreting and null-cell 28.6%. Elevated mitotic index was observed in
Elias University Emergency Hospital, Bucharest, Romania.
20% (nZ25), Ki-67 labeling index S3% in 44.4% (nZ27) and p 53 nuclear
staining in
41.2% (nZ17). During a mean follow-up of 11.5G6.3 years,
8 patients died (5 ACTH-cell adenoma) one with extracranial systemic metastases
(carcinoma).
Diabetes insipidus is mainly associated with dehydration as a complication,
Conclusions
hyponatremia being very rare. We report the case of a 75 years old female,
In our cohort ACTH-secreting tumours presented a more aggressive clinical
from Switzerland, who presented with nausea and vomit, diarrhea, asthenia
course. One limitation of our study was incomplete histopathological data,
and general sickness at the emergency room, where blood tests revealed
however, the majority of patients who died, presented atypical features.
hyperglycemia of 320 mg/dl and hyponatremia of 115 mmol/l, the patient
A continuous multicenter collaboration could help to identify prognostic markers
knowing to have diabetes insipidus and diabetes mellitus type II, with
and enable a different approach.
insulin and desmopressin. Following emergency equilibration, we rec-
ommended monitoring water intake, urine excretion in the absence of
DOI: 10.1530/endoabs.49.EP1049
desmopressin, with control of glycemic profile every 4 hours, for the next
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1050
Methods
All women of this group diagnosed between 1996 and 2016 and followed-up in a
Effects of somatostatin analogs on glucose metabolism in acromegalic
large specialist centre were included in the study.
patients: a meta-analysis of prospective interventional studies
Results
Tiziana Feola1, Alessia Cozzolino1, Ilaria Simonelli2, Emilia Sbardella1,
We identified 17 women with diagnosis of prolactinoma after menopause (median
Giulia Puliani1, Elisa Giannetta1, Patrizio Pasqualetti2, Andrea Lenzi1 &
age at diagnosis 62 years, range 52-70). Headaches and/or visual deterioration
Andrea M Isidori1
were the most commonly reported presenting signs (47%). Acute pituitary
1Department of Experimental Medicine - Sapienza University of Rome,
apoplexy was diagnosed at presentation or during follow-up in
18%. Two
Rome, Italy;2Department of Neuroscience- Fatebenefratelli Hospital-Isola
prolactinomas were detected incidentally (12%). The median serum prolactin was
Tiberina-Rome, Rome, Italy.
18 553 mU/L (range 4153-238479). In all cases, IGF-I values were not consistent
with GH hypersecretion. Macroprolactinomas comprised 94% of the tumors and
Introduction
88% of them had parasellar extension. All patients with macroprolactinoma were
Glucose metabolism impairment is a common complication of acromegaly.
offered dopamine agonist therapy; the median duration of their follow-up,
Somatostatin analogs (SSAs) are used as both first and second line treatment. The
determined by the date of starting dopamine agonist until last serum prolactin
effect of SSAs on glucose metabolism in acromegaly is still debated.
measurement, was 91 (5-186) months. Normal prolactin was achieved in 94%
Aim
and adenoma shrinkage was observed in all women. Improvement or resolution of
To address the following questions: 1) do SSAs affect glucose metabolism?
the visual disturbances documented at presentation was observed in 86% of cases.
2) does the effect correlate with disease control? 3) do different SSAs - Lanreotide
Conclusions
(LAN) and octreotide LAR (OCT) - affect metabolism differently?
The clinical phenotype of prolactinomas diagnosed after menopause differs from
Methods
that of premenopausal women, possibly due to the lack of clinical signs and
We performed a meta-analysis of prospective interventional studies reporting the
symptoms of hyperprolactinemia in non-menstruating patients. Most tumours
use of SSAs for the treatment of acromegaly. We searched MEDLINE, EMBASE,
were macroadenomas, with frequent parasellar extension and a relative high rate
and SCOPUS for English-language studies. Inclusion criteria: minimum 6-month
of pituitary apoplexy. In this very rare group of tumours, response to dopamine
follow-up, glyco-metabolic outcomes before and after SSA treatment. The pooled
agonists is good.
estimate of a weighted mean was obtained for all outcomes using a random effects
DOI: 10.1530/endoabs.49.EP1051
model.
Results
Forty-one studies have been included, 20 for LAN (354 patients) and 21 for OCT
(569 patients). LAN treatment induced a significant decrease in fasting plasma
insulin (FPI) (effect size K8.32, 95% CI: K10.44 to K6.20; P!0.001) and
HOMAi (K2.11, 95% CI: K3.54 to K0.69; PZ0.004), without changes of
fasting plasma glucose (FPG), HbA1c, triglyceridemia, weight and BMI. OCT
induced a small increase in HbA1c (C0.146, 95% CI: 0.043-0.249; PZ0.005), a
borderline rise of glucose during OGTT (0.47, 95% CI: K0.01 to 0.95; PZ0.053)
and significant decrease in FPI (K6.78, 95% CI:K9.37 to K4.18; P!0.001),
triglyceridemia (K0.41, 95% CI K0.55 to K0.28; P!0.001), HOMAi (K1.44,
EP1052
95% CI:K2.54 to K0.34; PZ0.010) and HOMAb (K36.65, 95% CI:K63.21 to
Ipilimumab induced hypophysitis - an insight from a case series in the
K10.08; PZ0.007), without any change of FPG. Meta-regression analysis
United Kingdom
revealed an association between the degree of GH reduction and lowering of
Punith Kempegowda1, Lauren Quinn2, Anitha Vijayan Melapatte1,
HbA1c (PZ0.03). Meta-regression also showed a worse post-therapy Hb1Ac
Ankit Jain1, Neil Steven1, Helena Gleeson1 & Andrew Toogood1
outcome with increasing pre-therapy IGF1 levels (PZ0.002). The percentage of
1Queen Elizabeth Hospital Birmingham, Birmingham, West Midlands, UK;
patients at target for GH and baseline IGF1 explained up to 58% of variance of
2University of Birmingham Medical School, Birmingham, West Midlands,
HbA1c.
UK.
Conclusions
LAN and OCT induce a significant decrease in FPI and in HOMAi, without
adverse change in FPG. OCT seems to reduce HOMAb and increase HbA1c,
Aims
while reducing trygliceridemia. IGF1 and GH-response partially explain the
To assess the incidence of Ipilimumab associated hypophysitis and its common
metabolic effect of SSAs.
presentations.
Methods
DOI: 10.1530/endoabs.49.EP1050
All patients who developed Ipilimumab induced hypophysitis following
treatment for Malignant melanoma at a large tertiary care centre in West
Midlands, United Kingdom from 2012 to 2014 were included in the study.
Patients with known pituitary disease prior to treatment and/or received other
systemic immunotherapy following Ipilimumab treatment were excluded. All
surviving patients were followed up to December 2016. Relevant data - clinical
features, hormone profiles and radiological findings
- were extracted from
patients’ medical records.
Results
Overall,
59 patients were treated with Ipilimumab for malignant melanoma
EP1051
during the period of interest. The incidence of hypophysitis in the cohort was
Prolactinomas diagnosed after menopause: presentation and outcomes
15.3% (9/59). The median age for patients with hypophysitis was 64 years (IQR,
from a large specialist centre
60-68 years); 44.4% (4/9) were male. 66.7% (6/9) presented with mild to
Sandhya Santharam1,2, Metaxia Tampourlou1,2, Wiebke Arlt1,2,
moderate symptoms and 33.3% (3/9) patients developed severe symptoms
John Ayuk2, Neil Gittoes1,2, Andrew Toogood2, Rachel Webster3 &
secondary to Ipilimumab induced hypophysitis resulting in hospitalisation.
Niki Karavitaki1,2
Fatigue (7/9; 77.8%) was the most common presenting symptom; headache and
1Institute of Metabolism and Systems Research,College of Medical and
visual disturbance was reported by 33.3% (3/9) and 22.2% (2/9) respectively.
Dental Sciences University of Birmingham, Birmingham, UK,2Centre for
Secondary hypogonadism (5/9; 55.6%) and secondary hypoadrenalism (4/9;
Endocrinology, Diabetes and Metabolism, Birmingham Health Partners,
44.4%) were the most commonly affected pituitary systems. One patient
Birmingham, UK,3Department of Clinical Biochemistry, Queen Elizabeth
developed panhypopituitarism. 33.3% (2/6) patients developed diffuse enlarge-
Hospital Birmingham, Birmingham, UK.
ment of pituitary gland. All patients had clinical recovery following adequate
hormone replacement.
Conclusions
Introduction
Disturbances in pituitary axis are common with Ipilimumab treatment and can
Most prolactinomas in females are diagnosed during the years of reproductive age
present with subtle symptoms. Therefore, regular assessment of pituitary function
and the majority are microadenomas. Prolactinomas diagnosed after menopause
during Ipilimumab treatment is recommended. Affected patients should be
are very rare with limited published data on their presentation and outcomes.
managed jointly by oncology and endocrinology teams to prevent serious
Aim
complications and allow Ipilimumab treatment to continue.
The aim of our study was to assess the presenting clinical, biochemical and
DOI: 10.1530/endoabs.49.EP1052
imaging findings, as well as the outcomes of women diagnosed with a
prolactinoma in the post-menopausal period.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1053
R2 analysis fibrinogen itself accounted for
10% of the variance. Moreover,
T1-weighted coronal scans were inversely correlated with VES (PZ0.01).
Mammary duct ectasia due to prolactin-secreting pituitary adenoma
Conclusions
I¸ılay Kalan Sarı, Suheyla Gorar & Oykun Kola
˘ası
This study describes a reduction of pituitary volume and quantitative T1-weighted
Antalya Research and Training Hospital, Antalya, Turkey.
intensity in obese patients, that seems related to a low-grade inflammation. Data
could be explained by a relative change in pituitary stromal tissue in this cohort of
Introduction
patients.
Mammary duct ectasia (MDE) is an inflammatory breast disease characterised by
DOI: 10.1530/endoabs.49.EP1054
dilation of major ducts and periductal inflammation. MDE occurs commonly in
women undergoing menopause. The etiology has not been well defined but
previous studies described an association between high prolactin and MDE.
Case Report
A 42-year-old female was admitted to our hospital with complaints of
galactorrhea, amenorrhea, mammary gland tenderness and breast discomfort.
Tests revealed serum prolactin level of 85 ng/ml and breast ultrasound showed
EP1055
dilated anechoic ducts and marked cystic ectasia. A 15!12 mm complex cystic
Hypogonadotropic hypogonadism in a patient with long-term primary
lesion in right breast and several enlarged lymph nodes were found in right
hypothyroidism
axillae. Mammography revealed thickened breast tissue with diffuse MDE
Raquel Vaz de Castro1, José Maria Aragués2, Florbela Ferreira1,
without any calcification. Pituitary MRI showed 5.5!5.0!2.5 mm pituitary
Vânia Gomes1, Ana Wessling1 & Maria Joa˜o Bugalho1
adenoma. Treatment with cabergoline 0.5 mg twice a week, warm compress and
1Santa Maria Hospital, Lisbon, Portugal;2Beatriz Ângelo Hospital, Lisbon,
antibiotic started. Cabergolin dose is progressively increased to 2 mg per week.
Portugal.
Prolactin level reached to 20 ng/ml and tumor size reduced to 3!3!1.5 mm in
6 months. Although treatment with cabergoline, resulted in improvement of breast
symptoms and galactorrhea, diffuse MDE was reported in repeat ultrasound.
Abstract
Cabergoline dose is increased and the patient is still being followed up.
We report the case of a 65-year-old man who presented with erectile dysfunction
Discussion
to an appointment in our Endocrinology department. He referred fatigue, weight
In the present case, we hypothesize that there was an association between
gain and constipation as secondary complaints that had been steadily evolving
abnormal prolactin secretion and development of MDE. Shousha et al. discribed
throughout the past 4 years. He denied other symptoms such as visual impairment
three cases with marked MDE and chromophobe adenomas. Peters et al.
or headaches as well as the consumption of any medications or drugs. His past
concluded that MDE is due in part to increased prolactin secretion. They also
medical history was unremarkable. On examination, BMI was 25.8 kg/m2, arterial
concluded that MDE may cause transient hyperprolactinemia. MDE induced by
blood pressure 112/64 mmHg, heart rate 71 BPM and temperature 36.4 8C. Neck
sulpiride-associated hyperprolactinemia was also discussed in literature. In our
palpation revealed a diffuse thyroid enlargement. Visual acuity and visual fields
case; diffuse MDE may have been developed as a result of changes in prolactin
were unaltered. Blood tests revealed elevated TSH (69.8 uU/ml) with low FT4
levels. We conclude that increased prolactin secretion leading to chronic
(0.18 ng/dl), consistent with the diagnosis of primary hypothyroidism, and
inflammation and fibrosis may cause to persistence of ductal dilatation.
hypogonadotropic hypogonadism (testosterone
74.3 ng/dl). PRL levels were
DOI: 10.1530/endoabs.49.EP1053
slightly elevated (38 ng/ml). Magnetic resonance imaging (MRI) of the pituitary
showed a 17!14!12 mm sellar mass, without compression of the pituitary stalk
or optic chiasm. The patient was started on levothyroxine 100 mcg per day. Three
months later, the erectile dysfunction had resolved and thyroid function and total
testosterone had returned to normal - TSH 0.90 uU/ml, FT4 1.16 ng/dl, and total
testosterone 522.8 ng/dl. The control MRI taken one year after starting therapy
revealed regression of the pituitary enlargement. This is a peculiar case of HH
EP1054
likely associated with pituitary hyperplasia, in the context of long standing
primary hypothyroidism, successfully treated with levothyroxine.
Quantitative analysis of the pituitary gland at magnetic resonance
imaging in obese patients
DOI: 10.1530/endoabs.49.EP1055
Giulia Puliani1, Carla Lubrano1, Marco Fiorelli2, Emilia Sbardella1,
Chiara Graziadio1, Daniele Gianfrilli1, Andrea Lenzi1 & Andrea M Isidori1
1Department of Experimental Medicine - Sapienza University of Rome,
Rome, Italy;2Department of Neurology and Psychiatry - Sapienza
University of Rome, Rome, Italy.
Background
Hypothalamic-pituitary function and adipose tissue are deeply interconnected.
EP1056
Obesity has been linked to morpho-functional changes in several endocrine
Effects of pasireotide treatment on cardio-metabolic risk in patients
glands (thyroid, adrenal, gonads). No study has quantified the appearance of the
with Cushing’s disease: an Italian, multicenter study
pituitary gland in obese subjects.
Adriana Albani1, Francesco Ferrau1, Erika Messina1, Rosario Pivonello2,
Aim
Carla Scaroni3, Carla Giordano4, Alessia Cozzolino2, Marialuisa Zilio3,
To measure pituitary signal intensity, homogeneity and texture of the pituitary
Valentina Guarnotta4, Alessandro Ciresi4, Davide Iacuaniello2,
gland at magnetic resonance (MR) in obese subjects free of focal pituitary disease.
Angela Alibrandi5, Annamaria Colao2 & Salvatore Cannavo6
Materials and Methods
1Department of Clinical and Experimental Medicine, University of Messina,
Sixty-four overweight and obese patients were prospectively enrolled and
Messina, Italy;2Department of Clinical Medicine and Surgery, Endo-
underwent metabolic, hormonal, body composition (DEXA scan) and pituitary
crinology Unit, University of Naples Federico II, Naples, Italy;3Department
MR assessment. Texture of the pituitary gland was quantified recording pixel
of Medicine (DIMED), Division of Endocrinology, University of Padua,
density and distribution at sagittal and coronal non-enhanced T1-weighted images
Padua, Italy;4Biomedical Department of Internal and Specialist Medicine
using ImageJ software. Two operators independently placed the region of interest
(DIBIMIS), Section of Cardio-Respiratory and Endocrine-Metabolic
to entirely cover the pituitary gland, calculating mean intensity and its standard
Diseases, University of Palermo, Palermo, Italy;5Department of Econ-
deviation. All analyses were normalized for both white and gray brain matter
omics, University of Messina, Messina, Italy;6Department of Human
intensity. Pituitary volume (PV) was calculated using the ellipsoid formula.
Pathology of Adulthood and Childhood, University of Messina, Messina,
Results
Italy.
MR showed an empty sella in 12/64 (18.7%) patients. Mean PV was 384G
147 mm3 (427G120 mm3, excluding the empty sella). An inverse correlation was
found between PV and ultrasensitive C-reactive-protein
(PZ0.004) and a
borderline association between PV and BMI (PZ0.056). Pituitary intensity in T1-
Patients with Cushing’s disease (CD) have increased cardiovascular risk due to
weighted images was negatively correlated with BMI (PZ0.03) and truncal fat
metabolic alterations caused by glucocorticoids excess. Pasireotide, a multi-
(PZ0.04). Linear regression analysis revealed that, after adjusting for age and
receptor-targeted somatostatin analogue, is a therapeutic option in CD patients in
sex, the percentage of truncal fat and fibrinogen were significant predictors of the
whom surgery is not curative or not feasible. Pasireotide has been shown to be
mean intensity of coronal and sagittal T1-weighted scans (PZ0.001). The model
effective in controlling hypercortisolism and to improve metabolic features.
explained up to 29% of variance of pituitary signal intensity, and in a step-wise
Recently, the visceral adiposity index (VAI) has been proposed as a marker of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
visceral adipose tissue dysfunction (ATD) and of the related cardio-metabolic
1Department of Endocrinology, Diabetes and Metabolism of Centro
risk. We aimed to assess the effects of 12-month pasireotide therapy on cardio-
Hospitalar de São João, Porto, Portugal;2Faculty of Medicine, University of
metabolic and cardiovascular risk in CD patients. In 16 CD patients (11 females),
Porto, Porto, Portugal;3Department of Pediatric Endocrinology, Hospital
referred to the Endocrine Units of four Italian University Hospitals, we assessed
Pediátrico Integrado, Centro Hospitalar de São João, Porto, Portugal;
anthropometric, clinical and biochemical parameters and calculated VAI, ATD
4Department of Pediatrics, Centro Hospitalar de Entre o Douro e Vouga,
severity, Framingham and Atherosclerotic CardioVascular Disease Risk Scores
Santa Maria da Feira, Portugal.
(FRS and ASCVD respectively), at baseline and after 6 and 12 months of therapy
with pasireotide
(1200-1800 mcg/daily). Before starting pasireotide therapy,
ATD was present in 8/16 patients (severe in 2/16, mild in 2/16, moderate in 3/16).
Introduction
After 12 months of treatment: i) UFC levels (PZ0.003), BMI (P!0.001), waist
During childhood and puberty, growth hormone(GH) is essential for linear
growth. Consequently, children with isolated GH deficiency(GHD) must receive
circumference
(PZ0.001), LDL-cholesterol
(PZ0.033), total-cholesterol
replacement therapy. GH has also important metabolic actions. GHD in adults is
(PZ0.032), triglycerides
(PZ0.03), VAI
(PZ0.015) and ATD severity
associated with altered body composition. However, long-term consequences of
(PZ0.026) were significantly decreased as compared to baseline; ii) ATD was
GH treatment in adults is not sufficiently known.
present in only 1/16 patients; iii) prevalence of diabetes (PZ0.015) and HbA1c
Objective
levels (PZ0.001) were significantly increased as compared to baseline; iv) FRS
To evaluate GH treatment during pediatric age in patients with isolated GHD.
and ASCVD scores were not statistically different from pre-treatment values. In
Methods
conclusion, twelve-month pasireotide treatment reduces cardio-metabolic risk in
Retrospective study of patients with isolated GHD followed in a tertiary hospital,
CD patients.
which had undergone reassessment after finishing growth period. Anthropometric
DOI: 10.1530/endoabs.49.EP1056
and analytical parameters before and after treatment were collected. SDS of
anthropometric variables were calculated according WHO curves. IGF1
(Immulite 2000w) was analyzed considering SDS values adjusted for pubertal
stage.
Results
Sample composed by 27 patients, 63% males. Before treatment: mean age was
10.5G3.7 years, mean height-SDS K2.82G0.77, IGF1-SDS levels K2.41G
EP1057
1.59 ng/ml with a mean difference of 2G1.5 years between chronological and
DHEA-S as a marker of the secondary adrenal insufficiency following
bone age. All patients performed GH stimulation tests (clonidine, glucagon or
craniospinal irradiation
insulin tolerance test) - peak values !7.0 mg/l. Three patients had abnormal
Alla Yudina1, Maria Pavlova1, Tatiana Tselovalnikova1,
pituitary MRI. Mean treatment duration was 5G3 years. Mean maximal dose
Nadezhda Mazerkina2, Irina Arefyeva2 & Olga Gheludcova3
administered was 0.03G0.01(mg/kg/day). No adverse effects were registered. At
1Sechenov First Moscow State Medical University, Moscow, Russia;
the end, final height-SDS was K1.63G0.64 and IGF1-SDS K0.83G2.34. Final
2Burdenko Neurosurgery Institute, Moscow, Russia;3Russian Scientific
height and target height differed in K4.72G6.07 cm. Nine patients kept follow-
Center of Roentgenoradiology, Moscow, Russia.
up in Endocrinology: 3 performed insulin tolerance test, all having normal results.
Only 2 patients presented IGF-1 levels !-2 SDS (one of them proposed for
treatment).
Abstract
Discussion
The secondary adrenal insufficiency (SAI) is life-threatening disease. 30-50% of
As expected, patients with isolated GHD treated at our center showed good
patients have SAI following craniospinal irradiation (CSI). The “gold standard”
clinical outcomes, with mean final height reaching close target height. Current
of SAI diagnosis is the insulin tolerance test but it is demanding for patient and
recommendations consider to treat with GH, adults with documented persistent
medical staff. The simple and reliable test would allow to use ITT rarely. The aim
deficiency. In this series all patients with isolated GHD with normal MRI had a
was to evaluate probability of using DHEA-S in SAI diagnosis. 41 patient after
transitory deficit and did not required treatment in the adult age.
CSI non-pituitary brain tumors survivor and 23 healthy were included. The mean
DOI: 10.1530/endoabs.49.EP1058
age was 20.5G3,6 years (16-30), follow-up was more than 2 years. Cortisol,
DHEA-S, ACTH were determinate and then ITT was performed. The patients
were divided into SAI-group and without SAI (W-SAI) after ITT.
Results
18/41 had SAI by ITT. DHEA-S was significantly lower in SAE-group 2.65G
1.4 mmol/l than in W-SAI and healthy (5.2G2.1 and 7.6G4.4 mmol/l, PZ0.001).
Cortisol in SAI and healthy was the same (326G99.4 and 390.5G161 mmol/l,
PZ0.2) but lower that W-SAI (495.2G186 mmol/l, PZ0.05). ACTH was not
EP1059
differ. DHEA-S/cortisol ratio was lower in SAI (PZ0.002), ACTH/cortisol was
What should central diabetes insipidus and panhypopituitarism point
the same. There was the significant correlation between SAI and cortisol (rZ0.57,
out in a patient with lung adenocarcinoma in remission?
PZ0.02) and SAI and cortisol (rZ0.49, PZ0.02). There was not correlation
Sule Canlar, Caglar Keskin, Asena Gokcay Canpolat, Sevim Gullu &
between age and DHEA-S. DHEA-S did not have gender difference within SAI
Demet Corapcioglu
and W-SAI. AUC cortisol was 0.79; AUC DHEA-S 0.9; AUC DHEA-S/cortisol
Ankara University Faculty of Medicine, Ankara, Turkey.
0.67. All patients who had basal cortisol lower than 200 nmol/l or DHEA-S lower
than 2.0 mmol/l were in SAI-group, and who had cortisol or DHEA-S more than
500 and 3.7 respectively did not have SAI by ITT. Cut-off DHEA as 3.7 had Se
Objectives
73% and SP 100%. When linear regression has applied, AUC cortisolCDHEA-S
Pituitary gland is an uncommon site for metastasis of malignant tumors. Breast
was 0.96.
and lung are the most common cancer sites. Most pituitary metastases are
Conclusion
asymptomatic, with only 7% symptomatic and central diabetes insipidus is the
DHEA-S had higher sensitive and specificity that cortisol for diagnosis of SAI
most common symptom.
in patients younger than 30 years following craniospinal irradiation. DHEA-S
Case presentation
can used without gender accounting in this group. Combined examination by
A 54 year-old woman presented with nause, emesis and diplopia to emergency
DHEA-S and cortisol is optimal.
department. Her relatives stated that she had poliuria, nocturia, polidipsia for
DOI: 10.1530/endoabs.49.EP1057
three months. Her history revealed that she had been operated because of lung
adenocarcinoma and postoperatively had underwent adjuvant chemotherapy. She
was at follow-up in remission. Laboratory tests denoted hypernatremia and MRI
scan images demonstrated that hypointense contrasted hypophysis and
infundibular enhacement. She possesed central diabetes insipidus and desmo-
pressin treatment administered primarily. On observation, central hypothyroidism
and secondary adrenocortical defficiency developed. Medical oncology depart-
EP1058
ment assesed the patient, no metastatic lesion was detected in thoracoabdominal
CT additionally PET scan, so that they didn’t consider pituitary metastasis. We
Clinical and laboratorial reassessment of patients with isolated growth
didn’t reveal any autoimmune, infectious and inflammatory diseases that can
hormone deficiency during the transition phase
cause hypophyseal involvement. Transnasal-transsphenoidal hypophysis biopsy
Ana Saavedra1,2, Juliana Oliveira3, Alexandra Martins4, Ana Azevedo4,
was occured, but histopathological sampling was insufficient. The patient refused
Rita Santos-Silva2,3, Cíntia Castro2,3, Elisabete Rodrigues1,2,
second biopsy, so she was discharged with replacement therapy in clinical stable
Davide Carvalho1,2 & Manuel Fontoura2,4
state. But two weeks later, the patient applied with emesis-vomitting and diplopia
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
and MRI scans showed progression. Also she had seizures, periferal facial
hypophysitis as a result of performed tests is discussed hereby in the case report.
paralysis and drop foot. The progression of lesions necessitated exact diagnosis
A 30 year old male patient presented to out clinic with fatigue, malaise,
and transcranial biopsy was carried out by the same neurosurgeon. After biopsy,
somnolence and headache. It was learned that the onset of the complaints was
her clinical course worsened and she lost her life. Meanwhile, histopathological
three months before and they gradually increased since then. There was no
examination resulted as metastasis of lung adenocarcinoma to hypophysis.
chronic disease, medication, herbal agent or alcohol use in the patient anamnesis.
Conclusions
Overall medical condition of the patient was moderate with
36.78C body
A past history of cancer should be kept in mind in a patient presenting with sellar
temperature, 80/50 mmHg arterial blood pressure and 50/min heart rate. Physical
mass even if the cancer is in remission. Especially, presence of diabetes insipidus
examination revealed no abnormal finding other than icteric sclera. Due to the
and MRI scan findings are clues for metastatic disease.
pathologic findings of
0.05 ng/dl free thyroxine level,
2.04 pg/ml free
DOI: 10.1530/endoabs.49.EP1059
triiodothyronine level and
0.46 u/ml of thyroid-stimulating hormone, further
tests were performed on the patient for a pre-diagnosis of central hypothyroidism.
Tests performed for etiology resulted in
0.82 ug/dl cortisol,
0,1 mlu/ml
luteinizing hormone, 7.97pg/ml adrenocorticotropic hormone and 2.68 mlu/ml
follicle stimulating hormone. Panhypopituitarism was considered due to these
results. Levothyroxine and prednisolone treatment was initiated. Diagnostic
magnetic resonance (MR) imaging was performed. Imaging revealed height of
pituitary gland 14 mm higher than normal. No heterogeneity was observed at
pituitary gland level. Biopsy of pituitary gland was performed for establishing
EP1060
diagnosis and result was concordant with granulomatous hypophysitis. TORCH
Is there any relationship between nonfunctional pituitary adenoma and
panel, herpes simplex virus, Brucella, Epstein-Barr, parvovirus, varicella-zoster,
arterial stiffness?
T. pallidum tests were negative. Adenosine deaminase (ADA) level was 45, in the
Yavuz Cagir1, Mustafa Altay2, Erman Cakal3, Busra Betul Cagir4,
upper limit. Tuberculin skin test
(PPD) resulted in
22 mm induration and
Tolga Akkan1, Murat Dagdeviren2 & Esin Beyan1
QuantiFERON-TB gold test was positive. Hypophysitis developed secondary to
1Kecioren Education and Research Hospital, Internal Medicine, Ankara,
tuberculosis was considered. In addition to the current treatment, anti-tuberculosis
Turkey;2Kecioren Education and Research Hospital, Endocrinology and
(isoniazid, streptomycin, pyrazinamide, rifampin) treatment was initiated. The
Metabolism, Ankara, Turkey;3Diskapi; Education and Research Hospital,
dose of administered prednisolone was gradually (24 -O 18 -O 12 -O 8 -O 75
Endocrinology and Metabolism, Ankara, Turkey;4Diskapi; Education and
-O 5 -O 4 mg / day) increased along the course of treatment. The need for steroid
Research Hospital, Internal Medicine, Ankara, Turkey.
was completely eliminated by month 6 of tuberculosis treatment. In cases such as
tubercular hypophysitis developing due to secondary causes, early diagnosis is
very important given that panhypopituitarism may be completely eliminated in
Introduction
clinical terms following an effective anti-tuberculosis treatment. Therefore,
In a recent study, it was determined that morbidity rates due to cardiovascular
tubercular hypophysitis should be kept considered for cases referred with
diseases were affected as a result of long-term follow-up in patients with
hypopituitarism clinic and suggesting secondary hypophysitis.
nonfunctional pituitary adenoma. And cardio/cerebro vascular diseases were the
DOI: 10.1530/endoabs.49.EP1061
most frequent cause of mortality when mortality rates were examined. In the
literature, there are not enough studies evaluating this condition in patients with
nonfunctional pituitary adenoma without traditional cardiovascular risk factors.
The aim of our study was to determine the peripheral and central blood pressures
and arterial stiffness by Pulse Wave Analysis
(PWA) in patients with
nonfunctional pituitary adenoma without traditional risk factors.
Material & methods
In ourstudy, 60 participants (30 patients with nonfunctional pituitary adenoma
and 30 healthy volunteers) without traditional cardiovascular risk factors were
EP1062
evaluated. All participants were similar in terms of gender, age and body mass
T2-weighted MRI signal and response to somatostatin analogs in
index. Peripheral and central blood pressure and PWA measurements were
acromegaly
performed with a Mobile-O-Graph PWA / ABPM instrument (I.E.M. GmBH,
Luis Cerqueira, Ana Palha, Luisa Cortez, Amets Sagarribay,
Stolberg, Germany). In the nonfunctional pituitary adenoma group radiological
Fernando Fonseca & Ana Agapito
and biochemical data were obtained retrospectively.
Centro Hospitalar Lisboa Central, Lisbon, Portugal.
Results
In the nonfunctional pituitary adenoma group, systolic blood pressure (SBP),
diastolic blood pressure (DBP), mean arterial pressure (MAP), central SBP,
Introduction
central DBP, augmentation index that corrected based on pulse rate of 75 bpm
somatostatin analogs
(SSA) are largely prescribed in acromegalic patients,
(Aix@75) and pulse wave velocity (PWV) were significantly higher than control
whether as adjuvant or primary therapy. Response is variable and seems
group. There was no significant correlation between biochemical parameters and
dependent of histological subtype. Intensity T2 signal in MRI has been related to
arterial stiffness parameters in the group of nonfunctional pituitary adenoma.
granulation patern and accordingly with response to SSA.
Conclusion
Objective
Peripheral and central blood pressure and arterial stiffness parameters are
To evaluate whether T2 MRI signal is correlated with effectiveness of SSA
negatively affected in patients with nonfunctional pituitary adenoma known as
Material and methods
cardiometabolically innocent, without traditional cardiovascular risk factors.
Retrospective analysis of acromegalic patients treated with SSA and available T2
Measurement of arterial stiffness in this patient group will lead to early detection
MRI. We considered response as complete (normal GH and IGF1), partial (GH
of mortality and morbidity due to possible cardiovascular pathologies
and/or IGF1 reduction R50%) and no response (%50%). MRI were analysed by
DOI: 10.1530/endoabs.49.EP1060
one neuroradiologist blinded for clinical and pathological data. Visual assessment
only or direct measurements of signal intensity using ROI cursors on T2 coronal
sections classified adenomas as hypointense or hyperintense, according MRI
signal % temporal lobe white matter or R grey matter, respectively. Signal
intensity between grey and white matter defined isointensity.
Results
Fourteen patients (8 males) were treated with SSA for a minimum of 6 months.
All but 5 patients were surgically treated (3 refused, 1 approach failed due to
bleeding,
1 is waiting surgery). T2
MRI hypointensity was documented in
EP1061
8 patients (group 1) and hyperintensity in 6 (group 2). Group 1 included 3 non
A rare cause of hypophysitis: tuberculosis
responders, 3 with partial and 2 with complete response. Group 2 comprised 3 non
Ihsan Ates & Nisbet Yilmaz
responders, 2 with partial and 1 with complete response to SSA. Considering
Ankara Numune Training and Research Hospital, Ankara, Turkey.
isolated GH reduction (R 50%), hypointensity was more often observed (62,5%).
Comments
In this cohort of acromegalic patients we observed no relationship between T2
Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it
signal intensity on MRI and hormonal response to SSA. One major limitation is
causes headache and visual defects, it mimics sellar tumors in clinical and
the small sample analysed.
radiological aspects. It may occur due to primary or secondary causes.
Tuberculosis is one of the rare secondary causes of hypophysitis. A young
DOI: 10.1530/endoabs.49.EP1062
male patient presented with fatigue and headache and diagnosed with tubercular
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1063
insufficiency documented in 3 of 4 patients tested by GHRH C Arginine (7%).
One patient displayed a concomitant GH insufficiency and low TSH level while in
“Toxic” Goiter Reveals Cushing’s Disease
another subject we found GH deficit and low FSH, LH and testosterone values
Madalina Musat1,2, Dan Hortopan2, Luciana Oprea2, Andreea Duceac2,
even if his gonadotropin response was normal after LHRH test. Surprisingly, none
Dana Manda2, Andra Caragheorgheopol2, Carmen Iordachescu2,
of the patients displayed altered PRL values.
Claudiu Tupea2 & Vasile Ciubotaru3
Conclusions
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
Mild to moderate TBI was followed by pituitary dysfunction documented in
2C.I.Parhon National Institute of Endocrinology, Bucharest, Romania;
13.3% of subjects. Higher frailty of GH and gonadotropin secretion by pituitary
3Emergency Clinical Hospital Bagdasar Arseni, Bucharest, Romania.
was confirmed, while altered PRL secretion was not documented.
DOI: 10.1530/endoabs.49.EP1064
Case presentation
Mrs. S presented in an endocrine clinic for fatigue, weight loss, restlessness and
goiter. She was obese with a BMI of 51 kg/mp, hypertensive and had a medium
size, nontender goiter. Lab test revealed hyperglycaemia, suppressed TSH
(!0.03mUI/L), on two separate occasions, mid-normal fT4 and T3. Thyroid
ultrasound revealed multinodular goiter. A diagnosis of polynodular goiter with
subclinical hyperthyroidism was made and patient was commenced on thiamazole
EP1065
30 mg/day. She was also scheduled for a RAIU. Three weeks later she was
The pseudo-tumoral adénohypophysitis: A rare disorder of the
admitted in the endocrine unit with a BMI of 47kg/mp. At presentation she had
postpartum
plethora, purpura on her breasts and bruised easily at venipuncture sites. FBC
Ghizlane El Mghari, Nassiba Elouarradi & Nawal El Ansari
revealed neutrophilia with lymphocytopenia, normal platelets. Thyroid function
Endocrinology and Diabetes Department, University Hospital Mohamed VI,
tests revealed suppressed TSH (0.0164 mUI/L) with low fT4. Thiamazole was
Marrckech, Morocco.
stopped. RAIU revealed low radioiodine uptake in the thyroid. Midnight plasma
and salivary cortisol were high, morning plasma cortisol was borderline high,
with increased ACTH. Urine cortisol was 10 fold upper limit of normal, low
Introduction
dexamethasone suppression test was negative. MRI of the pituitary revealed left
The pseudo-tumoral lymphocytic adénohypophysitis is an autoimmune disorder
sided pituitary microadenoma of 7,5/7 mm. Diagnosis of Cushing’s disease has
responsible for anterior hypophysis insufficiensy.It is a rare cause of pituitary
been made and transsphenoidal adenomectomy was perfomed. At 3 weeks
hypofunction which predominantly affects young women in the peripartum
postoperatively patient has returned to clinic with symptoms of cortisol
period. We report the case of a patient in whom the pseudo-tumoral lymphocytic
withdrawal while on 30 mg of cortisone daily. She had a BMI of 42 kg/mp, no
adénohypophysitis was the cause of a pituitary failure.
plethora and no purpura. Cortisol day curve was within the therapeutic range. Off
Case presentation
therapy, morning plasma cortisol was 8.89 mcg/dL, normal ACTH, midnight
The patient was a 44 year-old woman, who presented with headache and vomiting
plasma cortisol of 1.44 mcg/dL and lower normal range of urinary free cortisol.
without visual disturbance at the 7 th month of pregnancy. She was admitted to
Thyroid function tests were normal.
our institution in post-partum for secondary amenorrhea combined with the
Conclusion
absence of lactation without diabetes insipidus.In the hormonal evaluation, we
Hypercortisolism is known to alter pituitary hormones, however it is not usual that
have a ante-pituitary insufficiency with: cortisol Z0,01ug/dl, EstradiolZ16pg/ml
mild Cushing’s disease to suppress TSH to ‘thyrotoxic’ level. In this case of
FSHZ5.85 mUI/ml, LHZ0.4 mUI/ml, TSHZ0.008 uUI/ml, T4Z2.19 ng/dl and
unsuspected Cushing’s disease, thyroid function test alteration led to diagnosis.
a prolactinZ0.15 ng/ml. Magnetic resonance (MR) imaging of the pituitary
DOI: 10.1530/endoabs.49.EP1063
revealed a pituitary mass (18!14 mm) evoking a pituitary adenoma. The patient
is maintained on oral hydrocortisone and thyroxine. The evolution was favorable
and the controlled pituitary MRI, two years after, showed a normal pituitary gland
with disappearance of the pituitary mass.
Discussion
The pseudo-tumoral lymphocytic adénohypophysitis is a rare and previously
under-recognised disorder, most commonly affecting young females in the post-
EP1064
partum period. It presents clinically with symptoms and signs related to either a
pituitary mass or hypopituitarism, frequently mimicking a pituitary adenoma. It is
Low incidence of hyperprolactinemia following traumatic brain injury
difficult to distinguish lymphocytic hypophysitis from a pituitary adenoma on pre-
Anna Tortora1, Domenico La Sala1, Anna Luna Tramontano1,
operative imaging and definitive diagnosis rests on histology which classically
Francesca Bisogno1, Elisabetta Angrisani2, Mario Carrano2 &
demonstrates destruction of anterior pituitary acini by an inflammatory infiltrate
Mario Vitale1,2
rich in plasma cells and T lymphocytes.
1Department of Medicne, Surgery and Dentistry, University of Salerno,
Salerno, Italy;2AOU San Giovanni di Dio e Ruggi D’Aragona, Salerno,
DOI: 10.1530/endoabs.49.EP1065
Italy.
Background
Traumatic brain injury (TBI) is a major cause of disability and death, and a cause
of neuroendocrine dysfunction. Partial or complete pituitary dysfunction is a
EP1066
frequent event occurring in 25-50% of subjects after a TBI as result from damage
Clinically nonfunctioning pituitary adenoma: a case report
to either the pituitary or the hypothalamus. This large variability depends on the
Tugba Arkan, Gokcen Selma Kilic Halhalli & Seyyid Bilal Acikgoz
screening methods and on the difficulty to predict the effects of the trauma on
Kocaeli Derince Education and Research Hospital, Kocaeli, Turkey.
pituitary. Growth hormone deficiency and gonadotropin deficiency are the most
frequently documented pituitary dysfunctions after TBI. Also hyperprolactinemia
Objective and importance
has been documented as result of hypothalamic-pituitary stalk damage.
Clinically nonfunctioning pituitary adenomas (NFPA) are the most common
Aim of the study
pituitary tumors after prolactinomas. The absence of clinical symptoms of
Aim of our study was to determine the incidence of pituitary dysfunctions
hormonal hypersecretion can contribute to the late diagnosis of the disease.
following mild to moderate TBI.
Clinical presentation
Methods and patients
A 52-year-old man presented with muscle weakness, weight loss, fatigue and a
All subjects followed at the emergency room of our institution 12-6 months
long term history of depression. He had no headaches and no vision problems.
before were invited to a screening of pituitary function by measuring: FSH, LH,
Physical exam was unremarkable. Neck and thorax CT was performed because of
TSH, IGF-1, Testosterone (T) in (man), 17-beta-estradiol (in women) and PRL.
lung malignancy suspicious. Neck CT detected a cranial mass. Cranial MRI was
When IGF-1 was below the reference range a GHRH C Arginine test was
performed. Magnetic resonance imaging (MRI) revealed a pituitary macro-
performed to document a GH deficency. LHRH test was performed when FSH
adenoma (3.5 cm high, 2.5 cm wide and 2.3 cm deep). It extended up and out of
and LH and T or 17-beta-estradiol were below the reference range to document
the sella turcica, stretching the optic chiasm and optic nerves. The levels of
gonadotropin deficiency.
prolactin and the other pituitary hormones (except for testosterone) were normal
Results
and the lesion was given a diagnosis of a non-secreting pituitary adenoma.
Forty-five subjects aged 18-63 years joined the screening. Single or multiple
Endoscopic trans-nasal trans-sphenoidal pituitary adenoma resection was
pituitary failure was found in 14 patients (31%). Hypogonadotropic hypogonad-
performed. The tumour was completely removed, identified as a pituitary
ism was documented in 3 males (6.8%), low IGF-1 in 10 patients (22%) and GH
adenoma with intracapsular hematoma.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
Aim
Nonsecretory pituitary tumors are called null-cell tumors measuring a few
To determine and evaluate the clinical and hormonal characteristics of cases with
millimeters are common and found in up to 25% of autopsies. These may grow
Sheehan’s syndrome diagnosed and follow-up in our Clinic, during the last ten
slowly, destroying normal pituitary function, or they may compress nearby
years.
structures and cause neurologic problems. In our case report we discuss
Subjects and methods
asymptomatic pituitary macroadenoma.
We included, in this retrospective study, 13 patients, mean age 58G10.9 years,
DOI: 10.1530/endoabs.49.EP1066
diagnosed with Sheehan’s syndrome. Data about medical history, routine
laboratory determinations, hormonal parameters, pituitary imaging and therapy
were reviewed. All the cases presented a history of severe uterine bleeding after
last delivery.
Results
The age at diagnosis for these patients varied between 19 and 54 years. The period
of follow-up from the moment of diagnosis was between 3 and 48 years. All
except one of the cases had an assisted deliverance, but more than half of the cases
(53.8%) came from rural area. Due to severe uterine bleeding, hysterectomy was
EP1067
performed in 7 patients
(53.8%). In
12/13
subjects, breastfeeding was not
Nonfunctioning pituitary incidentaloma - delayed onset of acromegaly
possible. The diagnostic of Sheehan’s syndrome was established after 0.5 to 28
and concomitant primary adrenocortical insufficiency
years from pathological deliverance. The longest delay between the moment of
Serban Radian1,2, Diana Deciu1,2, Antonia Lefter1,2 & Catalina Poiana1,2
delivery and those of diagnostic was
28
years. All the cases presented
1C. Davila University of Medicine and Pharmacy, Bucharest, Romania;
corticotropin, thyreotropin and gonadotropins deficiency in the moment of
2C.I. Parhon National Institute of Endocrinology, Bucharest, Romania.
diagnosis. Growth hormone deficiency was documented in 2 patients and one
subject was diagnosed with central diabetes insipidus. Hormonal substitution
therapy with thyroxine and glucocorticoids was used in all the cases.
Introduction
Gonadotropins deficiency was treated with estroprogestative in younger subjects
Pituitary incidentaloma (PitInc), defined as an unsuspected mass observed on
and GH replacement treatment was given in two cases. Desmopressin was given
imaging studies performed for unrelated conditions. Most such lesions are not
in one patient for ADH deficiency.
clinically significant at initial evaluation and current guidelines recommend
Conclusion
periodic follow-up.
Sheehan’s syndrome is still present in clinical practice, even in the condition of
Aim
assisted deliverance and well-managed uterine haemorrhage.
To present a rare case of delayed onset of acromegaly in a patient with a
nonfunctioning PitInc, raising the question of the utility of prolonged follow-up of
DOI: 10.1530/endoabs.49.EP1068
PitInc.
Methods
Clinical examination, biochemical and imaging studies.
Case report
Following a contrast head CT for headache, a 63 years old female presented with
EP1069
a 11!5 mm intrasellar pituitary mass, no clinical signs of pituitary hypersecre-
tion and normal serum prolactin and IGF-I. Subsequent follow-up showed non-
Mental disorders in the hospitalized patients with Cushing’s disease
progression of mass size on CT/MRI and normal prolactin/IGF-I. 10 years from
Denis Almaev1, Elena Starostina3, Janna Belaya2, Irina Komerdus3 &
initial diagnostic, unexplained hyperkalemia prompted re-evaluation, revealing
Aleksey Bobrov1
mild skin hyperpigmentation, absence of other signs of adrenal failure, a small
1Moscow Research Institute of Psychiatry, Moscow, Russia;2Endo-
increase in shoe size, without other acromegalic features. IGF-I was high (2.2-2.9
crinology Research Centre, Moscow, Russia;3Moscow Regional Research
xULN), the GH nadir during OGTT was diagnostic for acromegaly. Review of
and Clinical Institute, Moscow, Russia.
MRI scans revealed a minimal lesion size progression and cystic changes. Visual
fields were normal. The patient was offered surgery but chose to start cabergoline,
Objective
dose-titrated to 3 mg/week, leading to IGF-I normalization. ACTH was elevated
To study the frequency and features of mental disorders in hospitalized patients,
and increased progressively, 8 AM serum cortisol was normal, with subnormal
suffering from Cushing’s disease (CD).
response to Synacthen, suggesting subclinical primary adrenocortical failure. An
Materials and methods
adrenal CT scan excluded adrenal masses, but revealed a discrete left adrenal non-
We studied 70 patients (59 women and 11 men) with verified diagnosis of CD,
nodular hyperplasia. Serum
17
HO-progesterone was elevated, suggesting
aged 41G12 years. Their mental health was evaluated with ICD-10 criteria and
concomitant congenital adrenal hyperplasia. The patient is clinically well on
verified by the Mini-International Neuropsychiatric Interview questionnaire
glucocorticoid and mineralocorticoid replacement and hyperkaliemia resolved.
(MINI 6.0). 45 patients had overt hypercortisolism (untreated CD and relapse),
Conclusions
25 people had remission after treatment.
The current PitInc guideline
(Endocrine Society
2011) does not specify a
Results
maximum follow-up period. Prolonged clinical and hormonal evaluation may be
Majority of the patients with CD suffered from comorbid mental disorders
warranted, as delayed onset endocrine disease can occur. In our case, incidental
(88.5%). 61.6% of them had different forms of affective disorders including
hyperkalemia prompted endocrine re-evaluation revealing multiple endocrine
bipolar disorder in 22/70 (38%), hypomania in 8/70 (11.2%), depressive episode
abnormalities.
in
6/70
(8.4%), mania without psychotic symptoms
3/70
(4.2%), recurrent
DOI: 10.1530/endoabs.49.EP1067
affective disorder 3/70 (4.2%) and cyclothymia in 2/70 (2.8%) patients. The
frequency of neurotic, stress and somatoform disorders was 15/70 (21%), among
these, the frequency of obsessive-compulsive disorder (6/70, 8.4%) was higher
than population-based, while the frequencies of social phobia (3/70, 4.2%), panic
disorder
(2/70,
2.8%), agoraphobia without panic attacks
(2/70,
2.8%) and
adjustment disorder (2/70, 2.8%) were not increased. The rest of diagnoses did not
exceed population prevalence: unspecified dementia in 1 (1.4%), acute psychotic
disorder in 1 (1.4%), schizoid personality disorder in 1 (1.42%). Psychiatric
EP1068
comorbidity with presence of two or more mental disorders in the same patient
reached 37/70 (52.8%). The frequency of bipolar spectrum disorders and anxiety
Sheehan’s syndrome in clinical practice
disorders was similar in patients with active hypercortisolism and remission,
Mihaela Vlad1,2, Ioana Golu1,2, Daniela Amzar1,2, Melania Balas1,2,
although the lack of difference may be due to the small sample size.
Miruna Butaru2, Ioana Milos1,2 & Ioana Zosin1,2
Conclusions
1“Victor Babes” University of Medicine and Pharmacy, Timisoara,
Mental disorders in patients with CD are extremely high. A prominent frequency
Romania;2Emergency County Hospital, Timisoara, Romania.
of bipolar spectrum disorders and recurrent depression suggests, that the
dysregulation of biological cycles is an important mechanism of CD
Sheehan’s syndrome represents a rare cause of pituitary insufficiency, produced
development/recurrence. Besides, there are obviously specific psychological
by an ischemic pituitary necrosis due to a severe haemorrhage at deliverance.
adaptation patterns and a number of typical stress responses in such patients.
Epidemiologic data indicate that, nowadays, this disease is quite rare in developed
DOI: 10.1530/endoabs.49.EP1069
country.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1070
15 mm, P!0.001) and further suprasellar extension
(PZ0.015), cavernous
(PZ0.008) and sphenoidal sinus invasion (PZ0.006). Surgery occurred after a
Detailed assessment of hypothalamic damage in craniopharyngioma
median of 12 months (IQR 0-12), since imagiologic diagnosis and 26% (nZ25)
patients with obesity
required a second intervention. 13% (nZ12) were submitted to radiotherapy.
Sigridur Fjalldal1, Cecilia Follin1, Sanaz Gabery2, Pia Maly Sundgren3,4,
After surgery, 11 patients (16%) had hormonal deficiencies, while 8 (12%)
Isabella Bjorkman-Burtscher3,4, Jimmy Lätt3, Peter Mannfolk3,
improved. In the EO group, we found de novo hypogonadism in 3 patients and
Carl-Henrik Nordstrom5, Lars Rylander6, Bertil Ekman7, Anna Pålsson1,
hypothyroidism in 1. No significant tumour growth was observed and none
˚sa Petersén2 & Eva-Marie Erfurth1
suffered apoplexia.
1Department of Endocrinology, Skåne University Hospital, Lund, Sweden;
Discussion
2Translational Neuroendocrine Research Unit, Department of Experimental
Patients that underwent surgery were in average 10 years younger, had more
Medical Science, Lund University, Lund, Sweden;3Department of Medical
neuro-ophthalmologic symptoms and bigger tumours at presentation. Those in
Imaging and Physiology, Skåne University Hospital, Lund, Sweden;
vigilant observation did not present significant tumour growth, new hormonal
4Department of Diagnostic Radiology, Clinical Sciences, Lund University,
deficiencies or apoplexy. Facing literature data, our population underwent fewer
Lund, Sweden;5Department of Neurosurgery, Skåne University Hospital,
surgeries. EO may be a valuable option in selected NFPAs.
Lund, Sweden;6Division of Occupational and Environmental Medicine,
Lund University, Lund, Sweden;7Department of Endocrinology and
DOI: 10.1530/endoabs.49.EP1071
Medical and Health Sciences, Linkoping University, Linkoping, Sweden.
Background/objectives
Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor
Craniopharyngioma (CP). Attempts have been made to predict the risk of HO
based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but
EP1072
none have included volumetry. Qualitative and quantitative (volumetric) analyses
Risk factors for progression of the surgical remnant of non-functioning
of HT damage was performed. The results were explored in relation to feeding
pituitary adenomas in patients treated with dopamine agonists
related peptides and body fat.
Elena Fernández González, Miguel Sampedro Nun˜ ez, Ana Ramos Leví, Ana
Subjects/methods
Rabé Caón, Isabel Hughet, Nerea Aguirre Moreno, Clara Marijuán Sánchez,
A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was
Bego
˜aPlaPeris,ÁngelesMailloNieto,AliciaVicun˜a Andrés, Pedro
performed at median 22 years after 1st operation. 41 CPs, median age 35 (range
Martínez Flores & Mónica Marazuela Azpiroz
18-56), of whom 23 had HT damage, were compared to 32 controls. After
Hospital Universitario La Princesa, Madrid, Spain.
exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome
measures were the relation of metabolic parameters to HT volume and qualitative
analyses of HT damage.
Introduction
Results
Surgery is the treatment of choice for non-functioning pituitary adenomas
Metabolic parameters scored persistently very high in vascular risk particularly
(NFPA), but remnants are frequently observed. Management of these remnants
among HT damaged patients. Patients had smaller HT volumes compared to
include observation (OBS), radiotherapy (RT) and/or dopamine agonist (DA)
controls 769 (35-1168) mm3 vs 879 (775-1086) mm3; P!0.001. HT volume
therapy. In this study, we evaluate the progression-free survival (PFS) of NFPA
correlated negatively with fat mass and leptin among CP patients (rsZK0.67;
with postoperative remnant and the potential factors involved.
P!0.001; rsZK0.53; PZ0.001), and explained 39% of the variation in fat mass.
Methods
For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI:
We performed a single-center ambispective study of a cohort of 72 patients (age
1.5-3.9; P!0.001). Qualitative assessments revealed HT damage in 3 out of 6
56G15 years, 32 women), with NFPA and tumor remnant after transsphenoidal
patients with normal volumetry, but HT damage according to operation records.
(TS) surgery, followed-up between 1994 and 2015. We categorized patients as
Conclusions
stable (nZ36) or progression (nZ21), according to radiological criteria. No
A decrease in HT volume was associated with an increase in fat mass and leptin.
follow-up data were available for 10 patients and 5 cases died. We evaluated
We present a reproducible method with a high inter-rater reliability (0.94) that can
differences between patients according to the three postoperative approaches:
be applied by non-radiologist for the assessment of HT damage. The method may
OBS, DA and/or RT. Statistical analysis was performed with STATA v12.0. We
be valuable in the risk assessment of diseases involving the HT.
present data for progression-free time medians (p 25-75), correlation coefficient
DOI: 10.1530/endoabs.49.EP1070
(r) and Hazard Ratio (HR).
Results
Progression-free survival (PFS) of the total cohort of patients was 154 months
(77-184). Subgroup analysis suggested longer PFS in OBS patients (154m) vs.
RT(184m)
(PZ0.07). Univariate analysis indicates an increased risk of
progression in patients without RT (HR: 3.6; [0.8-15]; PZ0.09). Duration of
DA treatment was positively correlated with PFS (rZ0.60; P!0.05), and each
EP1071
additional month showed a favorable trend for an increased PFS (HR: 0.98; [0.95-
1.00]; PZ0.06). Sex, age, and postoperative tumor diameter were not associated
Surgery versus expectant observation in clinically non-functioning
with PFS. Subanalysis of the subgroup of patients who received DA(nZ20)
pituitary adenomas - a 20-year single centre experience
showed that the only influencing factor for progression was female sex (c2Z5.05;
Claudia Matta-Coelho1, Rui Almeida2 & Olinda Marques1
PZ0.02).
1Endocrinology Department, Braga Hospital, Braga, Portugal;
Conclusions
2Neurosurgery Department, Braga Hospital, Braga, Portugal.
RT of operated NFPA seems to be associated to a higher PFS in our cohort.
Prolonged treatment with DA also favored an increased PFS. Long-term follow-
Background
up and active management of patients with NFPA are important.
Clinically non-functioning pituitary adenomas (NFPAs) are among the most
DOI: 10.1530/endoabs.49.EP1072
common pituitary lesions. Its management includes surgery, radiation or
observation. The authors aim to compare clinical characteristics and outcomes
between patients submitted to surgery or expectant observation (EO).
Methods
Retrospective review of medical records from 1996 to 2016. In our centre, there is
only 1 pituitary surgeon and NFPAs patients are referred to surgery according to
EP1073
the presence of neurologic symptoms, mainly visual disturbances, and tumour
Aggressive macroprolactinoma - exception to the rule
growth. Statistical analysis: SPSSvs20.
Alina Daniela Belceanu1, Georgiana Constantinescu1, Iulia Crumpei1,
Results
Anamaria Bursuc1, Daniel Rotariu2, Aurora Constantinescu3,
We found 179 patients, 52% (92 females), with a median follow-up time of 5
Vasile Ciubotaru4, Cristina Preda1 & Carmen Vulpoi1
years
(IQR 3-10), 54% (nZ96) underwent surgery. Besides indication for
1Endocrinology Department, University of Medicine and Pharmacy Gr. T.
surgery, 2 patients refused and 3 did not have clinical conditions. Patients that
Popa, Iasi, Romania;2Neurourgery Department, University of Medicine and
underwent surgery were younger (58 vs 68 years, P!0,001), had more neurologic
Pharmacy Gr. T. Popa, Iasi, Romania;3Neurology Department, University
symptoms at diagnosis (62 vs 39%, PZ0.011) and visual disturbances (64 vs
of Medicine and Pharmacy Gr. T. Popa, Iasi, Romania;4Neurosurgery
22%, P!0.001) than patients in EO. There were no differences in hormonal
Department, University of Medicine and Pharmacy Carol Davila, Bucharest,
deficiencies (P!0.001). The surgery group presented larger adenomas (26 vs
Romania.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
cardiometabolic dysfunctions. Susceptibility to metabolic syndrome in IHH
Prolactinoma is the most frequent pituitary tumour. However, peculiar aspects
patients on HRT should be further investigated.
may induce difficulties in their evolution and management. Malignant
DOI: 10.1530/endoabs.49.EP1074
prolactinoma is exceptionally rare and it cannot be diagnosed on histological
grounds alone. We report the case of a recurrent, possibly malignant
macroprolactinoma.
Case report
46 years old female, addressed for bitemporal hemianopia, without other clinical
signs. MRI confirmed a pituitary macroadenoma (22/19/35 mm) with suprasellar
evolution. Hormonal profile revealed hyperprolactinemia with secondary thyroid
EP1075
and gonadal insufficiency, for which Cabergoline was started, with initial good
The E in POEMS syndrome: what to expect?
evolution. Three years later she presented pituitary apoplexy with acute
Francisca Caimari1, Shirley D’Sa2, Michael Lunn3 &
intracranial hypertension, solved by partial transcranial adenomectomy.
Stephanie E Baldeweg1
Gamma knife radiation completed the treatment, with succeeding adrenal and
1Department of Endocrinology, University College London Hospitals,
thyroid insufficiency. After 4 years of stationary evolution under Cabergoline and
London, UK;2Haematology Department, University College London
substitutive treatment, an aggressive tumour progression imposed a new surgical
Hospitals, London, UK;3Neurology Department, University College
intervention
(transsphenoidal adenomectomy). One year later, intensive
London Hospitals, London, UK.
vertiginous syndrome enforced reinvestigations. MRI identified two cerebral
tumours (meningioma?), one of them at the cranio-spinal junction, which needed
urgent excision. Pathology identified pituitary adenoma cells and a Ki-67 index of
Introduction
2%. Post-operatory, the patient complained of gait dysfunction, nausea and
POEMS syndrome is a rare multisystemic disorder including polyneuropathy,
headache. Left cranial nerves paresis X, XI, and XII was objectified. The patient
organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder and
underwent six cycles of Temozolomide chemotherapy, with no improvement, last
skin changes. We aim to describe the course of the endocrine disease in the
MRI revealing further tumour evolution.
context of this paraneoplastic syndrome.
Conclusion
Methods
Elucidating the pathogenesis of aggressive prolactinomas remains largely
69 patients with POEMS have been under the MDT care in our hospital. Data is
unknown and continues to mesmerize the physicians. The diagnosis of pituitary
currently available for 32 patients who attended the joint haematological/neur-
carcinoma is confirmed only in the presence of metastasis. After initial good
ological/endocrine clinic from 06/1999 to 01/2017. All patients had regular
response to Cabergoline, our patient developed a rapid aggressive progression of
endocrine screening including pituitary, thyroid and calcium metabolism. Median
the tumour, with little effect of surgery and radiotherapy. Temozolomide was not
and interquartile range and meanGS.D. were used for quantitative variables and
efficient in controlling tumour evolution. In spite of the longer survival (9 years)
percentage for qualitative variables.
and the low proliferation index, we believe that new markers are needed in order
Results
to assess the aggressiveness of malignant prolactinoma.
Seventy-two patients were male. The age at diagnosis was 49.4(38.2-59.8) years
DOI: 10.1530/endoabs.49.EP1073
and the median follow-up was 4.6(2-7.4) years. At diagnosis, all patients
presented with polyneuropathy, 25% had hyperhidrosis and 50% endocrinopathy.
From those with endocrinopathy, 36.7% had thyroid disease, 26.7% hypogonad-
ism, 3.3% type 2 diabetes mellitus (2DM) and 6.5% Addison disease. None of
them had parathyroid disorders. 60% had more than one endocrinopathy at
diagnosis. During surveillance 90.3% of patients developed endocrinopathy.
68.8% of patients had hyperprolactinemia with a fold increase 1.8G0.99 above
the upper limit of the normal. Hyperprolactinaemia was transient in 72.7%. One
patient with hyperprolactinaemia had an empty sella on MRI.
59.4% had
hypothyroidism (37.5% clinical, 21.9% subclinical). This was transient in 27.8%
EP1074
of patients. Addison disease was diagnosed in 18.8% of patients and none of them
Body composition and bone mineral density in male patients with
recovered their adrenal function. 15.6% presented with type 2DM. 78.6% had
isolated hypogonadotropic hypogonadism
hypogonadism (19.1% secondary, 38.1% primary, 42.9% subclinical primary).
Małgorzata Kałuz˙na1, Magdalena Człapka-Matyasik2, Dorota Przeorska2,
Gonadal function recovered in 3 patients.
Katarzyna Ziemnicka1 & Marek Ruchała1
Conclusion
1Department of Endocrinology, Metabolism and Internal Diseases, Poznan
Endocrinopathy in POEMS was described in 90% of our cohort. The MDT team
University of Medical Sciences, Poznan, Poland;2Department of Human
should include an endocrinologist. Patients should be systematically assessed for
Nutrition and Hygiene, Poznan University of Life Sciences, Poznan, Poland.
endocrinopathy. The most common deficiencies were hypogonadism, hyperpro-
lactinemia and hypothyroidism. Normalisation of the endocrinopathy was
Isolated hypogonadotropic hypogonadism (IHH) is known to decrease bone
common and should be considered when treating these patients.
mineral density due to lack of pubertal surge of gonadotropins and deficiency of
DOI: 10.1530/endoabs.49.EP1075
sex steroid hormone. Gonadal steroid hormones imbalance affects body
composition. Nineteen Caucasian men, 22-48 year old (meanGS.D. 33G7.65)
diagnosed with IHH (8 normosmic, 11 anosmic or hyposmic) were enrolled into
the study. 14 patients were on hormone replacement therapy (HRT), 5 patients
were started with HRT treatment. Nineteen healthy male volunteers (CON) with
matched age and BMI were also included. Body composition and bone mineral
density measurements were conducted with use of Air Displacement Plethysmo-
EP1076
graphy (BOD POD, Cosmed) and dual-energy x-ray absorptiometry DEXA
Pituitary adenoma and elevated ACTH: not always corticotrophinoma
(Lunar Prodigy,GE Healthcare), respectively. Hormonal status, lipid profile,
Mariana Cabac1, Alina Daniela Belceanu1, Iulia Crumpei1,
calcium and phosphorus levels, 25-hydroxy vitamin D concentration were also
Mirela Tirnovan1, Georgiana Constantinescu1, Anamaria Bursuc1,
measured. There was significant difference between fat-free-mass (FFM; kg) in
Aurora Constantinescu2, Voichita Mogos1 & Carmen Vulpoi1
IHH and matched controls (60.1 vs 66.0; PZ0.012), related to Gynoid FFM
1Department of Endocrinology, University of Medicine and Pharmacy ‘Gr.
distribution (IHH vs CON: 9.1 vs 10.3 kg; PZ0.003). IHH patients have marked
T. Popa’, Iasi, Romania;2Department of Neurology, University of Medicine
decreases in total bone mineral density compared to CON (1.21 vs 1.31 g/cm2,
and Pharmacy ‘Gr. T. Popa’, Iasi, Romania.
PZ0.009). Total bone mineral content, T-score and Z-score were also decreased
in IHH subjects (2982 vs 3271 g/cm, PZ0.05; 0.08 vs 1.06, PZ0.016; K0.40 vs
0.54, PZ0.013). High-density lipoprotein cholesterol (HDL) level was correlated
Introduction
with waist-to-height ratio
(WHtR) (rZK0.81, P!0.05) in IHH patients.
Hypothalamic-pituitary-adrenal (HPA) axis activation is the main neuroendo-
Significant correlations between insulin-like growth factor-1
(IGF-1) and
crine response to an environmental challenge. Drug abuse may activate HPA axis
WHtR were observed in IHH (rZK0.81, P!0.05; rZK0.82, P!0.05).
by interaction with neuromodulation systems.
Testosterone and 25Hydroxy vitamin D concentrations were not correlated with
Case report
body composition and densitometry measurements. To conclude, IHH patient are
28 year old man, was admitted in the Neurology Department for persistent
at increased risk for osteoporosis. Long testosterone deficiency in IHH resulted in
headache with spinal irradiation. With suspicion of multiple sclerosis, MRI
body composition changes related to fat free mass and distribution. WHtR, IGF-1
revealed pituitary macroadenoma (14 mm diameter) and subcortical, paraventric-
and HDL correlations in IHH patients might suggest their link with
ular and frontal white matter demyelinating lesions. Neurological examination
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
excluded multiple sclerosis and he was addressed to the Endocrinology
EP1078
Department. Anamnesis revealed a history of drug abuse (cocaine), alcoholism,
Inferior petrosal sinus sampling: experience of a terciary hospital
chronic smoking (1 pack of cigarettes/day) and depression. Clinical examination
Maria Manuel Costa1,2, José Luís Castedo1, Eduardo Vinha1,
revealed moderate weight excess (BMIZ27.14 kg/m2) and normal high blood
Josué Pereira2,4, Irene Bernardes5 & Davide Carvalho1,3
pressure (148/100 mmHg). Hormonal axes were normal, with the exception of the
1Department of Endocrinology, Diabetes and Metabolism, Centro Hospi-
HPA axis: high levels of ACTH (89.2 pg/ml), DHEAS (491.3 mg/dl) and free
talar de Sa˜o João, Porto, Portugal;2Faculty of Medicine, University of Porto,
urinary cortisol (216 mg/24 h), with normal morning and evening cortisol. 1 mg
Porto, Portugal;3Instituto de Investigac¸ão e Inovação da Saúde da
DXM overnight test was negative (cortisolZ4.28 mg/dl). It was re-evaluated after
Universidade do Porto, Porto, Portugal;4Department of Neurosurgery,
one month: persistency of normal cortisol values with constantly moderate high
Centro Hospitalar de São João, Porto, Portugal;5Department of
ACTH and good response to 1 mg DXM (1.12 mg/dl). The discordance between
Neurorradiology, Centro Hospitalar de São Joa˜o, Porto, Portugal.
ACTH, DHEAS and the rest of HPA axis suggested another possible etiology than
an ACTH secretion adenoma (cocaine use, smoking, depression). One year after,
biological parameters were constant, with insignificant increase of adenoma
Introduction
(16 mm diameter). Patient denied any further cocaine use for approximately 1
Inferior Petrosal Sinus Sampling (IPSS) is the gold standard test to distinguish
year, but admits that he is still smoking.
between Cushing Disease and ectopic ACTH secretion (EAS), mostly when the
Conclusions
biochemical tests are discordant and/or there is no lesion in MRI.
The dysregulation of HPA axis may increase vulnerability to depression and
Aim
numerous other psychiatric disorders, which can be puzzling for the
To evaluate the results of IPSS in the diagnosis of ACTH-dependent Cushing
endocrinologists in the diagnosis process. The peculiarity of the case is the
syndrome.
association of a pituitary macroadenoma with persistent increased levels of
Methods
ACTH. Investigations had not confirmed the suspicion of an ACTH secreting
Retrospective study that analysed IPSS results performed in the last decade in our
pituitary adenoma, and oriented to multiple ethology - drug abuse (cocaine,
centre and integrated in the clinical context of each patient. Basal central-
smoking) and depression.
to-peripheral ratioO2 or after CRH testO3 were considered diagnostic of CD.
DOI: 10.1530/endoabs.49.EP1076
Results
We analysed 31IPSS performed in 26 patients with biochemical diagnosis of CS.
Nine patients were excluded. Seventeen patients (2 Male) with a mean age of
38.4(11.8) years were included. One patient had to repeat IPSS due to haemolysis
and other had done 3 IPSS due to be on interfering medication. Eleven patients
had central-to-peripheral ACTH ratio suggestive of CD(6basal and 11after CRH
stimulation). The ratio was maximal at 50 in 45.4%(5/11) patients and at 2-30 in
36.3%(4/11). Pituitary MRI revealed microadenoma in 8 patients, macroadenoma
in one and 2 patients did not present any lesion. Three patients had a lesion on the
other side of pituitary when compared to the intersinus gradient. Immunohisto-
EP1077
chemical result revealed an ACTH expression adenoma in 6 patients, and
Pituitary apoplexy - presentation, management and outcome in 35 cases
expression of ACTH and GH in 2. There was no positivity for ACTH in 3 patients
Maria Manuel Costa1,2, Bruno Carvalho4, José Luís Castedo1,
who had MRI lesions, but one was cured after surgery and 2 underwent adjuvant
Eduardo Vinha1, Josué Pereira2,4, Irene Bernardes5 & Davide Carvalho1,3
therapy. Of the remaining 6 patients, 3 had results suggestive of ectopic EAS,
1Department of Endocrinology, Diabetes and Metabolism of Centro
one of which was submitted to lobectomy and had bilateral adrenalectomy
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of
by occult ectopic, but underwent pituitary surgery with a histological result
Porto, Porto, Portugal;3Instituto de Investiga
¸a˜o e Inovação da Saúde da
revealing ACTH expression. Of the other 3 patients, all with pituitary MRI lesion,
Universidade do Porto, Porto, Portugal;4Department of Neurosurgery,
2 patients underwent surgery that revealed CD and in the other the result was
Centro Hospitalar de São João, Porto, Portugal;5Department of
normal and patient underwent adrenalectomy. There were no significant adverse
Neurorradiology, Centro Hospitalar de São João, Porto, Portugal.
effects.
Conclusion
This study reinforces the utility of IPSS in identifying aetiology of SC, which was
Introduction
obtained in more than half of the patients, with no associated adverse effects. The
Pituitary apoplexy is a rare disease which results of haemorrhage and/or infarction
IPPS catheterization was not possible in 1 patient.
of pituitary gland. The optimal management of this problem still remains
DOI: 10.1530/endoabs.49.EP1078
controversial between surgery and conservative treatment.
Aims
To characterize the clinical presentation, diagnostic workup, treatment and follow
up of patients with apoplexy. Methods:Retrospective study of
35 pituitary
apoplexy followed in a portuguese hospital from 2006 to 2016.
Results
Thirty-five patients (21 males; mean age, 55.1(15.6) years) were identified. Three
patients had subclinical pituitary apoplexy and
9(28%) had more than one
EP1079
emergency evaluation until the diagnosis has been correctly made. Commonest
Cushing syndrome and pregnancy: a systematic review including three
presenting features were acute headache (84.4%), visual impairment (62.5%) and
new cases
vomiting
(15.6%). Five patients were known to have pituitary tumour at
Diogo China1, Ana Isabel Oliveira2, Sandra Belo2,3 & Davide Carvalho2,3
presentation, one of them was a Cushing Disease which became cured after PA,
1Faculty of Medicine, Porto, Portugal;2Department of Endocrinology,
and
3 were nonfunctioning adenomas. Nineteen patients had at least one
Diabetes and Metabolism Centro Hospitalar S. João, Porto, Portugal;
precipitating factor with antiaggregation being the most common (nZ4). Twenty
3Instituto de Investiga
¸
˜o e Inova
¸a˜o em Saúde, University of Porto, Porto,
patients had hypopituitarism at presentation, 14 had hyponatraemia, 9 had a
Portugal.
decreased in level of consciousness and 21 had visual impairment. 78.1% patients
proceeded to pituitary surgery and 3 developed diabetes insipidus after that. When
we compared those who underwent surgery and those treated conservatively,
Cushing’s Syndrome
(CS) is an uncommon disease worldwide, being
visual deficits were more common in first group (76% vs 28%, PZ0.032) and
characterized by an increased production of glucocorticoids, and if left untreated
hyponatremia in the second one (32% vs 86%; PZ0.027). There were no more
can lead to serious consequences and women with CS rarely get pregnant. The
differences between groups in other evaluated factors, namely in Pituitary
aim of our work is to make a systematic review of the cases of pregnancy in
Apoplexy Score (1.68 (1.21) vs 0.86 (1.21); PZ0.124). During follow-up 6(3)
patients with previously diagnosed CS, being performed an extensive research of
years,
1 patient had hypopituitarism reversal after surgery and
11 patients
the Medline and Web of Knowledge databases, and add three new cases observed
recovered from neuro-ophthalmologic deficits. Three patients passed away and 21
in our institution. We compared two different groups: the ‘active disease’ one and
have a MRI without lesion.
the ‘non-active disease’ and we found 17 pregnancies that were included in the
Conclusion
first group while other 20 pregnancies were in the second category. We observed
The diagnosis of pituitary apoplexy is often delayed as occurred in our
two spontaneous abortions and one ectopic pregnancy in the ‘active’ group, while
population.It is associated with a high rate of anterior hypopituitarism that does
in the ‘non-active’ category we found the same number of spontaneous abortions
not typically recover, unlike the visual symptoms. Patients with visual defects
besides a placental abruption and a medical interruption of the pregnancy.
were more likely to be managed surgically.
Cushing disease (CD) was the main cause behind CS (28 pregnancies), with
transsphenoidal surgery the preferred treatment. Within the ‘active’ category, we
DOI: 10.1530/endoabs.49.EP1077
reported nine full-term and five pre-term pregnancies and in the ‘non-active’
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
category we observed 11 full-term and three pre-term pregnancies, while two in
Introduction
this last group were non-specified. Hypertension was diagnosed in eight cases (six
The endocrine system is often affected in the course of HIV infection. However,
and two in the ‘active’ and ‘non-active’ group respectively) and gestational
hypopituitarism and diabetes insipidus are uncommon disorders in these patients
diabetes in four patients
(three and one in the
‘active’ and
‘non-active’
and have been related to drugs, infections of the central nervous system and
categories). Inability to breastfeed was one of the main perinatal events reported,
neoplastic infiltration, in extremely rare cases.
as a logical consequence of the treatment regimen adopted for CS. A major
Case report
concern in these patients refers to the medical control of CS activity, because
We present a case of a 42-year-old man with HIV infection known since 2005, but
hypercortisolism occurs physiologically during pregnancy. This is a topic with
undergoing antiretroviral therapy only since 2010 (emtricitabine/tenofovir and
extreme clinical significance since it is rare that a CS women conceives.
raltegravir), when he was diagnosed with hepatitis C, left parotid MALT-
DOI: 10.1530/endoabs.49.EP1079
lymphoma, and cerebral toxoplasmosis (treated with pyrimethamine/sulfadia-
zine). He has also a history of smoking, drug addiction, in a methadone
replacement program for 10 years, and hypothyroidism diagnosed for 1 year,
medicated with L-thyroxine. The patient was referred to the Endocrinology
department by bilateral gynecomastia, loss of libido and erectile dysfunction.
When specifically asked he also complained of polydipsia-polyuria. Breast,
testicular and thyroid ultrasonography showed no relevant changes, but the
hormonal study revealed: central hypothyroidism and hypogonadotropic
hypogonadism; normal prolactin levels; slightly decreased IGF-1 and GH levels;
EP1080
normal ACTH, cortisol and tetracosactide test; insulin-induced hypoglycemia test
20-year retrospective study of clinically non-functioning pituitary
showed normal glucocorticoid reserve. Plasma osmolality was 300 mOsmol/kg
adenomas - a single center experience
and urine osmolality 136 mOsmol/kg. Water deprivation test confirmed central
Claudia Matta-Coelho1, Rui Almeida2 & Olinda Marques1
diabetes insipidus. Pituitary MRI showed lack of neurohypophyseal bright signal.
1Endocrinology Department, Braga Hospital, Braga, Portugal;
He was started on testosterone therapy (250 mg, 3/3 weeks), desmopressin
2Neurosurgery Department, Braga Hospital, Braga, Portugal.
lyophilisate (0.06 mg bid) and maintained L-thyroxine (0.088 mg/day). Currently,
he refers a global clinical improvement, but still complains of erectile
Background
dysfunction, and was recently medicated with avanafil (100 mg).
Clinically non-functioning pituitary adenomas (NFPA) are the most common
Conclusion
pituitary adenomas but their treatment remains challenging. Our aim is to describe
The authors describe a rare case of hypopituitarism and diabetes insipidus in a
clinical, imagiological and hormonal characteristics of patients with NFPA
patient with HIV infection of possible multifactorial etiology
- uncommon
presenting at our department.
complication of cerebral toxoplasmosis and/or side effects of antiretroviral drugs.
Methods
This case reveals the need to keep in mind the possibility of hypopituitarism in
Retrospective review of medical records of patients with NFPA at our centre from
HIV-treated patients and a history of cerebral infection.
1996 to 2016. Exclusion criteria: prolactin O100 ng/ml or histologic evidence of
DOI: 10.1530/endoabs.49.EP1081
prolactinoma. Statistical analysis: SPSSv20.
Results
179 patients included, 52% (nZ92) female, with a median age of 61 years (IQR
48-73) and follow-up time of 5 years (IQR 3-10). The diagnosis were more
frequent in the last 10 years (nZ114, 64%). 40% (nZ62) had hypertension and
15% (nZ24) were diabetic. The initial presentation was neuro-ophthalmologic
symptoms (nZ87, 52%), incidentally discovered adenomas
(nZ36, 21%),
pituitary apoplexy (nZ30, 18%) and endocrine disorders (nZ16, 9%). Pituitary
function assessment showed that half
(nZ69) had at least one hormonal
deficiency, specifically; LH/FSH deficiency was detected in 45%, ACTH in 25%,
Steroid Metabolism C Action
TSH in 30% and GH in 15%. Hyperprolactinemia was present in 22% (nZ30).
EP1082
Five patients
(3%) had diabetes insipidus. The NFPA were mainly macro-
Social stress stimulates glucocorticoid regeneration in lymphoid organs
adenomas (nZ146, 89.5%) with suprasellar extension
(nZ89, 70%), 36%
Jiri Pacha, Peter Ergang, Anna Mikulecka, Karla Vagnerova & Ivan Mikšík
(nZ43) had sphenoidal and 30.3% (nZ36) cavernous sinus invasion. Surgery
Institute of Physiology, Czech Academy of Sciences, Prague, Czech
was performed in
54% patients
(nZ96), while the remaining maintained
Republic.
expectant observation. Immunohistochemical analyses showed 42 null-cell, 34
gonadotrophs, 1 silent thyrotroph, 2 silent corticotroph and 2 plurihormonal
adenomas.
The presence of the enzymes of local metabolism of glucocorticoids in lymphoid
Discussion
organs and many other tissues suggests that the local glucocorticoid signal is not
As in other series, our patients also presented with visual disturbances and
determined only by plasma level of glucocorticoids but also by the local activity
pituitary dysfunction at diagnosis, but we found and older population. We
of these enzymes. Using resident-intruder test the present study determined if
emphasize that a quarter of patients had ACTH and 30% TSH deficiency that can
chronic social stress modulates local metabolism of corticosterone and
cause a significant morbidity and had not been suspected before. Hence, earlier
11-dehydrocorticosterone in rats of Fisher 344 (F344) and Lewis (LEW) strains,
diagnosis of hypopituitarism and prompt treatment are imperative.
which differ in their response to social stressors and inflammation. We
DOI: 10.1530/endoabs.49.EP1080
demonstrated that social defeat significantly increased regeneration of corticos-
terone from
11-dehydrocorticosterone in thymus, spleen and mesenteric
lymphatic nodes (MLN) but not pituitary of both strains. When compared with
F344 strain, LEW rats showed lower corticosterone regeneration in pituitary of
unstressed and stressed animals and higher corticosterone regeneration in thymic
and MLN mobile cells after chronic stress. In contrast, stress-induced increase of
corticosterone regeneration in stroma tissues of all lymphoid organs was similar
in both strains. Social defeat was also associated with changes in expression of
enzymes participating in local metabolism of glucocorticoids: 11b-hydroxy-
steroid dehydrogenase type 1 (11HSD1), 11b-hydroxysteroid dehydrogenase type
EP1081
2
(11HSD2) and hexose-6-phosphate dehydrogenase (H6PDH). Whereas F344
Hypopituitarism and central diabetes insipidus in an HIV patient - a
rats exhibited significant upregulation of 11HSD1 mRNA, 11HSD2 mRNA and
late complication of cerebral toxoplasmosis and/or antiretrovirals?
H6PDH mRNA expression in thymus and 11HSD1 mRNA in spleen, LEW rats
Sofia Castro Oliveira1,2, Pedro Souteiro1,2, João Sérgio Neves1,2,
showed an apparent insensitivity to stress in all lymphoid organs and neither of
Cláudia Nogueira3, Celestino Neves1,2, Paula Freitas1,2 &
the transcripts was upregulated by stress. Our results indicate that social stress
Davide Carvalho1,4
amplifies glucocorticoid regeneration in the lymphoid organs including the
1Department of Endocrinology, Diabetes and Metabolism of São Jo
˜o
expression of genes involved in local metabolism of glucocorticoids and that this
Hospital Center, Porto, Portugal;2Faculty of Medicine, University of Porto,
process is partly determined by the genetic background. The study was supported
Porto, Portugal;3Department of Endocrinology, Diabetes and Metabolism
by Czech Science Foundation.
of Trás-os-Montes e Alto Douro Hospital Center, Vila real, Portugal;
DOI: 10.1530/endoabs.49.EP1082
4Instituto de Investigac¸ão e Inovaçao em Saúde, University of Porto, Porto,
Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations:
Reproductive Endocrinology
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Bone & Osteoporosis
heterogeneous and conflicting. The aim of this study was to investigate the effect
of HRT and tibolone on Lp(a) concentrations in post-menopausal women.
EP1083
Methods/design
Effects of male hypogonadism treatment on the bone mineral density
MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to
Mário Rui Mascarenhas1,2, Ana Paula Barbosa1,2, Ana Raquel
February 2016). Two researchers identified randomized controlled studies and
Coelho Gomes2, Catarina Silvestre2, David Barbosa2, Raquel Paix
˜o2,
extracted data. Potential controversies were resolved by a third reviewer.
Carolina Faria2, Ana Sofia Osório2, Vânia Gomes2, Joana Ferreira1,
Results
Manuel Bicho1 & Maria João Bugalho2
In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations
1Endocrinology and Metabolic Diseases, Faculty Medicine of Lisbon,
compared with placebo or no treatment (mean relative difference: K20.35%, 95%
Lisbon, Portugal;2Endocrinology, Diabetes and Metabolism Department,
CI: K25.33% to K15.37%, P!0.0001), with significant heterogeneity between
Santa University Maria Hospital-Chln, Epe, Lisbon, Portugal.
studies (I2Z98.5%), but without evidence of publication bias. No significant
effect was found for tibolone (nZ7) (mean relative difference: K23.84%, 95%
CI: K63.43% to 15.74%, PZ0.238) (I2Z98.7%, but without publication bias).
Increased recognition of the morbidity and mortality due to osteoporosis in men
Oral estrogen caused greater reduction in Lp(a) concentrations than transdermal
are main issues of public health. Ageing and the propensity to falls are the main
estrogen (nZ10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%,
risk factors for osteoporotic fractures in men; moreover, hypogonadism is an
P!0.0001), with significant heterogeneity between studies (I2Z99%), but no
important secondary cause of low bone mineral density (BMD), but very little is
evidence of publication bias. No difference was observed when continuous was
known about the effect of hypogonadism treatment on the BMD.
compared with cyclical HRT, conventional with low estrogen dose, and estrogen
Objective
monotherapy with combination with progestogen. No difference was observed
The aim was to study the impact on BMD of the treatment of male hypogonadism.
between HRT and tibolone regarding their effect on Lp(a).
Material and methods
Conclusions
A group of 26 men were devided in the hypogonadotrophic hypogonadism
HRT significantly decreases Lp(a) concentrations, with oral being more effective
(nZ17) and hypergonadotrophic hypogonadism (nZ9) groups. The BMD at
than transdermal estradiol. The type of HRT, dose of estrogen and addition of
several skeletal sites (assessed by DXA scans) was evaluated before and during
progestogen do not seem to modify the Lp(a)-lowering effect of HRT.
treatment (duration from 1 to 8 years, on average 3.1 (G2.3) years). Adequate
statistical tests were used (statistical significance P!0.05).
DOI: 10.1530/endoabs.49.EP1084
Results
The treatment did not improved significantly the mean BMDs at several skeletal
sites (Table 1). Moreover the BMDs were similar before and during the treatment
in the hypergonadotrophic hypogonadism group; nevertheless, in the hypogona-
dotrophic hypogonadism group the mean BMDs were significantly higher at the
Clinical Case Reports - Pituitary/Adrenal
lumbar spine, at the hip, at the forearm and at the whole body during therapy.
Conclusions
EP1085
After more than three years of treatment there was no improvement on the BMD
CHARGE Syndrome: a rare case of hypogonadotropic hypogonadism
significantly in the total hypogonism group. The treatment of male hypogonadism
Ana Sofia Osório, Carolina Faria, David Barbosa, Ema Nobre &
has improved the BMD at several skeletal regions just in the hyponadotrophic
Maria Joa˜o Bugalho
group.
Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa
Maria, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal.
Table 1 BMD qualification in hypogonadism before and during therapy.
Introduction
Hypogonadism before
Hypogonadism during
CHARGE Syndrome (CS) is a rare cause of hypogonadotropic hypogonadism
BMD
treatment nZ26 (100%) treatment nZ26 (100%)
(HH), usually diagnosed in paediatric age when pubertal development is
compromised. Herein, we report a case that presented a major criterion and
Normal
6
(23.1%)
8
(30.8%)
three minor criteria.
Reduced
12
(46.1%)
11
(42.3%)
Case report
Osteoporosis
8
(30.8%)
7
(26.9%)
At age ten, the patient was referred to the paediatric endocrinology unit due to
phenotypic alterations and psychomotor and cognitive impairment. She had no
DOI: 10.1530/endoabs.49.EP1083
family history of consanguinity, inherited or genetic disorders. At 8 years of age
she was diagnosed with semicircular channels bilateral agenesis with consequent
profound bilateral deafness. At physical examination there was a normal stature
and weight, facial asymmetry and dysmorphia, low ear implantation, cleft palate
and dorsocifoescoliosis. Genital examination revealed normal morphology and a
Tanner 2 stage. Pelvic ultrasonography was consistent with small ovaries and
uterus, without evidence of follicular activity. Basal FSH and LH were below the
normal range without response to LHRH stimulation. CHARGE syndrome was
considered and genetic tests were performed. The karyotype was 46 XX and a
Cardiovascular Endocrinology and Lipid Metabolism
missense mutation in the CHD7 gene was identified (c.484COT/p.Q162X). The
EP1084
patient initiated treatment with an estradiol/norgestrel combination at the age of
15 with marked improvement of pubertal development.
The effect of hormone replacement therapy and tibolone on lipoprotein
Conclusion
(a) concentrations in postmenopausal women: a systematic review and
CS should be considered in the differential diagnosis of HH particularly in
meta-analysis of randomized controlled studies
presence of an abnormal phenotype. Mutations in the CHD7 gene cause more than
Panagiotis Anagnostis1, Petros Galanis2, Vasileia Chatzistergiou1,
half of all cases of CS and most of the times are new mutations as occurred in the
John Stevenson3, Ian Godsland4, Irene Lambrinoudaki5, Mamas Theodorou6
current case. Different malformations may be present but the pattern varies among
& Dimitrios Goulis1
affected individuals justifying a long term follow up.
1Unit of Reproductive Endocrinology, First Department of Obstetrics and
Gynecology, Medical School, Aristotle University of Thessaloniki,
DOI: 10.1530/endoabs.49.EP1085
Thessaloniiki, Greece;2Center for Health Services Management and
Evaluation, Department of Nursing, National and Kapodistrian University
of Athens, Athens, Greece;3National Heart and Lung Institute, Imperial
College London, Royal Bromptonand Harefield NHS Foundation Trust,
London, UK;4Diabetes Endocrinology and Metabolic Medicine, Faculty of
EP1086
Medicine, Imperial College London, St Mary’s Campus, London, UK;
Combination of turner syndrome and congenital adrenal hyperplasia:
5Second Department of Obstetrics and Gynecology, National and
a rare case report
Kapodistrian University of Athens, Athens, Greece;6Health Policy and
Ivana Ságová1,2, Dušan Pávai1, Matej Stančík2, Helena Urbánková1,
Management Department, Open University of Cyprus, Nikosia, Cyprus.
Juliana Gregová1, Anton Va
ˇuga1,3 & Peter Vanˇ uga1
1Department of Endocrinology, National Institute of Endocrinology and
Introduction
Diabetology, Lubochna, Slovakia;2Department of Internal Medicine I,
Data on the effect of hormone replacement therapy (HRT) and tibolone on
University Hospital Martin, Martin, Slovakia;3Alpha Medical, s.r.o.,
lipoprotein(a) (Lp(a)), an independent risk factor for cardiovascular disease, are
Lubochna, Slovakia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Combination of Turner syndrome
(TS) and classical congenital adrenal
Functional hypogonadism has been described in association with acute severe
hyperplasia (CAH) is rare worldwide. Incidence of CAH - autosomal recessive
medical or surgical illness, subacute recovery and chronic disease. We present a
disorders characterized by enzyme defect of steroidogenic pathway, of which
case of transitory hypogonadism manifested during a peri-surgical period. A
90% ocuurs in the CYP21A2 gene coding 21-hydroxylase is 1:10000-16000.
42-year-old patient was sent to the endocrinology clinic due to hypertension and a
Incidencie of Turner syndrome is 1:2500 worldwide. Phenotypically, females
solitary adrenal mass. He was treated with bisoprolol and telmisartan, that he
with TS may present with a wide spectrum of clinical features. They may exhibit
maintains until today. The evaluation favoured non-functional adenoma but
short stature, virilization, premature ovarian failure and compromised fertility.
during the follow-up new complaints arose. He was diagnosed heart failure
We present a 57-year-old women suffering from both 45X0/46XX mosaic Turner
NYHA class-I related to aortic valve dysfunction and thoracic aortic aneurysm
syndrome and salt wasting form of CAH. After birth she was misdiagnosed as a
with surgical indication. He had recently visited the urologist due to complaints of
male. She had short stature and ambiguous genitalia - presence of the phallus with
erectile dysfunction and mentioned a normal scrotal US evaluation and the
perineoscrotal hypospadias and incomplete urogenital opening. Laparoscopy at
prescription of a phosphodiesterase inhibitor. These complaints started during the
age of six showed female sex organs. After this examination clitoroplasty and
pre-surgical period. He mentioned timed puberty (13 years old) and one daughter
vaginoplasty was done. Karyotyping revealed a 45X0/46XX pattern without sex
but declared reduced libido, reduced spontaneous erections, reduced turgor and
determining region Y on gene analysis. The presence of virilizing feature at
reduced need of shavings. He had BMI 21 kg/m2, no gynecomastia, normal sense
puberty could not explain the diagnosis of Turner syndrome. She had amenorhea,
of smell and adult volume testicles. His previous total testosterone
(TT)
marked hirsutism and was of short stature (height 130 cm). Laboratory tests
evaluations were within reference range (265 and 310 ng/dl). The new laboratory
revealed elevated level of 17-hydroxyprogesterone, dehydroepiandrosterone and
analyses showed low TT on two separate evaluations, 104 and 181 (RI 249-836)
low cortisol concentrations. Congenital adrenal deficiency was then suspected.
ng/dl with inappropriately normal LH 3.12 U/l and FSH 5.18 U/l. Prolactin, IGF1
With the genomic analysis, CYP
21A2 mutation in IN2G and united
and ACTH were normal. MRI could not be performed because of the new
deletion/conversion was detected. She was treated with hydrocortisone. In
prosthetic valve. He was started on monthly testosterone enanthate achieving
adolescent hydrocortisone was replaced by dexamethasone. Fludrocortisone was
normal TT levels (267 ng/dl) and remission of clinical complaints. After a period
added to the treatment, because laboratory tests revealed increased plasma renin
of 5 months, approximately 2 months after the heart surgery the patient felt he had
concentration. Under a continuous treatment, her state improved.
regained shaving frequency and sexual turgor, withdrawing both the phospho-
Keywords: Turner syndrome, congenital adrenal hyperplasia, 21-hydroxylase
diesterase inhibitor and the testosterone substitution. After 5 months of no therapy
deficiency, CYP21A2
he revisited the clinic and laboratory tests were performed with the finding of
normal TT 295 ng/dl, normal FSH and LH.
DOI: 10.1530/endoabs.49.EP1086
DOI: 10.1530/endoabs.49.EP1088
EP1087
EP1089
A rare case of short-term postpartum primary adrenal insufficiency
Myriam Briner1, Christina Gattlen2, Gunther Kaindl2, Martin
Congenital adrenal hyperplasia: case series, describing results of initial
Lukas Kaufmann2, Nic Zerkiebel1 & Natalia Rudovich1,3
dexamethasone therapy
1Department of Internal Medicine, Spital Bulach, Bulach, Switzerland;
Dragan Tesic1, Edita Stokic1, Milica Medic-Stojanoska1, Milena Mitrovic1,
2Department of Obstetrics and Gynaecology, Spital Bulach, Bulach,
Dragana Tomic-Naglic1, Tijana Icin1, Ivana Bajkin1, Djordje Popovic1,
Switzerland;3German Institute of Human Nutrition Potsdam-Rehbruecke,
Vuleta Dusan2 & Jovan Vlaski3
Nuthetal, Germany.
1Clinic of Endocrinology, Diabetes and Metabolic Diseases, Novi Sad,
Institut for
Serbia;2Obstetrics and Ginecology Clinics, Novi Sad, Serbia;3
Child and Youth Health Care, Novi Sad, Serbia.
Aims
Polyglandulare Autoimmune Sydnrome
(PAS) is a rare disease and the
development during pregnancy is seen even less often. PAS Type II presents
Introduction
with autoimmune adrenalitis and thyroiditis. Symptoms of adrenalitis such as
Congentital adrenal hyperplasia (CAH) comes to adult endocrinologist wheather
hypotension and hyperpigmentation are overlapping with physiological mani-
as transition from pediatritian (Case 3) or as still without diagnosis (Case 1, 2, 4).
festations during pregnancy making the diagnosis difficult.
The aim of this work is to describe typical forms of CAH initially sucessfuly
Clinical presentation
treated with dexamethasone therapy.
We are reporting the case of a 28-year old prima para prima gravida presenting
Case descriptions
two weeks postpartum (spontaneous preterm birth at 36 completed weeks of
Case 1: female, 1972y., presented in 1995y. (23y.) as severe hirsutism and
pregnancy) with hypotension, orthostatic presyncopal events and adynamia.
infertility managed by team of gynecologists. She refused any additional
Laboratory tests showed a low cortisol level, while adrenocorticotropic hormone
investigations and was severily depressed. Ex iuvantibus 0.5mg dexamethason
was augmented. Steroid-21-hydroxylase-antibodies and active renin were
therapy was followed with pregnancy. Case 2: female, 1990.y, presented in
increased. The medical history was significant for chronic lymphocytic thyroiditis
2008.y.(18y.). Non-classic CAH. Hirsutism, primary amenorrhoea. Dexametha-
with subclinical hyperthyroidism under L-thyroxin substitution. Synopsis of all
sone therapy 0.5 mg at night. After 4 month estabished menstruation, after 18m.
findings led us to the diagnosis of PAS type II.
became pregnant with healthy male baby born. Case 3: female, 1994y, presented
Conclusion
2012.y. (18y.) Classic CAH, salt wasting form. At birth classical low sodium,
The aim of this case report was to show that during pregnancy or postpartum we
high potassium. Established therapy with fludrocortison and hydrocortison, at
should take symptoms of adrenalitis in women with known autoimmune
night dexamethason 0.5 mg. Still primary amenorrhoea. On CT sevear vaginal
thyroiditis seriously and test for PAS.
stenosis. Case 4: male, 1980y, presented in 2014.y.(34y. old), when he was
diagnosed for the first time! Classic CAH, simple virilising form and
DOI: 10.1530/endoabs.49.EP1087
glucocorticoid-remediable aldosteronism, suprarenal hyperplasia on one gland
and incidentaloma on the other. Unilateral testicular adrenal rest tumour (TART),
azoospermia. Therapy hydrocortisone and dexamethasone at night. Soon he
normalised aldosterone, ACTH, 17-OH progesterone but lowered testosterone.
After 2y. CT of testes confirmed enlargement and the regression of TART.
Discussion
We have described two cases of CAH which solved the problem of fecundity
EP1088
(Cases 1 and 2). One treatment confirmed the need for additional surgical
Hypogonadotropic hypogonadism, functional and transitory
treatment of developmental abnormality on external genitalia(Case 3). Finally the
Catarina Roque, Filipa Serra, Francisco Sousa Santos, Catia Ferrinho,
problem of TART has been solved without any invasive intervention (Case 4),
Ricardo Capita˜o, Carlos Bello & Carlos Vasconcelos
wheather diagnostic or therapeutic, which are not the rare case even in these
Endocrinology Unit, Hospital de Egas Moniz, C.H.L.O. E.P.E., Lisbon,
years.
Portugal.
DOI: 10.1530/endoabs.49.EP1089
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Case Reports - Thyroid/Others
Developmental Endocrinology
EP1090
EP1092
A rare cause of a 46, XY disorder of sex development diagnosed in an
Age and developmental stage dependent relationship between plasma
adult patient
concentrations of leptin, luteinizing hormone, follicle stimulating
Katrin Feller1, Christa Fluck2, Laura Audi3, Mónica Fernández-Cancio3 &
hormone, prolactin, testosterone and inhibin B in boys between the age
Christoph Stettler1
of 1 and 20 years
1Department of Diabetology, Endocriniology, Clinical Nutrition and
Afzaal Ahmed Naseem1, Mazhar Qayyum1, Maleeha Akram1,
Metabolism, University Hospital of Bern, Bern, Switzerland;2Department
Zubaria Iqbal1, Fahim Tahir2, Kiran Afshan3, Sarwat Jahan3 &
of Pediatrics, Divsion of Pediatric Endocrinology and Diabetology,
Syed Shakeel Raza Rizvi1
University Hospital of Bern, Bern, Switzerland;3Pediatric Endocrinology
1Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University
Research Unit Vall d’Hebron Institut de Recerca, Universitat Autonoma de
Rawalpindi, Rawalpindi/Punjab, Pakistan;2Reproductive Physiology,
Barcelona, Barcelona, Spain.
Public Health Laboratories Division, National Institute of Health (NIH),
Islamabad, Pakistan;3Department of Animal Sciences, Quaid-i-Azam
University, Islamabad, Pakistan.
The defective conversion of testosterone to dihydrotestosterone due to a steroid
5-alpha-reductase 2 deficiency results in a unique form of 46, XY disorder of
sexual development (DSD). Dihydrotestosterone is essential for the embryonic
Leptin is regarded as an essential adipokine for controlling energy homeostasis,
differentiation of the external male genitalia and the prostate. Steroid 5-alpha-
caloric intake reduction and increase of caloric expenditure by negative feedback
reductase 2 deficiency is an autosomal recessive disorder in which genetic males
mechanisms via receptors in the hypothalamus. Puberty is said to be triggered by
have a predominantly female phenotype with female external genitalia but male
leptin, which signals the hypothalamus that adequate fat reserves are available for
internal urogenital tract. We describe the case of an adult patient having migrated
initiation of energetically costly process of reproduction. Leptin activates
from Pakistan to Switzerland in whom a steroid 5-alpha-reductase 2 deficiency
gonadotropin releasing hormone (GnRH) system, which stimulates luteinizing
was diagnosed at the age of
29. Molecular genetic analysis identified a
hormone (LH) and follicle stimulating hormone (FSH) secretion from pituitary
homozygous point mutation in exon 4 of the 5-alpha-reductase 2 gene, leading
gonadotropes and subsequent secretion of testosterone (T) from testes. Never-
to an amino acid change from glutamic acid to lysine. To our knowledge, this is
theless, it is not clear whether leptin has any association with the secretion of
the second case of this mutation in the steroid
5-alpha-reductase
2 gene
FSH, prolactin (PRL) and inhibin B during puberty. This study examined possible
(SRD5A2) which was first described in 1997 (Anwar et al.).
associations between plasma concentrations of leptin and LH, FSH, PRL, T, and
DOI: 10.1530/endoabs.49.EP1090
inhibin B at different ages and developmental stages in boys between 1 and 20
years (27 boys/age group). The concentrations of leptin, LH, FSH, PRL, T and
inhibin B were determined using specific ELISA. Data were analyzed using
Student’s t-test, ANOVA and Pearson correlation r. The concentrations of leptin
and LH were positively correlated at 1st, 4thK10th, 12th, 16th, 20th year and at
infancy and early puberty. Leptin and FSH concentrations were positively
correlated at 1st-3rd, 8thK10th, 12th, 13th, 15th, 16th, 18th, 20th year and at
infancy, pre-puberty and early puberty. Leptin and PRL levels were positively
correlated at 1st, 3rd, 5th, 6th, 9th, 10th, 12th-14th, 19th year and at infancy, pre-
puberty and early puberty. Leptin and T concentrations were positively correlated
at 1st, 3rd, 6th, 7th, 9th, 10th, 12th and 16th year and at infancy and early puberty.
Leptin and inhibin B levels were positively correlated at 1st, 3rdK8th, 10th, 12th,
15th-19th year and at infancy, early and late puberty. Thus, leptin and LH, FSH,
PRL, T and inhibin B are positively correlated only at early puberty.
DOI: 10.1530/endoabs.49.EP1092
EP1091
Association of short stature, microcephaly, secondary amenorrhea and
consanguinity: clinical case report
Claudia Matta-Coelho & Selma B Souto
Endocrinology Department, Braga Hospital, Braga, Portugal.
Background
Endocrine Tumours and Neoplasia
In 1985, Mikati et al., described a new syndrome, which included microcephaly,
EP1093
hypergonadotropic hypogonadism, short stature, mental retardation and minor
Molecular mechanisms underlying progesterone-enhanced breast
anomalies in four out of nine siblings of consanguineous parents. No genetic
cancer cell proliferation
disorder was associated to the disease. No further references to this syndrome
Hui-Chen Wang
have been found in literature. The authors present a new possible case of Mikati-
Taipei Medical University, Taipei Taiwan, Taiwan.
Naijjar and Sahli syndrome (MNJS).
Clinical case
Forty-two-year-old female referred to the Endocrinology Department due to
Previously, we demonstrated that progesterone (P4) could enhance breast cancer
secondary amenorrhea for 6 years. History of menarche at eighteen with regular
cell migration through increasing formation of the p27-RhoA complex and RhoA
menstrual cycles. No access to prenatal and neonatal history. Personal history of
activation caused by the cSrc/AKT-mediated phosphorylation of p27 at T198.
primary hypothyroidism medicated with levothyroxine 50 mg. She was able to
Here, we further examined the effect of P4 on breast cancer cell proliferation. Our
help in some household duties, but lacked capabilities for satisfactory results at
results show that P4
(12.5-100 nM) concentration-dependently enhanced
school. Parents are 1st degree relatives. Two healthy brothers and one other with
proliferation in breast cancer cell lines (T47D and MCF-7). We also found that
microcephaly, not further investigated. Physical examination Microcephaly
increases of cytoplasmic p27 localization are responsible for the P4-enhanced
(46 cm), weight 50 kg, height 129 cm. Also, narrow forehead, synophrys and
breast cancer cell proliferation. Our results demonstrated that P4 activated the
micrognathia. Tanner V. Unremarkable neurological exam. No relevant findings
cSrc/PI3K/AKT signaling pathway, subsequently activating RSK1, which in turn
in biochemical study besides hypergonadotropic hypogonadism. She had normal
increased phosphorylation of p27 at T198. PI3K/AKT activation also increased
prolactin, dehydroepiandrosterone sulphate, delta-4-androstenedione, sex hor-
phosphorylation of p27
at T157. Both p-p27T157
and p-p27T198
caused
mone-binding globulin and total testosterone. Normal uterus and ovary
cytoplasmic mislocation of p27 protein. In addition, P4 induced KIS activation,
ultrasound. Karyotype 46, XX.
which in turn increased phosphorylation of nuclear p27 at S10, subsequently
Discussion
causing p-p27S10 translocation from the nucleus to the cytosol. The decreased
The patient presented with multiple congenital abnormalities, which do not
level of nuclear p27 protein reduced its inhibition in the cyclin-CDK2 system,
occur in any known syndrome to our knowledge, besides MNJS. However, our
subsequently increasing phosphorylation of CDK2 at T160 and p27 at T187,
patient presented with secondary amenorrhea unlike the female patient in
hence causing translocation of p-p27T187 from the nucleus to the cytosol. In the
MNJS kindred with primary amenorrhea and Tanner II. Like the genetic defect
cytosol, both p-p27S10
and p-p27T187
were degraded by the ubiquitin-
was not studied in MNJS it will be challenging to ascertain if it is the same
proteasome pathway. Importantly, the P4-enhanced proliferation in breast cancer
syndrome.
cell lines was abolished when p27 was knocked-down or phosphorylation of 27
DOI: 10.1530/endoabs.49.EP1091
was inhibited. Taken together, our results demonstrated that P4 enhanced breast
cancer cell proliferation through increasing p27
degradation due to its
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
cytoplasmic mislocation. The findings from the present study highlight the
(ALT) and levels of total bilirubin. Furthermore, treatment with INH, RIF and
molecular mechanisms underlying P4-enhanced proliferation in breast cancer cell
PZA significantly (P!0.05) reduced the levels of luteinizing hormone, estrogen
lines.
and prolactin. In contrast, there were no significant differences (PO0.05) in the
DOI: 10.1530/endoabs.49.EP1093
levels of follicle stimulating hormone and progesterone in rats treated with anti-
TB drugs when compared to controls. Moreso, INH, RIF, EMB and PZA caused
significant (P!0.05) increase in the uterine malondialdehyde (MDA) levels by
281, 214, 273 and 190%, respectively, while INH and EMB increased the ovarian
MDA levels by 111% and 129%, respectively. All the anti-TB drugs significantly
(P! 0.05) decreased the activities of ovarian glutathione-S-transferase and
uterine glutathione peroxidase, superoxide dismutase and catalase. Histopatho-
logical examinations showed severe erosion of uterine mucosa, cellular debris in
EP1094
lumen of uterus and under-developed follicles in ovary of the rats. These results
Study of CYP17 and PSA G158A polymorphisms in prostate cancer
confirmed that the first line anti-TB drugs elicited reproductive toxicity in female
Suzana Vladoiu1, Dana Manda1, Sabina Oros1, Sorina Schipor1,
rats via mechanism that involved oxidative stress.
Adrian Preda3, Ismail Gener3, Catalina Picu1, Roxana Rosca1,2 &
DOI: 10.1530/endoabs.49.EP1095
Corin Badiu1,2
1‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;
2‘Carol Davila’ University of Medicine and Farmacy, Bucharest, Romania;
3Clinical Institute Fundeni, Bucharest, Romania.
The relationship between the level of genetic variation in CYP17, PSA genes and
prostate cancer has been extensively studied but the results are still unclear. A
EP1096
450c17a
(CYP17) polymorphism A1/A2 was described to be significantly
Development of hepatic steatosis and inflammation by chronic insulin
associated to prostate cancer. A SNP in the promotor PSA gene is an A to G
and hCG exposure in female rats: possible implications in PCOS
substitution at position K158 (G158A) was proposed to interact differently with
patients with NAFLD
AR, thereby modifying the expression pattern and occurrence of prostate cancer.
Ruijin Shao1, Yuehui Zhang1,2, Min Hu1 & Håkan Billig1
Objective
1The Sahlgrenska Academy at the University of Gothenburg, Goteborg,
The aim of the study was to investigate the association between CYP17 and PSA
Sweden;2First Affiliated Hospital, Heilongjiang University of Chinese
gene polymorphisms with advanced prostate cancer.
Medicine, Harbin, China.
Subjects and methods
The study was conducted on 48 patients with advanced prostate cancer (Gleason
score O 7) and 13 benign prostate hyperplasia subjects. Patients were enrolled
Accumulating clinical data suggest that women with polycystic ovary syndrome
after they gave their informed consent. DNA was isolated from prostatic tissue
(PCOS) are at high risk for nonalcoholic fatty liver disease (NAFLD). However, it
with PureLink Genomic DNA (Invitrogen). Genotyping of the A1/A2 and G/A
is not clear whether hyperinsulinemia and hyperandrogenism act concomitantly
polymorphisms in the promoter region of CYP17 and the PSA, respectively, were
or independently to induce hepatic steatosis and inflammation, and the molecular
determined by a PCR-RFLP assay. PCR product was digested with restriction
mechanisms behind the interactions between insulin resistance and hyperan-
enzyme NheI (PSA G-158A) and MspA1I (CYP17). Preoperatory serum PSA was
drogenism in the female liver remain largely unexplored. To achieve
assayed by immunochemiluminescence.
hyperinsulinemia, insulin resistance, and hyperandrogenism, we treated rats
Results
chronically with insulin, human chorionic gonadotropin (hCG), or a combination
Genotype distribution differ for PSA G-158 between the prostate cancer and the
of insulin and hCG. We showed that the different treatments induced varying
control group (25% GG, 25% AA, 50% AG vs. 8% GG, 23% AA, 69% AG) and
degrees of hepatic steatosis in rats. While hCG-treated rats had strongly
for CYP 17 (36% A1, 45% A1A2, 19% A2 vs. 22% A1, 64% A1A2, 14% A2).
aggravated hepatic inflammation, insulinChCG-treated rats exhibited the
The frequency of A1 allele was 0.41, and 0.59 for A2 allele. In control group the
hallmarks of metabolic alterations and hepatocyte cell damage. Further
frequency of A1 allele in population was 0.46, for A2 allele the frequency was
mechanistic study revealed that the expression of a number of genes (Srebp-1,
0.54. Neither CYP17 nor PSA polymorphisms associated with prostate cancer.
Srebp-2, Gpam, Ppara, Pparg, Lxra, E2f1, Il-6, Mcp1, Tgfb, and Ctgf) and
Serum levels of PSA did not differ between genotypes.
proteins (AceCS1, p-ACL, IRb, p110-PI3K, p-Akt (T308), AS160, p-GSK3b,
Conclusion
p-JNK, TNFa, and IL-1b) was significantly different in the liver between
In our study groups CYP17 and PSA gene polymorphisms did not significantly
treatment and control groups. In parallel, we observed that expression of genes in
associated with prostate cancer or serum PSA levels. Further studies are needed
adipose tissues that are related to M1/M2
macrophages was differentially
on larger cohorts.
regulated by the different treatments. In summary, our study presents several lines
Acknowledgement
of in vivo evidence that hyperinsulinemia and hyperandrogenism, either alone or
This work was funded by UEFISCDI grant no. 192/2014
in combination with insulin resistance, alter hepatic lipid metabolism, liver and
DOI: 10.1530/endoabs.49.EP1094
adipose tissue inflammatory responses, and cellular function and that the effects
of the different conditions are distinct from each other. By deciphering the
metabolic, endocrine, and molecular alterations along with morphological
changes, our findings offer a new understanding of how hyperandrogenism itself
or combined with insulin resistance contributes to liver damage in women with
PCOS.
DOI: 10.1530/endoabs.49.EP1096
Female Reproduction
EP1095
Administration of first line anti-tuberculosis drugs induces ovarian and
uterine oxidative stress and disruption of endocrine balance in rats
Oluwatosin Adaramoye, Olayinka Adebayo, Omolola Adesanoye,
Amos Abolaji & Aderemi Kehinde
EP1097
University of Ibadan, Ibadan/South West, Nigeria.
Frequency of nodular goiter and autoimmune thyroid disease and
association of these disorders with insulin resistance in polycystic
The first line anti-tuberculosis (anti-TB) drugs; isoniazid (INH), rifampicin (RIF),
ovary syndrome
ethambutol (EMB) and pyrazinamide (PZA) were effective in the treatment of
Mellia Karakose1, Sema Hepsen2, Erman Cakal1, Muyesser Arslan1,
pulmonary tuberculosis. However, the toxicity of these drugs has been of great
Esra Tutal1, Safak Akin1, Ilknur Unsal1 & Mustafa Ozbek1
concern in clinical settings. This study was designed to evaluate the toxic effects
1Diskapi Training and Research Hospital, Department of Endocrinology and
of anti-TB drugs on reproductive system in female rats. Thirty-five female Wistar
Metabolism, Ankara, Turkey;2Diskapi Training and Research Hospital,
rats were assigned into five groups of seven animals each. The control received
Department of Internal Medicine, Ankara, Turkey.
normal saline, while others received INH (5 mg/kg), RIF (10 mg/kg), EMB
(15 mg/kg) and PZA (15 mg/kg) via gavage thrice in a week for eight consecutive
Background and aim
weeks. Results showed that anti-TB drugs significantly (P! 0.05) reduced both
Polycystic ovary syndrome (PCOS) is one of the most common endocrine
uterine and ovarian weights, and relative weight of uterus relative to controls. In
disorder in women with reproductive age. Nodular goiter and autoimmune thyroid
addition, anti-TB drugs increased the activities of alanine aminotransferase
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
disease (AITD) are frequently seen endocrinological abnormalities. The aim of
EP1099
this study was to identify the prevalence of AITD and nodular goiter in PCOS
Serum sclerostin and dickkopf-1 levels in polycystic ovary syndrome
patients and investigate whether PCOS related hormones and metabolic factors
patients
affect these thyroid disorders.
Ogun Bilem, Yildiz Bilem, Mustafa Eroglu, Hakan Turkon,
Methods
Yasemin Sefika Akdeniz & Mehmet Asik
Ninety-seven with PCOS and seventy-one healthy female volunteers were
Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale,
recruited in the present study. Serum free thyroxine (fT4), thyroid stimulating
C¸ anakkale, Turkey.
hormone
(TSH), anti-thyroperoxidase antibody
(anti-TPO Ab), and anti-
thyroglobulin antibody (anti-Tg Ab) were measured. Thyroid ultrasonography
was performed and thyroid volume (TV) was calculated.
Introduction
Results
Polycystic ovary syndrome (PCOS) is the most common endocrine pathology in
The BMI, waist/hip ratio, fasting blood glucose, fasting insulin, HOMA-IR, TG
premenopausal women and it is a complex syndrome affecting various systems.
and LDL-C were significantly higher in PCOS patients (P!0.05). HDL-C were
Numerous studies have been made about how the PCOS effects on bone
significantly higher in control group (PZ0.005). The mean thyroid volume was
metabolism, but currently there is no clear information. Wnt pathway plays
11.4G4.7 ml in PCOS patients while 9.9G2.8 ml in controls (PZ0.022). Twenty
important role in the regulation of bone metabolism. The sclerostin(Scl) and
nine PCOS patients (29/97; 29.9%) had thyroid nodule whereas only eleven
Dickkopf-1
(DKK1) inhibit this pathway and they has recently become a
control subjects had thyroid nodule (11/71; 15.5%) (PZ0.043). The frequency of
therapeutic target of osteoporosis. In this study, we aimed to show the Scl and
AITD was significantly higher in PCOS patients
(PZ0.001). Statistically
DKK1 levels in women with PCOS.
significant relationship was found between thyroid volume and age, BMI, fasting
Methods
glucose, fasting insulin, HOMA-IR (P!0.05). Participants with thyroid nodule
This study was conducted in C¸ anakkale Onsekiz Mart University Endocrinology
were older and had higher BMI, fasting glucose, fasting insulin and HOMA-IR
department. Thirty-six women with PCOS and 35 healthy volunteers were
values compared to participants without thyroid nodule (P!0.05).
examined in this study. Both groups were compared in terms of respect
Conclusion
demographic, anthropometric, biochemical and Scl and DKK levels.
Our study showed that TV and frequency of nodular goiter were increased in
Results
PCOS patients. This result has been associated with insulin resistance. Therefore
PKOS grubunda sklerostin duzeyi 42.68G13.28 pg/ml, kontrol grubunda ise
we recommend PCOS patients must be monitored for the development of nodular
45.69G11.79 pg/ml olarak olçulmu¸ olup iki grup arasında istatistiki anlamlı fark
goiter and AITD.
olmadıg˘ı tespit edilmi¸tir. DKK1
duzeylerinin ise PKOS’lularda
1444.73G
DOI: 10.1530/endoabs.49.EP1097
611.30 pg/ml, kontrol grubunda 1204.26G660.88 pg/ml oldug˘u gosterilmi¸ olup
iki grup arasında anlamlı fark olmadıg˘ı saptanmı¸tır. The proportion of clinical
hirsutism (FGSR8) in PCOS group were significantly higher than the control
group. PCOS group compared to the control group in BMI and WHR were found
to be high, although the difference is not statistically significant.
Conclusions
This is the first study on this subject. C¸ alı¸mamızda PKOS’lu kadınlarda
sklerostin ve DKK1 duzeylerinin de
˘i¸medig˘i gosterilmi¸tir. PKOS’lu hastaların
EP1098
KMY olçumleriyle olan çalı¸malarda da çeli¸kili sonuçlar çıkmı¸tır. Her ne kadar
Association of basal and post-synacthen stimulated 17-hydroxypro-
amenore bu hastalarda kemik kaybına yol açıyorsa da, hiperandrojenemi ve
gesterone levels with insulin resistance in polycystic ovary syndrome
hiperestrojenemi gibi durumlar kemik uzerine olumlu etkiler yaparak bu etkiyi
Eleni Kandaraki1, Georgios Papadakis2, Sofia Tsirona3,
dengeliyor gorunmektedir.
Athina Asimakopoulou4, Nikolaos Chiotinis5, Genovefa Chronopoulou5,
Keywords: Polycystic Ovary Syndrome, Osteoprosis, Sclerostin, Dickkopf-1
Georgia Kassi4 & Evanthia Diamanti-Kandarakis3
DOI: 10.1530/endoabs.49.EP1099
1Endocrinology Department, Red Cross Hospital, Athens, Greece;2STEPS
Stoffwechselzentrum, Biel/Bienne, Switzerland;3Department of Endo-
crinology, Diabetes and Metabolic Diseases, Euroclinic Hospital, Athens,
Greece;43rd Department of Internal Medicine, Endocrinology Unit, Sotiria
Hospital, Athens, Greece;5Biochemical Department, Euroclinic Hospital,
Athens, Greece.
Objective
EP1100
17-alpha-hydroxyprogesterone caproate therapy during pregnancy has been
associated with insulin resistance. The aim of this study was to highlight any
Phthalates induce ovarian failure through disturbance in
folliculogenesis and steroidogenesis
possible association of 17OHP with insulin resistance in women with PCOS.
Dinh Nam Tran, Jae Hwan Lee, Changhwan Ahn, Jin Yong An,
Design
Seon Young Park & Eui-Bae Jeung
Forty-five women with PCOS underwent 75 g OGTT test and short Synachten test
Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
with sampling of stimulated 17OHP. Women were divided into two subgroups
according to basal 17OHP cut-off level of 0.8 ng/ml.
Results
Introduction
Women with basal 17OHP more than 0.8 ng/ml had significantly higher glucose
Phthalates are chemicals used to improve the plasticity of industrial polymers and
levels at 600 min: Glu60: 111.36G22.37 mg/dl vs 133.11G32 mg/dl, PZ0.047,
used in commercial products such as toys, paints, packaging materials, medicals
and at 900 min Glu90: 93.50G13 mg/dl vs 113.50G27 mg/dl, PZ0.038 and more
devices and personal care items. Phthalates, endocrine disrupting chemicals, have
often polycystic ovarian morphology in ultrasound compared to those with basal
been documented to cause adverse effects to the human health such as breast
17OHP levels below 0.8 ng/ml. The mean percentage increase of 17OHP at 600
cancer in female, reduced uroogenital distance and changed the expression of
after Synachten test was 223%. According to this, women were subdivided into
steroidogenesis and folliculogenessis. In this study, we investigated the impact of
two categories depending on whether the intraindividual percentage increase of
di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl
post-Synachten 17OHP levels was higher or lower than the mean percentage
phthalate
(BBP) on loss of ovarian function through folliculogenesis and
increase. A total of 26 women with hyperresponsiveness of 17OHP at 600 minutes
steroidogenesis. 4-Vinylcyclohexene diepoxide (VCD), a disruptor of ovarian
appeared with significant higher insulin resistance and post glucose challenge
small pre-antral follicles, was used as a positive control.
hyperinsulinemia when compared to 19 women with lower percentage increase of
Methods
17OHP, i.e. their mean insulin levels at 300 minutes were: Ins30: 130.9G98.7 vs
Female Spargue-Dawley rats (8 weeks of age, 160-180 g bodyweight) were
59.3G30.9 mU/ml, PZ0.05, at 600
minutes: Ins60:
182.4G124.9 vs 74.4G
administered VCD
(80 mg/kg) by intraperitoneal, DEHP
(25 mg/kg), BBP
32.1 mU/ml, PZ0.01, at 900 minutes: Ins90: 177.2G128.2 vs 67.9G34.1 mU/ml,
(250 mg/kg) and DBP (250 mg/kg) by oral gavage in 0.3 ml of corn oil at LOAEL
PZ0.01, and at
1200
minutes: Ins120:
121.6G65.2
vs
67.1G45.8 mU/ml,
during 6 weeks. Vaginal smear was collected at 9 a.m every day to check estrus
PZ0.05.
cycle. Blood, pituitary, uterine and ovaries were collected after
24 h final
Conclusions
injection.
17OHP could possibly be related to the metabolic abnormalities in women with
Results
PCOS and this should me taken into account especially during pregnancy when
There was significantly increased in body weight of DEHP groups compared to
insulin resistance increases.
other groups. Estrus cycle in DEHP and DBP groups showed no difference
DOI: 10.1530/endoabs.49.EP1098
comparing with vehicle group. However, diestrus phase in VCD and BBP groups
drew out compared to vehicle group. The transcriptional levels of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
folliculogenesis-related genes (Foxl2, Kitl and Amh) and steroidogenesis-related
found. No significant relation between age, BMI, w_h, E2, T, SHBG
genes (Star and Cyp11a1) were changed.
concentrations, duration of E2
use and FSFI domains in TS patients was
Conclusion
detected. 41% (nZ11) of TS used NE2, 26% (nZ7) were on COCs and 33%
Our findings suggest that these phthalates can induce premature ovarian failure by
(nZ9) were in no_E group. NE2 or COCs users had higher total FSFI score
disturbance in folliculogenesis and steroidogenesis and failure in hormone
(25.36G9.10 vs 17.89G13.62; PZ0.008) and reported better lubrication (4.60G
regulation.
1.84; PZ0.031), satisfaction (4.83G1.72 vs 3.20G2.57; PZ0.008), pain (4.67G
DOI: 10.1530/endoabs.49.EP1100
1.69 vs 2.97G2.46;Z0.03) during sexual intercourse compared with no_E. NE2
users had better desire (3.81G1.36 vs 2.01G2.15,Z0.005), lubrication (4.58G
1.78 vs 2.35G2.48; PZ0.014), arousal (4.03G1.63 vs 2.37G2.33; PZ0.009),
orgasm (3.85G1.86 vs 2.20G2.37; PZ0.05), satisfaction (4.54G1.81 vs 2.71G
2.83; PZ0.001), pain (4.90G1.73 vs 2.26G2.46; PZ0.011) and total FSFI score
(25.74G9.33 vs 14.09G14.38; PZ0.001) when compared with COCs users.
Conclusion
Sexual function in TS did not differ compared with controls. Higher FSFI score
EP1101
was found in E2 users compared with untreated patients and in NE2 users
Efficacy comparison of oral rosuvastatin versus oral progesterone and
compared with COCs users.
bevacizumab on regression of surgically endometriotic implants in rats
DOI: 10.1530/endoabs.49.EP1102
Ayse Gul Kebapcilar, Tolga Tuyan Ilhan, Duygu Dursunoglu, Kubra Kurt,
Suleyman Hilmi Ipekci, Suleyman Baldane, Mustafa Gazi Ucar,
Cem Onur Kirac, Levent Kebapcilar & Cetin Celik
Selcuk University, konya, Turkey.
Aim
Thirty female Wistar albino rats with surgically endometriotic implants were
randomly randomized into three treatment groups: oral rosuvastatin (20 mg kg per
day; oral rosuvastatin group 1; nZ10), oral progesterone (Dienogest group 2;
EP1103
nZ10), and intraperitoneal bevacizumab (2.5 mg/kg of single intaperitoneal
BMP8 sustains expansion and survival of cumulus cells in vitro
injection of bevacizumab; group 3; nZ10) respectively, for 10 day and post-
Fang-Ju Wu & Ching-Wei Luo
treatment variables were compared.
National Yang-Ming University, Taipei, Taiwan.
Results
The endometrium foci as were measured on days 1 and 10. Rosuvastatin group
showed higher reduction for the glandular epithelium and uterine vessels of
histopathological scores values than progesterone group
(both, P!0.017;
Cumulus cells are a group of specialized granulosa cells that surrounds
respectively). The median glandular epithelium and uterine vessels and
oocytes and are critical for female fertility. During ovulation, cumulus cells
histopathological scores values did not show statistically significant difference
need to be expanded systematically in order to support the maturation,
among group 1 and group 3 (PO0.017). No significant different reduction was
ovulation and fertilization of oocytes, whereas their apoptosis will result in
observed in between the three groups for the myometrium, endometrial stroma, in
the decline of fertilization rate and pregnancy outcome. However, the
histopathological scores (PO0.017). Endometrial thickness and uterine volume
molecules as well as their signalings involved in the control of cumulus cell-
values analyzed in all treatment groups. Endometrial thickness values and uterine
oocyte complex (COC) expansion are complicated and await more studies.
volume values was more significantly reduced in the oral rosuvastatin medication
By analyzing several microarray and RNA-seq datasets, we intriguingly
than oral progesterone group
(both, P!0.017; respectively). Moreover,
noticed that BMP8 expression in cumulus cells was positively correlated to
endometrial thickness and uterine volume values were not different in groups I
human oocyte maturation and zygote developmental competence. Using a
compared with group 3 (PO0.017).
rat superovulation model, we found that Bmp8 transcripts were up-regulated
Conclusion
by the luteinizing hormone signaling and were abundant in cumulus cells of
In conclusion, rosuvastatin and intaperitoneal injection of bevacizumab may
pre-ovulatory follicles. Furthermore, BMP8 treatment can induce COC
causes more significant regression of surgically endometriotic implants in rats
expansion as well as the expression of COC expansion-related genes.
than oral progesterone medications.
Hoechst-propidium iodide double staining further revealed that BMP8 can
decrease cumulus cell apoptosis in ovulated COCs. BMP8 can induce the
DOI: 10.1530/endoabs.49.EP1101
phosphorylation of both SMAD1/5/8 and SMAD2/3 in isolated COCs.
Signaling dissection by inhibitors further indicated that blockage of
SMAD2/3 pathway can impair BMP8-induced COC expansion, whereas
blockage of either SMAD1/5/8 pathway or SMAD2/3 pathway dampens the
protective role of BMP8 against cumulus cell apoptosis, indicating that both
pathways are needed for BMP8-mediated cumulus cell survival. Taken
together, our data demonstrated that BMP8 sustains both expansion and
survival of cumulus cells through different SMAD downstreams. With these
EP1102
capabilities, BMP8 can contribute to the maintenance of oocyte quality and
The relation between sex hormones and sexual function in women with
this may have clinical applications when doing in vitro fertilization.
Turner syndrome
DOI: 10.1530/endoabs.49.EP1103
Ruta Kriksciuniene, Birute Zilaitiene, Justina Sematonyte &
Rasa Verkauskiene
Lithuanian University of Health Sciences, Kaunas, Lithuania.
Objectives
To evaluate sexual function in women with Turner syndrome (TS) in the relation
with sex hormones.
Methods
The study was undertaken in Lithuanian University of Health Sciences. 65 women
EP1104
with genetically confirmed TS (18-45 years) were enrolled and compared with 65
Serum concentrations of betatrophin and its association with indirect
age-matched healthy controls. Sexual function was evaluated using The Female
indices of insulin resistance and beta cell function in women with
Sexual Function Index (FSFI). Risk for sexual dysfunction was defined as FSFI
polycystic ovary syndrome
score % 26.55. BMI, waist-hip ratio (w_h), concentrations of estradiol (E2),
Agnieszka Adamska1, Agnieszka Lebkowska1, Malgorzata Jacewicz1,
testosterone (T), sex hormone binding globulin (SHBG) were evaluated. TS
Anna Krentowska1, Justyna Hryniewicka1, Slawomir Wolczynski2,
patients were divided into 3 groups: natural estrogens users (NE2), combined oral
Maria Gorska1 & Irina Kowalska1
contraceptives users (COCs) and untreated (no_E).
1Department of Endocrinology, Diabetology and Internal Medicine,
Results
Medical University of Białystok, Bialystok, Poland;2Department of
38% (nZ27) TS had sexual intercourse and filled out FSFI. 33% (nZ9) of TS and
Reproduction and Gynecological Endocrinology, Medical University of
42% (nZ25) of controls were at risk for sexual dysfunction (PO0.05). No
Białystok, Bialystok, Poland.
difference in FSFI score depending on karyotype (classic or mosaicism) was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1106
The accumulated data underline the role of betatrophin in glucose
The functional state of hypophysis - gonad axis in patients with
homeostasis. Polycystic ovary syndrome (PCOS) is characterized by insulin
polycystic ovary syndrome (PCOS)
resistance and high risk of developing prediabetes and diabetes. The aim of
Yulduz Urmanova1,2, Feruza Khodgaeva1,2, Dinara Alieva1,2,
our study was to investigate the relationship of serum betatrophin
Salim Sodikov1,2, Nazira Rikhsieva1,2 & Maryam Abduvakhabova1,2
concentrations with indirect indices of insulin resistance and insulin
1Paediatric Medical Institute, Tashkent, Uzbekistan;2Center of the
secretion in women with PCOS, comparing to the control group. The
Scientific and Clinical Study of Endocrinology, Tashkent, Uzbekistan.
study group comprised 43 women with PCOS and 16 controls matched for
BMI and age. An oral glucose tolerance test (OGTT) with estimation of
serum betatrophin concentrations was performed. Insulin resistance was
The aim
assessed by HOMA-IR and Matsuda index. Insulin secretion was evaluated
To study the functional state of axis of hypophysis-gonads for women with PCOS.
by HOMA-B. Glucose load resulted in an increase of serum betatrophin
Material and methods of investigation
concentrations only in the control group (PZ0.02). Consequently, serum
Under our supervision in the department of neuroendocrinology of The Center of
betatrophin concentrations at 1200 of OGTT were lower in women with
Endocrinology of PHM of Republic of Uzbekistan ambulatory in a period from
PCOS in comparison to the control group (PZ0.02). We observed a positive
September 2015 for July, 2016 120 patients of fertile age were inspected with
relationship between baseline serum betatrophin concentrations and
polycystic ovary syndrome (PCOS). Middle age of patients - 25.5G4.3 years.
baseline serum insulin concentrations
(rZ0.42, PZ0.004) in PCOS
The remoteness of disease hesitated in limits from 7 months to 9 years. 20 healthy
group. Additionally, correlations between baseline serum betatrophin
women of corresponding age made a control group. The complex of researches,
concentrations and HOMA-IR (rZ0.39, PZ0.008), HOMA-B (rZ0.38,
including clinical, biochemical hormonal, ultrasound investigations of uteri/o-
PZ0.01) and Matsuda index (rZK0.31, PZ0.004) were observed in
varies, pituitary MRI was executed all patients.
women with PCOS. We found relationship between D betatrophin and
Results
serum total testosterone concentration in the entire group
(rZK0.32,
Patients were divided into two groups: 1 g - patients with primary sterility are 94
PZ0.01). Multiple regression analysis revealed that HOMA-B (bZ0.47,
cases, 2 r. - patients with secondary sterility are 26 cases. In a 1 group of patients
PZ0.001) was an independent factor connected to serum betatrophin levels
with primary sterility the reliable decline of both pituitary and ovarian hormones
in women with PCOS. Serum concentrations of betatrophin is connected
was marked on a background hyperandroenemiya and hyperprolactinemiya. In
with insulin resistance and beta cell function and did not change after
the second group of patients the reliable decline of pituitary hormones was also
glucose load in women with PCOS.
educed on a background hyperandroenemiya and hyperprolactinemiya. While an
DOI: 10.1530/endoabs.49.EP1104
ovarian function was within the limits of norm.
Conclusions
In both groups of patients took place hypogonadotropinemiya combining
moderate hyperprolactinemiya and hyperandrogenemiya.Thus, the most
expressed violations of the system of pituitary - ovarian function were found
out in the first group of patients with PCOS with primary sterility, at that the
reliable decline of the functional state of pituitary-gonads was marked, namely
decline of LH, FSH, estradiol and progesterone of plasma of blood on 14 day of
menstrual cycle.
DOI: 10.1530/endoabs.49.EP1106
EP1105
Short term intervention with liraglutide and metformin increased
fertility potential in a subset of obese PCOS proceeding IVF
Vesna Sˇ alamon2, Mojca Jensterle1, Andrej Janež1 & Eda Vrtačnik Bokal2
1Department of Endocrinology, Diabetes and Metabolic Diseases,
University Medical Centre Ljubljana, Ljubljana, Slovenia;2Department of
Human Reproduction, Division of Obstetrics and Gynecology, University
Medical Centre Ljubljana, Ljubljana, Slovenia.
EP1107
Efficacy of FSH alone, FSH C LH, hMG or FSH C hCG on ART
outcomes in the ‘personalized’ medicine era: a meta-analysis
Objective
Daniele Santi1,2, Livio Casarini2,3, Carlo Alviggi4 & Manuela Simoni1,2
Obese PCOS have poor IVF outcomes. The aim of this study was to evaluate the
1Unit of Endocrinology, Department of Biomedical, Metabolic and Neural
impact of weight reduction with metformin alone or in adjunct with liraglutide on
Sciences, University of Modena and Reggio Emilia, Modena, Italy;2Unit of
oocyte maturity and embryo quality in infertile obese PCOS population.
Endocrinology, Department of Medicine, Endocrinology, Metabolism and
Design/participants/main outcome measure
Geriatrics, Azienda USL of Modena, Modena, Italy;3Center for Genomic
A 12-week prospective randomized study was conducted with 40 infertile PCOS
Research, University of Modena and Reggio Emilia, Modena, Italy;
(30.77G3.742 aged years, BMI 36.69G3.51 kg/m2, mean G SD) who had been
4Department of Neuroscience, Reproductive Science and Odontostomatol-
previously poor responders to lifestyle intervention. They were assigned to
ogy, University of Naples Federico II, Naples, Italy.
metformin (MET) 1000 mg BID or MET 1000 mg BID and liraglutide 1.2 mg QD
S.C.
(COMBI) or to controls (CON). CON direclty proceeded with ovarian
stimulation protocol, whereas MET and COMBI started with stimulation after 4
Background
weeks medication free period.
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the
Results
same receptor, activating different signal transduction pathways. The role of LH
Eleven women on MET, 13 on COMBI and 11 CON completed the study.
or hCG addition to follicle stimulating hormone (FSH) as well as menopausal
Patients in MET lost 6.70G6.70 kg (P?0.001) compared with 7.68G3.74 kg loss
gonadotropins (hMG) in controlled ovarian stimulation (COS) is debated.
in COMBI (P!0.001), COMBI not being superior to MET (PZ0.103). COMBI
Aim
resulted in a reduction of visceral adipose tissue area
(K20.65G7.40 cm2;
To compare FSHCLH, or FSHChCG or hMG vs FSH alone on COS outcomes.
PZ0.028). More than 5% of weight reduction was achieved in 76.9% in COMBI
Design
and 45.5% of patients in MET. In high responders who lost more than 5% of body
A meta-analysis according to PRISMA statement and Cochrane Collaboration
weight numbers of blastocysts/patient were greater in both treatment arms than in
was performed, including prospective, controlled clinical trials published until
CON (3.67G4.82 in COMBI; 3.60G6.95 in MET; vs 2.09G2.07 in CON). High
July 2016, enrolling women treated with FSH combined with other gonado-
responders in COMBI had the highest numbers of oocytes/patient 14.67G9.59
tropins. Trials enrolling women with polycystic ovarian syndrome were excluded.
and of mature oocyte 11.22G9.27 (PZNS). In COMBI 3 patients became
Results
spontaneously pregnant before IVF in medication free period.
Considering 70 studies, the administration of FSH alone resulted in higher
Conclusion
number of oocytes retrieved than FSHCLH or hMG. The MII oocytes number did
Women who lost more than 5% of body weight before IVF had increased fertility
not change when FSH alone was compared to FSHCLH, FSHChCG or hMG.
potential. COMBI resulted in the highest number of high responders and was
Embryo number and implantation rate were higher when hMG was used instead
associated with the highest number of blastocysts/patient. The high rate of
of FSH alone. Pregnancy rate was significantly higher in FSHCLH-treated group
spontaneous pregnancies in COMBI implies the potential role of GLP-1 in
versus others. Only twelve studies reported live birth rate, not providing protocol-
reproduction.
dependent differences. Patients’ stratification by age (medianZ32.5 years) and/or
DOI: 10.1530/endoabs.49.EP1105
by GnRH agonist/antagonist identified patient subgroups benefiting from specific
drug combinations.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
cigarette smoke extract
(CSE) affects the cell proliferation, migration and
In COS, FSH alone results in higher oocyte number. However, hMG improves the
endocrine hormone activity of JEG-3 human placental cancer cells. JEG-3 cell
collection of mature oocytes and embryos and increases implantation rate,
proliferation was significantly reduced by all CSEs in a concentration-dependent
although the final increased pregnancy rate is evident only in GnRH agonist
manner. Moreover, CSEs decreased proliferating cell nuclear antigen (PCNA)
protocol. On the other hand, LH addition leads to higher pregnancy rate. This
levels in JEG-3 cells in western blot. Increased migration or invasion ability of
study supports the concept of a different clinical action of gonadotropins in COS,
JEG-3 cells following CSE treatment was also confirmed by a scratch or
reflecting previous in vitro data.
fibronectin invasion assay in vitro. Additionally, protein levels of E-cadherin as
DOI: 10.1530/endoabs.49.EP1107
an epithelial maker were down-regulated, while the mesenchymal markers
N-cadherin, snail and slug were up-regulated in a time-dependent manner. The
metastasis marker, cathepsin D, was also down-regulated by CSE. Finally, CSEs
significantly reduced the expression of hCG-b protein in JEG-3 cells. Overall,
these results indicate that exposure of placental cells to CSE deregulates the cell
cycle by altering the expression of cell cycle-related proteins and stimulates cell
metastatic ability by altering EMT markers and cathepsin D expression. CSE
exposure may also decrease hCG-b production as an endocrine marker, implying
that cigarette smoke has adverse effects during pregnancy. (This research was
EP1108
supported by a grant (14182MFDS977) from the Ministry of Food and Drug
May thiol/disulfide homeostasis predict adult PCOS?
Safety, Republic of Korea, in 2016.)
Hakan Sevimli1, Cemile Koca2, Mahmut Senyurt1, Ozcan Erel2,
Keywords: Cigarette smoke extract, placental cells, cell cycle, metastasis, human
Esra Laloglu3 & Ayse Carlioglu1
chorionic gonadotropin beta subunit
1Regional Training and Research Hospital, Erzurum, Turkey;2Yildirim
DOI: 10.1530/endoabs.49.EP1109
Beyazit University Faculty of Medicine, Ankara, Turkey;3Public Health
Laboratory, Erzurum, Turkey.
Purpose
The purpose of this study was to evaluate the relation polycystic ovarian syndome
(PCOS) and the thiol/disulfide balance, used as a marker of oxidative stress, by
measuring that exchange using a novel technique.
Material/methods
EP1110
Fourty nine subjects diagnosed with PCOS and 44 healthy were included in the
Hyperandrogenism and overweight/obesity, independently and inter-
study. Thiol/disulfide homeostasis concentrations were measured by a newly
actively, increase the risk of metabolic syndrome and type 2 diabetes in
developed method. After native thiol, total thiol and disulfide levels were
women - a Prospective, Population-based Cohort Study
determined; measures such as disulfide/native thiol, disulfide/total thiol, and
Meri-Maija Ollila1, Kari Kaikkonen2, Sirkka Keinanen-Kiukaanniemi3,4,
native thiol/total thiol were calculated.
Katri Puukka5, Aimo Ruokonen5, Marjo-Riitta Järvelin3,6,
Results
Juha Tapanainen1,7, Steve Franks8, Terhi Piltonen1 &
Lipid accumulation product
(LAP) index
(P!0.001), total testesterone
Laure Morin-Papunen1
(P!0.001), insulin
(PZ0.003), total cholesterol
(PZ0.02), triglyceride
1Department of Obstetrics and Gynaecology, University of Oulu and Oulu
(PZ0.004), disulfide (PZ0.007), disulfide/native thiol ratio
(P!0.001) and
University Hospital, Medical Research Center, PEDEGO Research Unit,
disulfide/total thiol ratio (P!0.001) were significantly higher and native thiol
Oulu, Finland;2Division of Cardiology, Department of Clinical Medicine,
(PZ0.01), total thiol (PZ0.04) and native thiol/total thiol ratio (P!0.001) were
Medical Research Center, University of Oulu and Oulu University Hospital,
sig-nificantly lower in patients with PCOS compared to control subjects.
Oulu, Finland;3Institute of Health Sciences, University of Oulu, Oulu,
Correlation analysis reveals negative correlation of FGS, cycles, WC, LH: FSH
Finland;4Unit of General Practice, Oulu, Finland;5NordLab Oulu,
ratio and Tg with native thiol and total thiol in cases. Also there was a significant
Department of Clinical Chemistry, University of Oulu and Oulu University
negative correlation between LAP index, BMI and native thiol. DHEA-S had a
Hospital, Medical Research Center Oulu, Oulu, Finland;6Department of
positive correlation between disulphide. Stepwise logistic regression model
Epidemiology and Biostatistics, MRC-PHE Centre for Environment and
showed that significantly high disulfide levels, disulfide/native thiol ratio and
Health, School of Public Health, Imperial College London, London, UK;
disulfide/total thiol ratio in patients with PCOS were found to be independent of
7Department of Obstetrics and Gynaecology, University of Helsinki and
age and BMI. Receiver operating characteristic curve analysis showed that areas
Helsinki University Hospital, Helsinki, Finland;8Institute of Reproductive
under the curve for native thiol, total thiol, native thiol/total thiol ratio and
and Developmental Biology, Imperial College London, London, UK.
disulfide, disulfide/native thiol ratio, disulfide/total thiol ratio were
0.660
(PZ0.008),
0.601
(PZ0.096),
0.714
(P!0.001),
0.663
(PZ0.007),
0.701
(PZ0.001), 0.701 (PZ0.001), respectively.
The significance of hyperandrogenism (HA) as a metabolic risk factor in women
Conclusion
is controversial. HA can be defined as either clinical (hirsutism) or biochemical
It can be concluded that oxidative stress is increased in patients with PCOS, can
(elevated androgen levels). We aimed to investigate whether HA at age 31
play a pathophysiological role in the development of PCOS and this increase is
associates with metabolic syndrome (MetS), type 2 diabetes mellitus (DM2) or
not associated age and BMI. However, studies with larger sample sizes are needed
carotid intima media thickness (CIMT) by age 46. In a prospective, general
in this area.
population-based follow-up birth cohort (nZ5889 women) blood samples were
DOI: 10.1530/endoabs.49.EP1108
collected at age 31 in 3127 women and at age 46 in 3280 women. HA was defined
as presence of hirsutism, serum testosterone O2.3 nmol/l
(determined by
LC-MS/MS) or free-androgen-index (FAI) O5.6 at age 31. MetS was defined
according to IDF criteria. An oral glucose tolerance test (OGTT) was performed
at age 46 in 2780 women. Glucose metabolism was defined according to the
WHO standards. Diagnosis of DM2 was also verified and completed from the
national drug and hospital discharge registers. Regression models were used to
study if HA associates with cardiovascular risk factors at age 46. As expected,
EP1109
women with HA had significantly greater BMI at age 46 (27.54G6.2 vs 26.58G
Effects of cigarette smoke extracts on proliferation, migration, and
5.23 kg/m2, PZ0.018), compared to controls. HA at age 31 was significantly
hCG-b protein expression of JEG-3 human placental cancer cells
associated with MetS (ORZ1.5, 95%CI: 1.1-2.0) and DM2 (ORZ3.1, 95%CI:
Cho-Won Kim, Hae-Miru Lee & Kyung-Chul Choi
1.8-5.2) at age 46. The significance remained in the multivariate regression
Laboratory of Biochemistry and Immunology, College of Veterinary
analysis including BMI at age 31 (for MetS: HA: ORZ1.4, 95%CI: 1.1-2.0;
Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic
BMI: ORZ4.0, 95%CI: 3.1-5.2; for DM2: HA: ORZ2.7, 95%CI: 1.6-4.6; BMI:
of Korea.
ORZ4.1, 95%CI: 2.4-7.0). There were no significant differences in the CIMT
between women with HA compared to controls. These results indicate that HA
Maternal smoking during pregnancy is known to be related to adverse pregnancy
per se may increase the prevalence of MetS and DM2 in a general population.
results associated with trophoblast proliferation and cell cycle progression.
However, BMI seems to have a greater impact on the presence of these metabolic
Moreover, many previous studies have shown that cigarette smoke is correlated
risks, with two-fold higher odds ratios than HA.
with human chorionic gonadotropin beta
(hCG-b) subunit produced from
DOI: 10.1530/endoabs.49.EP1110
syncytiotrophoblasts during pregnancy. Thus, we further investigated whether
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1111
Conclusion
Our study suggests that S1PRs play a role in ovarian follicle growth and oocyte
Natural history of the Swyer Syndrome
maturation.
Katarzyna Doroszewska1, Tomasz Milewicz1, Marta Kialka1 &
Sandra Mrozinska2
DOI: 10.1530/endoabs.49.EP1112
1Department of Gynecological Endocrinology UJ CM, Cracow, Poland;
2Department of Metabolic Diseases UJ CM, Cracow, Poland.
We present a case of a eighteen-year-old woman admitted to the Gynecological
and Endocrinological Department because of primary amenorrhea. Physical
examination showed excessive pubic hair and clitoral hypertrophy. Laboratory
EP1113
tests showed the increased level of foliculotropina (FSH) 90 mIU/ml (normal
range 3.5-12.5 mIU/ml) and the estradiol level below 10 pmol/l (normal range
Polycystic ovary syndrome and euthyroid hashimoto’s thyroiditis:
46-607 pmol/l). An ultrasound-imaging of the abdomen and pelvis showed the
possible influence of thyroid autoantibodies
uterus of normal size and shape. Bands of connective tissues were present at the
Mustafa Utlu, Ozge Timur & Ayse Carlioglu
Regional Training and Research Hospital, Erzurum, Turkey.
site of ovaries. Because of the clinical presentation a genetic test was done which
revealed the XY karyotype. Based on the results the Swyer syndrome was
diagnosed. A hormonal substitution therapy was introduced and the surgical
Thyroid disorders and polycystic ovary syndrome (PCOS) are two of the most
removal of the streak gonads was planned because of the risk of malignancy. The
common endocrine disorders in general population. Autoimmune thyroid diseases
patient did not give consent for the operation and did not report for the follow up
are common autoimmune disorders that affect about 5% to 20% of women in
visits. Three years later, the woman reported back to the Clinic because of acute
childbearing age. In this study, we evaluate the comorbidity rate of euthyroid
pain in the lower back, dyspnoea and increasing abdominal circumference. The
Hashimoto’s Thyroiditis (HT) in PCOS patients and possible influence of thyroid
computer tomography of the minor pelvis showed the presence of lumpy mass in
autoantibodies on clinical and laboratory findings of PCOS. This study includes
the pelvic cavity. The patient underwent an operation. Intraoperatively numerous
285 PCOS patients attending to our outpatient Endocrinology Clinic at Erzurum
metastasis were found in the abdomen and pelvis. Radical hysterectomy was
Region Training and Research Hospital. The control group include 32 age and
performed. Histopathological examination of the streak gonads showed
body mass index matched healty women. In PCOS group 88 of 285 (%30.87)
dysgerminoma and gonadoblastoma on the left gonad and dysgerminoma on
patients have euthyroid Hashimato’s disease where as in control group 2 of 32
the right one. After operation the patient was given 4 cycles of chemotherapy.
(%6.25) have disease. These findings are statistically significant (PZ0.003).
This case presents the natural history of the Swyer syndrome.
None of the euthyroid Hashimato’s patients take L-thyroxine replacement therapy.
DOI: 10.1530/endoabs.49.EP1111
Anti-TPO and anti-TG were significantly higher in patients with PCOS
(PZ0.000; PZ0.01; respectively). Anti-TPO had a significantly positive
correlation between PCOS presence (rZ0.119; PZ0.036), and clinical indicators
of PCOS such as cycle time (rZ0.709; PZ0.000), Ferriman-Gallwey score (rZ
0.376; PZ0.001), DHEAS
(rZ0.132; PZ0.04), testosterone
(rZ0.124;
PZ0.043), and LH/FSH
(rZ0.136; PZ0.025). TPO was seen to be an
independent risk factor from body mass index, age and TSH in PCO patients.
EP1112
Anti-TPO and anti-Tg were also sensitive and spesific in diagnosing PCOS. AUC
value of Anti-TPO was 0.843 (PZ0.000) and Anti-Tg was 0.843 (PZ0.000). In
Biological activity mediated by sfingosine-1-phospate receptors in
ROC analysis, TPOR4.9 had 99.6% sensitivity and 71% specificity, anti TG R18
human primary granulosa cells and immortalized granulosa cell line
had 94.8% sensitivity and 75% specificity in predicting PCOS. In our study
in vitro
thyroid autoantibodies were significantly higher in patients with PCOS. We think
Livio Casarini1,2, Giulia Fornari1, Manuela Simoni1,3 & Francesco Potì4
that thyroid autoantibodies can affect the clinical and laboratory course of PCOS.
1Unit of Endocrinology, Department Biomedical, Metabolic and Neural
We have found that the euthyroid HT may be observed at higher rates in PCOS
Sciences, University of Modena and Reggio Emilia, Modena, Italy;2Center
patients, independent of the thyroid function tests.
for the Genomic Research, University of Modena and Reggio Emilia,
Keywords: polycystic ovary syndrome, Hashimoto’s Thyroiditis, thyroid
Modena, Italy;3Azienda Ospedaliero-Universitaria di Modena, Modena,
autoantibodies
Italy;4Department of Neurosciences, University of Parma, Parma, Italy.
DOI: 10.1530/endoabs.49.EP1113
Introduction
Sphingosine-1-phosphate (S1P) is a sphingolipid mediating proliferative signals
in human ovarian follicles, acting through five receptors
(S1PR1-5). We
characterized the effects of S1PR1 and S1PR3 in vitro, as those mostly expressed
in human primary granulosa cells
(hGLC) and immortalized, tumor-like
granulosa cell line (hGL5).
Methods
The S1P-mediated signaling, as well as the activity of S1PR1- and S1PR3-specific
agonists (SEW281 and CYM5541, respectively), was evaluated in hGLC and
EP1114
hGL5 cells. Dimethyl-sulfoxide-, cholera toxin- and phorbol-12-myristate-
Novel insulin resistance index using C-peptide is reliable predictor of
13-acetate
(PMA)-treatments served as controls. The kinetics of pERK1/2,
insulin resistance in women with PCOS
pAKT and pCREB activation were evaluated over 2 h by Western blotting, while
Ivana Bozic-Antic1, Dusan Ilic1, Jelica Bjekic-Macut2,
total cAMP production was measured by ELISA. The downstream cell viability
Danijela Vojnovic-Milutinovic3, Sanja Ognjanovic1, Tamara Bogavac1,
was measured by MTT assay over 72 h, GFSH. Differences were significant for
Bojana Popovic1, Tatjana Isailovic1, Valentina Elezovic1,
P!0.05 (two-way Anova; nZ2-12).
Olivera Stanojlovic4 & Djuro Macut1
Results
1Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of
Dose-response experiments revealed that 0.1 mM S1P, 1.0 nM SEW2871 and
Medicine, University of Belgrade, Belgrade, Serbia;2CHC Bezanijska
1.0 nM CYM5541 are the most effective concentrations, in terms of pERK1/2 and
Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia;
pAKT activation. In hGLC, pERK1/2 activation occurs within 5-60 min by S1P,
3IBISS, University of Belgrade, Belgrade, Serbia;4Institute of Physiology,
and, in a lesser extent, within 15-30 min by SEW2871 and CYM5541. In hGL5
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
cells, SEW2871- and CYM5541-dependent pERK1/2 activation is prolonged
until
2 h. We describe for the first time S1P- and, to a lesser extent,
SEW2871/CYM5541-mediated pCREB activation in both cell models, occurring
Introduction
in spite of no pAKT and cAMP recruitment. All the agonists increased cell
Recently, it was suggested that insulin resistance index using C-peptide (CIR)
viability in hGL5 cells, an effect reverted in the presence of 50 nM FSH. Only S1P
could be a better marker of insulin resistance than homeostasis model assessment
mediated anti-apoptotic effects in hGLC, while the treatment by SEW2871 and
(HOMA-IR) in patients with type 2 diabetes mellitus. The aim of this study was to
CYM5541 impacts negatively cell viability.
investigate performance of CIR index in PCOS subjects.
Discussion
Methods
We found S1PRs-mediated cAMP-independent steroidogenic potential and
We evaluated 187 PCOS women (PCOS: 25.38G6.32 kg/m2; 26.01G5.16 years)
different signaling kinetics in hGLC and hGL5 cells, revealing opposite effects
diagnosed using ESHRE/ASRM criteria and
42 healthy women (Controls:
on the downstream cell signaling, depending on the cell model.
22.56G5.46 kg/m2; 28.33G5.62 years). In follicular phase of menstrual cycle
total testosterone, SHBG, lipids, glucose, insulin and C-peptide were determined.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Novel CIR index (20/(fasting C-peptide!fasting plasma glucose)) and HOMA-
EP1116
IR (fasting plasma glucose! fasting insulin)/22.5 were calculated in all subjects.
Hirsutism in reproductive aged Korean women
Euglycaemic hyperinsulinemic clamp (EHC) was performed in PCOS group and
Yeon Ah Sung1, Sei Hyun Baik2 & Dong Sun Kim3
the whole body disposal rate (M, mg/kg per min) was determined as the mean of
1Ewha Womans University School of Medicine, Seoul, Republic of Korea;
the glucose infusion rate during the last 30 min of EHC. Insulin sensitivity index
2Korea University College of Medicine, Seoul, Republic of Korea;
(M/I) was calculated by dividing M by the steady state plasma insulin level during
3Hanyang University College of Medicine, Seoul, Republic of Korea.
the last 30 min of EHC. All analyses were adjusted for BMI and age.
Results
In comparison to controls, PCOS had significantly lower CIR index (14.72G2.21
Hirsutism, excessive terminal hair growth in a male-like pattern as a marker of
vs 9.65G1.02, respectively; PZ0.040) and higher HOMA-IR (2.91G0.36 vs
hyperandrogenism, affects 5-10% of reproductive-age women worldwide. The
3.70G0.16, respectively; PZ0.047). CIR index strongly correlated with HOMA-
frequency of hirsutism seems to decrease in Asians and the lower cut-off modified
IR (rZK0.447, P!0.001), M/I (rZ0.461, P!0.001), BMI (rZK0.381,
hirsutism score is suggested. We performed the study to estimate the frequency,
P!0.001) and waist circumference (WC)(rZK0.335, P!0.001). HOMA-IR
bio-metabolic characteristics, correlates and determinants of hirsutism in
correlated with M/I (rZK0.404, P!0.001), BMI (rZ0.349, P!0.001), WC
reproductive aged Korean women. A total of
2682
female volunteers of
(rZ0.348, P!0.001) and, unlike CIR index, also with SHBG (rZK0.411,
reproductive age (15-39 years) were recruited for the genetic study of PCOS.
P!0.001).
Menstrual history was taken and hirsutism was diagnosed when modified
Conclusion
Ferriman-Gallway
(mFG) score S8 was noted. Anthropometric features,
Novel CIR index could be a good surrogate marker of IR in PCOS. The absence of
hormones (total testosterone, SHBG, 17OH progesterone, prolactin, and TSH)
liver clearance of C-peptide is the reason for stronger correlation of CIR index
and metabolic parameters (glucose, insulin and lipids) in blood were measured.
with M/I in comparison to HOMA-IR.
The frequency of hirsutism is 133 (4.96%) in a total 2682 subjects. Fifty nine %
DOI: 10.1530/endoabs.49.EP1114
(1582) of subject had m-FG score of zero; 30.0% (805) had m-FG score between 1
and 4; 6.0% (162) were between 5 and 7. The m-FG values of 25th, 50th, 75th,
and 95th percentiles were 0, 0, 2, and 7 respectively. m-FG score significantly
correlated to age, waist circumference, serum total and free testosterone, SHBG,
postprandial plasma glucose, fasting and postprandial plasma insulin, and
HOMA-IR. Logistic regression analysis showed younger age, increased fasting
insulin and free testosterone levels were associated with mFG score. In conclusion
the estimated frequency of hirsutism among reproductive aged Korean women
was 4.96%, which is comparable to other races. Hirsutism is associated with
fasting plasma insulin, serum free testosterone level and younger age.
EP1115
DOI: 10.1530/endoabs.49.EP1116
Omentin-1, a potential link between chronic low grade inflammation,
metabolic and reproductive features of polycystic ovary syndrome
Soulmaz Shorakae1,2, Sally Abell1,2, Barbora de Courten1,2,
Gavin Lambert3,4, Danielle Hiam5, Nigel Stepto1,5, Eveline Jona1,
Lisa Moran1 & Helena Teede1,2
1Monash Centre for Health Research and Implementation, Monash
EP1117
University, Melbourne, Australia;2Diabetes and Vascular Medicine Unit,
Monash Health, Melbourne, Australia;3Human Neurotransmitters Labora-
Pharmacokinetics and bioavailability of non-polar phytocomponents of
tory, Baker IDI Heart & Diabetes Institute, Melbourne, Australia;
Aloe vera gel and their role as an endocrine modulator in letrozole
4Department of Physiology, Monash University, Melbourne, Australia;
induced PCOS rat model
5Institute of Sport Exercise and Active Living (ISEAL), Victoria University,
Arpi Dey, Shweta Vasoya & Laxmipriya Nampoothiri
Melbourne, Australia.
The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
Background
Background and aim
Polycystic ovary syndrome
(PCOS) is associated with features linked to
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in
metabolic syndrome including visceral adiposity, dyslipidemia and impaired
women of reproductive age with an estimated prevalence of 5-10%, is one of the
glucose homeostasis. Adipose tissue produces adipocytokines which contribute to
most common causes of female infertility. The therapeutic options for PCOS are
regulation of insulin sensitivity and reproduction. Omentin-1 is an adipokine with
limited. Thereby, traditional knowledge of Ayurveda has been exploited to
anti-inflammatory and insulin sensitizing roles produced by adipocytes. The exact
identify an herbal therapeutic target for PCOS. Pharmacokinetic (PK) studies on
role of mentin-1 in PCOS remains unclear as studies have reported reduced or
bioactive constituents of herbal drugs provide valuable information on bio-
unchanged levels in PCOS.
transformed metabolites, dosage form, doses and potential herb-drug
Methods
interactions. Thereby, the aim of the study was to study the pharmacokinetics
To determine the relationships between PCOS status, adipocytokines including
and bioavailability of the non-polar phytocomponents of Aloe vera gel and their
omentin-1 and etiological features of PCOS we measured serum omentin-1,
role as an endocrine modulator in PCOS pathology.
interleukin-6 (IL-6), high sensitivity CRP (hs-CRP), androgens, SHBG, fasting
Methodology
glucose and insulin levels in an observational study of community recruited
PCOS was induced in rat using letrozole and validated for structural and
PCOS and controls.
metabolic characteristics of PCOS. Blood and tissues
(ovaries, adrenal,
Results
hypothalamus, pituitary, uterus and liver) were collected upto
48 h after
49 women with PCOS (age 29.8G5.9 years, BMI: 29.0G5.4 kg/m2) and 25
petroleum ether extract of dried Aloe vera gel (1.0 g) were administered orally
healthy controls (age 37.6G7.8 years, BMI: 28.9G4.0 kg/m2) were recruited.
to rats. Metabolites of Phytosterols were identified using GC/MS and quantified
Homeostatic model assessment for insulin resistance (HOMA-IR) (PZ0.006),
using HPLC. Progesterone and estradiol were analysed using ELISA.
free androgen index (FAI) (PZ0.01) and Ferriman-Galway score (P!0.001)
Steroidogenic enzymes as well as important enzymes responsible for
were higher in PCOS. Women with PCOS had lower omentin-1 (median (IQR):
biotransformation were evaluated along with the toxicity parameters.
68.76(67.17) vs 112.45(67.42)) (PZ0.005) independent of obesity. Omentin-1
Results
correlated significantly with hs-CRP, IL-6, HMW-adiponectin, BMI, percentage
PCOS animals demonstrated altered estrus cyclicity, serum testosterone levels
of body fat, insulin, low density lipoprotein (LDL), triglycerides and total ovarian
and oral glucose tolerance test profile when compared to controls. An increase in
volume in women with PCOS. Multiple regression analyses revealed omentin-1
the estradiol (P!0.01) and progesterone levels (P!0.05) were observed in the
was explained by triglycerides (Beta: K0.177, PZ0.03) and total ovarian volume
plasma after
24 h. Several phytosterols and their modified oxysterols were
(Beta: K0.009, PZ0.025).
identified in the plasma and tissues which could be well-correlated with the
Conclusion
functional changes observed in hormone profile.
Omentin-1
is significantly lower in women with PCOS and correlates
Conclusion
significantly with other inflammatory markers, metabolic parameters and total
This study elucidates the bioavailability and functionality of phytosterols/
ovarian volume. This finding suggests omentin-1 as a potential link between
oxysterols obtained from Aloe vera gel towards management of PCOS. This study
metabolic and reproductive features of PCOS and chronic low grade
will be helpful in identification of a naturally derived drug target and add to its
inflammation.
economic viability at national and international level.
DOI: 10.1530/endoabs.49.EP1115
DOI: 10.1530/endoabs.49.EP1117
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1118
clinical symptoms of hyperandrogenism was observed - hirsutism, assessed
according to the Ferriman-Gallwey scale, as compared to the control group
Influence of peroxisome proliferator-activated receptor (PPAR)-g exon
(PZ0.048). Full-blown PCOS was diagnosed in 6.52% of the girls from the study
2
(Pro12Ala) and exon 6 (His447His) and Gly972Arg insulin receptor
group, whereas none of the patients from the control group met all the criteria for
substrate (IRS)-1 polymorphisms on insulin resistance (IR) and beta cell
the diagnosis of PCOS (P!0.05). There were no significant differences in plasma
function in Southern Mediterranean women with polycystic ovary
concentrations of leptin, adiponectin and apelin-36 between the study and control
syndrome (PCOS)
groups.
Giuseppina T Russo1, Maria Angela Pappalardo2, Annalisa Giandalia1,
Conclusions
Elisabetta L Romeo1, Angela Alibrandi3, Flavia Di Bari1, Roberto Vita1,
Hormonal disorders such as hyperprolactinemia, hyperandrogenaemia and PCOS
Domenico Cucinotta1 & Salvatore Benvenga1,4
are more frequently diagnosed in girls with oligomenorrhea. In girls with
1Department of Clinical and Experimental Medicine, University of Messina,
oligomenorrhea, elevated levels of leptin and decreased levels of adiponectin may
Messina, Italy;2Centro Polispecialistico Rizzo, Torregrotta, Messina, Italy;
be considered as new biomarkers for insulin resistance and hyperandrogenaemia.
3Department of Economicsm University of Messina, Messina, Italy;
4Interdepartmental Program of Molecular and Clinical Endocrinology, and
DOI: 10.1530/endoabs.49.EP1119
Women’s Endocrine Health, University hospital Policlinico G. Martino,
Messina, Italy.
The Pro12Ala and His447His polymorphisms of PPAR-g, and Gly972Arg
polymorphism of IRS-1 have been implicated in insulin resistance (IR) and
adiposity. In this study, we investigated the possible influence of these
polymorphisms on metabolic features of 53 PCOS women compared with 26
EP1120
healthy women (controls). All women underwent a clinical, anthropometric and
Global methylation pattern and endocrine-metabolic profile during
biochemical evaluation, including a 75-g oral glucose tolerance test; insulin
early infancy and puberty in sons born to women with polycystic ovary
secretion and sensitivity indices were calculated. In the two groups, frequencies of
syndrome (PCOS)
PPARg polymorphisms did not differ from those predicted by the Hardy-
Teresa Sir-Petermann1, Nicolas Crisosto1, Barbara Echiburu1,
Weinberg equilibrium. Instead, the IRS-1 Gly972Arg allele was significantly
Manuel Maliqueo1, Francisco Perez-Bravo2, Daniel Sandoval3 &
more frequent in the PCOS group compared to controls. The frequency of
Sergio Recabarren3
different allelic combinations was unequal in the two groups, with IRS1C/ex-
1Laboratory of Endocrinology and Metabolism, University of Chile,
on2K/exon6K detected in 66% of PCOS and IRS-1K/exon2K/exon6K in 73% of
Santiago, Chile;2Nutrigenomic Laboratory, Department of Nutrition,
controls. In PCOS women, the IRS-1 Gly972Arg allele was associated with lower
University of Chile, Santiago, Chile;3Laboratory of Animal Physiology and
E2
levels
(PZ0.030), while the PPARg Pro12Ala allele with lower free-
Endocrinology, University of Concepcion, Concepcion, Chile.
testosterone levels
(PZ0.021). No other relationships were noted. When
compared with wild-type women, in PCOS group, IR was: 1) trendwise greater
in carriers of the variant allele in IRS-1 gene (borderline higher HOMA-IR,
Prenatal and postnatal environment can regulate gene expression through multiple
insulinogenic and disposition indices); 2) trendwise lower in carriers of the
epigenetic mechanisms, being DNA methylation among the most relevant.
variant PPAR-g exon6 allele (lower HOMA-IR and higher Matsuda index, lower
Metabolic and reproductive function may be modified by this mechanism. Sons
insulinogenic and disposition indices); 3) lower (P!0.01) in carriers of the
born to women with PCOS show altered markers of metabolic and reproductive
PPAR-g exon2 variant (lower HOMA-IR values and higher insulinogenic and
function during childhood and adulthood. However, these functions have not been
disposition indices). Furthermore, within the IRS-1C/PPAR-g-exon2K PCOS
studied during puberty. The aim of the present study was to assess the global
women, PPAR-g- exon6C women had higher Matsuda index
(PZ0.03)
methylation pattern and its possible association with anthropometrics, endocrine
compared with the noncarriers
(PPAR-g-exon6K). Our data support the
and metabolic variables in a cohort of early infants and peripubertal boys born to
protective influence of PPAR-g-exon2 and exon6 variants on IR and beta-cell
women with PCOS. Global DNA methylation was measured from blood
function, whereas IRS-1 polymorphism is associated with a more unfavorable
leucocytes, in 21 sons born to control women (C-Sons) and 15 born to women
metabolic profile. However, these associations do not fully explain the high
with PCOS (P-Sons) at early infancy (2-3 months old). In addition, 50 P-Sons (12
metabolic risk PCOS-associated.
prepubertal (Tanner I), 28 pubertal (Tanner II-IV) and 10 late pubertal (Tanner
V)) and 61 C-sons (13 prepubertal, 30 pubertal and 18 late pubertal) were studied.
DOI: 10.1530/endoabs.49.EP1118
Weight, height and waist circumference were determined. A 75-gr oral glucose
tolerance test with insulin and glucose measurements was performed. HOMA-IR
and ISI composite were calculated. In the fasting sample circulating AMH,
17-OH-Progesterone, androstendione, testosterone, estradiol and lipids were
measured. P-Sons showed lower global methylation at early infancy (PZ0.027),
whereas at pubertal age a higher global methylation was found (PZ0.035). No
differences were observed during pre and late puberty. At early infancy, no
EP1119
differences were observed in anthropometric variables between C-Sons and
Hormonal disturbances and adipokines levels in girls with
P-Sons. In prepubertal age, fasting and 120-min glucose were higher in P-sons
oligomenorrhea
compared to C-Sons (PZ0.038 and 0.046, respectively). At puberty, waist
Violetta Skrzypulec-Plinta, Agnieszka Drosdzol-Cop & Dominika Sajdak
circumference and androstenedione levels were higher (PZ0.032 and 0.006,
Medical University of Silesia in Katowice, Katowice, Poland.
respectively) and cholesterol tended to be higher (PZ0.06) in P-Sons compared
to C-Sons. At late puberty, no differences were observed between groups. These
results suggest that the methylation pattern can be modified from early infancy to
Aim
the pubertal age in sons born to PCOS women. During puberty, global
The aim of this study was to evaluate hormonal disturbances and adipokines
methylation increased concomitantly with circulating androstendione levels and
levels in girls with oligomenorrhea.
waist circumference suggesting that the endocrine and metabolic milieu may be
Materials and methods
associated with DNA methylation in these boys.
The study comprised a group of 46 girls, aged 16-18 years, who were diagnosed
with oligomenorrhea, and a control group with 37 healthy girls, aged 16-18 years,
DOI: 10.1530/endoabs.49.EP1120
with no diagnosed menstrual disorders. In the first stage of the study, all girls had
their medical history assessed. Subsequently, anthropometric measurements
(height, weight) were measured, severity of hirsutism -according to the Ferriman-
Gallwey score - was assessed and a pelvic ultrasound was conducted. In the blood
serum, the following parameters were determined: LH, FSH, estriadol, TSH,
SHBG, total and free testosterone, androstenedione, DHEA-S, prolactin, insulin
and glucose. Assessment of adipokines in plasma included: leptin, adiponectin
and apelin-36. Insulin resistance was assessed using the indirect method, setting
EP1121
HOMA-IR and on the basis of a standard model, free androgen index (FAI) was
Natural history of autoimmune primary ovarian insufficiency
also calculated.
progresses through several stages from normal ovary function to
Results
clinically overt ovary dysfunction
The incidence of hyperprolactinemia in the study group is 32%, while there was
Giuseppe Bellastella1, Ofelia Casciano1, Mariluce Barrasso1,
no disturbance among any of the girls from the control group. Furthermore,
Maria Ida Maiorino1, Dario Giugliano1, Katherine Esposito2,
among the group of girls with oligomenorrhea, a significantly greater increase in
Lorenzo Scappaticcio1 & Annamaria De Bellis1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Endocrinology and Metabolic Diseases Unit, Department of Medical,
Conclusion
Surgical, Neurological, Metabolic Sciences and Aging, University of
Our study indicate that no association between E2 levels and existence of benign
Campania ‘L. Vanvitelli’, Naples, Campania, Italy;2Diabetes Unit,
lesions in different organs according to the radiologic investigations in
Department of Medical, Surgical, Neurological, Metabolic Sciences and
premenopausal women. And, TSH levels were found related to upper BIRADS
Aging, University of Campania, ‘L. Vanvitelli’, Naples, Campania, Italy.
grades in premenopausal women.
DOI: 10.1530/endoabs.49.EP1122
Context
Women with autoimmune Addison’s disease with normally ovulatory cycles but
positive for steroid cells antibodies
(StCA) have been considered at risk of
premature ovarian insufficiency (POI).
Design
Thirty-three women younger than 40 years, with subclinical-clinical Addison’s
disease but with normally ovulatory menses, were followed-up for 10 years to
EP1123
evaluate the long-term time-related variations of StCA, ovarian function and
Heterogeneous hCG and hMG commercial preparations result in
follicular reserve. All patients and 27 control women were investigated at start
biased intracellular signaling but induce similar progesterone response
and every year for the presence and titer of StCA (by indirect immunofluores-
in vitro
cence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian
Laura Riccetti1, Danièle Klett2, Mohammed Akli Ayoub2,3, Thomas Boulo2,
function along four consecutive menses every year.
Julie Mariot2, Elisa Pignatti1,4, Simonetta Tagliavini5, Manuela Varani5,
Results
Tommaso Tranti5, Alessia Nicoli6, Giovanni Battista La Sala6,
At start of the study StCA were present in 16 women (group 1), at low/middle titer
Yves Combarnous2, Eric Reiter2, Manuela Simoni1,5 & Livio Casarini1,4
(%1:32) in seven of them (43.75%, group 1A), at high titer (O1:32) in the
1Unit of Endocrinology, Department Biomedical, Metabolic and Neural
remaining nine patients (group 1B, 56.2%), while they were absent in 17 patients
Sciences, University of Modena and Reggio Emilia, Modena, Italy;
(group 2). During the follow-up period, all women in group 1A persisted StCA
2Biologie et Bioinformatique des Systèmes de Signalisation (BIOS) group,
positive at low/middle titer with normal ovulatory menses and normal
INRA, UMR85, Unité Physiologie de la Reproduction et des Comporte-
gonadotropin and AMH levels, while all patients in group 1B showed a further
ments; CNRS, UMR7247, F-37380 Nouzilly, Nouzilly, France;3Biology
increase of StCA titers (1:128-1:256) and progressed through three stages of
Department, College of Science, United Arab Emirates University, Al Ain,
ovarian function. None of patients in group 2 and controls showed appearance of
United Arab Emirates;4Center for Genomic Research, University of
StCA or ovary dysfunction during the follow-up.
Modena and Reggio Emilia, Modena, Italy;5Azienda Ospedaliero-
Conclusions
Universitaria di Modena, Modena, Italy;6Unit of Obstetrics and
The presence of StCA at high titers could be considered a good predictive marker
Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
of subsequent development of autoimmune POI. To single out the stages of
autoimmune POI may allow a timely therapeutic choice in subclinical and early
Human chorionic gonadotropin (hCG) is the pregnancy hormone marketed as a
clinical stage.
drug for assisted reproduction technologies to support follicle-stimulating
DOI: 10.1530/endoabs.49.EP1121
hormone action. Several hCG formulations are commercially available, differing
in source, purification methods and biochemical composition. In this study, we
investigated the molecular features and the intracellular signaling mediated by
five urinary and recombinant hCGs. The drug comparisons were performed by
quantifying the hormones by immunoassay, calibrated against the hCG standard
(5th IS; NIBSC
07/364). Immunoreactivity pattern, isoelectric point and
oligosaccharide content of hCGs were evaluated by reducing and non-reducing
Western blotting, capillary isoelectric-focusing immunoassay and lectin-ELISA,
respectively. Functional studies were performed in order to evaluate intracellular
and total cAMP, progesterone production, as well as b-arrestin two recruitment by
EP1122
ELISA and BRET, in both human primary granulosa lutein cells (hGLC) and
LH/hCG receptor (LHCGR)-transfected HEK293 cells stimulated by increasing
Relationship between anabolic hormones and benign lesions in different
hormone doses. Heterogeneous profiles were found among preparations,
organs in premenopousal women
revealing hormone-specific molecular weight patterns
(20-75 kDa range),
Zeynep Nilufer Tekin1, Berçem Ayçic¸ek1 & Tuna Demirba¸2
isoelectric points (4.0-9.0 pI range) and lectin binding (Two-way ANOVA and
1Darıca State Hospital, Kocaeli, Turkey;2Tekirdag˘ State Hospital,
Bonferroni post-test; P!0.05; nZ5). These drug-specific compositions are
Tekirdag˘, Turkey.
linked to different potencies on cAMP production (EC50 1.0-400 ng/ml range)
and partial agonism on b-arrestin 2 recruitment (EC50 0.03-2.0 mg/ml) in hGLC
Objective
and transfected HEK293 cells (Mann-Whitney’s U test; P!0.05; nZ3 or 5).
We aim to detect co-occurence of uterine myomas, thyroid nodules and breast
However, the treatment of hGLC with hCGs resulted in similar progesterone
lesions in premenoposual women with menstruel disorders and investigate
production after 24 h of exposure (Mann-Whitney’s U test; PR0.05; nZ3).
association between these benign tumors with anabolic hormon levels.
Therefore, although hCG preparations consist of different glycosylated isoforms
Design
and mediate drug-specific early signaling, they result in similar downstream
Records of 8008 premenopausal women were analyzed who had been admitted to
steroidogenesis in vitro. Commercial gonadotropins calibration relies on their
the hospital for routine breast image investigation which was performed by the
in vivo activity (Pharmacopea), which can be reached with different mixtures of
same radiologist in between 2010 and 2015.
isoforms with various half-lives and receptor binding activities. Here, we
Study and Methods
demonstrate that commercial hCG preparations, likely with different assortments
251 patients who had both Thyroid Ultasound (US), Pelvic Ultrasound (US) and
of isoforms, exhibit similar steroidogenic activity in vitro, by triggering biased
Breast Imaging Reporting and complain about menstruel disorders in the same
intracellular signaling pathways.
year, were extracted from 8008 premenapousal woman. All data were obtained
DOI: 10.1530/endoabs.49.EP1123
from file records and ICD-10 diagnosis code of electronic database of the hospital.
For breast examination, Breast Imaging Reporting and Data System (BIRADS)
terminology had been used. Tiroid stimulating hormone (TSH) and Estrodiol (E2)
levels were recorded for investigate of situation of anabolic hormon levels, which
had been taken from premenopousal women at the time of third day of menstruel
cycle.
Results
EP1124
The mean age of the patients at the admission to the hospital was 32G5.7 years.
Etiopathogenetical aspects of endocrine infertility
From 251 patients only 9 patients had benign lesions in all three organs, whereas
Gulyamova Xilola & Ibragimova Kamilla
63 patients had both thyroid nodules and breast lesions and 5 patients had thyroid
Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan.
nodules and uterine myoma, and seven patients had BIRADS 2,3 lesions and
uterine myoma, respectively. There was only found a relationship between age
and existence of myoma uteri and thyroid nodule. (PZ0.008, for both). Only TSH
Urgency
levels were found lower in patients with BIRADS 2,3 lesions than with BIRADS
According to WHO the frequency of infertile unions is high amount 25-30% in
1
(PZ0.017).
developed countries. There are following reasons of infertility by women: 1) tubal
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
infertility; 2) endocrine infertility-it takes the 2nd place among the reasons of
expression and promoter methylation of the particular CpG sites of follicle
infertility; 3) anomalies of the vagina and uterus; 4) immunological reasons, that
maturation involved genes.
are caused by sensibilisation of female organism, also there are patients, the
Keywords: GATA6, FST, Gene Expression, Promoter Methylation, Prenatal
reason of infertility of that is not ‘explainable’, when there not obvious violations
androgenisation
of reproductive system, it is called ‘unexplained infertility’ - 8-10% and an
DOI: 10.1530/endoabs.49.EP1125
emotional form of infertility.
Research aim
Studying etiological and pathogenetic mechanisms of infertility’s development
by women.
Materials and methods
Retrospective analyses of scientific literature from 2010 to 2016 years.
Results of the research
EP1126
Endocrine infertility- complex of hormonal disorders, that follow irregular
ovulation or its absence. By every 3rd infertile woman the reason is the pathology
Graduated response to pulsatile GnRH therapy in hypothalamic
of endocrine system. These are:
1) unovulation;
2) hypothalamic-pituitary
amenorrhea
Natacha Germain1,2, Anais Fauconnier1, Jean-Philippe Klein3,4,
dysfunction; 3) hyperandrogenism of ovarial or adrenal henesis; 4) function
Amelie Wargny2, Yadh Khalfallah1, Chrysoula Papastathi-Boureau1,
disorders of thyroid; 5) estrogen and progesterone deficiency; 6) severe somathic
Bruno Estour1,2 & Bogdan Galusca1,2
pathology; 7) obesity; 8) resistance ovary syndrome, when there is an insensivity
1Endocrinology Department, University Hospital of Saint Etienne, Saint
to the gonadotrophini, that stimulates an ovulation, that is manifested with
Etienne, France;2EA 7423, Jean Monnet University of Saint Etienne, Saint
amenorrhea;
9) premature menopause in younger women to
35-38
y.o;
Etienne, France;3Histology and Embryology Department, University
10) mutations of sex chromosomes. Abortions and infections, that cause tube-
hospital of Saint Etienne, Saint Etienne, France;4UMR INSERM 1059,
peritoneal forms of infertility among to 50% of all patients with infertility.
Jean Monnet University of Saint Etienne, Saint Etienne, France.
According to WHO more than 20% of patients with infertility have expressed
anatomical changes of fallopian tubes. Obstruction of FT we can see by 11-15%
of observing, 30% of cases-endometrioid heterotopia.
Introduction
Conclusions
Pulsatile GnRH therapy is currently used to restore LH pulse and induce
For prophylaxis of endocrine infertility: 1) preventing of child infections, chronic
physiological ovulation, with effectiveness demonstrated in all types of
tonsillitis, rheumatism;
2) preventing the developing of patholodical birth,
hypothalamic amenorrhea (HA). Anorexia nervosa (AN) is characterized by
abortion, inflammatious infections of women reproductive system; 3) proper
self-starvation-induced undernutrition leading to functional hypothalamic
maintenance of pregnancy, judicious use of hormones during the pregnancy.
amenorrhea (HA). Weight recovery does not always restore menses despite no
DOI: 10.1530/endoabs.49.EP1124
apparent clinical and biological undernutrition residual signs. Only few specific
studies on persistent amenorrheic weight-recovered AN (Rec-AN) have evaluated
pulsatile GnRH therapy, including small number and under nourished patients.
Comparison data on hormonal response of the different causes of HA (weight-
recovered AN, primary and secondary HA non-related to eating disorders) is also
lacking. Therefore, this study was designed to evaluate hormonal and clinical
responses to GnRH pulsatile treatment in three groups of HA patients: weight-
EP1125
recovered anorexia nervosa patients
(Rec-AN) with persistent functional
hypothalamic amenorrhea (HA), secondary and primary HA.
Prenatal androgen exposure alters gene expression and promoter
Patients and method
methylation of two ovarian follicle maturation factors
This retrospective, observational ambulatory study included
41 females: 15
Marziyeh Salehi Jahromi1,2, Fahimeh Ramezani Tehrani1 &
secondary HA without any eating disorders patients (SHA), seven primary HA
Jennifer W Hill3
patients (PHA), and 19 Rec-AN (BMIO 18.5 kg/m2 without menses recovery),
1Reproductive Endocrinology Research Center, Research Institute for
who underwent GnRH pulsatile therapy. Baseline Estradiol
(E), LH and
Endocrine Sciences (RIES), Shahid Beheshti University of Medical
Progesterone plasma level and their changes during induction cycles were
Sciences, Tehran, Iran;2Cellular and Molecular Endocrine Research Center,
evaluated. Ovulation, follicular recruitment and pregnancies rate were also
Research Institute for Endocrine Sciences (RIES), Shahid Beheshti
studied.
University of Medical Sciences, Tehran, Iran;3Center for Diabetes and
Results
Endocrine Research (CeDER), Department of Physiology and
Rec-AN displayed higher basal E and LH plasma levels after GnRH injection
Pharmacology, College of Medicine and Life Sciences, University of
compared to SHA and to PHA. WE observed higher E and LH levels during
Toledo, Toledo, Ohio, USA.
induction cycles in Rec-AN compared to SHA and PHA. PHA displayed the
lowest hormonal plasma levels. Follicular recruitment was higher in Rec-AN.
Background
Ovulation rate was higher in Rec-AN and SHA compared to PHA.
Follicles imaturation, as the hallmark of polycystic ovarian syndrome caused by
Conclusions
prenatal androgen exposure, is suspected to be effected through expression
This study showed increased gonadal status and higher Estradiol response to
changes of related genes. The aim of this study was to evaluate gene expression
pulsatile GnRH therapy in persistent amenorrheic weight-recovered AN
and promoter methylation of GATA6 and Follistatin (FST), two factors involved
compared to SHA and PHA. Pulsatile GnRH therapy seems less efficient in
in follicle maturation, in adult female rats prenatally exposed to androgen excess
primary hypothalamic amenorrhea.
by comparing them with non-treated rats.
DOI: 10.1530/endoabs.49.EP1126
Material and methods
Eight pregnant Wistar rats in the experimental group were treated by
subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while
controls (nZ8) received 500 ml of solvent. DNAs and RNAs were extracted from
ovarian theca cells of adult female off-springs of PNA (nZ24) and controls
(nZ24). Relative expression and promoter methylation levels were measured
using Cyber-green Real-Time PCR and bisulfite sequence PCR (BSP) methods,
EP1127
respectively.
Relationship between steroid hormones and metabolic profile in women
Results
with polycystic ovary syndrome
Compared to the control group, the relative expression of GATA6 and FST genes
Zora Lazúrová2, Jana Figurová2, Simona Ujházi2, Jana Mašlanková1,
in the treated group was 2.08 fold (95% CI: 1.62-2.55; P!0.0001) for GATA6
Silvia Toporcerová1 & Ivica Lazúrová1
and 0.85 fold (95% CI: 0.73-0.97; PZ0.058) for FST. Along with decrease in the
1Medical Faculty, Košice, Slovakia;2University Hospital, Košice, Slovakia.
methylation percentage of 11 CpG sites of GATA6 promoter in the PNA group in
comparison with controls, the methylation of K480 position, was significantly
decreased by 6.72G4.66 and 41.69G15.78 percent for PNA and the controls,
Background
respectively (PZ0.03). No significant difference was seen in methylation of FST
There is evidence that polycystic ovary syndrome
(PCOS) is commonly
promoter although the percentage of 17 CpG sites increases slightly in PNAs.
associated with higher cardiometabolic risk. Aim of the study was to compare
Conclusions
various sex streoids in PCOS women with overweight or obesity (BMI O27) and
These results reveal that manifestation of PCOS-like phenotype following
those with lower BMI. Second aim of the study was to determine the relationship
prenatal exposure to excess androgen is associated with alteration in the
of various sexual setroids to cardiovascular risk in PCOS women.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Subjects and methods
1Erzincan University, Department of Medical Genetics, Erzincan, Turkey;
Study included 64 Caucasian women with PCOS. Fasting blood samples were
2Erciyes University, Department of Medical Genetics, Kayseri, Turkey;
collected in an early follicular phase and were analyzed for metabolic parameters
3Erciyes University, Department of Endocrinology, Kayseri, Turkey.
and sexual steroid hormones
(androgens, estrogens and adrenal androgen
precursors).
Results
Introduction
Women with BMI R 27 had worse metabolic profile and higher serum free
Hirsutism affects
5-8% of the whole female population. In most patients,
testosterone (FT), free androgen index (FAI), estrone (E1) (PZ0,014 for FT,
hirsutism is associated with hyperandrogenemia and the most common cause of
PZ0.02 for FAI and PZ0.01 for E1) and slightly higher dihydrotestosterone
androgen excess is polycystic ovary syndrome; however, the clinical presentation
(DHT) with borderline significance
(PZ0.06). There were no significant
of non-classical congenital adrenal hyperplasia(NCAH) in females is often
indistinguishable from other hyperandrogenic disorders because of common
differences in total testosterone (TT), androstenedione (ASD) and dehydroepian-
clinical signs with hirsutism and poly cystic ovary syndrome(PCOS).
drosterone sulphate (DHEAS). E1 positively correlated with BMI (PZ0.0067),
Objective
serum insulin (PZ0.0046) as well as HOMA IR (PZ0.0125) and negatively
The aim of the study is to evaluate the prevalence of NCAH in woman presenting
correlated with HDL-cholesterol (PZ0.009). FAI was in positive correlation with
with hirsutism and distinguish the underlying causes.
total cholesterol (PZ0.0457), TAG (PZ0.0001), HOMA IR (PZ0.037), serum
Subject and Method
insulin (PZ0.0428) and glycemia (PZ0.0001) and negatively correlated with
122 women admitted to the Endocrinology Clinic at Erciyes University Hospital
HDL cholesterol (PZ0.029). In multiple linear regression model E1 most
with hirsutism enrolled the study voluntarily between January
2013
and
significantly predicted HOMA IR, whereas FT predicted HDL-cholesterol and
December 2014. All protein encoding exons and exon-intron boundaries of
BMI.
CYP21A2, CYP11B1, HSD3B2 and CYP21A2 promoter changes determined by
Conculsion
direct gene sequencing from genomic DNA isolated from peripheral blood
We conclude that PCOS women with marked overweight or obesity have
leukocytes.
significantly worse cardiometabolic profile than those with lower BMI. They also
Results
have higher FT, FAI, E1 and slightly higher DHT. Among steroid hormones E1
Detailed clinical, hormonal and DNA sequencing analyses of the volunteers have
and FT predicted cardiometabolic risk, whereas other sexual steroids were not in
resulted in 91 (74.6%) PCOS, 12 (9.8%) IHA, 14 (11.4%) IH and 5 (4.1%)
relationship to CVD risk.
NCAH. All NCAH were steroid 21-hydroxylase deficient and there was neither
DOI: 10.1530/endoabs.49.EP1127
11B-hydroxylase nor 3-beta-hydroxysteroid dehydrogenase deficient NCAH.
Sequencing analyses revealed 5 novel mutations; A89V (c.266 COT), M187I
(c.571 GOA) and G491S (c.1471 GOA) located on CYP21A2 and V188I (c.562
GOA) and G87A (c.260 GOC) located on CYP11B1 gene in homozygous and
heterozygous states.
EP1128
Conclusion
Secondary amenorrhea after bone marrow transplantation and
NCAH prevalence in Turkish woman with hirsutism found higher compare to
adjuvant chemotherapy misdiagnosed as disorder of sex development: a
similar studies. It might be because of not only doing sequencing analyses of
case report
CYP21A2 but also promoter region since 3 of them have promoter changes in
Mouna Elleuch, Mouna Ammar, Faten Hadj Kacem, Dorra Ghorbel,
addition to protein coding. However, the study confirmed that promoter region of
Nabila Rekik, Nadia Charfi, Mahdi Kalthoum, Mouna Mnif &
the CYP21A2 should be sequenced as well for true genetic diagnosis and genetic
Mohamed Abid
counselling.
Department of Endocrinology and Diabetes Hedi Chaker, Sfax, Tunisia.
DOI: 10.1530/endoabs.49.EP1129
Introduction
Disorders of sex development (DSD) is a congenital condition in which the
development of chromosomal, gonadal or genital sex is atypical. A female
appearance patient with secondary amenorrhea and 46 XY karyotype seems to be
EP1130
solid evidences to diagnose Y-chromosome-related DSD diseases, while it is not
Effects of photoperiod on estrous cycle in the Mongolian gerbil
necessarily the accurate diagnosis. We here report a case of a 16- year-old girl
(Meriones unguiculatus)
with secondary amenorrhea and
46
XY karyotype after bone marrow
Nayeli Ortega1, Marcela Arteaga2 & Pilar Duran1
transplantation (BMT) and adjuvant chemotherapy misdiagnosed as DSD.
1Universidad Nacional Autonoma de Mexico, Mexico City, Mexico;
Case report
2Universidad Autonoma Metropolitana, Mexico City, Mexico.
A 16-year-old lady who gets her first period at age 13, was referred with a 3 years
history of secondary amenorrhoea. The patient presented female appearance. She
had normal female genitalia and she was at Tanner stage 3. Her medical history
Gerbil
(Meriones unguiculatus) a non traditional laboratory model with
included BMT and chemotherapy because of acute leukemia (AL) when she was
reproductive state influenced by photoperiod, was used to analyze those
13 years old. So far there is no sign of AL recurrence. Laboratory examination
photoperiodic mechanisms involving reproductive regulation. The
14:10
showed a 46 XY karyotype, elevated follicle stimulating hormone and luteinizing
photoperiod has been widely used for reproductive research since 1950 (Everett).
hormone, low estrogen, and normal prolactin. Perineal and pelvic ultrasound
As is well known gerbils locomotor activity cycle has been reported to be
scans showed developed uterus and vagina, and two small ovaries with no
crepuscular and reproductive cycle presents two annual peaks. As for the estrous
follicular activity. Furthermore, we found that she received BMT from her brother
cycle (EC), it has been analyzed mainly under a12hr:12hr light (L)dark(D)
and adjuvant chemotherapy 3 years ago. Her karyotype changed from normal
photoperiod, and reported as mostly irregular. In this research, female gerbils
were exposed to 8:16, 12:12, 14:10 and 16:8 LD conditions. The EC were
female to a karyotype of donor
(her brother) origin after BMT. Adjuvant
monitored by cytology via vaginal smears every four hours (ZT) for 3 consecutive
chemotherapy for AL may impair her ovarian function and finally bring about
cycles, where ZT2 was the first (ZT0 was the light onset). Under the 14:10
primary ovarian insufficiency.
photoperiod, the EC was the most stable. Cycles lengthen in between to five and
Conclusion
four days and stable phase duration. When the other photoperiods were analyzed
The present case serves as a reminder that a correct diagnosis depends on the
the EC showed not only less stability (3-9 days) but also variability in the phase
comprehensive collection of present and past medical history, complete physical
duration, i.e. diestrus increased its duration under 8:16 and12:12 LD, meanwhile
examination, and careful evaluation of related adjuvant tests.
at
16:8 photoperiod diestrus and estrus, showed a significant increase when
DOI: 10.1530/endoabs.49.EP1128
compared with 14:10 LD. In a period of 15 days an average of 2 cycles on 16:8,
12:12 and 8:16 and 3 EC for 14:10 were presented. Proestrus and metaestrus did
not show a significative variance under any condition. A shift in the time of the
day when estrus phase become settled was reported; vaginal smear showed
predominantly cornified cells under 12:12 and 14:10 LD at ZT6; for 6:8 LD ZT2,
EP1129
and under 8:16 photoperiod a shift to the dark phase was found starting at ZT22.
NCAH prevalance with novel CYP21A2 and CYP11B1 mutations in
As cytological examination of vaginal smears is a good indicator for endocrine
hirsut turkish women
condition of the female, the estradiol and progesterone level are being analyzed
Seher Polat1, Sulbiye Karaburgu3, Kursad Unluhizarci3, Munis Dundar2,
by ELISA.
Yusuf Ozkul2, Zuleyha Karaca3 & Fahrettin Kelestimur3
DOI: 10.1530/endoabs.49.EP1130
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1131
met-group was smaller. BMI levels have reached a plateau after 3 months of
metformin treatment. TSH levels decreased (7.2C/K 1.6 mUI/ml vs. 4.8C/K
The regulation of LHCGR-dependent signaling is linked to circadian
2.2 mUI/ml) significantly in the metformin group, compared to a smaller decrease
gene expression
in the non-metformin group (5.6C/K2.2). Significant decrease was registered for
Lisa Gilioli1, Marco Marino1,2, Manuela Simoni1,3 & Livio Casarini1,2
the LH/FSH ratio (5,10C/K0.9 vs. 2,1C/K0.45), AMH (9.80C/K1.6 vs. 7.9C/
1Unit of Endocrinology, Department Biomedical, Metabolic and Neural
K1.2 ng/ml) and testosterone levels; antral follicle count and ovarian volume
Sciences, University of Modena and Reggio Emilia, Modena, Italy;2Center
improved in met-group (in a similar fashion to the gross ultrasound appearance),
for Genomic Research, University of Modena and Reggio Emilia, Modena,
while in non-met group, the 3 and 6 months values were similar to baseline.
Italy;3Azienda Ospedaliero-Universitaria, Modena, Italy.
Conclusion
Metformin treatment administered in high doses (3000 mg/day) on a 6 months
Introduction
period was useful for weight loss, improvement of ovarian function and decrease
Reproduction exhibit a regular cyclicity and is regulated by complex interactions
of androgen levels in obese PCOS patients with hypothyroidism. It also improved
between circadian signals, gonadotropins and sex steroid hormones. Peripheral
supplementary the thyroid function parameters. AMH can be used a prognostic
circadian rhythm is generated upon cyclic transcription of clock genes expressed
marker for metformin response in PCOS obese patients with thyroid dysfunction,
in several cells, e.g. granulosa cells in the ovary. Here we investigated whether
especially if (transvaginal) ultrasound scanning is not available.
cyclic intracellular events occurring in response to gonadotropins are linked to
DOI: 10.1530/endoabs.49.EP1132
expression of clock genes.
Methods
Primary human granulosa cells (hGLC), naturally expressing luteinizing hormone
(LH)/chorionic gonadotropin (hCG) receptor (LHCGR), were maintained under
continuous exposure to LH/hCG over 24 h, and the expression of clock genes
(PER1, PER2, ARNTL, CLOCK), gonadotropin receptors (LHCGR and LHCGR-
exon
6A variants, FSHR) and genes regulating steroidogenesis
(STARD1,
EP1133
CYP19A1, etc.) was analysed by real-time PCR. Cyclicity of cAMP production,
Influence of thyroid stimulating hormone (TSH) level in in-vitro
G proteins and b-arrestins and ERK1/2 phosphorylation were evaluated by
fertilization (IVF) success
ELISA, Western blotting and immunofluorescence.
Carolina Faria, Ana Gomes, Joaquim Nunes, Sandra Sousa, Aguiar Ana,
Results
Rodrigues Cátia, Sampaio Joaquim & Calhaz-Jorge Carlos
Treatments by gonadotropins de-synchronize CLOCK and ARNTL gene
Hospiyal de Santa Maria, Lisboa, Portugal.
expression, as well as LHCGR mRNA isoforms, STARD1 and CYP19A1 gene
expression (two-way Anova; P!0.05; nZ3). Immunostainings revealed a 4-5 h-
rhythmic, up- and down-regulation of Gas protein and b-arrestin1/2, as well as G
Introduction
protein coupling/uncoupling to LHCGR upon gonadotropin treatment. 17 h-
Prevalence of hypothyroidism is 2-5% in women in the reprodutive age group.
treatment is linked to rounded shape of the cells and intracytoplasmic vacuoles,
Hypothyroidism can affect fertility due to anovulatory cycles, luteal phase
LHCGR internalization and translocation of Gas protein to cytoplasm. These
defects, hyperprolactinemia and sex hormones imbalance. Some data also report
gonadotropins-induced changes are accompanied by
3-5 h-oscillatory intra-
that TSH levels are inversely proportional to the fertilization rate at ART (assisted
cellular cAMP production over 24 h, in spite of LHCGR internalization.
reproductive technologies).
Discussion
Objective
We found a link between circadian rhythm, LHCGR up-/down-regulation and
To evaluate if a relationship exists between pregnancy rates in women undergoing
interaction with Gas protein and b-arrestin1/2, resulting in the modulation of
in vitro fertilization (IVF) and their basal thyroid stimulating hormone (TSH)
cAMP-dependent signalling.
levels.
Conclusions
Study design
These data suggest that the kinetics of LHCGR activation and downstream events
We performed a retrospective cohort study in which women with known TSH
are influenced by circadian rhythm, which modulates the cell response to
level who were submitted to IVF in our Hospital during 2014 and 2015 were
gonadotropins and secondary waves of cell signalling activation.
included. They were divided in two groups, according to their initial TSH level:
DOI: 10.1530/endoabs.49.EP1131
O or ! 2.5 mU/l. Pregnancy was defined by ultrasound visualization of
gestational sac.
Results
A total of 132 women met inclusion criteria. The mean age was 34.6 years old.
75.7% of women with TSH data had oligomenorrhea. Thyroid autoantibodies
were requested only in 6 cases. 36.3% of the patients had a TSH O2.5 mU/l. In
that group 39% of the women had pregnancy compared to 42.8% in the group
EP1132
with TSH !2.5 mU/l (PZ0.636).
Conclusion
High dose metformin effect on weightloss, androgen levels and thyroid
No statistically significant difference was observed between the two groups
function in obese hypothyroid patients with PCOS
concerning pregnancy rates after IVF. We cannot exclude that it is the presence of
Aurelian-Emil Ranetti1,2 & Anca-Pati Cucu1
thyroid autoantibodies and not the TSH value per se that is associated with lower
1“Dr. Carol Davila” Central University Emergency Military Hospital,
pregnancy rates. Further studies are needed to confirm this hypothesis.
Bucharest, Romania;2Carol Davila University of Medicine and Pharmacy,
Bucharest, Romania.
DOI: 10.1530/endoabs.49.EP1133
Objective
to evaluate the effects of metformin use on weight loss, improvement of ovarian
and thyroid function in obese women with polycystic ovarian syndrome.
Material and Methods
30 obese (BMI 30-34.99 kg/m2) hypothyroid (TSH 6-10 mIU/ml) women of
EP1134
age
25-35
years old were included. The patients received appropriate
The efficiency of metformin in polycystic ovarian syndrome is not
levothyroxine treatment according to TSH levels and body weight. A number
necessarily attributable to the improvement of insulin resistance
of 15 patients added metformin gradually increased from a starting dose of
Zsuzsanna Szanto & Adelina Micheu
500 mg/day to a final dose of 3000 mg/day over a period of 6 months. Baseline
University of Medicine and Pharmacy, Targu Mures, Romania.
levels, 3 months and 6 months levels of TSH, fT4, T3, AMH, LH/FSH ratio,
testosterone, along with BMI and ultrasound ovarian volume and antral follicle
count were determined. No adverse events that might have led to discontinuation
Insulin resistance has a pivotal role in the pathogenesis of polycystic ovarian
of the treatment were recorded. Mild nausea was registered in 8 patients after
syndrome (PCOS), thus insulin sensitizer therapy is beneficial. Purpose. Our
2 weeks of treatment with 3000 mg/day of metformin, respectively softer stools
purpose was to study the effectiveness of metformin in PCOS women, including
(but no diarrhoea) in 5 patients in the first week of treatment (500 mg/day), but the
those without insulin resistance. Matherials and methods. This study was
symptoms relieved with disappearing within the mentioned time frame.
conducted on 24 pacients (12 obese or overweight and 12 lean women), aged 21-
Results
31 years, diagnosed and treated with PCOS at the Clinical Department of
BMI levels decreased significantly in the first 3 months in metformin group
Endocrinology Targu-Mure, during January
2013-March 2015. All patients
(32.5C/-1.65 kg/m2
vs.
28.4C/K 1.95 kg/m2). BMI variation in the non
received metformin therapy, including those without insulin resistance.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
EP1137
Menstrual cycle disturbances
(anovulation, bradi-oligomenorrhoea) before
Oxidative status imbalance in patients with polycystic ovary syndrome
metformin therapy appeared in 91.6% of the obese or overweight women, and
Alina Crenguta Nicolae1, Cristina Manuela Dragoi1,
83.3% of the lean women (21 cases from the 24). In 15 cases insulin level,
Andreea Letitia Arsene1, Nicoleta Petruta Burlacu1, Crina Filisan2,
glycaemia were measured, and HOMA-IR calculated. Mean insulin level was
Alice Albu1,2 & Carmen Gabriela Barbu1,2
13.06G14.53 mIU/l in the obese group, and 6.82G1.92 mIU/l in the lean group,
1University of Medicine and Pharmacy Carol Davila, Bucharest, Romania;
and the corresponding mean HOMA-IR was 4.23G3.42 vs. 1.29G0.43. Among
2Elias Hospital, Bucharest, Romania.
the
21 women (11 obese and 10 lean) with menstrual disturbance before
metformin therapy these disturbances improved or pregnancy occurred in 11
cases (5 obese and 6 lean) during metformin treatment alone, which means a
Polycystic ovary syndrome (PCOS) is one of the most frequently encountered
significant improvement (PZ0.0085, RRZ3.16, 95% CIZ1.12-8.87). During
endocrine pathologies in women of reproductive age, being regarded as a chronic
metformin treatment alone, 14 women from the 24 presented normal menstrual
systemic disease instead of the simple local one. It is frequently associated with
cycle, normalized progesterone level or pregnancy occurrence (PZ0.002, RRZ
insulin resistance, hyperandrogenemia and chronic inflammation. PCOS reunites
3.83,
95% CIZ1.33-11.03). Conclusion. Metformin therapy might resolve
multiple and diversified pathological combinations like: ovulatory functional
menstrual cycle disturbances not only in insulin resistant obese PCOS women, but
disorders directly impacting on the reproductive system, carbohydrate and lipid
also in those with normal weight and/or without insulin resistance.
metabolism disorders which can be explained at least partially through an
DOI: 10.1530/endoabs.49.EP1134
increased oxidative stress. Oxidative stress occurs due to an imbalance between
the generation of reactive oxygen species (ROS) and the antioxidant defense
systems. In women, oxidative stress may be a major cause of infertility. In this
clinical study, comprising 55 PCOS patients and age-matched healthy subjects,
we aimed to assess the relationship among different metabolic risk factors, such as
triglycerides, cholesterol and glycaemia, and the reactive oxygen species levels in
patients diagnosed with polycystic ovary syndrome. For an accurate determina-
tion of the biochemical markers, diagnostic kits (Dialab, Austria) have been used,
EP1135
whereas for the determination of the reactive oxygen species
(ROS)
Serum Vitamin D status in women with the polycystic ovary syndrome
concentration, the chemiluminescent method was chosen. The triglycerides,
Justyna Kuliczkowska-Plaksej1, Andrzej Milewicz1, Renato Pasquali2,
glycaemia and cholesterol levels were significantly higher in the group of patients
Agnieszka Lenarcik-Kabzda1, Lukasz Laczmanski1, Felicja Lwow3,
compared with the control group (P!0.05), suggesting a considerable imbalance
Diana Jedrzejuk1 & Marek Bolanowski1
in patients with polycystic ovary. The serum concentration of the reactive oxygen
1Department of Endocrinology, Diabetology and Isotope Therapy, Wroclaw
species
(ROS) represents a marker of the global oxidative stress. The
Medical University, Wroclaw, Poland;2Department of Medical and
experimental results obtained following the assessment of the ROS concentration
Surgical Sciences, Division of Endocrinology, University of Bologna,
revealed a significantly higher value in the patient group with polycystic ovary as
Bologna, Italy;3Department of Health Promotion, University School of
compared to the control group, which translates into an enhanced oxidative stress
Physical Education, Wroclaw, Poland.
in patients diagnosed with polycystic ovary syndrome. Correcting oxidative stress
with antioxidants along with monitoring the antioxidant status could have a
beneficial effect on oxidative stress induced insulin resistance and hyperan-
Objective
drogenism in the PCOS diagnosed women.
To measure the levels of 25-hydroxyvitamin D (25(OH)D) and vitamin D binding
protein (VDBP) and assess their relationships with metabolic features in patients
DOI: 10.1530/endoabs.49.EP1137
with the polycystic ovary syndrome (PCOS).
Methods
267 women, aged 20-35 years (24.7G4.9): 167 with PCOS, 100 healthy women
as a control group were studied. Study groups were divided according to body
mass index (BMI). Biochemical and hormonal parameters, 25(OH)D, VDBP
were measured. Free and bioavailable
25(OH)D were calculated using the
mathematical equations. The percentage of body fat and visceral fat deposit were
EP1138
assessed by DXA.
Utility of oral glucose tolerance test (OGTT) in patients with polycystic
Results
ovary syndrome (PCOS)
In the normal weight control group total, free and bioavailable 25(OH)D were
Oana Alexandra Petre1, Ivona Gheorghe1, Irina Nicolaescu1, Dragos Albu2,3
significantly (P!0.001 for all) higher than in its overweight/obese counterpart. In
& Alice Albu1,2
women with PCOS both total 25(OH)D (P!0.001), and VDBP (P!0.001) were
1Elias Hospital, Endocrinology and Diabetes Department, Bucharest,
lower in the overweight/obese subgroups than in the normal weight one. VDPB
Romania;2Carol Davila University of Medicine and Pharmacy, Bucharest,
was negatively correlated with fasting insulin, positively with SHBG in control
Romania;3Medlife, Maternal Fetal Medicine and Human Reproduction,
group. In PCOS group, VDPB was negatively correlated with abdominal fat
Bucharest, Romania.
deposit, BMI, fasting glucose and insulin and positively with HDL and SHBG.
Conclusions
Background
Despite lower total 25(OH)D in obese PCOS women, all women with PCOS (lean
PCOS patients associate an increased risk of glucose metabolism abnormalities.
and obese) had comparable free and bioavailable 25(OH)D which might be a
Although Hb A1c was suggested as a good diagnostic test for prediabetes/
result of concomitantly lowered serum VDBP levels in obese PCOS women.
diabetes, in PCOS patients its diagnostic value could be inferior to OGTT as
VDBP might play important role in the regulation of availability of active
previously suggested. Aim of the study was to evaluate which are the clinical and
fractions of 25(OH)D in PCOS women. VDBP is strongly associated with cardio-
paraclinical parameters associated with impaired glucose tolerance (IGT) in order
vascular risk factors such as BMI, waist circumference, visceral fat, fasting
to identify the profile of the patients that will benefit from OGTT.
insulin in women with PCOS.
Material and methods
449 patients (mean age years, mean body mass index (BMI) kg/sqrm) diagnosed
DOI: 10.1530/endoabs.49.EP1135
with PCOS based on Rotterdam criteria evaluated with OGTT were retro-
spectively selected from our PCOS database.
Results
From the 449 patients included in the study 23 (5.1%) had impaired fasting
glycemic (IFG) and 28 (6.2%) IGT. Patients with prediabetes (IGT and IFG) were
older, had higher BMI, waist circumference (WC), insulinemia (fasting and 2 h),
HOMA-IR in comparison to patients with normal glucose. Patients with IFG were
EP1136
not different from those with IGT with respect to age, clinical and biochemical
hyperandrogegism, adiposity, HOMA-IR, fasting insulinemia and metabolic
parameters, except the 2 h insulinemia and serum FSH level which were higher
Abstract withdrawn.
and lower respectively in patients with IGT (P!0.05).
Conclusion
Our patients with IGT and IFG were similar in terms of clinical and paraclinical
baseline parameters, making impossible their identification without an OGTT.
DOI: 10.1530/endoabs.49.EP1138
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1139
Following vitamin D supplementation for 3 months, significant improvement of
BMI and metabolic parameters like FPG, 2 hr glucose, HOMA IR, HOMA B, TG
Diagnostic performance of non-invasive markers for the presence of
levels and TC was observed in women who followed LSM. However, there was
nonalcoholic fatty liver disease in premenopausal women with and
no change in serum testosterone.11/30 patients in the supplementation group who
without polycystic ovary syndrome
did not comply with LSM also showed significant decrease in FPG, 2 hr PG, and
Evangeline Vassilatou1, Sophia Lafoyianni2, Dimitra-Argyro Vassiliadi3,
HOMA IR.
Dimitrios Ioannidis2, Stavroula Paschou1, Maria Mizamtzidi1 &
Conclusion
Andromachi Vryonidou
Vitamin D supplementation has beneficial effect on insulin resistance and
1‘Red Cross’ Hospital, Athens, Greece;2‘Amalia Fleming’ General
metabolic parameters in vitamin D deficient PCOS women. Both vitamin D
Hospital, Athens, Greece;3‘Evangelismos’ Hospital, Athens, Greece.
supplementation and LSM have complementary effects in improving BMI and
HOMA indices, glucose and lipid metabolism in the setting of PCOS with vitamin
Introduction
D deficiency, suggesting a role of vitamin D in the management of PCOS.
Several markers based on anthropometric and biochemical parameters like fatty
DOI: 10.1530/endoabs.49.EP1140
liver index (FLI), lipid accumulation product (LAP) index and visceral adiposity
index (VAI), have been proposed for the detection of nonalcoholic fatty liver
disease (NAFLD).
Objective
To evaluate the diagnostic performance of FLI, LAP and VAI as markers of
NAFLD in premenopausal women with and without polycystic ovary syndrome
(PCOS), assessed for hepatic steatosis (HS) by ultrasonography.
Design
Prospective, cross-sectional study.
Patients and methods
EP1141
Anthropometric measurements, biochemical testing and abdominal ultrasono-
graphy after excluding causes of secondary liver disease were performed in 145
Epigenetics of female hypogonadotropic hypogonadism: analysis of
premenopausal women with PCOS (Rotterdam criteria) and 145 BMI-matched
mRNA expression of engaged in IHH genes
healthy controls. The three markers VAI, FLI and LAP were calculated and their
Anna Loktionova1, Irena Ilovayskaya1, Natela Eneva2,
diagnostic performance for predicting HS was evaluated with receiver operating
Karina Khusniyarova2, Lidia Nefedova2, Alexander Kim2 &
characteristic (ROC) analysis.
Alexander Dreval1
Results
1M.F. Vladimirsky Moscow Regional Research and Clinical Institute,
HS by ultrasonography was detected in 132/290 (45.5%) women, while the
Moscow, Russia;2Lomonosov Moscow State University, Moscow, Russia.
prevalence of HS was increased in PCOS women compared to controls [78/145
(54%) kai 54/145 (37%), PZ0.01]. FLI, LAP and VAI values were higher in
Hypogonadotropic hypogonadism is a syndrome which may be manifested
HS(C) compared to HS(K) women [68.7G26.7 vs 26.5G24.8, P!0.001,
clinically by low sex steroids because of low
(or inappropriately normal)
61.1G39.3 vs 23.7G15.2, P!0.001 kai 2.4G1.8 vs 1.2G0.6, P!0.001),
gonadotropins. To date, more than 30 genes were reported as possible reason for
respectively] as well as in PCOS women compared to controls. The area under the
this condition, but genetic basis is still unknown for w60% of HH cases. Due to
curve (AUROC) for FLI, LAP and VAI were 0.87G0.02, 0.84G0.02 and 0.77G
this fact we decided to analyze mRNA expression of several HH-related genes
0.03, respectively, in the whole group of women. When AUROCs of the three
which can be found in leukocytes of peripheral blood: GNRHR and GNRH1
indices were calculated separately for PCOS women and controls, no statistical
(which are necessary for adequate biological effect of GnRH); PROK2 and
differences were observed.
CHD7 (which are responsible for the migration of GnRH neurons), WDR11 and
Conclusions
DUSP6 (which are involved in normal sexual development). A quantitative
FLI, LAP and VAI can detect NAFLD in premenopausal women with a similar
determination of mRNA expression of these genes were comlpeted in the fresh
diagnostic performance. The presence of PCOS has no effect on the diagnostic
peripheral blood sample by PCR in real time.
performance of these indices.
Examined patients
DOI: 10.1530/endoabs.49.EP1139
Ten women with hypogonadotropic hypogonadism (age from 18 to 53 y.o.); 4 of
them suffer from amenorrhea I and 6 - amenorrhea II. Reasons of amenorrhea II
were: stress, excessive exercises, rapid body weight loss, past use of oral
contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.;
with regular ovalutory menstrual cycle, some of them have children.
Results
mRNA expression of examined genes differed from normal patterns in each case
of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6
mRNA expression were found in most of cases. However variations of mRNA
expression were multidirectional in each case and there was no similarity among
EP1140
expression profiles of patients according to anamnestic factors; but some affinities
Complementary effect of Vitamin D supplementation and lifestyle
were found among patients who suffer from primary amenorrhea. According to
modification on anthropometric and metabolic parameters in young
our preliminary results, in women with hypogonadotropic hypogonadism the
polycystic ovary syndrome women with Vitamin D deficiency: a
functional activity damage of ‘reproductive-responsible’ genes could be found in
3-month prospective interventional study
each case. Probably mRNA expression measuring could be a perspective method
Ramesh Jayanthy1 & Prasanna Belgundi2
for proving hypothalamo-pituitary level of reproductive disorders and may help to
1Sai’s Institute of Endocrinology, Hyderabad and Visakhapatnam, India;
determine which genes should be tested for DNA impairment.
2Osmania Medical College, Hyderabad, India.
DOI: 10.1530/endoabs.49.EP1141
Background
PCOS women usually have metabolic disturbances particularly insulin resistance.
Previous studies suggest that vitamin D deficiency may contribute to the
development of insulin resistance. Our aim is to study the effect of vitamin D
supplementation on clinical and biochemical parameters in vitamin D deficient
PCOS women.
Methods
EP1142
At baseline, 50 PCOS women were enrolled (37 vitamin D deficiency and 13
How far is possible to make a diagnosis of infertility
vitamin D sufficiency). Thirty-seven PCOS women on LSM (low-calorie diet
Daniela Dias, Joana Simo˜es-Pereira, Sara Donato & Conceição Pereira
1000-1200 kcal/d and aerobic exercise walking 3.2 km/d, 5 days/wk) received
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,
60 000 IU cholecalciferol weekly for 8 weeks followed by once a month. Clinical,
Portugal.
anthropometric and biochemical parameters were performed at baseline and after
12 weeks.
Results
Introduction
Thirty PCOS women completed the study.
25(OH) D levels significantly
Chemotherapy may be an important cause of primary infertility, especially in girls
increased from
7.55G4.10 at baseline to
34.16G4.14 ng/ml at
3 months.
submitted to this therapy at very young ages.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical case
EP1144
A 20-year-old female was diagnosed with acute lymphoblastic leukaemia at the
Serum activities of dipeptidyl peptidase-4 and adenosine deaminase and
age of 1. She was submitted to chemotherapy: intrathecal methotrexate and
parameters of oxidative stress in polycystic ovary syndrome: association
cyclophosphamide and i.v. doxorubicin, vincristine, mercaptopurine, asparagi-
with obesity
nase and bone marrow transplantation at the age of 2. She was referenced to
Seda Kahraman1, Alev Eroglu Altinova1, Serenay Elgun Ulkar2, Mehmet
Endocrine Rehabilitation Clinics at the age of 6.75 years-old. Her auxology
Muhittin Yalcin1, Banu Aktas Yilmaz1,
¸ igdem Ozkan1, Mujde Akturk1 &
evidenced: height 109.8 cm (p3-10); predicted adult stature: 155 cm (p10); and
Fusun Balos Toruner1
identical bone and chronological ages. In terms of puberty, her Tanner stages
1Faculty of Medicine, Gazi University, Ankara, Turkey;2Faculty of
were A1P1B1. Blood analysis evidenced IGF1 of 344 ng/ml (p90) and normal
Medicine, Ankara University, Ankara, Turkey.
thyroid and gonadal axes. At the age of 11, she remained pre-pubertal, with
increased levels of FSH (76.3 mUI/ml) and LH (17.2 mUI/ml). Her bone age was
11 years. At this time, we started inducing puberty with oestradiol. After 2 years,
Dipeptidyl peptidase 4 (DPP-4) is thought to play a role in the pathophysiology of
Tanner stages were A4P4B3. Menarche was achieved at 13.41 years old. At the
metabolic and inflammatory diseases. Increased ADA activity has been suggested
age of 18, she reached A5P5B5, after 7 years of estradiolCnorgestrel. She
to induce insulin resistance and inflammation. We investigated DPP-4 and ADA
withdrawal this therapy when she was 20 and scarce menses were observed.
activities, serum nitric oxide (NO) level and nitric oxide synthase (NOS) activity
Blood tests evidenced FSH of 84.1 mUI/ml and LH of 26.7 mUI/ml and pelvic
which are the oxidative stress parameters in patients with PCOS. Fifty two women
ultrasound was normal. At this age, given her desire to become pregnant, she
with PCOS and 41 healthy women were included in this study. Serum ADA
underwent ovarian stimullation, which was unsuccessufull. However, 12 months
activity (0.33 (0.17-0.67) vs 0.26 (0.12-0.60) IU/l; PZ0.006), NO level (24.5
later she became pregnant.
(13.25-58) vs 12.25 (6-24.50) mmol/l; P!0.001) and NOS activity (5.46 (3.38-
Discussion
12.71) vs 4.54 (2.55-10.13) IU/ml; P!0.001) were significantly higher in PCOS
This case reports the complex and not fully understood process of gonadal
group while there was no difference in serum DPP-4 activity (19.54G7.01 and
function after chemotherapy gonadotoxicity. We believe that the fortunate
18.24G6.73 IU/l; PZ0.369) between the groups. The groups were divided into
pregnancy result in our patient was probably due to previous gonadotrophins
subgroups as obese and nonobese. In obese PCOS group; ADA, NO and NOS
stimulation performed in a very young woman, which enabled the reactivation of
were significantly higher than obese controls
(PZ0.044, P!0.001
and
the gonadic axis.
P!0.001), while there was no difference in DPP-4 activity (PZ0.356) between
DOI: 10.1530/endoabs.49.EP1142
the groups. In nonobese PCOS group; NO and NOS were significantly higher than
nonobese controls (P!0.001 and PZ0.006), while there were no differences in
DPP-4 and ADA activity (PZ0.802 and PZ0.128). There was a negative
correlation between ADA and DPP-4 activity in PCOS group (PZ0.047). A
positive correlation was observed between ADA and BMI in the whole group
(PZ0.022). In conclusion, we found that there was no significant change in serum
DPP-4 activity in women with PCOS. However, we demonstrated increased
serum ADA activity as well as its association with obesity in PCOS. Also, our
finding that increased NO level and NOS activity in PCOS which is independent
of obesity may result from a compensatory mechanism for the oxidative stress
in PCOS.
DOI: 10.1530/endoabs.49.EP1144
EP1143
Physiological changes of adipokines and selected steroids during the
menstrual cycle
Monika
ˇ rámková1,2, Michaela Dušková1, Jana Vítk
˚1, Josef Vcˇelák1,
Petr Matucha1, Olga Bradnová1, Jose Cordeiro1 & Luboslav Stárka1
1Institute of Endocrinology, Prague, Czech Republic;2Faculty Hospital
Motol, Prague, Czech Republic.
EP1145
Context
Oocyte donation in women with Turner’s syndrome: successful outcome
The cyclical effects of hormones during the menstrual cycle (MC) are responsible
can be achieved with a specialist multidisciplinary approach
for driving ovulation. The information about roles of adipokines within the scope
Matilde Calanchini1,3, Kathy Baker2, Andrea Fabbri3, Ashley Grossman1,
of MC are not definite. Leptin plays a role in sexual function and regulating the
Elizabeth Orchard4, Tim Child2 & Helen Turner1
onset of puberty. Thin girls often fail to ovulate or release an egg from an ovary
1Oxford Centre for Diabetes, Endocrinology and Metabolism - Churchill
during menstruation cycles. Leptin also acts on specific receptors in the
Hospital, University of Oxford, Oxford, UK;2Oxford Fertility Institute of
hypothalamus to inhibit appetite. Levels of leptin are increased in women
Reproductive Sciences, Oxford, UK;3Department of Endocrinology CTO
suffering from premenstrual syndrome. The aim of our study was to describe
Alesini & S. Eugenio, University of Rome Tor Vergata, Rome, Italy;
physiological changes of selected steroids and adipokines at healthy women
4Cardiology Unit, John Radcliffe Hospital, Oxford, UK.
during the MC.
Introduction
Methods
Although oocyte donation (OD) is increasingly utilised in women with Turner’s
Twenty-seven women with regular menstrual cycles were included in the study,
syndrome
(TS) few data are available. Reported clinical pregnancy rates
and their hormonal spectrum and adipokines were measured in regular intervals
following OD range from 17 to 40%. Complications of 2% death from aortic
starting from the first day of their MC.
dissection and severe hypertension are reported.
Results
Aim
Classical changes in gonadotropins, estrogens and progesterone during the
To analyse the OD-pregnancy success rate and materno-fetal outcomes in women
menstrual cycle are accompanied by less striking but significant changes in
followed in a TS-dedicated centre.
17-hydroxyprogesterone and testosterone. No significant changes show dehy-
Methods
droepiandrosterone and its
7-oxygenated metabolites. Adipokines show a
A retrospective study of 114 adult TS patients analysed cardiovascular risk
tendency to increase during ovulation, while ghrelin and resistin decrease.
factors, feto-maternal morbidity and mortality in women undergoing OD (1997-
There is also a remarkable association of sex hormone-binding globulin on the
2015). Data were compared with spontaneous pregnancy (SP) 14/114 patients,
day of the cycle.
mean age 24 years (Calanchini et al. 2016, for SP data comparison).
Conclusion
Results
Our results demonstrate that changes to adipokines dutiny the menstrual cycle are
Eleven patients underwent egg donation cycles (total 27) using fresh (16) or
not substantial, but nonetheless can play a role in the changes of food intake
frozen (3) donated eggs or embryos frozen and stored from a previous egg
described in the literature. Precise descriptions of physiological changes in
donation cycles (8). Endometrial preparation achieved endometrial thickness
healthy women are important in helping us understand the significance of the
R7.3 mm, mean 10.2 mm. 1 or 2 embryos were transferred between day 2 and 5.
changes accompanying various pathological states.
Mean recipient age at first IVF was 32.5 years (24-41) and at delivery 33.8 years
DOI: 10.1530/endoabs.49.EP1143
(26-41). 3/11 were 45X, 3/11 were 45X/46XY and 5/11 other TS-karyotypes.
Five had cardiovascular malformations (4 bicuspid aortic valve, 1 treated aortic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
coarctation), four treated hypertension, and two pre-existing aortic dilatation.
underlying this association are incompletely clarified. The aim of the present
12/27 (44%) cycles had positive pregnancy-tests and 5/27 (19%) resulted in live
study is to evaluate the factors associated with thyroid autoimmunity in patients
births. The cumulative live birth rate per patient undergoing treatment was
with PCOS. We performed a retrospective study which included 126 PCOS
therefore 5/11(46%). Increased aortic diameter occurred in 1/5, and gestational-
patients (mean age 24G4.5 years, mean body mass index, BMI 27G7.33 kg/sqm)
diabetes 1/5. No patient developed gestational-hypertension compared with 7%
diagnosed based on Rotterdam criteria between January 2015 and January 2016.
SP. No cardiovascular or fetal complications were noted. One emergency
We found that anti-thyroid peroxidase antibodies (ATPO) serum levels were
caesarean section (37C1w, twin pregnancy).
positively correlated with HOMA-IR
(rZ0.234, PZ0.019), fasting insulin
Conclusions
(rZ0.218, PZ0.025), waist circumference (WC, rZ0.267, PZ0.007) and BMI
OD showed a 19% live birth rate per cycle and 46% per patient in TS, was safe
(rZ0.203, PZ0.04). We found no association between ATPO and total
even in women with cardiac risk factors, and unassociated with increased feto-
testosterone, free androgen index, gonadotropins, TSH, leptin and adiponectin
maternal complications compared with TS SP. This emphasises the importance of
serum levels. In a multivariate linear regression model with ATPO as dependent
early discussion of assisted reproductive technology and alongside monitoring in
variable only HOMA-IR was an independent predictor of ATPO values after
a TS-dedicated multidisciplinary centre.
adjustment for adiposity markers. In conclusion, in PCOS patients insulin
DOI: 10.1530/endoabs.49.EP1145
resistance seems to be the main factor involved in thyroid autoimmunity.
DOI: 10.1530/endoabs.49.EP1147
EP1146
The features of young women reproductive health with type 1 diabetes
Kateryna Kondratiuk1, Nazarii Kobyliak1, Iryna Nikitina2,
Valentyna Kondratiuk3 & Petro Bodnar1
EP1148
1Bogomolets National Medical University, Kyiv, Ukraine;2Sumy State
Metformin treatment decreased free androgen index among
University, Sumy, Ukraine;3State Institution ‘Institute of Pediatrics,
PCOS women
Obstetrics and Gynecology of NAMS of Ukraine’, Kyiv, Ukraine.
Sandra Mrozinska1,3, Anna Wajda2, Patrycja Czekanska2,
2, Marta Kialka2,3 & Tomasz Milewicz2,3
Barbara Zdzierak
Background
1Department of Metabolic Diseases, Jagiellonian University, Medical
Leading position among endocrine pathology of adolescence and young women is
College, Krakow, Poland;2Department of Gynecological Endocrinology,
type 1 diabetes (T1D), which in recent years had been proved to have a strong
Jagiellonian University, Medical College, Krakow, Poland;3University
association with reproductive dysfunction among such patients. The purpose was
Hospital, Krakow, Poland.
to investigate the features of reproductive health in 120 young women (18-22
years old) with T1D.
Methods
Hyperinsulinemia is one of biochemical features of polycystic ovary syndrome
Retrospectively we studied the features of puberty and prospectively examined
(PCOS). Metformin is a common drug used in PCOS. Recent studies have shown
level of blood glucose and HbA1c, levels of gonadotropin (LH, FSH) and sex
that metformin has impact on clinical and biochemical parameters in PCOS
hormones (prolactine, estradiol, progesterone, testosterone) (ELISA, France) and
patients. The aim of our study was to assess retrospectively the influence of
determined antibodies to ovarian tissue (Euroimmune, Germany) in peripheral
metformin on total testosterone, sex hormone binding globulin (SHBG) and free
blood, held pelvic ultrasonography (MyLabSeven, Italy).
androgen index (FAI) in women with PCOS in polish cohort. A total of 54
Results
patients with PCOS and irregular menses were examined. The duration of
The proportion of patients with delayed puberty and physical development of type
metformin treatment between the baseline and final blood results was about six
1 diabetes with the debut in the pre-puberty was in 62.5%, in the early puberty
months. There were statistically significant differences in the total testosterone
(3-7 years) - 15.0%, in the active adolescence (11-14 years) - 11.7% of post-
(1.9
(1.4-2.6) vs 1.2 (0.6-2) ng/ml), SHBG (34.8 (27.2-53.1) vs 49.4 (35.9-81.7)
puberty (over 14 years) - 10.8%. Ovarian failure occurred in 76.7% of the
nmol/l) levels and FAI (5.3 (3.2-9.8) vs 2.3 (1.3-4.3) before and after the
patients, and was expressed in the increased LH, estradiol and free testosterone
metformin administration (all P!0.0001). In addition the patients were divided
levels. The positive correlation relationships were detected between blood levels
into two groups according to FAI. There was no difference in age (29 (26-32) vs
of estradiol (rZ0.77, P!0.05), testosterone (rZ0.56, P!0.05) and level HbA1c;
28
(25-31) years, PZ0.7) and BMI (22.5 (19-24.1) vs (22 (20.7-28.1) kg/m2,
negative correlation relationship were revealed between progesterone blood level
PZ0.35) between group with FAI!5 and group with FAIO5, respectively. Our
(rZ0.67, P!0.05) and level of HbA1c. Fiction revealed correlations between the
study showed that metformin therapy ameliorates the total testosterone and FAI
levels of sex hormones and the regime of insulin therapy. Autoimmune ovarian
both in women with FAI greater and lower 5 but improves SHBG levels only
failure was detected in the 4.2% cases. The presence of ovarian insufficiency was
among patients with FAIO5. The groups did not differ in difference between
accompanied by an increase in ovarian volume and number of antral follicles
baseline and final testosterone and SHBG levels but differed in FAI change. Our
in them.
study suggest that metformin effectiveness could differ between PCOS patients
Conclusion
according to the phenotype.
Type 1 diabetes adversely affect the formation of future reproductive health of
girls, realized at hormonal dysfunction, ovarian failure and pathological changes
DOI: 10.1530/endoabs.49.EP1148
in the structure of the ovaries.
DOI: 10.1530/endoabs.49.EP1146
EP1147
The determinants of thyroid autoimmunity in patients with polycystic
ovary syndrome
EP1149
Alice Albu1,2, Oana Petre2, Irina Nicolaescu2, Ivona Gheorghe2 &
Dragos Albu1
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;
Abstract withdrawn.
2Elias Hospital, Bucharest, Romania.
It was suggested that polycystic ovary syndrome
(PCOS) patients have an
increased risk for autoimmune thyroid disease. However the mechanisms
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1150
normal BP; excessive hair on chin, forearms and lower abdomen; no striae, no
acanthosis nigricans, normal thyroid. High levels of insulin, LH, total
Biochemical and clinical characteristics of polysystic ovarian syndrome
testosterone, androstendione and low levels of SHBG and progesterone in the
(PCOS) in women with and without type 1 diabetes (TID)
luteal phase were found. An oral glucose tolerance test, fasting lipid profile and
Anjuli Gunness1, Agnieska Pazderska1, Mohamed Ahmed1, Niamh Phelan1,
concentrations of TSH, prolactin, 17OHP were normal. A pelvic ultrasound
Gerard Boran1, AE Taylor2, MW O’Reilly2, Wiebke Arlt2, Kevin Moore1,
confirmed polycystic ovaries. The clinical and lab. tests were consistent with
Lucy-Ann Behan1, Mark Sherlock1 & James Gibney1
PCOS. Therapy with life style changes (weight reduction) and metformin was
1Department of Endocrinology and Clinical Chemistry, Adelaide and Meath
started (500 mg bid). After 10 months of treatment, she lost 8 kg, menstrual cycles
Hospital, Tallaght, Dublin 24, Ireland;2Institute of Metabolism and Systems
were regular (26-28 days), concentrations of LH, testosterone, progesterone and
Research (IMSR), University of Birmingham, Edgbaston, Birmingham B15
insulin were normal. The patients with PCOS are treated according to their
2TT, UK.
symptoms, risks and desire for pregnancy. The OCs are the mainstay of
pharmacologic therapy for women with PCOS for managing hyperandrogenism
Abstract
and menstrual dysfunction. The case has showed impact of the OC on the
PCOS prevalence is reported to be increased in reproductive-age women with
pituitary-ovarian suprresion. There are relatively few publications examining the
type-1 diabetes (T1DM) but measurement of androgens, crucial for diagnosis, has
effect of the OC on ovarian function in women and it’s less clear whether the
been with inaccurate immunoassays. No studies have been reported using liquid-
pituitary-ovarian suppression induced by the OCs has any impact on functional
chromatography-mass-spectrometry (LCMS). Reproductive-age T1DM women
ovarian reserve, so we need further evaluation. Although, the use of metformin in
attending a single centre were evaluated for PCOS (NIH criteria). Women with
the treatment of PCOS is off-label, in this case, metformin had showed as safe and
T1DM and PCOS (T1/PCOS) were compared to T1DM women without
effective. Benefit was made on oligomenorrhea, fertility and obesity.
hyperandrogenism (T1/no HA), and to two groups of non-diabetic women with
DOI: 10.1530/endoabs.49.EP1151
PCOS - one group BMI-matched (PCOS-lean) and the other overweight (PCOS-
overweight). 16 (18%) of T1DM women had PCOS. TIDM women with PCOS
compared to the overall group were younger (26.5 vs 29) and had a lower BMI
(23.4 vs 25.3). Compared to T1/no HA, testosterone (1.3 vs 0.8 nM, PZ0.004)
and androstenedione (7.1 vs 4.6 nM, PZ0.0016) were elevated but no differences
in DHEA-OX, DHEAS, SHBG or free testosterone was noted. They had an older
age of menarche (13 vs 12.5 years, PZ0.024), and were more likely (PZ0.024)
to have a positive family history of PCOS. There were no differences in androgen
levels between T1/PCOS and PCOS-lean women, but both of these groups
demonstrated greater androstenedione levels (7.1 vs 5.5 nM, PZ0.0247) than
PCOS-overweight women. In summary, PCOS is common in T1DM. Women
with T1/PCOS are leaner than T1 women without PCOS but are more likely to
have a family history of PCOS. They have a similar biochemical phenotype to
lean women with PCOS but differ from overweight women with PCOS. The
mechanisms underlying PCOS in T1DM and its clinical significance are
EP1152
unknown.
Does radioactive ıodine therapy affect fertility?
DOI: 10.1530/endoabs.49.EP1150
Berna Evranos Ogmen1, Sevgul Faki2, Sefika Burcak Polat2,
Nagihan Bestepe1, Reyhan Ersoy2 & Bekir Cakir2
1
Ataturk Education and Research Hospital, Department of Endocrinology
and Metabolism, Ankara, Turkey;2Yildirim Beyazit University, Faculty of
Medicine, Ataturk Education and Research Hospital, Department of
Endocrinology and Metabolism, Ankara, Turkey.
Introduction
Thyroid carcinoma is common in young women. Radioactive iodine (RAI)
therapy has been confirmed as a useful treatment in the management of
differentiated thyroid carcinoma (DTC). For women with DTC, the effect of RAI
therapy on gonadal and reproductive function is an important consideration. We
aimed to evaluate effects of RAI therapy on ovarian function.
Method
Women younger than 40 years old and diagnosed with thyroid cancer that
required RAI treatment were enrolled in this study.Patients with ovarian
insufficiency were excluded. Early follicular phase serum follicle stimulating
EP1151
hormone (FSH) and anti-mullerian hormone (AMH) levels were measured before
A case of polycystic ovary syndrome (PCOS)
and 3-6 months after RAI therapy. Friedman test is used to detect changes in FSH
Kristina Kljajic Babic, Dubravka Majic Milotic, Kristijan Peros &
and AMH levels by RAI therapy with time.
Lea Smircic Duvnjak
Results
Clinical Hospital Merkur, Zagreb, Croatia.
Eighteen patients with a mean age of 31.9G4.9 years were enrolled in this study.
Median AMH levels were 4.2 (2.96-17.42) ng/ml, 2.21 (0.84-3.69) ng/ml, 2.08
(0.86-6.12) ng/ml before and 3-6 months after RAI therapy, respectively. Median
FSH levels were 5.5 (3.78-15.5) mIU/ml, 5.32 (4.19-35.36) mIU/ml, 6.07 (4.24-
Polycystic ovary syndrome (PCOS) is one of the most common endocrine
13.69) mIU/ml before and 3-6 months after RAI therapy, respectively. AMH
disorders in women of reproductive age. It’s a heterogeneous functional disorder
levels before RAI were higher than after RAI (PZ0.021).AMH levels after
of unclear etiology. The features of PCOS are disorders of ovulation, androgen
RAI at 3 and 6 months were not different. FSH levels were similar before and
excess, polycystic ovaries; it’s associated with presence of associated risk factors
after RAI.
for cardiovascular disease
(obesity, glucose intolerance, dyslipidemia). The
Conclusion
diagnosis of PCOS is made using the Rotterdam 2003 criteria. 23yo female
Anti-mullerian hormone (AMH) is considered an important marker of ovarian
patient was evaluated for oligomenorrhea. At the age of 17, she consulted for the
reserve. Ovarian reserve decreases in first 6 months after RAI therapy. Further
first time her gynecologist because of irregluar menstrual cycles since the
large prospective studies are necessary to determine its predictive interest for
menarche (age 14) and excessive hair growth. A diagnosis of PCOS was made and
post-treatment residual fertility.
oral contraceptives (OC) were introduced in therapy. After 1.5 yrs, OC were
excluded because of undetectable levels of LH and FSH. Without them, the
DOI: 10.1530/endoabs.49.EP1152
menstrual cycle length was 40-120 days. Examination revealed high BMI 25;
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1153
P!0.01. In PCO group, it was higher before (3.54G0.58 ng/ml) than after
treatment (2.79G0.39 ng/ml), with P!0.01.
Androgen profiling by liquid chromatography-mass spectrometry
Conclusion
(LC-MS) in reproductive-age women with and without diabetes
AMH is higher in PCO subjects and its levels decreases significantly with the
Anjuli Gunness1, Agnieska Pazderska1, Mohamed Ahmed1, Niamh Phelan1,
insulin sensitizer metformin and it can be used as a marker for treatment efficacy
Gerard Boran2, AE Taylor3, MW O’Reilly3, Wiebke Arlt3, Kevin Moore1,
with metformin.
Lucy-Ann Behan1, Mark Sherlock1 & James Gibney1
Keywords: PCO, Anti-Mullerian hormone (AMH), Metformin.
1Department of Endocrinology, Adelaide and Meath Hospital, Tallaght,
Dublin 24, Ireland;2Department of Clinical Chemistry, Adelaide and Meath
DOI: 10.1530/endoabs.49.EP1154
Hospital, Tallaght, Dublin 24, Ireland;3Institute of Metabolism and Systems
Research (IMSR), University of Birmingham, Edgbaston, Birmingham B15
2TT, UK.
Abstract
The prevalence of hyperandrogenism has been reported to be increased in
EP1155
reproductive-age women with type-1
diabetes
(T1DM). This observation
Influence of BMI in response to ovarian stimulation and live birth in
however is based on findings using inaccurate immunoassays. No studies have
IVF
been reported in diabetes using liquid-chromatography-mass-spectrometry
Patrícia Tavares1, Catarina Machado1, Lucinda Calejo2, Gustavo Rocha1,
(LCMS). We compared LCMS-measured androgens in T1DM-women with
Ana Margarida Póvoa2, Sandra Soares2, Sónia Sousa2 & Maria João
age-/ BMI-matched normal women, and compared findings with those in women
Oliveira1
with type-2 diabetes (T2DM) also compared to a matched control group (Table
1Centro Hospitalar Vila Nova de Gaia/Espinho, Endocrinology Department,
Below). Compared to non-diabetic women, androstenedione and SHBG were
Vila Nova de Gaia/Porto, Portugal;2Centro Hospitalar São João,
greater in T1DM while estimated free-testosterone was lower. In contrast,
Reproductive Medicine Department, Porto/Porto, Portugal.
compared to non-diabetic women, androstenedione, DHEA-OX and SHBG levels
were lower in T2DM while free-testosterone and DHEAS were greater. Total
testosterone did not differ between groups in either comparison. T1DM and
Introduction
T2DM are associated with differing effects on androgen levels. These differences
The deleterious effects of obesity on spontaneous reproduction are well
are likely to reflect differences in insulin sensitivity and differing effects of
recognized, although the literature on obesity and assisted reproductive
exogenous insulin administration. Their clinical significance requires further
technology outcome remains heterogeneous and inconsistent.
investigation.
Objective
Mean (G SEM); P-value vs matched non-diabetic.
To estimate the effect of BMI on ovarian stimulation response and live birth in
Median (range); P-value vs matched non-diabetic.
women underwent in vitro fertilization (IVF).
Methods
Retrospective observational study that included women submitted to a first IVF
Non-diabetic
Non-diabetic
cycle in an infertility center of a public hospital in 2015.
TID (NZ63; median
(NZ42; median
T2D TID (NZ32;
(NZ55; median
Results
age Z32; median
age Z34.5; median
median age Z38;
age Z34; median
BMIZ25.5)
BMIZ27.4)
median BMIZ36)
BMIZ35.1)
We included 102 women with a mean age of 33.2 years (G3.7). 69 (67.6%) were
in normal weight range, 22 (21.6%) were overweight and 11 (10.8%) were obese.
Androsten-
5.1
(1.4-13.1)
3.6
(0.0-16.9)
2.5
(0.0-14.1)
3.8
(0.4-15.5)
dione (nM)
PZ0.0005
PZ0.0035
The mean values of basal serum FSH and LH were 6.6 mIU/ml (G2.7) and
DHEA-OX
10.1
(2.0-44.0)
12.0
(1.3-43.7)
5.7
(0.0-15.3)
13.5
(1.1-51.0)
5.9 mIU/ml (G3.8) respectively. The antral follicles count (AFC) on day 2-3 of
(nM)
P !0.0001
the cycle was on average 14.2 (G6.9). 46 (45.1%) women underwent IVF cycle
DHEAS
5
(1.3-14.3)
5.0
(1.1-14.7)
6.0
(2.2-13.9)
4.3
(1.3-13.1)
(uM)
PZ0.0045
and 56 (54.9%) underwent IVF with intracytoplasmic sperm injection. The
FT (%)
1.1
(G SEM 0.05)
1.4
(G SEM 0.07)
2.0
(G SEM 0.11)
1.6
(G SEM 0.056)
average duration of stimulation and dose of FSH administered was 9.8 days
PZ0.0015
PZ0.0005
(G2.3) and
1622.1UI
(G647.7) respectively. There were no statistically
significant differences in the 3 groups of BMI in relation to the women’s age,
FSH levels, AFC and neither in relation to the number of oocytes obtained. In our
sample, age and AFC were the factors that correlated with the number of oocytes
DOI: 10.1530/endoabs.49.EP1153
(P!0.001). Obese women had significantly fewer live births than overweight
women (PZ0.027) and this last BMI group (average BMI 26G0.9) had more live
births. There were no differences in embryo quality or number of embryos frozen
in these three groups.
Conclusions
Increased age and decreased AFC are negative determinants in the number of
oocytes obtained. Although BMI groups had no difference in the number or
EP1154
quality in the oocytes collected, obese women had a significant lower probability
Anti-mullerian hormone a marker for metformin therapy efficacy in
of having a live birth after IVF.
PCO: a pilot study on Egyptian population
DOI: 10.1530/endoabs.49.EP1155
Nermin Sheriba, Mona Mohamed Abdelsalam, Bassem Mourad,
Madiha Mamdouh & Eltohamy Samia
Ain Shams University, Cairo, Egypt.
Background
Polycystic ovarian syndrome (PCO) is the most common endocrinopathy in adult
women, and is emerging as a common cause of menstrual disturbance in the
EP1156
adolescent population. Insulin resistance, which is considered one of its
Anti-Mullerian hormone level is independently affected only by the
underlying causes, has increased substantially in the past decade, putting more
ovarian factor among clinical and endocrinological factors in polycystic
adolescent girls at risk for PCOS and its complications. Anti - Mullerian hormone
ovary syndrome
(AMH) is secreted by the granulose cells of ovarian follicles and correlated with
Toshiya Matsuzaki, Munkhsaikhan Munkhzaya, Takeshi Iwasa,
count of small antral follicles and it is expressed throughout folliculogenesis.
Altankhuu Tungalagsuvd, Kiyohito Yano, Yiliyasi Mayila &
Objective
Minoru Irahara
Evaluation of AMH in Egyptian women with PCOS and if it might serve as a
Tokushima University, Kuramoto-cho, Tokushima, Japan.
prognostic marker for treatment efficacy with metformin.
Patients and methods
The study included 30 women with PCOS (group 1) and 30 healthy women
without PCOS (group 2). AMH is measured in both groups and before and after
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-10% of
treatment with metformin (2550 mg) for 3 months in group I.
women. We evaluated the correlations between the serum AMH level and various
Results
endocrine and metabolic features in PCOS. Serum AMH level was compared
AMH levels was higher in PCO groups before (3.54G0.58 ng/ml) and after
between 114 PCOS patient (PCOS group) and 95 normal menstrual cycle women
treatment (2.79G0.39 ng/ml) than the control group (2.14G0.49 ng/ml) with
(Control group). Correlations between serum AMH level and various endocrine
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
and metabolic factors were analysed in PCOS group. The serum AMH level was
Aim
significantly higher in the PCOS group (8.35G8.19 ng/ml) than in the Control
Has testosterone undecanoat 1000 mg injection (NebidoR; Bayer), 1/3month
group (4.99G3.23 ng/ml). The serum AMH level was independently affected by
negative effect on prostate?
age and the presence of PCOS on multiple regression analysis. Ovarian volume
Material and method
per ovary (OPVO) showed the strongest positive correlation (rZ0.62) with the
i) PSA (ng/ml) was registred retrospective (from files) and prospective analysis
serum AMH level among clinical factors. OPVO was the only independent factor
(onset 2010). ii) Patients: PSA analysis was done before treatment and recorded at
that affected the serum AMH in PCOS on multiple regression analysis. Serum
T1 to T12 [2 weeks to 9 years] (see Pisoschi, this Congress). iii) Statistical
AMH level is determined only by ovarian morphological factor and the other
analysis: Student test, simple correlation, multiple regression.
pathophysiological factors such as androgen, severity of anovulation and insulin
Results
resistance are not determinant factors in PCOS even if significant relationship
A. Patients at onset: 160 men, 18-96 years, average: 60.38; median: 60; no
exists.
prostatic cancer. B. Prostatic volume (cmc): average: 34.81. C. Average PSA (no
DOI: 10.1530/endoabs.49.EP1156
patients): before treatment Z1.60 (160); 1yZ1.69 (110); 2yZ1.4 (83); 3yZ1.85
(57); 4yZ2 (46); 5yZ1.86 (34); 6yZ1.51 (30); 7yZ2.86 (2); 8yZ1.99 (11);
9yZ1.90 (4). D. Statistical difference of increasing average: nonsignificant for all
times from 2 weeks to 9 years. E. Correlation between age and PSA was 1.
significant at: T0: rZ0.29; 1y: rZ0.35; 2y rZ0.28. 2. nonsignificant for 3 to 9
years (rZ0.14-0.73). F. Correlation between PSA and prostatic volume was
significant, both before and after treatment
(depending on group size).
G. Observations: 7 patients died; 1 during treatment, Klinefelter, 41 y, cerebral
tumor; remaining 6 after 2 years stoping tretament, 60& 83-91 y, most cardiac
stop. H. Multiple regression test shows p values /0.001 for all years (examples):
Male Reproduction
1y: R2 Z0.58, FZ50.24 / 9y: R2 Z1, FZO1000.
EP1157
Conclusions
i) Testosterone undecanoat 1000 mg injectable i.m. at 3 months did not increased
Analysing by decade, testosterone undecanoat depot injectable does not
PSA level after up to 9 years administrations. ii) PSA level post testosterone does
increases prostate volume. Study during up to 9 years on hypogonadic
not depend on testosterone administration but on age, prostatic volume, before
patients. (December 2016)
and after treatment, and initial PSA level, i.e. before testosterone administration.
Matei Pisoschi1, Dana Cristina Staicu2 & Dan Peretianu2
1Hospital CF2, Department of Urology, Bucharest (Bucuresti), Romania;
DOI: 10.1530/endoabs.49.EP1158
2Medical Center Povernei, Department of Endocrinology, Bucharest
(Bucuresti), Romania.
Aim
Re-analyzing
(study starting in
2007) the effect of injectable testosterone
undecanoat depot (TUD) in hypogonadic patients.
Materials and Methods
A. Patients: at onset 231 men with hypogonadism (median: 62 y). B. Distribution:
by decade (starting with 20y); no Z4, 14, 24, 61, 63, 49, 17, 1. C. TUD (NebidoR-
Bayer) 1000 mg injected one/3 months i.m. D. Prostate volume (PV) appreciated
EP1159
by per-abdominal ultrasound:
3.5-5 MHz probe, elliptical/3D
(cm3). E.
12
patients were opperated before starting testosteron, 2 patients were opperated
Induction of male puberty in patients with hypogonadism hypogona-
during treatment. F. Analysis Time: before starting testosterone (T0), after 1/2
dotrope with subcutaneous gonadotropin
month (T1Z231), 3m (T2Z182), 6m (T3Z149), 1y (T4Z123), 2y (T5Z90), 3y
Paloma Moreno-Moreno, Concepción Mun˜ oz-Jiménez, María
(T6Z62), 4y (T7Z48), 5y (T8Z40), 6y (T9Z33), 7y (T10Z22), 8y (T11Z11),
Rosa Alhambra-Expósito & María Ángeles Gálvez-Moreno
9y (T12Z4). G. Maximum increment from T0 noted D M %. Average increment
Management Unit of Clinical Endocrinology and Nutrition, University
noted D A %. H. Statistical analysis: Student test.
Hospital Reina Sofía, Córdoba, Andalucia, Spain.
Results
I. All average prostatic volume for decade - tabulated (see pdf). Maximum
Objective
increment (D M %) per decade, including the moment (D M % at) and average
The most used therapeutic guidelines for the induction of male puberty in
increment (D A %) - tabulated (see pdf). II. PV at T0 increases with age, from
hypogonadotropic hypogonadism (HH) are GnRH in subcutaneous pulsatile
minimum 15.38
(19-29y) to maximum
45.5
(80-89y), PZ0.0007. III.
infusion and HCG in monotherapy or combined with FSH in intramuscular
Considering all observations, TUD did not increase PV significantly; in fact the
injection. The objective of this study was to evaluate the efficacy of subcutaneous
average of increment in all patients was negativeZK22.38%. D M % per decade:
HCG with or without FSH in induction of male puberty in patients with HH.
45.95; 31.82; 56.41; 55.77; 45.45; 64.41; 42.11; 20 IV. Inside a specific decade no
Patients and methods
significant increased in PV was registered: all PO0.05; exception: 80-89 decade,
Descriptive study of patients with HH treated with HCG subcutaneously (s.c.)
PZ0.002, from 3 to 5 y. V. In some patients, especially from 40-79 years, TUD
with or without FSH, for induction of male puberty (2004-2015). The Treatment
could decrease slightly prostatic volume.
was initiated with HCG 500 UI/72h s.c., periodic monitoring of testosterone,
Conclusions
testicular volume and semen analysis was realized, adjusting doses up to 2500
Considering the risk for prostate (in elderly), testosterone undecanoat 1000 mg
UI/72h. If no answer obtained after one year, combined treatment with FSH s.c.
depot injectable is a safe treatment, even after
9 years of administration.
was started.
Precautions should be accorded to men over 80 y old, after the 2nd year
Analyzed data
administration.
Cause of HH, age, testosterone levels, testicular volume, semen, dose of HCG and
DOI: 10.1530/endoabs.49.EP1157
FSH treatment. Pubertal development assessed by testosterone levels, testicular
volume and normalization of spermatogenesis.
Results
Nine patients. 17.2G1.8 years old (15-20). Cause of HH: four Idiopathics, four
craniopharyngiomas and one adenohypophysis hypoplasia. Dose of HCG: 1666G
821.6U/72 h. Two patients required combined treatment with FSH. Treatment
period: 32.2G9.5 months. Testosterone levels were normalized in 100% of cases
(7.34G5.1 ng/ml). 95% increased testicular volume: 13.5G4.4 ml (10-20). The
spermiogram was performed in 80% of cases at the end of treatment, with
oligospermia in all cases. No presence of side effects.
Conclusions
EP1158
Subcutaneous gonadotropin therapy is effective in induction of male puberty in
After 9 years observation, testosterone undecanoat 1000 mg at 3 months
HH. Treatment with subcuataneous HCG alone is successful. No presence of side
did not increased Prostatic Specific Antigen level (December 2016)
effects.
Matei Pisoschi
DOI: 10.1530/endoabs.49.EP1159
1Department of Urology, Hospital CF2, Bucharest (Bucuresti), Romania;
2Medical Center Povernei, Bucharest (Bucuresti), Romania.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1160
Conclusion
Patients with lymphoma have an increased risk for poor semen quality before any
Semen quality in young, healthy men is not related to serum
treatment.
74% of these men in our study had abnormal semen parameters
concentration of vitamin D (AndroLS)
according to the WHO. Generally, all patients with newly diagnosed lymphoma’s
Pawel Jozkow1, Aleksandra Zagrodna1, Marek Medras1,2, Felicja Lwow3 &
need counselling about their reproductive function and semen cryopreservation
Malgorzata Slowinska-Lisowska1
should be offered before undergoing gonadotoxic treatment.
1Department of Sports Medicine and Dietetics, University School of
Physical Education, Wroclaw, Poland;2Department of Endocrinology,
DOI: 10.1530/endoabs.49.EP1161
Diabetology and Isotope Therapy, Wroclaw Medical University, Wroclaw,
Poland;3Department of Health Promotion, University School of Physical
Education, Wroclaw, Poland.
Introduction
Relationships between vitamin D and male fertility are not fully elucidated.
EP1162
Studies in infertile/subfertile subjects suggest that vitamin D status may be
associated with semen parameters (1, 2). Data from healthy men is inconclusive
(3,
4). Our purpose was to evaluate the andrological status and a range of
biochemical, dietary and lifestyle variables in healthy men aged 18-35, living in
Abstract withdrawn.
the region of Lower Silesia (Poland) (AndroLS).
Material and methods
We invited
5000
subjects to participate in the study. From among
500
respondents, we acquired necessary material (semen and blood) from 177 men.
The specimens were collected in autumn and winter. The semen samples were
evaluated according to WHO 2010 criteria by a single experienced medical
analyst.
Results
Only minority of the studied subjects (18%) had serum 25(OH)2D3 concentration
above the lower limit
(20 ng/ml).
39% had severe vitamin D deficiency
(!10 ng/ml). Mean (GS.D.) 25(OH)2D3 was 13.7G8.9 ng/ml. Mean (GS.D.)
semen volume in the volunteers was: 3.1G1.5 ml, sperm concentration: 60G
44!106/ml, total sperm count: 170G137!106/ejaculate, percent of normal
forms: 14.7G6.5%. None of the studied semen parameters correlated with serum
concentration of
25(OH)2D3. We did not observe any correlations after
adjustments for: alcohol consumption, cigarette smoking, carrying a mobile
EP1163
phone in pants’ pockets, body mass index, caffeine consumption and physical
Gonadal profile in men with early-onset androgenetic alopecia: does a
activity, either.
male PCOS-equivalent syndrome exist?
Conclusions
Rossella Cannarella1, Rosita A Condorelli1, Sandro La Vignera1, Laura
Our data suggest that serum concentration of 25(OH)2D3 cannot indicate semen
M Mongioì1, Enzo S Vicari1, Giuseppe Micali2 & Aldo E Calogero1
quality in healthy men.
1Department of Clinical and Experimental Medicine, University of Catania,
DOI: 10.1530/endoabs.49.EP1160
Catania, Sicily, Italy;2Dermatology Clinic, University of Catania, Catania,
Sicily, Italy.
Importance
Early-onset androgenetic alopecia (AGA) has been suggested as a phenotypic
sign of the male polycystic ovary syndrome (PCOS)-equivalent since men with
this feature have a PCOS-like hormonal pattern. No study has evaluated the
gonadal function of these men.
Objective
EP1161
To study the gonadal function of men with early-onset AGA and to identify
suggestive criteria of male PCOS-equivalent.
Semen quality in patients with newly diagnosed lymphoma’s
Kristijan Peros, Dubravka Majic Milotic, Tomislav Bozek, Mia
Design
Sunjic Stakor, Kristina Kljajic Babic, Vesna Dermanovic Dobrota &
This case-control study was conducted from January 2014 to June 2016.
Sasa Magas
Setting
Vuk Vrhovac University Clinic, Clinical Hospital Merkur, Zagreb, Croatia.
The study was carried out on patients referring to hospital for andrological
check-up.
Participants
Objective
Forty-four men with early-onset AGA (19-30 years) and 37 aged-matched
To analyse the semen quality in patients with newly diagnosed lymphoma’s
healthy men (controls) were enrolled. A subgroup of patients was assumed to
before starting the treatment.
have the male PCOS-equivalent (sAGA) when at least one of the following
Materials and methods
parameter was present: BMI O25 kg/m2, insulin-resistance (IR) (HOMA index
We evaluated semen quality in 131 patient with lymphoma who underwent sperm
O2.5), SHBG !25 nmol/l. The remaining patients were considered to have AGA
banking in our clinic over a
14-year period.
102 patients had Hodgkin’s
alone (aAGA).
lymphoma, and 29 had non-Hodgkin’s lymphoma. Semen samples were collected
Main outcome(s) and measure(s)
by masturbation after 2-7 days of sexual abstinence. Age at banking, semen
The primary outcome was to evaluate the gonadal function and the
volume, sperm concentration, and total and progressive sperm motility were
metabolic/hormonal features of men with early-onset AGA. The secondary
recorded. Semen parameters were compared to established World Health
outcome was to identify which parameters may be used to suspect the male
Organisation
(WHO) reference values
(WHO Laboratory Manual for the
PCOS-equivalent syndrome among men with early-onset AGA.
Examination and Processing of Human Semen, Fifth Edition, 2010).
Results
Results
Patients had higher mean (GS.D.) BMI (25.5G3.8 vs 23.7G3.0 kg/m2; P!0.05)
The median age of these patients was 26 years (range 17-43); median semen
and 17aOH-progesterone (2.05G0.90 vs 1.51G0.62 ng/ml; P!0.05) compared
volume was 2.0 ml (range 0.1-6.5); median sperm concentration was 63.8!106
to controls. sAGA had higher levels of insulin (11.8G1.7 vs 6.0G0.4 mU/ml;
per ml (range 0-413); median total and progressive sperm motility were 40%
P!0.01) and LH (4.9G2.1
vs
3.8G1.4 mIU/ml; P!0.05), lower total
(range 0-84) and 24% (range 0-69), respectively. According to the reference
testosterone (TT) levels (5.2G1.7 vs 6.3G1.6 ng/ml; P!0.05) and left testicular
values of the WHO 34 patients (26%) in this series had a semen quality within the
volume (TV) (12.3G2.8 vs 15.4G4.1 ml; P!0.05) compared to aAGA. sAGA
normal range, and 97 patients (74%) had abnormal semen quality. In 2 patients
also had higher fat-mass percentage
(17.6G4.1
vs
13.2G5.3%; P!0.05),
(1.5%) the semen samples were not frozen because of azoospermia
(no
DHEAS (323.3G112.6 vs 257.8G107.1 mg/dl; P!0.05) and seminal fluid
spermatozoa in the ejaculate).
69
patients
(52.7%) had single damages
volume (4.2G2.8 vs 2.8G1.3 ml; P!0.05), lower TT (5.16G1.70 vs 6.47G
(oligozoospermia or asthenozoospermia) and 26 patients (19.8%) had combined
4.30 ng/ml; PZ0.016) and left TV
(12.3G2.8 vs 15.0G4.3 ml; P!0.05)
damages (oligoasthenozoospermia).
compared to controls.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion and relevance
Introduction
Men with early-onset AGA and at least one among the following parameters BMI
The prevalence of cardiometabolic disorders such as type 2 diabetes mellitus,
O25 kg/m2, IR, SHBG !25 nmol/l had a borderline-low left TV and a impaired
dysipidemia and metabolic syndrome is increased in patients with Klinefelter
gonadal steroidogenesis. Hence, they might have a greater risk to develop a
syndrome (KS). The mechanism by which cardiometabolic risk increases in
gonadal dysfunction later in life. These criteria may be used to suspect the male
patients with KS remains to be completely elucidated. We investigated the
PCOS-equivalent.
presence of inflammation, insulin resistance and endothelial dysfunction in an
DOI: 10.1530/endoabs.49.EP1163
unconfounded population of KS.
Methods
A total of 31 patients with KS (mean age 21.59G1.66 years) and 33 healthy
control subjects (mean age: 22.15G1.03 years) were enrolled. The demographic
parameters, Asymmetric dimethylarginine (ADMA), high sensitive C reactive
protein
(hs-CRP) and homeostatic model assessment of insulin resistance
(HOMA-IR) levels were measured in patients and controls.
Results
The patients had higher insulin, HOMA-IR and ADMA levels (P! 0.001 for all)
and lower HDL-C (PZ0.002) and total testosterone (P! 0.001) levels, compared
to the healthy controls. There were significant negative correlations between the
total testosterone levels and ADMA (rZK0.479, P! 0,001), hsCRP (rZK
0.291, PZ0.034), and significant positive correlation with HDL-C (rZ0.429,
EP1164
PZ0.001) levels. The multivariate analysis has shown that total testosterone
Improved conception of the normative values of testosterone in men
(bZK0.412, PZ0.001) and TG (bZ0.332, PZ0.009) levels were the significant
with type 2 diabetes
independent determinants of the plasma ADMA levels.
Irina Khripun1, Sergey Vorobyev1, Elizaveta Dzantieva1, Igor Belousov1,
Conclusion
Michail Kogan1 & Michael Zitzmann2
The results of the present study show that endothelial dysfunction and insulin
1Rostov State Medical University, Rostov-on-Don, Russia;2University
resistance are prevalent even in the very young subjects with KS, who have no
Clinics Muenster, Muenster, Germany.
metabolic or cardiac problems at present.
DOI: 10.1530/endoabs.49.EP1165
Background
Men with type 2 diabetes mellitus (T2DM) have significantly lower levels of
testosterone (T) than nondiabetic controls. But androgen deficit symptoms may be
detected in males with normal T levels.
Aim
To analyze parameters of lipid, carbohydrate metabolism and endothelial function
in diabetic males with low normal and middle-to-high normative T levels.
Patients and methods
We examined 86 men with T2DM and serum T levels higher than 12.1 nmol/l.
Parameters of total T, lipid metabolism, HbA1c, biochemical markers of
EP1166
endothelial function
- NO, endothelial NO synthase type
3
(NOS3) were
Testosterone is poorly related to erectile dysfunction in young/middle
analyzed. The patients were divided into two groups: 1-23 men with T levels
aged human immunodeficiency virus-infected men
12.1-14.9 nmol/l, 2-63 patients with T levels S15.0 nmol/l. Statistic analysis
Sara De Vincentis1, Daniele Santi1, Maria Chiara Decaroli1,
was performed using Mann-Whitney U-test and Spearmen rank correlation
Flaminia Fanelli2,3, Marco Mezzullo2,3, Alessia Fazzini2,3, Anna Ansaloni1,
method.
Uberto Pagotto2,3, Giovanni Guaraldi4 & Vincenzo Rochira1
Results
1Unit of Endocrinology, University of Modena and Reggio Emilia, Modena,
The HbA1c value was 8.7% (6.7; 9.8) in 1st group and 7.7% (6.4; 9.2) in 2nd
Italy;2Unit of Endocrinology, University of Bologna, Bologna, Italy;
group (PO0.39), but the proportion of patients with HbA1c levelO7% was
3Center for Applied Biomedical Research, University of Bologna, Bologna,
higher in group 1 (71% vs 58.6%) as compared to group 2 (PZ0.002). In patients
Italy;4Unit of Infectious Diseases, University of Modena and Reggio
with T levels lower than 15.0 nmol/l, higher levels of serum cholesterol (38.1% vs
Emilia, Modena, Italy.
27.6%), triglycerides (40.0% vs 24.1%) and low density lipoproteins (26.3% vs
17.2%) as compared to the 2nd group were found (P!0.01). There was a
significant correlation in the T concentrations with NOS3 levels jrjZ0.350 in 1st
Background
and jrjZ0.266, (P!0.05) in 2nd group. Vascular endothelial dysfunction as
human immunodeficiency virus (HIV)-infection is strongly associated to erectile
assessed by ultrasonographic measurement of the dilatation of the brachial artery
dysfunction (ED) in men. Preliminary data suggests that ED is poorly associated
was more frequent in patients of group 1 compared to group 2 (55.6% vs 23.8%,
with serum T in HIVC men.
PZ0.02).
Aim
Conclusion
To investigate in HIV-infected men the relationship between sexual function as
Males with T2DM and low-normal T level are at higher risks of dyslipidemia,
assessed by the validated International Index of Erectile Function (IIEF-15) and
endothelial dysfunction and progression of T2DM as compared to men with
T deficiency using Liquid Chromatography-tandem Mass Spectrometry
serum T higher thanO15 nmol/l.
(LC-MS/MS).
Acknowledgments
Methodology
Supported by RSF, grant No. 14-25-00052.
Prospective, cross-sectional, observational study on HIV-infected male patients
DOI: 10.1530/endoabs.49.EP1164
with ongoing Highly Active Antiretroviral Therapy (HAART), attending the
Clinic of Infectious Diseases. IIEF-15 and IIEF-5 questionnaires were used to
define ED, while LC-MS/MS was used for hormonal assays.
Results
233 consecutive HIV-infected patients were enrolled (mean age 45.29G5.33
years). Eight patients (3.4%) had total T !300 ng/dl, while 142 patients (61.5%)
had ED (score %25). Age, hormonal data and duration of HIV-infection and
HAART did not differ among groups of patients according to the degree of ED.
The direct comparison of each ED cluster showed that months of infection were
EP1165
significantly higher in men with severe ED compared to mild ED (PZ0.037). The
Endothelial dysfunction, inflammation and insulin resistance in patients
erectile function domain at IIEF-15 was directly correlated with IIEF-5 score
with Klinefelter Syndrome
(0.778, P!0.001), as expected. Moreover, the IIEF-15 score was inversely
Cem Haymana1, Aydogan Aydogdu1, Ibrahim Demirci1, Mustafa Dinc1,
related to months of infection (K0.147, PZ0.026), but not to months of HAART
Orhan Demir1, Deniz Torun2, Fatih Yesildal3, Coskun Meric1,
therapy (K0.121, PZ0.071).
Yalcin Basaran1, Alper Sonmez1 & Omer Azal1
Conclusions
1Gulhane Training and Research Hospital, Department of Endocrinology
To the best of our knowledge, this is the first, properly-designed prospective study
and Metabolism, Ankara, Turkey;2Gulhane Training and Research
aiming to investigate the relationship between erectile function and serum T,
Hospital, Department of Medical Genetics, Ankara, Turkey;3Selahaddin
assessed by LC-MS/MS in HIV-infected men. In our cohort, i) IIEF-5 is reliable
Eyyubi Public Hospital, Department of Biochemistry, Diyarbakir, Turkey.
as IIEF-15 for ED diagnosis, ii) ED is not associated with serum T, iii) erectile
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
function is not influenced by T and HAART, but only by HIV-infection duration.
EP1169
In conclusion, several specific factors, such as the duration of HIV infection, are
Can salivary testosterone be used in the monitoring of men using
involved in erectile function in HIV-infected men and should be carefully
transdermal testosterone replacement therapy?
considered in this setting, while hormonal status seems to be less important.
Tomas Ahern1, Jo Adaway2, Phillip Monaghan1, Peter Trainer1 &
DOI: 10.1530/endoabs.49.EP1166
Brian Keevil2
1The Christie NHS Foundation Trust, Manchester, UK;2University Hospital
of South Manchester, Manchester, UK.
In community-dwelling men, salivary testosterone (Sal-T) concentrations are
thought to represent tissue hormone levels and correlate strongly with serum free-
T levels. Measurement of salivary glucocorticoid concentrations is a non-invasive
and objective means of assessing cortisol exposure in users and non-users of
hydrocortisone therapy. We assessed relationships of Sal-T with transdermal
testosterone replacement therapy (TD-TRT) and with markers of testosterone
EP1167
exposure. In 40 men aged 50.7 (G13.9) years who were attending a university
Early arterial stiffness and chronic inflammation in male equivalents of
hospital endocrinology clinic, we measured serum and salivary androgen
polycystic ovary syndrome
concentrations by immunoassay and liquid chromatography tandem mass
Mehmet Sozen1, Suleyman Baldane2, Sedat Abusoglu3, Levent Kebapcilar2,
spectrophotometry (LC-MS/MS) respectively. In our unit, TD-TRT (Tostran
Aysegul Kebapcilar4, Fatma Akyurek5, Ali Unlu3 & Suleyman
2% Gel at an initial dose of 30-60 mg of testosterone once daily) is offered to men
Hilmi Ipekci2
with sexual symptoms and low fasting serum testosterone (Ser-T) concentrations
1Deparment of Internal Medicine, Selcuk University Faculty of Medicine,
on at least two consecutive occasions. Ser-T concentrations did not differ between
Konya, Turkey;2Division of Endocrinology and Metabolism, Selcuk
users
(nZ23) and non-users
(nZ17) of TD-TRT (16.6G10.2 vs
11.4G
University Faculty of Medicine, Konya, Turkey;3Department of
4.4 nmol/l, PZ0.131). Sal-T concentrations, however, differed greatly (17.14G
Biochemistry, Selcuk University Faculty of Medicine, Konya, Turkey;
15.25 vs 0.23G0.15 nmol/l, P!0.001) as did salivary androstenedione (Sal-A4)
4Department of Obstetrics and Gynecology, Selcuk University Faculty of
concentrations (2.57G4.50 vs 0.17G0.04 nmol/l, P!.001) and Sal-T/Sal-A4
Medicine, Konya, Turkey;5Department of Dermatology, Selcuk University
(16.26G14.25
vs
1.45G0.94, P!0.001). Haematocrit and serum prostate
Faculty of Medicine, Konya, Turkey.
specific antigen concentrations (PSA) did not differ significantly between the
two groups (0.44G0.05 vs 0.43G0.05 l/l, PZ0.563 and 1.06G0.66 vs 0.79G
0.53 ng/ml, PZ0.170 respectively). With TD-TRT, there was a rise in blood
Introduction
testosterone (4.7G4.2 to 7.9G5.7 nmol/l, PZ0.162), haematocrit (0.42G0.05 to
There is some evidence that a rise in the androgen hormone levels increases the
0.44G0.04 l/l, PZ0.049) and PSA (0.68G0.33 to 1.06G0.76 ng/ml, PZ0.021)
risk for the development of a cardiovascular disease, obtained from the studies
levels. Two hours after a dose of TD-TRT, Ser-T rose modestly (10.5G13.2 to
conducted on women with polycystic ovary and on men with androgenic alopecia.
16.6G11.0 nmol/l, PZ0.003) and Sal-T rose tremendously (7.7G8.1 to 17.0G
Inflammatory substances tend to increase in polycystic ovary syndrome and in
16.9 nmol/l, PZ0.004). Despite normal Ser-T, haematocrit and PSA concen-
androgenic alopecia. On this basis, we conducted a study that aimed to evaluate
trations, Sal-T concentrations are 75-fold greater than normal in men using
the early cardiovascular and metabolic effects in male patients with androgenic
TD-TRT. This is unlikely due to contamination (Sal-A4 concentrations are also
alopecia.
high) and may be due to a conduit between skin, the lymphatic system and
Methods
salivary ducts. Measurement of Sal-T is unlikely to be useful in the monitoring of
A total of 81 people, of whom 41 were patients with androgenic alopecia and 40
men using TD-TRT.
were healthy controls, were included in the study. Aged from 25 to 45, none of
DOI: 10.1530/endoabs.49.EP1169
them had any cardiovascular risk factors, malignancy, any active infections and
any liver or kidney diseases. Ambulatory blood pressure was measured for 24 h
and sensitive CRP and galectin-3 were studied so as to assess the cardiovascular
and metabolic risk.
Results
There were no differences between the patient and control groups in terms of
ambulatory blood pressure of 24 h, sensitive CRP and galectin-3. A positive
correlation was found in the patient group between sensitive CRP and waist and
neck circumferences. While there was a positive correlation in the patient group
between galektin-3 and HOMA-IR, waist and neck circumferences, a negative
correlation was seen with free testosterone. Alopecia level correlated positively
with daytime pulse wave velocity and night time reflection magnitude.
Conclusion
EP1170
We did not find any difference in our study in terms of arterial stiffness and
Changes of dihydrotestosterone within the life in men
chronic inflammation in the early period when the control and androgenic
Hana Pospíšilová, Michaela Dušková, Martin Hill & Luboslav Stárka
alopecia groups were compared; however, a positive correlation between alopecia
Institute of Endocrinology, Prague, Czech Republic.
level and daytime pulse wave velocity and night time reflection magnitude may be
considered as an early signal for atherosclerosis.
DOI: 10.1530/endoabs.49.EP1167
Abstract
Dihydrotestosterone (DHT) is the most powerful naturally occurring androgen
with three to six times higher biopotency than testosterone. Time onset of benign
prostatic hyperplasia and alopecia in middle life could be the result of an
imbalance between androgens. The decline of testosterone during lifespan is well
known, controversial data can be found concerning the age dependence of DHT
levels. We analysed the levels of testosterone, dihydrotestosterone and SHBG
from 3076 men and we observed changes of their relationship and the ratio of total
and free fraction of T and DHT, depending on age in men. We found that the
DHT/T and fDHT/fT ratios during the life of adult males are constant, and that
there is no evidence of a reversal in ratios of these hormones after puberty. Given
EP1168
that the ratio DHT/T remains constant during the age, the role in the development
of androgenetic alopecia and benign prostatic hyperplasia is rather unlikely. The
question remains, however, local status in androgen-dependent tissues, which
Abstract withdrawn.
would change the expression of enzyme, it could be caused just by local change in
this ratio. This study was supported by the project MZCR for conceptual
development of research organization 00023761 Institute of Endocrinology and
grant 17-28692A.
DOI: 10.1530/endoabs.49.EP1170
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1171
dose, form or duration of intake were included in the review. Main outcomes were
AAS effects on the reproductive system of athletes, as assessed by medical
Male pseudohermaphroditism with 45,X/46,X,idic(Y) karyotype: a case
history, clinical examination, hormone analysis and/or semen analysis.
presenting with dysgenetic testis on one side and almost normally sized
Results
testis on the other side
Twenty-six studies were included in the review, involving 963 participants, with
Flavia Di Bari1, Roberto Vita1 & Salvatore Benvenga1,2
the median (25th-75th percentile) duration of AAS intake being 16 (8-100.8)
1Department of Clinical and Experimental Medicine, University of Messina,
weeks. Most studies showed that gonadotropin and testosterone levels decreased
Messina, Italy;2Interdepartmental Program of Molecular & Clinical
during the period of AAS intake, whereas following AAS cessation, they
Endocrinology, and Women’s Endocrine Health, University hospital
gradually returned to normal levels. The majority of AAS users demonstrated
Policlinico G. Martino, Messina, Italy.
prolonged hypogonadism with persistently low gonadotropin and testosterone
levels, lasting for several weeks to months after AAS withdrawal. Most studies
have also shown that AAS use results in structural and functional sperm changes,
Dicentric Y chromosome [idic(Y)] is the most common structural abnormality of
reduction of testicular volume, as well as clitoromegaly and menstrual
this chromosome, and generally results from altered meiotic breakage and reunion
irregularities. Only 2 out of 26 studies determined AAS effects on fertility and
of sister chromatids. Since this rearrangement is unstable, idic(Y) may be lost in
only 2 studies involved female athletes.
subsequent cell cycles, resulting in a mosaic 45,X cell line. Variable are the
Conclusion
phenotype and gonads (from streak gonads to ovotestes or dysgenetic testes). Few
AAS use results in profound and lasting effects on the reproductive system of
cases of 45,X/46,X,idic(Y) male pseudohermaphroditism with testes have been
athletes and potentially on fertility. Targeted education about AAS abuse and
reported. We report the case of a 26-yr-old 45,X/46,X,idic(Y) male born at 38
thorough monitoring are needed to prevent negative long-term effects.
weeks’ uncomplicated gestation who consulted us for infertility. At 3 years, he
DOI: 10.1530/endoabs.49.EP1172
presented with cryptorchidism, micropenis and scrotal hypospadias. Congenital
adrenal hyperplasia was excluded (17OH-progesterone 0.7 ng/ml, testosterone
!20 ng/ml). Scrotal ultrasound revealed the absence of the right testis (RT). RT
was eventually found in the pelvis, where uterus and ovaries were absent.
Hypospadias repair was performed. The undescended RT, which histologically
was described as testicular tissue with fibrosis, was surgically fastened inside the
scrotum. At age 26, the patient was slightly overweight (BMI 25.8 kg/sqm), with
a male phenotype, normal androgenization and no gynecomastia. He had a
satisfactorily engagement with her partner. The RT was hardly palpable, while the
left testis was reduced in volume and consistency. At ultrasound, RT was atrophic
(1.4 ml), while the left was 10 ml, and both had a hypoechoic and inhomogeneous
texture. FSH, androstenedione and 17OH-progesterone were high (30 mU/ml, 4.1
and 3.4 ng/ml), LH high-normal (9.6 mU/ml), total testosterone low-normal
(348 ng/dl), and calculated free-testosterone low (6.1 ng/ml). The response of
17OH-progesterone after cosyntropin stimulation was normal. E2, progesterone,
EP1173
and SHBG were within the female reference range (53 pg/ml, 3.4 ng/ml, and
Gonadal status in males with acute coronary syndrome and the extent of
37.7 nmol/L). Azoospermia was detected at semen analysis. Considering the risk
coronary artery disease: a comparative cross-sectional analysis
of malignancies within the dysgenetic gonad
(10-15%), we advised right
Adriana Bednárová, Tomáš Koller, Martin Kužma & Juraj Payer
gonadectomy.
Comenius University Faculty of Medicine, 5th Department of Internal
DOI: 10.1530/endoabs.49.EP1171
Medicine, University Hospital Bratislava, Bratislava, Slovakia.
Introduction and aims
Association between coronary artery disease (CAD) and male gonadal status has
been previously suggested, but still remains inconclusive. Aims of our study in
males with recent acute coronary syndrome
(ACS) were to evaluate the
prevalence of hypogonadism, to compare their gonadal status with non-ACS
matched controls and to evaluate gonadal status by the extent of CAD.
Subjects and Methods
A cross-sectional retrospective study included all consecutive males with recent
ACS and age and BMI matched non-ACS controls. Basic demography and
standard CAD risk factors were recorded as well as fasting serum levels of total
testosterone (TT), sex hormone binding globulin (SHBG), estradiol, follicle-
stimulating and luteinizing hormone (FSH and LH) and calculated free androgen
index (FAI). First, we evaluated the prevalence of hypogonadism (TT! 7 nmol/l
and FAI!24%). Second, we compared patients and control group for ACS
associated factors on univariate and multivariate analysis. Third, using the same
analysis in patients undergoing coronary angiography we aimed at identifying
EP1172
factors associated with CAD extent (0-1 vessel vs 2-3 vessel disease).
Effects of anabolic androgenic steroids on the reproductive system of
Results
athletes
96 patients and 49 controls were included. Hypogonadism was confirmed in
Maria Christou1,2, Panagiota Christou1, Georgios Markozannes2,
20.8% of patients. Patients had lower levels of TT (12.638G6.138 vs 15.702G
Agathocles Tsatsoulis1, George Mastorakos3 & Stelios Tigas1
4.903, P!0.01), FAI (30.292G12.489 vs 36.902G9.816, P!0.01) and higher
1Department of Endocrinology, University of Ioannina, Ioannina, Greece;
levels of LH (5.58 IQR 4.4-8.21 vs 5.0 IQR 3.64-6.35, PZ0.04) compared with
2Department of Hygiene and Epidemiology, Ioannina, Greece;3Endocrine
controls. In multivariate analysis, smoking, hypertension, dyslipidemia and FAI
Unit, Aretaieion Hospital, National and Kapodistrian University of Athens,
were identified as factors independently associated with ACS.
73 patients
Athens, Greece.
underwent coronary angiography,
43
had findings of
2-3
vessel disease.
Hypertension, BMI and FAI were found as associated factors with CAD extent
and FAI as its single independent risk factor.
Background
Conclusion
Anabolic androgenic steroids (AAS) are widely used to improve performance
Lower gonadal status was found common (20.8%) in males with recent ACS.
and/or enhance appearance. The aim of this study was to assess the impact of AAS
It was independent on standard ACS risk factors and was independently
on the reproductive system of athletes.
associated with CAD extent.
Methods
DOI: 10.1530/endoabs.49.EP1173
An electronic literature search was conducted, using the databases MEDLINE,
CENTRAL, Scopus and Google Scholar. Studies including AAS use in any type,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1174
EP1176
An unusual karyotype in a young adult with a clinical phenotype
Methylation of the CPG islands from MTHFR promoter in male
suggesting a Klinefelter syndrome
infertility
Lourdes Garcia-Garcia-Doncel, Isabel Torres-Barea,
Suzana Vladoiu1, Anca Botezatu2, Daniela Dinu Draganescu1,
Manuel Cayón-Blanco, Rosa Marquez-Pardo, Rosario Lopez-Velasco &
Dana Manda1, Sabina Oros1,3, Diana Paun3, Roxana Rosca1,3,
Gloria Baena-Nieto
Corin Badiu1,3 & Gabriela Anton2
Jerez Hospital, Jerez, Spain.
1‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;
2‘Stefan S. Nicolau’ Institute of Virology, Bucharest, Romania;3‘Carol
Davila’ University of Medicine and Farmacy, Bucharest, Romania.
Introduction
46 XX testicular DSD (disorder of sex development) is a rare syndrome
characterized by 46 XX karyotipe, male external genitalia, azoospermia, sterility
and usually hypergonadotropic hypogonadism in adulthood. Approximately 85%
A large number of studies are now focused on the causes of male infertility.
of individuals present after puberty with normal penile size, small testes and
Among these are epigenetic modifications, which are important contributors to
gynecomastia.
reproductive pathology in the male by providing dynamic changes of the
Case report
phenotype according to the environmental and metabolic factors. The most
We present a 34-year-old male who was referred for endocrine evaluation due to
known epigenetic modification is DNA methylation and alterations in this pattern
slightly high prolactin levels. He underwent surgical correction of bilateral
in several genes could induce male infertility. Alterations in DNA methylation
inguinal hernia at the age of 1.8 years old. Three years later, surgery was needed
patterns in several genes may lead to abnormal male sexual development and
to descend trapped right testicle, showing testicular atrophy. At age 33, the patient
infertility. MTHFR is an enzyme involved in the folate pathway and in de novo
requested medical evaluation after one year unsuccessfully attempting to father a
nucleotide biosynthesis but also a good example for gene-environment interaction
pregnancy. Erectile dysfunction and lack of libido were not present. Semen
in phenotype development. This study investigates the promoter methylation
analysis revealed azoospermia. Serum hormone evaluation detected high
status of MTHFR in infertile men from by quantitative methylation-specific PCR
gonadotropines, low-normal testosterone and normal prolactin levels: LH
in order to investigate possible correlations with sperm abnormalities. Our study
13,9 mIU/ml, FSH
32.11 mIU/ml, prolactin
15 ng/ml
[4-15], testosterone
includes patients (nZ27, median age 31 years, range 26-41 years) recruited from
311.20 ng/dl [250-836]. Physical examination revealed a descended left testicle
men seeking advice for couple infertility and control group (nZ11, median age
of 12 cm3 and a right testicle unnoticed to palpation. There was no hypospadias
30.5 years, range 24-37 years). DNA was isolated from sperm samples and
and penile size was within the normal range. Patient’s height and weight was
promoter methylation of MTHFR was quantified in qMS-PCR using bisulphite
177 cm and 70 kg, respectively. Klinefelter syndrome was suspected. Cytogenetic
treated DNA samples (EpiTect Bisulfite Kit - Qiagen). Were detected significant
procedures demonstrated a 46 XX kariotype, and the presence of SRY gene on
correlations that indicate a tendency towards promoter hypermethylation in
one of the X comosomes was detected by fluorescent in situ hibrydization.
spermatozoa with low motility
(PZ0.0130, r2Z0.3886), poor morphology
Conclusions
(PZ0.0138, r2Z0.3833) and with low sperm count (PZ0.0092, r2Z0.4184).
46 XX testicular DSD SRY-positive should also be considered in the differential
Our data suggest that the methylation patterns of the promoter of MTHFR is
diagnosis of adult hypergonadotropic hypogonadism with small testes and
linked with sperm anomalies of motility, morphology and sperm count, which
sterility. Adult diagnosis can be challenging because of normal sexual
could lead to male infertility.
development and phenotypic similarities between patients with 46 XX DSD
DOI: 10.1530/endoabs.49.EP1176
and Klynefelter syndrome, althought the latter are usually taller and show less
incidence of cryptorchidism.
DOI: 10.1530/endoabs.49.EP1174
EP1177
How relevant are the complications associated with testosterone
treatment in men with hypogonadism?
Ricardo Capitão1, Raquel Castro2, Cátia Ferrinho1, Francisco Santos1,
Catarina Roque1, Carlos Bello1, João Sequeira1, Catarina Saraiva1 &
1
Carlos Vasconcelos
EP1175
1Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal;2Centro Hospitalar
A case with taurodontism and Klinefelter syndrome
Lisboa Norte, Lisboa, Portugal.
Isilay Taskaldiran1, Tulay Omma1, Anara Karaca1, Alper Taskaldiran2 &
Nese Ersoz Gulcelik1
Introduction
1Ankara Education and Research Hospital, Endocrinology and Metabolism,
Testosterone treatment in patients with hypogonadism has been associated with
Ankara, Turkey;2Balgat Dental Public Hospital, Ankara, Turkey.
cardiovascular and prostatic complications.
Objective
To describe the evolution of analytical parameters associated to the complications
In this paper we present an 18-year-old patient with Klinefelter syndrome who has
of testosterone treatment in a male population with hypogonadism treated with
taurodontism. Klinefelter syndrome is the most common abnormality of sex
testosterone. Methods A retrospective, longitudinal study in which the clinical
chromosomes. It is characterized by hypogonadism, gynaecomastia, azoospermia
data of male adults with hypogonadism under intramuscular testosterone therapy
or oligospermia, and increased levels of gonadotropins. Associated medical
were analysed in 2 tertiary centres. The duration and doses of testosterone were
disorders can be categorized as follows; cancer, autoimmune disorders,
recorded. Haematocrit (Hct), total cholesterol (TC), LDL cholesterol (c-LDL),
intellectuel and psychiatric disorder, osteoporosis, endocrine disorders, venous
total prostate-specific antigen (PSA) and total testosterone levels were assessed at
disease and taurodontism. Taurodontism is a developmental anomaly of a tooth
the beginning and at the end of follow-up. Paired-t-test was used to compare
characterized by large pulp chamber and short roots. It affects 0.5-3% of the
means and the results are shown in mean and standard deviation.
general population. Taurodontism is observed with several syndromes and
anomalies including Klinefelter syndrome. Endodontic treatment of taurodont
teeth is tend to be complex and difficult because of the complexity in the tooth
morphology, extraction of the taurodont teeth may be difficult and these teeth
C-LDL
have risk for early decay. This feature can be seen in permanent and primary teeth,
Hct (%)
TC (mg/dl)
(mg/dl)
PSA (ng/ml)
in a single tooth, or in several molars, and can be unilateral or bilateral.
Taurodontism must be the part of comorbidity evaluation and patients with
First
42.9G5.0
194.3G41.5
114.1G37.3
1.4G1.7
Klinefelter syndrome should have regular dental examination and care in order to
measurement
provide long term oral health and improve quality of life of patients with
Final
44.0G4.4
191.7G30.2
110.8G28.3
1.7G2.4
Klinefelter syndrome.
measurement
Difference
1.1G4.4
K2.6G38.2
K3.4G34.8
0.3G1.6
DOI: 10.1530/endoabs.49.EP1175
P-values
0.01
0.68
0.60
0.30
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
1Department of Microscopy, Laboratory of Cell Biology, Abel Salazar
We analysed 128 patients, 35% primary and 65% secondary hypogonadism. The
Institute of Biomedical Sciences (ICBAS), University of Porto, Porto,
mean age was 49.6G17.3 years. The follow-up time was 2.6 years (0.6-9.4 years).
Portugal;2Unit for Multidisciplinary Research in Biomedicine, Abel Salazar
The mean interval between injections was 4.4G2.3 weeks. The final testosterone
Institute of Biomedical Sciences (UMIB-ICBAS), University of Porto,
was 392.0G112.7 ng/dl. The results are summarized in the table below:
Porto, Portugal;3Department of Anatomy, Abel Salazar Institute of
Treatment with testosterone resulted in increased Hct and PSA values, however
Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal;
only the Hct difference proved statistically significant. Spearman correlation test
4i3S - Instituto de Investiga
¸a˜o e Inovação em Saúde, University of Porto,
revealed a positive and statistically significant correlation between the increase of
Porto, Portugal.
testosterone levels and the increase of Hct (rZ0.21; PZ0.03). No hospital-
izations for cardiovascular events were reported.
Discussion
Current lifestyle, characterized by physical inactivity and a poor diet, is
The rise of Hct, although statistically significant, was low. The remaining
heavily linked with an increased incidence of metabolic diseases. One of the
parameters did not show statistically significant increases so testosterone therapy
most serious silent co-morbidities of those diseases is infertility. The
appears to be safe from a cardiovascular and prostatic perspective.
hormonal link between food intake and energy homeostasis is mediated by
the leptin ghrelin axis. Compelling evidence suggests that direct leptin’s
DOI: 10.1530/endoabs.49.EP1177
action regulates cellular glucose homeostasis and mitochondrial biogenesis.
We have recently shown that leptin modulates the nutritional support of
spermatogenesis, which may be related with obesity-related male
subfertility/infertility. Herein, we hypothesized that leptin directly affects
mitochondrial function, dynamics and biogenesis of Sertoli cells (SCs). Rat
Sertoli cells (Ser-W3) were treated (nZ5 for each group), during 24 h at
378C 5% CO2, with different concentrations of leptin (5 ng/ml as reported in
EP1178
normal mice, 25 ng/ml as reported in obese mice and
50 ng/ml as a
Evolution of healthcare demand in a public gender identiy clinical
supraphysiological concentration) and the results were compared to a
center in Valencia (spain)
condition without leptin. Western Blot was performed to determinate
Victor Atienza Moya1, Marcelino Gomez Balaguer1, Felipe
protein levels of mitochondrial complexes. qPCR was performed to
Hurtado Murillo2, Santiago Garcia Torres1, Eva Maria Riera Sabater1,
determinate expression levels of several genes involved in mitochondrial
Christian Salim Vendrell1 & Antonio Hernandez Mijares1,3
biogenesis and to assess mitochondrial DNA copy number. Mitochondrial
1Endocrinology Service, Doctor Peset University Hospital, Valencia, Spain;
membrane potential was determined by JC-1. Direct leptin exposure did not
2Sexual psychology and reproductive health unit, Doctor Peset University
alter SCs proliferation rate, though all leptin concentrations decreased SCs
Hospital, Valencia, Spain;3Medicine department, University of Valencia,
metabolic activity. That was accompanied with alterations in the expression
Valencia, Spain.
levels of the different mitochondrial complexes and also of genes involved
in mitochondrial biogenesis. In addition, the highest concentration of leptin
decreased mitochondrial membrane potential. Finally, mitochondrial DNA
Introduction
copy number was not sensitive to the treatment with the different leptin
The prevalence of transsexuality in Europe is uncertain in absence of
concentrations. Overall, the results show a direct action of leptin on Sertoli
epidemiological studies, so it’s difficult to implement public healthcare strategies.
cells mitochondrial function and biogenesis with implications in the
Aim
nutritional support of spermatogenesis, which is a novel mechanism by
To describe healthcare demand evolution in a gender identity clinical service in
which leptin can affect the reproductive potential of males.
our country.
DOI: 10.1530/endoabs.49.EP1179
Methods
Our center is a public university hospital placed in Valencia (Spain). It is a
reference center on gender dysphoria from two provinces
(Valencia and
Castellon), with a target population of 2.646.801 inhabitants R14 years old
(50.8% women and 5.5% adolescents). We reviewed medical records of patients
referred from 2008 to 2016, excluding gender-non conforming people without
demand of hormonal or surgical intervention.
Results
EP1180
We attended 331 transsexual people with eligibility criteria for pubertal block,
Study of CDX-2 VDR gene polymorphisms in male infertility
cross hormonal treatment or surgery; 41.7% transsexual men (FxM) and 58.3%
Suzana Vladoiu1, Daniela Dinu Draganescu1, Anca Botezatu3,
transsexual women (MxF). 6% in FxM and 30% in MxF had previously started
Dana Manda1, Sabina Oros1,2, Roxana Rosca1,2, Gabriela Anton3,
any kind of treatment. 82% FxM and 56% MxF were living in desired role at the
Diana Paun2 & Corin Badiu1,2
initial evaluation. Before 2011 no adolescent was referred while between 2012
1‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania;
and 2016 were attended 82 of them. In adolescents, sex ratio was favoring natal
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;
males before
2014
(2.9:1) and it changed in
2015 and 2016 (1.7:1-1:1.5,
3‘Stefan S. Nicolau’ Institute of Virology, Bucharest, Romania.
respectively) favoring natal female. Minors represented 16% of patients in 2012-
2014 and 52% nowadays. We performed 34 hysterectomies (34.6% of patients
older than 18 years), 25 mastectomies (25.5%) and implanted 20 breast prosthesis
The CDX2 VDR polymorphism (rs11568820) is located in the promoter region of
(13.1%), surgeries preformed in private centers were not accounted. For
exon 1 in the 50 -untranslated region of the VDR gene.
genitoplasty surgery they were referred to another national surgery center.
Objective
The current investigation examines the association between CDX2
VDR
Conclusions
polymorphism and male infertility.
Demand for transexual care shows an important increase in our geographical area.
Subjects and methods
This increase is due to adolescent population. There is a significant variation of
The study was conducted on 69 infertile men, aged between 20 and 50 years,
sex ratio favoring transsexual men. This results can be explained by sociocultural
divided into three groups, based on spermatic parameters: group with
phenomena. Only one-third of FxM choose to perform hysterectomy and
azoospermia (19 subjects), group with severe oligospermia (38 subjects), group
adnexectomy.
with oligospermia (12 subjects), and 37 age-matched controls. CDX-2 VDR gene
DOI: 10.1530/endoabs.49.EP1178
polymorphisms were performed by PCR-RFLP. Vitamin D was assessed by
electrochemiluminiscent method.
Results
The evaluation of Vitamin D levels was found to be significantly decreased in
infertile patients group versus controls (PZ0.0198). The lowest Vitamin D levels
were characteristic for azoospermia patient group
(medianZ18.34 ng/ml,
rangeZ14.89-19.6 ng/ml), than controls
(medianZ24 ng/ml, rangeZ18.2-
EP1179
36.10 ng/ml). The analyses for CDX2 VDR polymorphism in infertile patients
Leptin modulates Sertoli cells mitochondrial function and biogenesis
showed that six cases were homozygote (GG), 28 heterozygote (GA) and 35
with implications for the nutritional support of spermatogenesis
homozygote (AA). The frequency of G allele was 0.29, and 0.71 for A allele,
Bruno M Moreira1,2, Ana D Martins1,2, Mariana P Monteiro2,3,
c2Z0.014. In control group the analyses of CDX2 VDR polymorphism revealed
Mário Sousa1,2, Marco G Alves2 & Pedro F Oliveira2,4
that 10 cases were homozygote for G allele (GG), 19 were heterozygote (GA) and
8 were homozygote (AA). The frequency of G allele in population was 0.53, for A
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
allele the frequency was 0.47, c2Z0.033. The controls and infertile groups were
Introduction
compared using c2-test and the difference was significant (PZ0.0229). The GG
Dysgonosomies are abnormalities of the number of gonosomes X and Y. They
genotype was found in a low percentage in patients group than controls (8.7% vs
have fewer Phenotypic repercussions than the aneuploidies involving autosomes,
27.03%), and the percentage of AA genotype was higher in infertile group
and are mostly viable. The 47 XYY are generally boys with normal phenotype.
(50.72% vs 21.62%).
The prevalence is around 1 per 1000 birth boy but undoubtedly under diagnosed
Conclusion
given the often normal phenotype associated with this chromosomal formula, in
Despite numerous publications, the influence of Vitamin D on reproductive health
addition to the lack of large-scale studies. There is no gonadal dysgenesis and
remains ambiguous. Our study showed that infertile patients present low levels of
often no infertility or criminality in the past.
Vitamin D. According the results the A allele may represents a potential risk for
Case report
male infertility.
Our case is a 48 years old patient consulting for primary hypofertility. The
DOI: 10.1530/endoabs.49.EP1180
anamnesis finds a type 2 diabetes, High blood pressure, orchi-epididymitis at the
age of 34 and bilateral unaccompared varicosele and hydrocele. The patient is an
active smoker. Clinically, he is an over weighted patient (BMI: 27 kg/m square)
with 180 cm height. No other dysmorphia is noted. In the Spermogram, we find an
azoospermia (00 SPZ), with 1 CC of ejaculation volume. Scrotal ultrasound
shows a normal-sized testicles with micro calcifications in the epididymis tail
with varicocele and bilateral hydrocele. An Epididymis Cytoponction recovering
SPZ (without cryopreservation).
EP1181
The hormonal status is:
CHARGE syndrome - late diagnosis in adulthood
FSH: 1.65 mIU/ml (0.95-11.95)
Maria Manuel Costa1,2, César Esteves1,2, JoséLuís Castedo1,
LH: 2.40 mIU/ml (0.57-12.07)
Duarte Pignatelli1 & Davide Carvalho1,3
Testosterone: 5.65 ng/ml (1.42-9.23) or a correct gonadal assessment
1Department of Endocrinology, Diabetes and Metabolism of Centro
Inhibin B 215.4 ng/ml (11.5-368.9) predicting the presence of SPZ in the biopsy
Hospitalar de São Joa˜o, Porto, Portugal;2Faculty of Medicine, University of
Caryotype 46 XY/47 XYY
Porto, Porto, Portugal;3Instituto de Investiga
¸a˜o e Inovação da Saúde da
The clinical examination and the exploration of the 31 years old partner is without
Universidade do Porto, Porto, Portugal;4Service of Medical Genetics,
anomalia. The patient is programmed for testicular biopsy in the optic of a
Centro Hospitalar de São João, Porto, Portugal.
possible ICSI.
Conclusion
Introduction
It appears that many men with 47, XYY syndrome will likely have decreased
CHARGE syndrome is a rare autossomal dominant genetic disorder with an
fertility potential. These patients may ultimately require assisted reproductive
estimated birth incidence of 1:10000. It affects multiple organ systems and can
techniques in order to achieve pregnancy.
have a variable phenotypic expression.
DOI: 10.1530/endoabs.49.EP1182
Case report
34-years-old man, referred to Endocrinology in the context of bilateral
gynecomastia. He had an acute corneal hydrops which was treated by
ophthalmology. Physical examination showed short stature (149 cm), obesity
(BMI 31.5 kg/m2), micropenis and cryptorchidism. He presented other problems:
coloboma of the iris, bilateral hearing loss, anosmia, craniofacial dysmorphisms
(abnormal ear shape, microstomia) and intellectual disability. Patient’s
Neuroendocrinology
investigation included among others: breast ultrasound which revealed bilateral
EP1183
gynecomastia; testicular ultrasound that demonstrated an empty scrotal sac with
the atrophic testes in the inguinal canals; biochemical evaluation showed
Prenatal intervention by P271 reduces LH pulsatility and testosterone
hypogonadotrophic hypogonadism
(FSH 0.42 mUI/ml
(n:1.5-12.4), LH!
levels in PCOS condition
0.10 mUI/ml (n:1.7-8.6), total testosterone 0.08 ng/ml (n:2.8-8.0) and a low
Sareh Zeydabadinejad1, Fahimeh Ramezani Tehrani1, Azita Zadeh-Vakili2
IGF-1 12 ng/ml (n:140-405). Pituitary had a 3 mm height on MRI; Karyotype
& Mahsa Noroozzadeh1
result was normal male (46, XY); He started monthly 250 mg/ml enanthate
1Reproductive Endocrinology Research Center, Research Institute for
testosterone with poor compliance. Otolaryngology evaluation excluded choanal
Endocrine Sciences (RIES), Shahid Beheshti University of Medical
stenosis/atresia (peri-nasal sinuses CT showed only exuberant deviation to the left
Sciences, Tehran, Iran;2Cellular and Molecular Endocrine Research Center,
of the nasal septum) and confirmed moderate sensorineural hearing loss
Research Institute for Endocrine Sciences (RIES), Shahid Beheshti
(audiogram with about
50 dB hearing threshold bilaterally and normal
University of Medical Sciences, Tehran, Iran.
tympanogram) but the patient refused auditory prosthesis. His echocardiogram
was normal. Family history was irrelevant for congenital malformations,
Background
intellectual disability, deafness or vision loss and endocrinological problems.
Polycystic ovary syndrome
(PCOS) is a frequent endocrine and metabolic
CHARGE Syndrome was suspected and molecular study of CHD7 gene was
disorder and the most common cause of infertility occurring in 5-10% of women
requested. A heterozygous pathogenic variant was identified
[c.3106COT,
of reproductive age. The characteristic endocrine abnormalities of PCOS involve
(p.Arg1036Ter)] and clinical suspicion was confirmed.
hypersecretion of androgens and LH (as a consequence of increased GnRH
Conclusion
frequency). Although PCOS signs generally become obvious at puberty, clinical
CHARGE acronym stands for C-coloboma, H-heart disease, A-atresia choanae,
and experimental evidence suggests an intrauterine origin for the syndrome. On
R-retarded growth and retarded development and/or CNS anomalies, G-genital
the other hand, kisspeptin antagonists have been shown to reduce LH pulse
hypoplasia, and E-ear anomalies and/or deafness. Diagnostic criteria currently
frequency and amplitude.
combined major and minor features are used. Pathogenic variants in CDH7 gene
Methods
are found in around 80% of CHARGE patients. We present CHARGE Syndrome
RNAs were extracted from hypothalamus of prenatally androgenized (PNA)
referred to our clinic due to gynecomastia. Most of CHARGE syndrome patients
(nZ18) and non-PNA female rats (nZ14) thought estrus cycle. The ability of
are diagnosed in childhood infancy and rarely in adulthood. With this clinical
prenatal administration of kisspeptin antagonist P271, to alter GnRH mRNA
report we would like to alert that in the presence of hypogonadotrophic
expression and gonadotropin and steroid hormone levels, was tested using Cyber-
hypogonadism associated with suggestive features, this diagnosis should be
green Real-time PCR and ELISA methods, respectively.
considered.
Results
DOI: 10.1530/endoabs.49.EP1181
Hypothalamic GnRH mRNA levels fluctuated in a cyclic-dependent manner, with
a robust increase in the afternoon of proestrus phase. P271 treated animals showed
reduced GnRH expression and gonadal steroid and gonadotropin levels.
Conclusion
PNA animals had increased GnRH mRNA expression and LH levels in diestrous
phase than controls, which reduced in response to prenatally administered P271.
This pilot study, for the first time, shows that prenatal intervention by P271 reduce
EP1182
LH pulsatility and T levels associated with PCOS.
Azoospermia revealing the uncommon Jacob’s syndrome
Keywords: Kisspetin, P271, Gene Expression, Prenatal androgenisation
Abdelkader Yahi, Zakaria Haouchine & Samia Ould-Kablia
DOI: 10.1530/endoabs.49.EP1183
Endocrinology Service, HCA, Algiers, Algeria.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1184
EP1186
Prenatal testosterone exposure increases anxiety-like behavior in
The dynamics of anthropometric data in fertile age women by various
female rats
types of the treatment
Aleksandra Rasic-Markovic1, Djuro Macut2, Dragan Hrncic1,
Saidganikhoja Ismailov & Maryam Abduvakhabova
Valentina Cirkovic1, Bojana Rankov-Petrovic1, Nikola Sutulovic1 &
Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.
Olivera Stanojlovic1
1Institute of Medical Physiology, Faculty of Medicine, University of
The aim
Belgrade, Belgrade, Belgrade, Serbia;2Clinic for Endocrinology, Diabetes
To study efficiency of pathogenetic therapy and dynamics of anthropometric
and Metabolic Diseases, Faculty of Medicine, University of Belgrade,
indexes for women with obesity of fertile age at different endocrinopathies to and
Belgrade, Serbia.
through 6 months after treatment.
Material and research methods
On the etiologic factor of patient with obesity were up-diffused on three groups:
Polycystic ovary syndrome (PCOS) is characterized by excessive androgen
1 g. are patients with obesity at the polycystic syndrome of ovaries (PCOS) - 30
secretion and women with PCOS are at risk of developing anxiety disorders.
patients, 2 g. are patients with hypothalamic obesity - 21 cases and 3 g. - patient
Maternal testosterone levels in humans have been shown to affect brain
with endocrine obesity (at a primary hypothyroidism) - 20 patients. Age of
development and to be correlated to mental function. During pregnancy,
patients in a 1th group hesitated 39 from 20 to and 28.3G0.64 averaged year. To
women with PCOS display high circulating androgen levels that may affect
all patients have been conducted spectrum of investigations, which include
the fetus and increase the risk of mood disorders in offspring. This study
clinical, biochemistry, hormonal analysis of the blood. Besides of this,
investigated whether maternal androgen excess causes anxiety-like behavior
electrocardiography, ultrasound investigation of uteri and ovarium during 11-
in offspring. Ten pregnant Wistar rats were injected s.c. with 100 mg/kg
14 days of periods, and MRY of pituitary. For the
1 g. we administered
testosterone undecanoate (TU) on gestational day 20, while control (C) rats
combination of Syofor 1000 mgs C spironolacton 100 mgs C yodmarinum
received only solvent. To investigate the presence of anxiety-like behavior
100 mgs CL-thyroxine 50 mgs in the morning C antiandrogens C antidepress-
in female offspring of TU and C dams, the elevated plus maze (EPM) and
ants. For the 2 group: combination of Syofor 1000 mgs C spironolacton 100 mgs
open field (OF) test was performed. In the EPM test, offspring of TU dams
C Yodmarin 100 mgs CL-thyroxine 50 mgs iC methaboliks C Reduxine
displayed decrease in the number of open arm entries and in the percentage
(Sibutramin)
15 mgs C antidepressants. For the 3 groupo: combination of
of time spent on open arms. OF test showed altered pattern of locomotor
Yodmarin 100 mgs CL-thyroxine 50 mgs.
activity in female TU offspring. Numerous data demonstrate that the early
The results
life environment, including in utero plays a key role in later life behavior.
In 1 and 2 groups of patients marked reliable decline of BMI 1 and 2 degrees after
The results of our research suggest that prenatal testosterone exposure
6 months of treatment, while for patients 3 groups of reliable changes of BMI
increases anxiety-like behavior in female offspring.
through 6 months of treatment were not attained at none of degree of BMI Thus,
DOI: 10.1530/endoabs.49.EP1184
for patients 1 and 2 groups with BMI 3 degrees through 6 months a tendency was
attained to the decline of BMI. In addition, renewal of fecundity and pregnancy
was attained for the patients of a 1 group - in 19,5%% cases (at 10 patients).
Conclusions
Optimization of treatment of obesity for the women of reproductive age is based
on drafting of the individual programs, the choice of that is determined by the
values of anthropometric indexes, state of hormonal and metabolic status, features
of food behavior and personality-emotional sphere, state of menstrual and
reproductive function.
Obesity
DOI: 10.1530/endoabs.49.EP1186
EP1185
Placental maternal and fetal vascular circulation in healthy non obese
and metabolically healthy obese pregnant women
Marina Shargorodsky1,2, Jacob Bar1,2 & Michal Kovo1,2
1Wolfson Medical Center, Holon, Israel;2Tel Aviv University, Holon,
Israel.
Background
EP1187
Obesity in pregnancy is associated with hyperinsulinemia, impaired endothelial
The disorder of secretion of somatotropic hormone in women with
function, inflammatory up-regulation and higher risk of placental pathological
obesity in the polycystic ovaries syndrome (PCOS) by comparison to
lesions. However not all obese individuals demonstrate similar metabolic profiles.
patients with the non-functional pituitary adenomas (NFPA)
The present study was designed to investigate placental histopathology in lesions
Saidganokhoja Ismailov & Maryam Abduvakhabova
that are associated with maternal and fetal circulation abnormalities, in nonobese
Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.
and obese women with and without metabolic alterations.
Methods
332 pregnant women were divided into three groups according to presence of
Aim
obesity and metabolic risk factors: Group 1 included 163 non-obese metabolically
To study the disorder of secretion of growth hormone for women with obesity in
normal (NOMN); Group 2 included 106 obese metabolically normal (OMN);
PCOS by comparison to patients with NFPA.
Group 3 consisted 63 obese metabolically abnormal (OMA) subjects.
Materials and methods
Results
Under our supervision in the department of neuroendocrinology of the Center of
Placental weight was significantly higher in OMN compared to NOMN
Endocrinology of PH Ministry of RUz ambulatory in a period from September
(P!0.000). Maternal vascular supply (MVS) abnormalities of the placental
2015 for December, to 2016, 15 adult patients of fertil age were observed with
bed differed significantly across groups, and increased from Group 1 to Group 3 in
obesity in PCOS and 15 - with NFPA. Middle age of patients to make 25.5 and
a continuous fashion (31, 38 and 54% respectively, P!0.005). Fetal vascular
28.9 accordingly. The remoteness of disease hesitated in limits from 7 months to
supply (FVS) abnormalities rate increased from group 1 to group 3, and was
9 years.
significantly higher in obese subjects with and without metabolic abnormalities,
Results
compared to non-obese subjects (9, 20 and 22% respectively, P!0.021). Willous
It was set that in both groups there were neuroendocrine violations peculiar to
maturation defect (WMD) rate was higher in OMN subjects compared to NOMN
each of pathologies. So, in a 1 group of patients with PCOS such violations, as
(P!0.018). In the logistic regression analysis, obesity emerged as a significant
obesity, met most often, strium, acanthosis, acne, hyperandrogenemiya.
predictor of fetal vascular supply abnormalities
(PZ0.001) and WMD
hyperpolymenorheya, and in the second is secondary amenorrheya, hyperpro-
(PZ0.011).
lactinemiya, pahhypopituitarism. In both groups there was anovulation, and also
Conclusion
decline of secretion of STH, IGF- 1. In addition, in the group of patients with
We demonstrated that obesity, per se, is associated with an increased rate of fetal
NFPA the most for certain mionectic basale levels of trope hormones of
vascular malperfusion abnormalities, Willuos maturation defect, as well as higher
hypophysis were educed - STH, LH, FSH on a background hyperprolactinemiya
placental weight and lower FPR, compared to non-obese subjects.
and normal values of IGF- 1, while for patients with PCOS the decline of STH,
DOI: 10.1530/endoabs.49.EP1185
LH, FSH, was marked on a background hyperandrogenemiya and declines of
IGF- 1.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
cells such as POU5F1, SOX2, and NANOG. Next, we investigated whether
1) It is set that in the group of patients with PCOS the most reliable decline of
female sex steroid hormones such as 17b-estradiol (E2) and progesterone (P4)
basale levels of IGF- 1 was educed, while the deficit of STH met rarer.
could alter the protein expression of epithelial-mesenchymal transition (EMT)
2) For patients with NFPA took place panhypopituiarism, namely combined
related markers as well as pluripotency markers such as POU5F1, SOX2, and
deficiency of STH, LH, FSH, TSH, while the deficit of IGF- 1 met rarer.
NANOG in human ES cells. The protein expressions of N-cadherin, SNAI1, and
3) The secretions of STH and IGF- 1 educed in our research of violation confirm
SNAI2 were increased while E-cadherin expression was decreased by treatment
these literatures that for patients with PCOS the decline of levels of STH and IGF-
of E2 or P4 and that the expressions of POU5F1, SOX2, and NANOG were
1 takes place on a background of hyperinsulinemiya and hyperandrogenemiya,
decreased by the treatment of E2 or P4. When E2 and P4 were treated in the
that requires further research.
combination with estrogen receptor inhibitor (ICI 182,780) and progesterone
DOI: 10.1530/endoabs.49.EP1187
receptor inhibitor (RU486), respectively, their effects on EMT and pluripotency
of ES cells were restored to the control levels. Collectively, these results suggest
that E2 and P4 may regulate EMT and pluripotency of human ES cells by
mediating their receptors. The present study might be useful to understand the
roles of sex steroid hormones in cellular biology of human ES cells. (This
research was supported by a grant from the Next-Generation BioGreen 21
Program (no. PJ011355-2015), Rural Development Administration, Republic of
Korea.)
Keywords: sex steroid hormones, human embryonic stem cells, pluripotency,
epithelial-mesenchymal transition
Paediatric Endocrinology
DOI: 10.1530/endoabs.49.EP1189
EP1188
17alpha-hydroxyprogesterone in non-CAH children and adolescents at
different ages
Christian Trummer1, Nicole Hacker1, Julia Munzker1,
Michaela Goschnik1,2, Kerstin Koschka1,2 & Barbara Obermayer-Pietsch1,2
1Medical University, Graz, Austria;2CBmed, Graz, Austria.
17a-hydroxyprogesterone (17OHP) is currently used as a diagnostic parameter in
children and young adults when a milder form of congenital adrenal hyperplasia
(CAH, late-onset) is suspected. A basal serum level of
17OHP (2 ng/ml;
6.0 nmol/l, respectively) has been discussed as cut-off for suspected late-onset
EP1190
disease. We analysed 17OHP in a cohort of children and adolescents without
Homo-dimerisation of cytochrome P450c17 resolves the conundrum of
CAH and in confirmed CAH patients to define reference ranges for these age
the dual activities of cytochrome P450c17
groups. For the analysis of 17OHP, we used a novel automated immunoassay in
Jessica Holien1, Michael Parker1,2, Alan Conley3, C Jo Corbin3,
506 anonymized samples from children and adolescents with a previous exclusion
Raymond Rodgers4 & Lisandra Martin5
of CAH by conventional hormone measurement. 302 girls and 204 boys in two
1St. Vincent’s Institute of Medical Research, Australian Cancer Research
age groups from 1-11 and 12-18 years were included. In a subgroup of 49
Foundation Rational Drug Discovery Centre, Fitzroy, VIC 3065, Australia;
probands, follow-up samples within one year were available, as well as in 17 out
2Department of Biochemistry and Molecular Biology, Bio21 Molecular
of initially 38 children with genetically confirmed CAH. In prepubertal children at
Science and Biotechnology Institute, University of Melbourne, Parkville,
the age of 1-11 years, mean 17OHP serum concentrations were 0.99 ng/ml G
VIC 3010, Australia;3School of Veterinary Medicine, University of
0.86
(STD) (reference limits 0.31-4.62) for girls and 0.85G0.59 (reference limits
California Davis, Davis, CA, USA;4Discipline of Obstetrics and
0.31-2.60) for boys, which was not statistically different (PZ0.852). There was
Gynaecology, School of Medicine, Robinson Research Institute, University
also no difference in mean 17OHP serum concentrations at the age of 12-18 years
of Adelaide, Adelaide, SA 5005, Australia;5School of Chemistry, Monash
between female 1.39G0.70 (reference limits 0.37-3.26) and male adolescents
University, Clayton, VIC 3800, Australia.
1.38G0.67 (reference limits 0.32-2.93) (PZ0.95). Repeated measurements in
follow-up samples showed a mean coefficient of variation (CV) for non-CAH
samples of 14.2 and 20.8% in CAH patient samples. In our study, baseline 17OHP
Reproduction requires the temporal and spacial control of specific and exact
was a useful marker for the exclusion of late-onset CAH in the majority of
signals, delivered by locally regulated hormonal flux. In the case of androgen
samples. Based on the established reference ranges, an overlap with confirmed
biosynthesis, cytochrome P450 17a-hydroxylase, 17,20-lyase (P450c17) is the
CAH patients was very small. In suspicious cases, additional hormonal tests as
key enzyme. However, P450c17 is a multi-functional P450, so, it synthesizes
well as stimulation tests of 17OHP have been defined as the standard of late-onset
cortisol in the zona fascicula of the adrenal cortex and also androgen precursors in
CAH diagnosis and therapy monitoring.
the adrenal zona reticularis and the gonads. The regulation of this dual activity has
been the focus of research studies over many decades and remains unresolved.
DOI: 10.1530/endoabs.49.EP1188
Functionally, it is known that each of these reactions of P450c17 require electrons
transferred by the electron donor cytochrome P450 oxidoreductase (CPR). The
first reaction, the 17a-hydroxylation of its substrate, occurs in all cells where
P450c17 is expressed. Remarkably, a second, subsequent reaction, namely the
17,20-lyase activity, only occurs in the zona reticularis and gonads. The
specificity of the second reaction is due to a non-redox ‘allosteric’ interaction with
the haem-protein cytochrome b5. Surprisingly, cytochrome b5 and cytochrome
P450 oxidoreductase have overlapping binding sites on the surface of the
Steroid Metabolism C Action
P450c17 enzyme. This poses the question as to how cytochrome b5
and
EP1189
cytochrome P450 oxidoreductase interact with P450c17 - structurally, function-
Effects of estrogen and progesterone on the protein expression of
ally and physiologically? This conundrum can be rationalized based on the
EMT- and pluripotency-associated markers in human embryonic
observation that P450c17
can homodimersise. A homodimer would allow
stem cells
cytochrome P450 oxidoreductase to bind to one P450c17
of the P450c17
Soo-Min Kim, So-Ye Jeon & Kyung-Chul Choi
homodimer, whilst cytochrome b5 could bind to the other P450c17 simul-
Laboratory of Biochemistry and Immunology, Veterinary Medical Center
taneously, at the surfaces distal to the dimer interface. We present our molecular
and College of Veterinary Medicine, Chungbuk National University,
modelling data that predicts that the P450c17 homodimer is a stable structure and
Cheongju, Chungbuk, Republic of Korea.
the CPR and cytochrome b5 proteins can assemble on the P450c17 dimer to form
a tetrameric
‘CPR:P450c17:P450c17:cyt b5’ assembly, predicted to be the
functional complex required for androgen biosynthesis. This model is fully
Embryonic stem
(ES) cells are pluripotent stem cells derived from a
consistent with extensive experimental data published over the last two decades.
developmental stage of preimplanted embryos. In this study, we investigated
Predictions derived from this model are currently being tested by a range of
the effect of female sex steroid hormones on the characteristics of human ES cells
in vitro and in vivo experimental approaches.
by using a feeder-free culture protocol. In a feeder-free condition without sex
DOI: 10.1530/endoabs.49.EP1190
hormones, human ES cells assumed the form of tightly packed cells that grow in a
monolayer. The cells also displayed clean and defined edges with no evidence of
differentiation and expressed several markers specific for undifferentiated ES
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1191
SHBG by immunoassay and free hormone fractions were calculated. Surgical
liver biopsies scored using NAFLD activity (NAS) and Steatosis, Activity and
Non-alcoholic fatty liver disease and its relation with sex steroids in men
Fibrosis (SAF) scores.
Frederique Van de Velde1, Yves Van Nieuwenhove2, Marlies Bekaert1,
Results
Anne Hoorens3, Marleen Praet3, Jean-Marc Kaufman1 & Bruno Lapauw1
Obese men showed lower T, free T (FT) and SHBG levels, lower (F)T/(F)E2 ratio
1Department of Endocrinology, Ghent University Hospital, Ghent, Belgium;
(all P!0.001) and higher FE2 (PZ0.019) compared to controls. Within the GBS
2Department of Gastro-Intestinal Surgery, Ghent University Hospital,
patients, no significant differences were found for sex steroid levels according to
Ghent, Belgium;3Department of Medical and Forensic Pathology, Ghent
NAS-based NAFLD severity. However, with increasing grade of steatosis, trends
University Hospital, Ghent, Belgium.
towards lower T and FT levels, and lower (F)T/(F)E2 ratios were observed
Background
(P!0.059). No associations between sex steroid levels and other NAFLD
Obesity associates with co-morbidities as non-alcoholic fatty liver disease
features were detected. Using SAF, we found that lower (F)T levels correlated
(NAFLD). Obese men often present with low testosterone (T) levels. As sex
with steatohepatitis (PZ0.014). These correlations were independent from age,
steroids undergo hepatic metabolization and their serum levels depend on hepatic
BMI, HOMA-IR and SHBG. Remarkably, no differences in SHBG or (F)E2
sex hormone binding globulin (SHBG) secretion, NAFLD could contribute to this
levels according to NAFLD severity were found.
phenomenon. Previous studies however were contradictory and not based on
Conclusion
state-of-the-art technology as mass spectrometry or biopsy-proven NAFLD.
This study confirmed lower T levels in obese as compared to normal-weight men.
Objective
In these obese men, overall NAS-based NAFLD severity was not associated with
To assess the relation between biopsy-proven NAFLD and sex steroid levels in
these lower T levels although presence of steatohepatitis and increasing grade of
obese men undergoing gastric bypass surgery (GBS).
steatosis was related to lower (F)T levels and FT/FE2 ratios.
Methods
DOI: 10.1530/endoabs.49.EP1191
This cross-sectional study included 56 obese men (mean age 44G11 years; BMI
41.6G4.6 kg/m2) and 56 healthy, age-matched control men (mean age 44G11
years; BMI 23.5G1.8 kg/m). T and estradiol (E2) measured using LC/MS-MS,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eposter Presentations: Thyroid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Clinical Case Reports - Thyroid/Others
thyroid. Ultrasonography of the neck revealed parathyroid adenoma at the inferior
pole of the right thyroid lobe and bilateral thyroid nodules. The patient was
EP1192
subjected to uncomplicated right inferior parathyroidectomy and synchronous
An adverse outcome in a thyrotoxic lady with propylthiouracil induced
total thyroidectomy. Postoperative histopathological examination confirmed the
necrotising leukocytoclastic vasculitis
diagnosis of parathyroid adenoma with coincidence of papillary thyroid
Emily T Mudenha, Anusha P Panthagani, Jonathan M Batchelor,
carcinoma. After surgery, serum parathormone and calcium returned to their
Rand Hawari, Roger Stanworth & David Hughes
normal values and patient was referred to the department of Nuclear Medicine for
Royal Derby Hospital, Derby, UK.
a radioactive iodine ablation therapy.
Conclusion
Concomitant papillary thyroid carcinoma and primary hyperparathyroidism is
A 37 year old lady with relapsing Graves’ thyrotoxicosis initially managed on a
rare. It still remains controversial whether these two pathologies happen
‘block and replace regime’ with propylthiouracil and levothyroxine for 7 years
coincidental or are caused by specific risk factors or genetic changes.
had her medication changed to carbimazole after a relapse from non-compliance
but developed agranulocytosis. She was then restarted on an increased dose of
DOI: 10.1530/endoabs.49.EP1193
propylthiouracil alone. Two weeks later, she developed tender purpuric lesions
and was admitted after developing painful bullous lesions to her lower limbs. She
had previously noted haemorrhagic lesions on her limbs but these would resolve
within a week. Investigations revealed positive MPOANCA antibodies, skin
biopsy confirmation of necrotising leukocytoclastic vasculitis and no evidence of
systemic involvement on imaging. She had rheumatology and dermatology input
regarding the vasculitic rash. Initial treatment involved stopping propylthiouracil,
starting beta blockers, short course of pulsed high dose methylprednisolone and
wound care. Within a few weeks, her skin lesions were improving, but she was
becoming progressively more thyrotoxic. She was commenced on potassium
iodide therapy in preparation for a total thyroidectomy. Unfortunately, her
temperature increased and she rapidly went into septic shock due to pneumonia
requiring inotropic and respiratory support on the intensive care unit before dying
a few days later.
EP1194
Discussion
Necrotising vasculitis remains a rare complication of propylthiouracil therapy. It
A case with langerhans cell histiocytosis having papillary
is classically, as in our patient, strongly associated with positive MPO-ANCA
microcarcinoma of thyroid: two birds in one nest
antibodies. Clinical presentation is variable. Treatment includes discontinuation
Hatice Ozisik1, Banu Sarer Yurekli1, Nilufer Ozdemir Kutbay1, Ilker Altun1,
of the drug, immunosuppression and good wound care. The prognosis in the
Yesim Ertan2, Ozer Makay3 & Gokhan Ozgen1
absence of major organ vasculitis as in our patient is usually good, and our patient
1Division of Endocrinology and Metabolism, Ege University, Izmir, Turkey;
seemed to be making good progress whilst being worked up for thyroidectomy.
2Division of Pathology, Ege University, Izmir, Turkey;3Division of General
However, her low grade tachycardia and raised inflammatory markers masked the
Surgery, Ege University, Izmir, Turkey.
early onset of sepsis. Our case highlights the importance of clinical vigilance for
sepsis in patients with the rare complication of propylthiouracil induced
Introduction
necrotising leukocytoclastic vasculitis.
Langerhans cell histiocytosis
(LHH) is an idiopathic, clonal, pleomorphic,
DOI: 10.1530/endoabs.49.EP1192
neoplastic disorder characterized by the presence of atypical histiocytic cells
which are locally or commonly seen in bone, lung, hypothalamus, liver, lymph
nodes, mucocutaneous tissues with damaging them.
Case
58 year-old male patient applied to our clinic due to fatigue. On his physical
examination, lymphadenopathy and hepatosplenomegaly were absent. In his
history, he had an operation owing to Large-cell neuroendocrine carcinoma in
2014. He took chemotherapy but no radiation. In surveillance, a thyroid nodule
was detected in PET-CT. Thyroid US revealed a nodule 5 cm in diameter in
the right lobe. He underwent bilateral total thyroidectomy. In pathological
examination, left lobe was reported as thyroid papillary microcarcinoma,
follicular variant and langerhans cell histiocytosis, right lobe was reported as
follicular nodular disease. The focus of papillary microcarcinoma in 0.2 and
0.1 cm diameter was seen in the left lobe and langerin positive focus was
observed in the morphology of langerhans cell histiocytosis consisting of
EP1193
langerhans cells and eosinophils. Bone marrow biopsy and abdominal MR
Synchronous papillary thyroid carcinoma and primary
were normal. On his laboratory examination urine dansity was normal. FSH:
hyperparathyroidism: a rare association
5.44 mlU/ml
(1.5-12.4), LH:
4.74 mlU/ml
(1.7-8.6), total testosterone:
Nadia Khessairi, Ibtissem Oueslati, Malika Chihaoui, Meriem Yazidi,
2.35 ng/ml
(2.8-8), prolactin:
5.87 ng/ml
(4.6-21.4), TSH:
0.37 mIU/ml
Ons Rjeb, Fatma Chaker & Hedia Slimane
(0.35-5.50), tyroglobulin!0.9 ng/ml
(1.6-60) were detected. In pituitary
Department of Endocrinology, La Rabta hospital, Tunis, Tunisia.
MRI, nodular focus with different contrast enhancement according to pituitary
gland referred as intermediate lobe was detected in the middle posterior of
pituitary gland
Introduction
Discussion
Although the association between parathyroid and thyroid diseases is not
In LHH and papillary thyroid carcinoma coexistence, papillary microcarcinoma
uncommon, the coexisting of parathyroid adenoma causing primary hyperpar-
was frequently encountered.Gold standard treatment for limited LHH is surgical
athyroidism (PHPT) and papillary thyroid carcinoma (PTC) is rare. Probably this
resection and it has usually good prognosis. Diffuse goitre (59%) or nodules
can be partially explained by different embryologic origin of thyroid and
(25.8%) can be detected in patients with LHH having thyroid gland involvement.
parathyroid cells. Herein, we report a case of PHPT associated with synchronous
Large cell neuroendocrine carcinoma of the lung is rarely seen and has poor
bifocal PTC.
prognosis.
Observation
A 65-year-old woman was referred to our department with incidental
DOI: 10.1530/endoabs.49.EP1194
hypercalcaemia and biochemical PHPT. A Technetium
(99mTc) sestamibi
scintigraphy showed a distinct functioning nodule in the lower right pole of the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1195
usually followed by a reduction of TRAb levels in variable degrees; the degree of
reduction remains controversial. The median TRAb value half-life has been
Amiodarone and refractory thyrotoxicosis in a patient with complex
estimated at 93.5 days after total thyroidectomy in patients without orbitopathy or
arrhythmia
smoking, such as our patient. This case therefore demonstrates that remnant
Nelson Cunha1, Leonor Gomes1,2, Diana Martins1,2, Diana Oliveira1,2,
thyroid cells after total thyroidectomy in Graves’ disease can become stimulated
Adriana Lages1, Mara Ventura1, Lúcia Fadiga1, Diana Catarino1 &
under the mediation of TRAb causing recurrent thyrotoxicosis. Revision surgery
Francisco Carrilho1
would be challenging and therefore radioactive iodine necessary.
1Endocrinology, Diabetes and Metabolism Department, University Hospital
of Coimbra, Coimbra, Portugal;2Faculty of Medicine, University of
DOI: 10.1530/endoabs.49.EP1196
Coimbra, Coimbra, Portugal.
Background
Amiodarone is a potent antiarrhythmic drug used to treat tachyarrhythmias.
However, is linked to a number of adverse effects, including thyroid dysfunction.
It is the main cause of drug-induced thyrotoxicosis. Here we report a clinical case
EP1197
of amiodarone-induced thyrotoxicosis (AIT) in a patient with complex ventricular
Where is the thyroxin disappearing?
dysrhythmia.
Ioannis Svilias, Filip Gabalec & Jan Cap
Case report
4th Department of Internal Medicine, Hematology and Endocrinology,
A 23 years-old women with dilated cardiomyopathy, severe depression of
Faculty of Medicine, Charles University Hospital, Hradec Králové, Czech
ejection fraction of left ventricle and complex ventricular dysrhythmia under
Republic.
amiodarone treatment
200 mg id since June of
2013, presented asthenia
and weight loss since march of 2016, with worsening of heart failure. TSH was
!0.008 mUI/ml (0.4-4.0), Free T4 (FT4) 3.4 ng/dl (0.8-1.9) and Free T3 (FT3)
Introduction
6.1 pg/ml (1.8-4.2). Autoimmunity was negative. Thyroid ultrasound: normal
The most common cause of loss of adequate substitution on a stable dose of
dimensions, without nodularity or increased vascularity at doppler study.
replacement therapy is noncompliance. Impaired absorption and weight gain are
99mTc-sestamibi thyroid scintigraphy: signal in lower limit of normality. It was
also possible. We present a rare case of renal loss of thyroxin in severe nephritic
started methimazole 30 mg/day and prednisolone 40 mg/day. After 3 months, she
syndrome.
presented undetectable TSH, FT4 2.4 ng/dl and FT3 4.0 pg/ml. Methimazole was
Case report
increased to 40 mg/day and prednisolone to 60mg/day and amiodarone was
We present a 46 year old female after total thyroidectomy for Graves-Basedow
suspended. After 2 months, TSH was still undetectable and FT4 2.2 ng/dl, with
disease. From 2005 she was euthyroid on a stable dose of L-thyroxin (100 mg/day).
development of steroids side effects. So thyroidectomy was performed, without
On physical examination she had oedemas of the lower extremities. A marked
complications. After surgery, started levothyroxine
75 mg/day, steroids were
hypercholesterolemia (17.49 mmol/l, normal range 0-5.2 mmol/l) and a very high
tapered and amiodarone was restarted. Three months after surgery, normal
TSH value (92.5 mU/l, normal range 0.27 - 4.2 mU/l) were found. Celiac disease
thyroid function and improvement of her clinical condition were observed.
was excluded, abdominal ultrasound was performed with a normal finding.
Conclusion
During examination proteinuria
(6.19 g/day, normal range to
0.14 g/d) and
In this case, a type 2 AIT was diagnosed, resistant to medical therapy and with
thyroxin loss in urine (50 mg/l) were found. Renal biopsy was performed with the
steroids side effects. This uncommon scenario illustrates the difficulty of
finding of membranous glomerulopathy (glomerulonephritis). Treatment will be
controlling thyrotoxicosis in a patient of high risk of sudden death, requiring an
started in nephrology department. After increase of L-thyroxin dose (300 mg/den)
invasive procedure to its resolution. Thereby, when thyrotoxicosis is uncontrol-
normalisation of TSH was established.
lable and patients are at high cardiovascular risk, thyroidectomy should be
Conclusion
considered for the resolution of AIT. This could be lifesaving by controlling the
Nephrotic syndrome increases L-thyroxine requirements because of urinary loss
disease, avoiding iatrogeny and maintaining the possibility of amiodarone
of free and protein-bound thyroid hormones. Physical examination, careful
therapy.
history taking and laboratory findings are the key to the accurate diagnosis. After
DOI: 10.1530/endoabs.49.EP1195
treatment of membranous glomerulopathy reduction of L-thyroxin dose is
expected.
DOI: 10.1530/endoabs.49.EP1197
EP1196
Relapsed Graves’ thyrotoxicosis following total thyroidectomy 20 years
earlier
EP1198
Edouard Mills, Ali Naqvi & Jeannie Todd
Hyalinizing trabecular tumor of the thyroid gland
Imperial Centre for Endocrinolgy, Imperial College NHS Trust, London,
Buket Yilmaz Bulbul1, Mehmet Celik1, Semra Ayturk1, Nuray Can2,
UK.
Ebru Tastekin2, Atakan Sezer3, Funda Ustun4 & Sibel Guldiken1
1Department of Endocrinology and Metabolism, Medical Faculty, Trakya
We report a 55-year-old non-smoker with a history of Graves’ disease diagnosed
University, Edirne, Turkey;2Department of Pathology, Medical Faculty,
in 1990 at age 29 years old. Due to poor compliance to therapy, she underwent a
Trakya University, Edirne, Turkey;3Department of Surgery, Medical
total thyroidectomy within 1 year of diagnosis. She remained well controlled on
Faculty, Trakya University, Edirne, Turkey;4Department of Nuclear
thyroid hormone replacement for over 20 years with Levothyroxine 100 mg daily.
Medicine, Medical Faculty, Trakya University, Edirne, Turkey.
However, in the two years before referral to the Endocrine Clinic, she had difficult
to treat hypothyroidism with persistent over-replacement; at the time of referral
Hyalinizing trabecular tumor is an uncommon, controversial lesion of thyroid gland.
she was taking Levothyroxine 25 mg daily. She reported no symptoms of over-
Hyalinizing trabecular neoplasm share similarities with medullary thyroid
replacement. She had no evidence of thyroid associated orbitopathy. Taking
carcinomas (MTC) and exhibit nuclear features resembling papillary thyroid
Levothyroxine 25 mg daily, TSH remained suppressed at !0.01 mIU/l, Free T4
carcinoma (PTC). However, the clinical behaviour unclear. We aimed to present a
14.5 pmol/l and Free T3 4.3 pmol/l. Thyroid autoantibodies were both positive:
rare case of hyalinizing trabecular tumor of thyroid gland and ten-year follow up.
thyroid peroxidase 285 unit/ml and TSH receptor 2.9 unit/ml. Ultrasound of the
A 54-year-old woman who was being followed up because of multinodular goiter
thyroid bed confirmed three hypervascular thyroid nodules measuring 8, 27 and
on examination of neck, the thyroid gland was nodular, measured 20 mm!
16 mm. Thyroid hormone replacement was discontinued. Subsequent NM
10 mm and non-tender. Serum FT3, FT4 and TSH were within normal limits.
Thyroid scan with uptake Technetium demonstrated three toxic nodules and
Ultrasonography showed a hypoechoic nodular lesion of 12 mm!6 mm in the
therefore concordant with the ultrasound. Graves’ disease is an autoimmune
right lobe and 29 mm!11 mm hypoechoic nodular lesion in the left lobe. Fine
condition characterised by the production of autoantibodies against the thyroid-
needle aspiration cytology the diagnosis was suspicious due to cells similar to
stimulating hormone receptor: TSH-receptor antibodies (TRAb). TRAb stimu-
papillary carcinoma cells. She underwent a total thyroidectomy. Histopatholo-
lates target organs with the majority developing hyperthyroidism from
gical examination showed the nuclei were oval, slightly pleomorphic, trabecular
stimulation of follicular cell production of thyroid hormone and about half
growth pattern, intratrabecular hyalinization and nuclei with grooves and
developing thyroid associated orbitopathy. Total thyroidectomy removes target
cytoplasmic pseudoinclusions. Immunohistochemically the tumor was thyroglo-
tissue for TRAb and controls hyperthyroidism. Surgical thyroid resection is
bulin positive, and calcitonin and HBME-1 negative, galectin 3 and TTF-1 focal
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
positive.The pathological diagnosis was hyalinizing trabecular tumor with
Conclusions
lympositic thyroiditis. L-thyroxine 0.1 mg/day therapy was started. The patients
The rare finding of increased thyroid hormones (T3 and T4) with normal or
treated was found to be euthyroid over the ten year follow-up period. Hyalinizing
increased TSH level presents a differential diagnosis between a TSH secreting
trabecular tumor is a unique neoplasm of follicular derivation. Most authors
pituitary adenoma and RTH. Mutational analysis of the TR-b gene enables both
consider this tumor to be benign. The differentiation of hyalinizing trabecular
definitive diagnosis of RTH and family screening. We present a novel mutation of
tumor from other thyroid tumors such as PTC and MTC, based on overlapping
this gene that has not been previously reported. Although, there have been
nuclear features. Cytological diagnosis of hyalinizing trabecular tumor has a
reported mutations affecting another aminoacid substitution at this position
characteristic trabecular growth pattern and hyalinizing stroma. The prognosis of
(L450P) in cases of RTH.
hyalinizing trabecular tumor is favorable.
DOI: 10.1530/endoabs.49.EP1200
DOI: 10.1530/endoabs.49.EP1198
EP1201
EP1199
Tuberculosis of the thyroid gland: a case report
Riedel thyroiditis presenting with pleuro-pericardial involvement
Imen Sakka, Ibtissem Oueslati, Fatma Chaker, Ons Rjeb, Meriem Yazidi,
Asena Gokcay Canpolat & Murat Faik Erdogan
Malika Chihaoui & Hedia Slimane
Department of Endocrinology and Metabolism, Ankara University Faculty
Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.
of Medicine, Ankara, Turkey.
Introduction
Riedel thyroiditis (RT) is a rare kind of chronic thyroiditis which may be a part
The involvement of the thyroid gland by tuberculosis is extremely uncommon
of a multifocal systemic fibrosis syndrome. When it is generally accepted as a
even in countries in which tuberculosis is endemic. In the majority of the reported
thyroid manifestation of IgG4 related systemic disease. We hereby present a 54
cases, thyroid function was preserved. Herein we report a case of thyroid
year old woman who was suffering from shortness of breath because of a mass
tuberculosis in a patient with a primary hypothyroidism.
lesion originating from thyroid and invading neck and upper mediastinal
Case report
structures, leading to dyspnea and dysphagia, as shown by CT, 15 years ago. After
A 52-year-old woman was referred to our department for a gradually growing
an isthmectomy and decompression surgery she was diagnosed as RT.
goiter without compressive symptoms. She presented with a productive cough.
Corticosteroid therapy was given as the firstline agent and she responded well
Her Past medical history included type 2 diabetes mellitus, goiter and primary
to the therapy, the dose was tapered off in about 6 months. However she was
hypothyroidism in the last fifteen years. On examination, she had a plunged
readmitted with severe dyspnea and chest pain with no large mass lesion at neck.
multinodular goiter. The rest of the clinical examination and laboratory tests were
Investigations revealed an exudative pleural and pericardial effusion and
normal. Chest radiography showed a nodule located in the right lung upper lobe.
mediastinal enlargement. The detailed evaluation of pleuropericardial effusion,
Cervical ultrasonography revealed an enlarged heterogeneous multinodular
did not point out any spesific etiology. Glucocorticoid theraphy was restarted
thyroid gland. Total thyroidectomy and lung nodule biopsy were performed to
along with colchicines and azathioprine. Alleviation of the symptoms were
the patient. Thyroid histopathological examination showed benign multinodular
achieved. She was followed by tamoxifene and colchicines on the long term. She
hyperplasia with epithelioid cell granulomas and giant cells. The histopatholo-
is now symptom-free with loss of the soft tissue mass and effusions for more than
gical examination of the lung biopsy showed foci of granulomatous inflammation
15
years. This case is interesting because of reporting pleuropericardial
along with caseous necrosis. The diagnosis of tuberculosis involving the lungs
involvement and the success of being in remission for more than 15 years.
and the thyroid gland was established. Then, patient was put on antitubercular
Although the etiology and definite treatment of the IgG4 related thyroid diseases
drugs with a good recovery.
are unclear; expanding knowledge about IgG4 related diseases will further clarify
Conclusion
the optimal approach to RT.
Although thyroid tuberculosis is a rare condition, it should be considered as
DOI: 10.1530/endoabs.49.EP1199
differential diagnosis of thyroid masses especially in an endemic country. In this
case, the use of fine needle aspiration biopsy can help to avoid unnecessary
surgical interventions.
DOI: 10.1530/endoabs.49.EP1201
EP1200
A Novel Thyroid Hormone Receptor Beta Gene Mutation: p.L450F
(c.C1633T) in a family with Resistance to Thyroid Hormone
Lourdes Garcia-Garcia-Doncel, Rosa Marquez-Pardo, Isabel Torres-Barea,
EP1202
Gloria Baena-Nieto, Rosario Lopez-Velasco & Manuel Cayón-Blanco
Follicular variant of papillary thyroid carcinoma with lung, bone, and
Jerez Hospital, Jerez, Spain.
soft tissue metastases
Constantinos Belis1, Stavroula Gavriilidou1, Aikaterini Afentoulidi1,
Kalliopi Xydiari1, Vasilios Athanasiou1, Sofia Malaktari- Skarantavou1,
Introduction
Sofia Saranti2 & Christos Savvidis1
Resistance to thyroid hormone
(RTH) is a rare autosomal dominant (AD)
1Department of Endocrinology, ‘Hippocratio’ General Hospital of Athens,
condition caused by mutations of the Thyroid Hormone Receptor Beta (TR-b)
Athens, Greece;2Nuclear Medicine Department, ‘Saints Anargyri’ Cancer
gene, resulting in generalized tissue resistance to thyroid hormone. Euthyroidism
Hospital, Athens, Greece.
is usually maintained at the expense of increased levels of thyroid hormones and
with non-supressed TSH.
Case report
We report on a case of a 63-year-old male patient with a history of metastatic
A 61 year-old-woman was evaluated for increased free T4 index: 2.29 ng/dl
DTC, with both lung and bone metastases and an additional paravertebral mass.
(normal, 0.9-2.1) and free T3 index: 4.59 pg/ml (normal, 2.57-4.43) and normal
The patient presented with enlargement of the left thyroid lobe. FNA was positive
TSH levels:3.22 mUI/ml (normal, 0.3-5)). Analysis were repeated and laboratory
for malignancy and subsequent CTs were negative for distant metastases, whereas
error was excluded. The patient was asymptomatic. A physical examination
laboratory tests showed elevated thyroglobulin (TgO500 ng/ml). The patient
detected a moderate diffuse goitre and a normal resting heart rate. Thyroid
underwent total thyroidectomy and the pathology report revealed a multifocal,
antibodies were negative. Sex hormone binding globulin and gonadotrophin
follicular variant of papillary thyroid cancer, with localized extrathyroidal
a-subunit were within the normal range and pituitary magnetic resonance imaging
extention. He was then referred to the Endocrinology Department. After
ruled out a pituitary adenoma. Thyroid ultrasound showed a multinodular goitre
withdrawal of levothyroxine (preablation laboratory results: TSH: 52.6 mIU/ml,
with micronodules (!6 mm size). Thyroid scintigraphy demonstrated a diffuse
Tg: 9900 ng/ml) the patient received 80 mCi of I131 (RAI uptake: 7,6%).. A
goitre with increased technetium uptake. A diagnosis of RTH was suspected.
subsequent SPECT/CT scan revealed lung and bone metastases (ribs with
Molecular genetic studies showed a change in exon 10 of the TR-b gene: p.L450F
adjacent soft tissue mass). Thoracic CT showed bilateral, scattered lung
(c.C1633T). Later, our patient’s daughter was also diagnosed of RTH and AD
metastases with lymph node enlargement of the hili as well as a paravertebral
inheritance was demonstrated in family segregation studies.
soft tissue mass 6.2!3.8 cm of diameter which metastasize to the 7th rib and the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
respective thoracic vertebra. Tc99m bone scan showed metastases in the ribs (6th,
results
(TSH:
12 U/mL; Free T4:
0.7 ng/dl) and therapy with
100 mg of
7th) as well as the 7th thoracic vertebra. The patient 6 months later received
L-thyroxine was initiated. Two months after therapy, thyroid function was
150 mCi I131. The post-therapeutic scan revealed radioiodine avid metastases in
normalized (TSH: 1.3
U/ml; Free T4: 1.1 ng/dl). Exophthalmia persisted, even
both lungs without response to the previous therapy as well as uptake in the right
though TSAb title was virtually undetected (0.6 U/l). At the age of 45, there was
maxillary area. The latter blood test (6 months after the 2nd RAI) showed
onset of binocular vertical diplopia and blurred vision. Upon administration of
biochemical improvement (Tg: 403 ng/ml, anti-Tg !42 IU/ml), while the last
500 mg ev Methylprednisolone, symptoms were only transiently relieved and
thoracic CT
(6
months after the
2nd RAI treatment) revealed radiologic
thereafter rapidly worsened. Persistent diplopia and mild exophthalmos were
improvement on the lung metastases and the paravertebral mass (5.6!3 cm), as
confirmed in ophthalmology appointments. The patient was clinically euthyroid,
well as disappearance of the right maxillary area lesion. The case presented is
thyroid function tests were normal under Levothyroxine replacement and TSAbs
about the management of a patient with DTC and distant metastases, without
remained negative. Computed tomographic scan and magnetic resonance imaging
objective benefit showed by the postablation scan, but followed by decreasing Tg
of the orbits showed symmetric bilateral exophthalmia (grade I/III) with inferior
and radiologic improvement revealed by computed tomography.
rectus muscle thickening on the right eye, consistent with Graves’ disease.
DOI: 10.1530/endoabs.49.EP1202
However, the single fiber electromyography revealed a moderate defect in
neuromuscular transmission. Anti-acetylcholine receptor antibodies were
14
times the reference value, compatible with the diagnosis of Myasthenia Gravis.
Moreover, the patient denied fatigue, movement disorders or other neurological
symptoms. By reporting this case, we would like to draw attention for a possible,
although rare, association of myasthenia gravis and Graves’ ophthalmopathy and
stress the importance of a clinical judgment.
EP1203
DOI: 10.1530/endoabs.49.EP1204
Severe acute hepatitis associated with thyrotoxicosis
Isabel Torres-Barea, Lourdes Garcia-Garcia-Doncel, Manuel Cayón-
Blanco, Gloria Baena-Nieto, Rosario López-Velasco &
Rosa Márquez-Pardo
Hospital De Jerez, Jerez De La Frontera, Spain.
EP1205
Pleiotropic function of vitamin D and goiter
Roman Kołodziejczak1, Alicja Łuczyn´ ska-Kołoldziejczak1 &
Liver dysfunction related to hyperthyroidism encompasses abnormalities
Anhelli Syrenicz2
associated with the effects of thyroid hormone excess, drug-related hepatic
1Ragional Hospital, Gorzów Wlkp, Poland;2Pomeranian Medical
injury, and the presence of concomitant liver disease. Mild liver abnormalities
University, Szczecin, Poland.
such as hypoalbuminemia and increased serum level of liver enzymes may be
seen in 45-90% of patients with hyperthyroidism. Nevertheless, there are a few
case reports of thyrotoxicosis associated with severe acute hepatitis. A 37 year old
Objective
woman presented to the Emergency Department with abdominal pain associated
Among women over 40 the prevalence of goiter in Poland is over 40% and the
with diarrhea for 2 weeks and new-onset jaundice for 2-3 days. She had been
prevalence of vitamin D deficiency is over 80%. There have not been any
diagnosed with hyperthyroidism 6 months before and it was prescribed treatment
previous studies that investigate the vitamin D level in women with and without
with methimazole but she decided to stop the treatment one month later. On initial
goiter.
physical examination there was significant jaundice and tachycardia. Blood
Methods
pressure and body temperature were normal. There was no exophthalmos and the
152 women-96 with and 56 without nontoxic goiter were examined in 2014. In US
thyroid gland was diffusely enlarged. There were no findings of heart failure,
examination we calculated the volume of the thyroid gland and volume of
chronic liver disease, lymphadenopathy or hepatosplenomegaly. Laboratory
nodules. Blood samples for 25-(OH) D total were taken. We made statistical
workup showed hyperthyroidism and abnormal liver function tests: FT3 was
analysis of correlation between volume of the thyroid gland, volume of the
21.59 pg/ml
(normal
2.57-4.43), FT4
7.77 ng/dl
(normal
0.9-2.1), TSH
nodules and levels of vitamin D.
0.01 mU/l (normal 0.3-4.2). Total bilirubin 8.47 mg/dl (normal 0.1-1), direct
Results
bilirubin
7.7 mg/dl
(normal
0.05-0.2), ALT
674 IU/l
(normal
0-31), AST
96 women with goiter size from 5.67 ml to 68.85 ml - mean 19.7 ml, median
664 IU/l (normal 0-31), GGT 42 IU/l (normal 5-36), albumin 2.9 g/dl (normal
15.6 ml, the total nodules volume varied from 0.1 to 39 ml mean 4.59 ml, median
3.4-4.8). After excluding other etiologies for her liver injury, she was treated with
0.94 ml and the control group of 50 women with thyroid volume in normal range
antithyroid medications. One week after starting treatment we observed an
from 5.1 to 19.9 mean 11.2, median 11.2 ml. The 25(OH) total levels varied in
important decline in FT3 to normal values, bilirubin and liver enzymes dropped
control group from 5.3 to 31.8 ng/ml, mean - 14.4, median 12.95, and in goiter
to half of maximal values. One month later normalization of thyroid hormones
group from 4.7 to 39.8 ng/ml, mean 15.00, median 13.3 ng/ml. Only 14% in
and near normalization of bilirubin and liver enzymes was documented. In
control and 22% in goiter group had vitamin level over 20 ng/ml. We found no
conclusion, severe acute hepatitis is rarely associated with thyrotoxicosis.
correlation between vitamin D level and volume of thyroid gland in goiter group
Hyperthyroidism should be rule out in patients with acute liver failure of
and no correlation between vitamin D level and summary volume of the thyroid
unknown origin.
nodules. There is negative correlation between vit. D level and thyroid volume
DOI: 10.1530/endoabs.49.EP1203
in healthy subjects.
Discussion
As vitamin D deficiency affects majority of both groups and can result in
osteoporosis, osteomalacia, and increased risk of fragility fractures, our study
demonstrates the importance of screening and educating a broader age group of
women with goiter disease but also in the ‘healthy’ population.
Conclusion
EP1204
There is an unacceptably high level of vitamin D deficiency among women in
both examined groups. The pleiotropic effects of vitamin D seems to be
Isolated ocular Miasthenia Gravis and Graves’ disease - a challenging
insignificant in development of goiter, but may play a role in healthy thyroid.
ophtalmopathy
Raquel Vaz de Castro1, José Maria Aragués2, Florbela Ferreira1,
DOI: 10.1530/endoabs.49.EP1205
Vânia Gomes1, Ana Wessling1, Ana Cláudia Fonseca1, Isabel Concei
¸ão1
& Maria João Bugalho1
1Santa Maria Hospital, Lisboa, Portugal;2Beatriz Ângelo Hospital, Lisboa,
Portugal.
EP1206
We report the case of a Caucasian woman presenting with a challenging
Amyloid goiter secondary to Crohn’s disease
differential diagnosis of ophtalmopathy. The patient was diagnosed with Graves’
Ana Saavedra1,2, Elisabete Rodrigues1,2, Ana Marques4 &
disease during postpartum at the age of 28 (TSH!0.001 U/ml; FT3 6.7 ng/dl;
Davide Carvalho1,2
FT4 2.2 ng/dl; TSAb 15 U/l). Besides 16 pack-year smoking history, no other
1Department of Endocrinology, Diabetes and Metabolism of Centro
previous disease was known. At examination, exophthalmos grade I/III with
Hospitalar de São João, Porto, Portugal;2Faculty of Medicine, University of
bilateral lid retraction was evident. Persistency of the disease despite optimal use
Porto, Porto, Portugal;3Instituto de Investiga
¸ão e Inovaça˜o em Saúde,
of medical antithyroid therapy led to radioactive iodine ablation (10 mCi) at the
University of Porto, Porto, Portugal;4Department of Pathology, Centro
age of 34.Three months afterwards, hypothyroidism was detected on blood tests
Hospitalar de São Joa˜o, Porto, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
Conclusion
Amyloidosis results from deposition of insoluble proteins in the extracellular
Although uncommon, extreme cases of thyroid dysfunction can occur in patients
space. It can be both primary or secondary to chronic inflammatory diseases.
on amiodarone therapy, underlining the importance of thyroid function
Although microscopic thyroid involvement is common, cases in which it becomes
monitoring.
clinically evident (amyloid goiter) are rare.
DOI: 10.1530/endoabs.49.EP1207
Case report
Woman, 45 years. In 2009, she was diagnosed with Crohn’s disease after
Bartholin’s gland abscess excision and evaluation for weight loss, anemia and
renal failure. In 2010, during hospitalization in Gastroenterology department, an
euthyroid diffuse goiter was identified (without compressive symptoms, except
easy choking) and she was oriented to endocrinology consultation. Due to chronic
kidney disease, she underwent renal biopsy (Jan/2011), that established the
EP1208
diagnosis of renal amyloidosis. Because she presented hepatic cytolysis a liver
Hashimoto’s thyroiditis in a patient with ectopic thyroid tissue
biopsy was also done, which revealed amyloid deposits in the wall of some portal
Nadia Khessairi, Ibtissem Oueslati, Ons Rjeb, Fatma Chaker,
arteries. She has been followed in Endocrinology since
05/2011, being
Meriem Yazidi, Malika Chihaoui & Hedia Slimane
asymptomatic, with diffuse goiter. Thyroid function tests and calcitonin are
Department of Endocrinology, La Rabta Hospital, Tunis, Tunisia.
normal with negative thyroid antibodies. Thyroid ultrasound has shown an
enlarged gland (LD 16!25!58 mm, LE 18!20!57 mm T!AP!L), with
increased echogenicity and diffuse heterogeneity, but without dimensional
Introduction
progression. Considering the imaging findings and the presence of systemic
Abnormalities in the development and migration of the thyroid gland are known
amyloidosis, she underwent thyroid core biopsy, which confirmed the amyloid
to produce ectopic thyroid tissue, usually in the midline between the tongue base
goiter diagnosis.
and the diaphragm. Hashimoto’s thyroiditis involving ectopic thyroid tissue is
Discussion
particularly unusual. Herein we report a case of Hashimoto’s thyroiditis
In the majority of cases of amyloid goiter there is a rapid thyroid growth (in weeks
developing in a midline thyroid cervical mass.
to months), although in the case described there was no progression. Despite the
Observation
widespread involvement of the thyroid by the disease, patients are usually
A 55-year-old man was referred for hypothyroidism. His physical and
euthyroid. Since amyloid deposits can also be found in association with medullary
psychomotor development was completely normal. His thyroid gland was not
thyroid carcinoma, this possibility must always be excluded. In conclusion, the
palpable in its normal pretracheal position. Elevated thyroid-stimulating hormone
diagnosis of amyloid goiter should be considered in patients with systemic
levels
(TSHZ19.8 mIU/ml, range 0.35-4.5) with low free serum thyroxine
amyloidosis or chronic inflammatory disease who present with bilateral and
(0.64 ng/ml) value were found. In addition, high titers of antiperoxydase
rapidly progressive enlargement of the thyroid, even in the presence of normal
antibodies (295.8 IU/ml) were detected. The neck ultrasound revealed a left
thyroid function.
lobar hypoplasia and a midline cervical mass representing aberrant thyroid tissue
DOI: 10.1530/endoabs.49.EP1206
due to migration defects. A Tc-99 m pertechnetate marked isotope showed
accumulation at the left thyroid lobe and at the midline cervical mass with no
uptake at the right thyroid lobe.
Conclusion
Ectopic thyroid tissue itself is not known to demonstrate a predilection for
Hashimoto’s thyroiditis. Despite its rarity, the presence of ectopic thyroid should
be considered in the differential diagnosis of all tongue, neck and trachea masses.
The ectopic tissue may be functional and affected by the same pathological
processes as the thyroid gland.
DOI: 10.1530/endoabs.49.EP1208
EP1207
Two case reports of amiodarone induced thyroid dysfunction:
thyrotoxic and myxedematous crisis
Francisco Sousa Santos, Cátia Ferrinho, Ricardo Capitão, Catarina Roque,
Carlos Bello, Clotilde Limbert & Carlos Vasconcelos
Servic¸o de Endocrinologia, Centro Hospitalar Lisboa Ocidental, Lisbon,
Portugal.
EP1209
Autoimmune thyroid disease occurring as a possible late complication
Introduction
after a non-occupational HIV Postexposure Prophylaxis
Amiodarone is a well-established antiarrhythmic drug frequently used in
Iulia Crumpei1,2, Voichita Mogos1,2, Maria-Christina Ungureanu1,2,
tachyarrhythmias. Side effects include hypothyroidism and hyperthyroidism.
Anamaria Bursuc1,2, Ioana Armasu1,2, Mirela Tirnoveanu1,2,
Extreme cases such as myxedematous and thyrotoxic crisis are very uncommon.
Valentina Adomnicai2, Georgiana Constantinescu1,2 & Carmen Vulpoi1,2
Here we report one case of each of these presentations.
1University of Medicine and Pharmacy, Iasi, Romania;2Department of
Case Report no.1
Endocrinology, Iasi, Romania.
A 73-year-old woman with history of atrial fibrillation under treatment with
amiodarone presented to the emergency department with headache, nausea and
Introduction
chest pain. On admission, she was tachycardic - atrial fibrillation with heart rate of
Nonoccupational postexposure prophylaxis (nPEP) is a three-drug antiretroviral
127 bpm. Her free T4 (fT4) and TSH were 31.5 rmol/l and !0.01 mU/l,
regimen used to decrease the risk for HIV infection after less than 72 h from
respectively and her antithyroid antibodies were all negative. Thyroid ultrasound
nonoccupational exposure to body fluids that might contain HIV. The most
demonstrated a micronodular gland with increased Doppler sign. Amiodarone
frequent side effects concern the gastro-intestinal intolerance, renal and hepatic
was discontinued and she was started on propylthiouracil, propranolol,
toxicity, with no hormonal imbalance to have been yet reported.
hydrocortisone, cholestyramine and Lugol’s iodine, without laboratorial or
Case report
clinical improvement
- sustained tachycardia and coma. As such she was
24 years old male patient, consulted for palpitations, hoarseness, shortness of
thyroidectomized. Her thyroid function tests and heart rate improved, however
breath, laryngeal tightness, weight loss
(4 kg /3 months), fatigue, insomnia,
she died due to sepsis secondary to MRSA on the 18th post-operative day.
recurrent panic attacks and anxiety-symptoms progressively installed since 3
Case Report no.2
months. Patient’s previous history contains a nonoccupational exposure to body
A 90-year-old woman with history of atrial fibrillation under treatment with
fluids containing HIV 8 months previously, treated with nPEP (Lamivudine,
amiodarone presented to the emergency department with a 12-h history of
Zidovudine and Kaletra- Lopinavir/Ritonavir), with a negative serology at the
diminished consciousness level. On admission, she was myxedematous,
check-ups. He presented high blood pressure and tachycardia, tremor,
hypothermic, bradycardic and with bradypnea. Laboratory studies revealed
hyperhidrosis and excessive preoccupation concerning his illness. Thyroid tests
respiratory acidemia, increased creatinine, toxic benzodiazepine levels, TSH
found an autoimmune thyroiditis with subclinical thyrotoxicosis: ATPOZ
80.2 mU/l and fT4 4.47 rmol/l (antithyroid antibodies were negative). She was
57.5 IU/ml (N: 0-35), TSHZ0.09 mIU/ml (N: 0.4-4), FT4Z1.35 ng/ml (N: 0.89-
started on IV fluids, non-invasive ventilation and antibiotherapy due to suspected
1.76), TRAb- negative, normal thyroid at the ultrasound. Cardiac evaluation was
pneumonia. Amiodarone was discontinued and IV L-thyroxine (250 mg) and
normal so the patient was advised to start betablocker and anxiolitic treatment,
hydrocortisone (200 mg) were administered and continued orally on the following
along with psychological counselling. At the one month follow-up, the blood test
days. She showed dramatical clinical improvement and was discharged after
has shown persistence of the thyroid autoimmunity with normalisation of the
10 days on oral L-thyroxine 75 mg/day.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
function: TSHZ0.602 mIU/ml, FT4Z1.38 ng/dl, without any other abnormal-
hemodynamic stability. He was discharged after radiofrequency ablation of an
ities.
abnormal signal pathway with EKC in sinus rhythm and amiodarone was
Conclusions
suspended. Thyroid ultrasound showed thyroid goiter (24.5 ml) with hetero-
The occurrence of the autoimmune thyroid disease after a 6 month period post
geneous structure. There was a lack of 99 mTc uptake in scintigraphy (0.5%).
nPEP has not yet been cited. It may be a result of either the autoimmune system
Normalization of hormones was reached after eight months of onset of the
rebound after the antiretroviral therapy or an inflammatory imbalance induced by
disease, with tiamazol 70 mg/day and prednisolone 20 mg/day.
the treatment with consecutive immune reconstitution syndrome.
Conclusions
DOI: 10.1530/endoabs.49.EP1209
Amiodarone-induced thyrotoxicosis occurs in 5-10% of patients and may cause
significant morbidity, especially in patients with significant cardiac disease and
when it cannot be discontinued. Differential diagnosis between type 1 and type 2
is not always easy and sometimes mixed forms occur, adding more challenges and
difficulty to the treatment, particularly when antithyroid drugs and corticosteroids
are ineffective.
DOI: 10.1530/endoabs.49.EP1211
EP1210
Recurrent Thyroiditis in an Amiodarone treated patient:
An Illustrative Case Demonstrating the Spectrum of Abnormalities
Mohit Kumar & David James Tymms
WWL Foundation Trust, G. Manchester, UK.
EP1212
A 65 yo gentleman was referred to the endocrinology department with
Atrial flutter with 1:1 atrioventricular conduction: An uncommon
thyrotoxicosis. He had a history of IHD and recurrent VT necessitating
cardiac manifestation of hyperthyroidism
amiodarone for 8 years. Routine TFTs had shown TSH undetectable, fT4 34.1,
Amal Rached, Mariem Yazidi, Imen Sakka, Ons Rejeb, Nedia Khessairi,
fT3 8.7. There were no symptoms or signs of thyrotoxicosis or cardiovascular
Malika Chihaoui & Hedia Slimane
compromise. He had been treated with carbimazole by his GP for the previous 3
La Rabta, Tunis, Tunisia.
weeks, this was discontinued at the initial evaluation due to recurrent vomiting.
TPO antibodies were negative, a thyroid uptake scan showed normal uptake
(2.86% at 20 mins) with a hot nodule in the isthmus. The thyroid function
Introduction
normalised over a period of 2 months with no medication. It was felt unsafe to
Atrial flutter (AFL) is a rapid, regular atrial tachyarrhythmia that occurs most
discontinue the amiodarone. Sixteen months later there was a further episode of
commonly in patients with underlying structural heart disease. Patients with
thyrotoxicosis, again asymptomatic with no CV compromise. A repeat thyroid
tachyarrythmias as a result of thyroid storm have been typically treated with beta-
uptake scan showed a cold thyroid. This episode too was managed conservatively.
blockers to decrease the heart rate and alleviate beta-receptor mediated
This was followed by a further two self-resolving episodes (2 and 3 years later);
symptoms. We report an unusual case of AFL with 1:1 atrioventricular (AV)
subsequently the patient developed permanent hypothyroidism treated with
conduction.
levothyroxine 100 mg. Amiodarone induced thyrotoxicosis (AIT) comes in two
Case report
forms: type 1 (iodine-induced excess thyroid hormone production) and type 2
Patient H, M 45 years old was admitted to our hospital with Graves Disease. He
(thyroiditis), though in some patients an overlap is thought to exist.
presented with typical symptoms which included tiredness, shaking, palpitations
Differentiation of these types can be difficult. Our case seems to demonstrate
and opthalmopathy. He had lost 36 pounds over 3 months. He had a heart rate of
both forms; initially type 1, then three episodes of type 2. Recurrent thyroiditis
280/min, blood pressure of 130/80 mmHg, a moderate sized goitre without signs
has been reported with suppurative thyroiditis and postpartum thyroiditis. Whilst
of right heart failure. An electrocardiogram revealed atrial flutter with 1:1 (AV)
there are reports of recurrence of thyroiditis with ongoing treatment with
conduction. The echocardiogram showed a preserved internal dimension and
amiodarone, to our knowledge this is the first case to show four episodes of AIT
overall normal systolic function. The diagnosis of hyperthyroidism was
with ongoing administration of this drug. The continuation of amiodarone is
confirmed: Thyroid stimulating hormone:
0.002 mIU/l, Free T4:
3.52 ng/dl
sometimes clinically necessary, but can lead to a longer time to cure if treated
(0.7-1.5). He was treated with propranolol 60 mg/day and thiamazole 40 mg/day.
with steroids. Thyroidectomy and perhaps radioiodine are options in troublesome
He was placed on anticoagulation with warfarin for a target INR of 2-3. We
cases.
performed a linear radiofrequency ablation and he reverted to sinus rhythm. His
DOI: 10.1530/endoabs.49.EP1210
symptoms improved and he was discharged 1 week later.
Conclusion
This case report shows that AFL with 1:1 AV conduction may be observed in
patients with hyperthyroidism and rapid supraventricular tachycardia.
DOI: 10.1530/endoabs.49.EP1212
EP1211
Thyroid storm subsequent to amiodarone-induced thyrotoxicosis
Catarina Machado, Patrícia Tavares, Sara Monteiro, Gustavo Rocha
& Maria João Oliveira
Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,
EP1213
Portugal.
Pharyngeal Irritation, Incidental Neck Masses; A difficult journey
Bonnie Grant1, Raj Tanday1, Augustine William1, Antony Pittathankal2,
1
Edel Casey1 & Khash Nikookam
Introduction
1Diabetes and Endocrinology Department, Barking Havering and Redbridge
Thyroid storm is a rare medical emergency with high mortality, which usually
University Trust, Greater London, UK;2Surgery Department, Barking
results from acute exacerbation of hyperthyroidism. Amiodarone is a highly used
Havering and Redbridge University Trust, Greater London, UK.
class III antiarrhythmic drug and amiodarone-induced thyrotoxicosis is an
infrequent effect of this medication, whose treatment may be difficult.
Case study
This is a case of a 48-year-old lady initially referred to respiratory clinic with
A 20-year old male with congenital cardiomyopathy (Fallot tetralogy and Ebstein
symptoms of breathlessness. She had a high-resolution CT thorax where an
anomaly), chronically medicated with amiodarone 200 mg/day since age 2, was
incidental finding of a right para-oesophageal 2.4-cm soft tissue density at the
admitted to the emergency room with palpitations, diaphoresis, nausea, vomiting
level of the thyroid gland identified. A CT neck was performed for further
and diarrhea. EKG showed atrial fibrillation with rapid ventricular response (HR
evaluation again showed the soft tissue mass (26 mm!37 mm) situated to the
160 bpm). Blood analysis showed hyperthyroidism - TSH !0.005 mUI/ml;
right of the oesophagus and another mass
(16 mm!26 mm) left of the
FT3 7.83 pg/ml (2.57-4.43) and FT4 5.50 ng/dl (0.93-1.70). Burch-Wartofsky’s
oesophagus. Discussion at the Lung MDT felt they may represent thyroid
score was 55. He started tiamazol 30 mg/day and prednisolone 40 mg/day, but
nodules but given location and relative normality of the rest of the thyroid
because of his cardiac disease, amiodarone could not be withdrawn. Despite
parenchyma, parathyroid adenomas were possibilities hence she was referred to
adequate treatment, there was no clinical response and patient remained
the endocrine surgeon. She then described symptoms of irritation in her throat on
hypotensive, taquicardic and at risk of cardiogenic shock. Potassium perchlorate
swallowing over the previous 6 weeks but no subsequent breathing problems. On
was initiated at 400 mg 8/8 h with subsequent normalization of heart rate and
neck examination, the thyroid lobes were just palpable, with no cervical
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
lymphadenopathy. She was clinically and biochemically euthyroid with a normal
multinodular thyroid disease. The thyroid function was normal, antithyroid
calcium and parathyroid hormone level. Ultrasound thyroid reported hypoechoic
antibodies were negative and calcitonin (Ct) serum levels were moderately
heterogenous solid masses posterior to the thyroid; 3 cm on the right and 2 cm on
elevated (28.9 pg/ml). The thyroid ultrasound will detect bilateral hypoechoic
the left. These masses appeared separate from the thyroid with minimal internal
areas the largest to the right of 2.4 cm with hypoechoic halo and peri- and
vascularity, likely representing parathyroid adenomas. MRI soft tissue neck could
intranodular vascularization. Total body CT scan showed splenomegaly almost
not differentiate between parathyroid and thyroid origin. Following Endocrine
breaking and so was made of splenectomy. The histology showed splenic
multi-disciplinary team discussion, the patient had a thyroid technetium scan and
localization of lymphoma diffuse large B cell. The PET/CT scan with F18 FDG
technetium MIBI scan with findings concordant that it was probably thyroid in
was positive of upper- and subdiaphragmatic lymph nodes and a right thyroid
origin rather than parathyroid adenomas. Endoscopic fine needle biopsies found
nodule. Immunochemotherapy was initiated according to the R-COMP protocol
small foci of follicular tissue with immunochemistry showing strong nuclear
and at the end a new PET/CT F18FDG detects activities only to the lower right
positive staining with positive thyroglobulin antibodies, suggesting thyroid tissue,
thyroid pole. A control of Ct showed an increase to 45.1 pg/ml and the calcium
not parathyroid.
gluconate infusion test was suggestive of MTC (peak Ct O2.000 pg/ml). Total
Conclusion
thyroidectomy and lymph node draining was performed. Histology showed a
This case highlights the difficulty differentiating between thyroid and parathyroid
MTC bifocal, 2.5-1.5 cm to the right and left respectively, with all node-negative.
masses found incidentally. Dedicated imaging and biopsies may be the only way
Screening for MEN 2 was negative. Seven months after surgery Ct levels are
to confirm the nature of these masses.
!1.0 pg/ml; molecular analysis of the RET gene showed no pathogenetic
DOI: 10.1530/endoabs.49.EP1213
variants. In conclusion, the two neoplasms appear to be independent and not
correlated to a multiple cancer syndrome; moreover also in the NHL detect on
palpation of the neck and then the morphological examinations a thyroid nodule
suggest the dosage of Ct.
DOI: 10.1530/endoabs.49.EP1215
EP1214
Papillary thyroid microcarcinoma in struma ovarii tissue: a case report
Cem Onur Kirac, Suleyman Baldane, Suleyman Ipekci & Levent Kebapcilar
Division of Endocrinology and Metabolism, Selcuk University Faculty of
Medicine, Konya, Turkey.
Introduction
Struma ovarii is an uncommon ovarian neoplasm that more than half of itself is
EP1216
made up of thyroid tissue. In clinical trials about the disease, malign
miRNAs microarray differential profile in papillary thyroid carcinoma
transformation has been detected at the rate of 0.5-5%. Because of the disease’s
Sorina Schipor1,2, Ana-Maria Niculescu3, Anca Botezatu4,
rareness, there is no absolute agreement about diagnosis and treatment of the
Dumitru Ioachim1, Dana Manda1, Andra Caragheorgheopol1,
disease.
Catalina Picu1, Oana Popa1, Ioana Nedelcu1 & Corin Badiu1,2
Case report
1National Institute of Endocrinology ‘C. I. Parhon’, Bucharest, Romania;
A 33-year-old woman admitted to gynecology department with abdominal pain.
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;
Her pelvic MR revealed 147!99 mm multiseptated cyst in right over which may
3Agilrom Scientific, Bucharest, Romania;4‘Stefan S. Nicolau’ Institute of
compatible with teratoma. On laboratory evaluation, her CA-125 level was
Virology, Bucharest, Romania.
43.8 U/ml (normal range: 0-35). The cyst was excised and frozen section analysis
was performed. The frozen section showed stuma ovarii so no additional surgical
procedure was performed. Diameter of 300 micron papillary thyroid carcinoma
Introduction
was determined at the histopathological examination. At postoperative
The deregulation in miRNA expression has been described in thyroid tumors, and
evaluation, there was no metastasis on thoracic and abdominal imaging. There
is considered an important factor in thyroid carcinogenesis. mRNA expression
was no nodule on thyroid USG. In the second operation, omentectomy, excision
profiling in cancer allows identifications of signatures associated with diagnosis,
of paraovarian palpable lymph nodes and right oophorectomy were performed.
staging, prognosis, and response to treatment.
Pathologic examination revealed no over invasion or lymph node metastasis.
Objective
Preoperative and postoperative thyroid function tests were measured in normal
We aimed to detect miRNAs species differentially expressed between tumor and
range; on the other hand postoperative thyroglobulin level was 0.071 ng/ml
peritumoral tissue in papillary thyroid carcinoma.
(normal range: 1.4-78) and anti-thyroglobulin value was 427 IU/ml (normal
Materials and methods
range:
0-115). Postoperative CA-125 level of the patient was found to be
After informed consent and study approval by ethics committee, 24 patients were
regressed to
12.9 U/ml. Because of the diameter of the tumor tissue,
included in the study: seven patients with classic papillary thyroid carcinoma
thyroidectomy or adjuvant radioactive iodine therapy treatment was not
(cPTC), 14 patients with follicular variant of papillary thyroid carcinomas
performed. There has been no recurrence in 1 year follow-up.
(fvPTC) and three patients with insular and sclerosing variant of PTC, using intra-
Conclusion
operatively obtained tumor and peritumoral normal tissue. RNA was isolated
There is still no consensus on the diagnosis and treatment of malignant SO. The
from thyroid tissue using Trizol
(Invitrogen, Life Technologies). miRNA
general approach is that low-risk cases can be followed without adjuvant
microarray analysis was performed using miRNA Microarray System with
radioactive iodine therapy such as primary thyroid papillary carcinoma. However,
miRNA Complete Labeling and Hyb Kit and SurePrint G3 Human miRNA r21
further studies are needed to determine the effect of this approach on recurrence
Array Kit
(Agilent Technologies). SureScan Microarray Scanner Agilent
and mortality rates.
(G2600D) with Feature Extraction v11.0 and Agilent GeneSpring GX v14.5
DOI: 10.1530/endoabs.49.EP1214
were used for data extraction and analysis.
Results
Our analysis showed that 2570 miRNA species differ between normal and tumor
tissues. From all these, a fold change (FC)O1.1 identified 2516 species, with 276
having a FCO2. Applying an asymptotic P value below 0.05 and Benjamini-
Hochberg correction for false-discovery rate we found eight miRNAs
significantly different between normal and tumor thyroid tissues, namely hsa-
EP1215
miR-181c-5p, hsa-miR-181d-5p, hsa-miR-221-3p, hsa-miR-34a-5p, hsa-miR-
Simultaneous occurrence of RET-negative Medullary Thyroid
34b-5p, hsa-miR-5703, hsa-miR-630
and hsa-miR-744-5p,
6
of them up-
Carcinoma (MTC) and extrathyroidal B large cell Non-Hodgkin
regulated and two of them downregulated in tumor vs normal tissue.
Lymphoma (NHL)
Conclusion
Serafino Lio
miRNA microarrays expression profile using a specific platform allowed a very
Department Medicine-Endocrine Unit-ULSS2, Oderzo-TV, Italy.
good differentiation between tumor and normal thyroid tissue, providing an
important tool for the individualized, specific variant-based management of
thyroid cancer.
The simultaneous occurrence of MTC and extrathyroidal B large cell NHL are
Acknowledgement
very rare. MTC may be sporadic or part of a MEN and NHL is not reported in
UEFISCDI grant PN-II-PT-PCCA-2011-3.2-1337.
association with MEN. A woman of 76 year old with a history of cholelithiasis
and hepatitis B, is admitted for left abdominal pain. On examination it is detected
DOI: 10.1530/endoabs.49.EP1216
inguinal, axillary and clavicular lymphadenopathy, splenomegaly and also a
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1217
(35/349). The highest false negative rates (15%) were in nodules !2 cm. There
was no significant difference in the false negative rates for nodules O4 cm (8%)
Simultaneous papillary and medullary thyroid carcinoma in siblings
or !4 cm (10%) respectively.
with RET 611 mutation. More than a coincidence?
Conclusions
Miguel Paja, Alba Zabalegui, Maddalen Dublang, Eider Etxeberría,
After adjusting for patient age and gender, nodules that measured O4 cm had a
Natalia C Iglesias, Laura A Calles, Cristina Arrizabalaga, Aitzol Lizarraga,
greater malignancy risk. The false negative rates were not higher for nodules
M Teresa Gutiérrez & Aitziber Ugalde
O4 cm. Thyroidectomy should not be recommended based solely on nodule size.
Hospital Universitario de Basurto, Bilbao, Vizcaya, Spain.
DOI: 10.1530/endoabs.49.EP1218
Germinal mutations of the oncogene RET originate the development of medullary
thyroid carcinoma (MTC) in carriers with phenotypic expression depending on
the mutated codon and other unknown factors. Simultaneous detection of
differentiated thyroid carcinomas is considered a casual phenomenon (collision
tumours). We communicate two brothers with double heterozygous mutation of
maternal inheritance at codon 611 of RET, TGC to TTT, changing to encode
EP1219
phenylalanine (C611F), with a simultaneous papillary thyroid carcinoma (PTC).
Struma ovarii - A report of thirteen cases
Case 1
Sara Donato, Hélder Simo˜es & Valeriano Leite
A 42-year-old male who underwent through total thyroidectomy and bilateral
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon,
central dissection (TTCBCD) after genetic diagnosis in 2006. Basal preoperative
Portugal.
calcitonin was 6.0 pg/ml and stimulated, 34 pg/ml. Histology showed a bifocal
MTC, the bigger of 3 mm, and a classic infiltrative PTC of 3 mm with intense
desmoplastic stromal reaction and four metastatic lymph nodes out of five in
Introduction
central compartment, two with extranodal extension. BRAFV600E mutation was
Struma ovarii (SO) is a rare ovarian teratoma characterized by the presence of
positive. He received 100 mCi of I131 with stimulated thyroglobulin of 1.9 ng/ml.
thyroid tissue in O50% of the tumour. Malignant transformation is rare and
Ten years later, he has undetectable calcitonin and excellent therapeutic response.
defined by the same histological criteria as for thyroid cancer. There is few data
Case 2
on the literature and treatment is controversial. The objective of this study was to
A 48-year-old male received TTCBCD after genetic diagnosis in 2016, with
describe the clinical, pathologic and treatment characteristics of women
basal calcitonin of 25.2 pg/ml and stimulated of 124.5 pg/ml. Histology showed a
diagnosed with SO in our centre.
bifocal MTC,
6 and 5 mm, and two foci (5C2 mm) of well limited not
Methods
encapsulated follicular variant of PTC, BRAFV600E negative. There was no
Retrospective analysis of the SO followed in our Institution between 2000 and
involvement by any of the two tumours in six resected nodes. After 3 months,
2015.
basal calcitonin is 0.8 pg/ml, and basal thyroglobulin, without radioiodo, reaches
Results
0.31 ng/dl. We are remarking simultaneous occurrence of MTC and PTC,
A total of 13 patients were identified with a median age at diagnosis of 46 years
originated from different thyroid cell types, in siblings bearing the same RET
(range 19-85). No patient had previous history of thyroid disease. In nine cases
mutation. This coincidence raises the possibility of an underlying common
the diagnosis was made by routine imaging exams and in three cases by associated
genetic drive in both PTC, although with different mutational events added that
symptoms (mostly pelvic pain). CA 125 and HE4 serum levels were normal in
explain distinct differentiation, among them BRAF V600E mutation.
every patient tested
(four and three patients respectively). Seven patients
DOI: 10.1530/endoabs.49.EP1217
underwent bilateral oophorectomy plus hysterectomy
(with or without
omentectomy or external iliac lymphadenectomy) and in six the surgical
procedure was a unilateral oophorectomy. Three cases were diagnosed as
malignant SO. In these cases thyroidectomy followed by radioactive iodine was
performed and papillary thyroid cancer (PTC) was diagnosed in two.131I-WBS
performed after surgery, showed no uptake in the pelvis in any patient. In one
benign SO case, thyroid imaging and fine-needle biopsy disclosed PTC as well.
During a median follow-up of 14 months (range 1-78), nine patients remained
EP1218
with no evidence of disease, one died with a non-related cause and one was lost to
Thyroid nodule size at ultrasound as a predictor of malignancy
follow-up. Two of the malignant SO patients were found to have biochemical
Gema López Gallardo1, Julia Sastre2, Abel González3, Sandra Arranz4,
evidence of disease.
Julia Silva5, Miguel Angel Valero6 & Jaime Aranda7
Conclusions
1Hospital Santa Bárbara, Puertollano/Ciudad Real, Spain;2Hospital Virgen
SO was frequently asymptomatic. Patients with malignant SO had often
de la Salud, Toledo, Spain;3Hospital General, Ciudad Real, Spain;
persistence of disease, although they had a good overall survival rate. An
4Hospital General, Albacete, Spain;5Hospital Mancha Centro,
important proportion of these patients developed thyroid cancer.
Alcázar/Ciudad Real, Spain;6Hospital General, Talavera, Spain;
DOI: 10.1530/endoabs.49.EP1219
7Hospital General, Cuenca, Spain.
Introduction
Most thyroid nodules are benign. Some studies have shown largest nodule size,
specially O4 cm, can predict malignancy and reduce fine needle aspiration
(FNA) accuracy. Recent studies, however, have shown conflicting results as to
whether nodule size may be used to distinguish at risk-lesions. We attempt to
EP1220
determine whether nodule size predicts thyroid malignancy and to examine
Diagnosis of medullary thyroid carcinoma at early stage
accuracy of fine needle aspiration (FNA) by size.
Cristina Stancu1, Cristina Corneci1, Andra Caragheorgheopol1,
Material and methods
Bogdan Stanescu2,3, Mirela Diana Ilie1 & Corin Badiu1,2
A multicenter, retrospective analytical study was performed on a total of 882
1‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;
patients with thyroid solitary nodules and put underwent partial or total
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;
thyroidectomy between 2010 and 2013. We compared nodules by size cutoffs
3Life Memorial Hospital, Bucharest, Romania.
using Chi-squared and Fisher exact test where appropriate. Binary logistic
regression analysis was used to identify the independent factors associated with
thyroid malignancy. All data were analyzed using SPSS software for Windows
(version 18.0).
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor derived
Results
from the thyroid C cells producing calcitonin, ac-counts for 0.6% of all
Of the 882 nodules, 664 (73%) were benign and 238 (27%) malignant. Nodules
thyroid cancers. It occurs either sporadically or in a hereditary form (RET
!2 cm had the highest malignancy rate (49.2%). Decreasing malignancy rates
mutation). MTC can be cured only by complete resection of the thyroid
(23.1, 16.8, 4.6, and 6.3%) were observed with increasing size (2-3 cm, 3-4 cm,
tumor and any loco-regional metastases. Calcitonin (CT) measurement is
4-5 cm, O5 cm). Thyroid nodule size O 4 cm was associated to less risk of
crucial to the early diagnosis and the follow-up of MTC. If the evaluation of
malignancy (OR O.589 (0.421-0.824)). After adjusting for patient age and
stimulated CT levels is required, a provocative test can be performed. We
gender, nodules that measured O4 cm had a greater malignancy risk compared to
report the case of a 52-year-old woman presenting with multinodular goiter,
those measuring !4 cm (OR 2.031 (P:0.001)). In nodules with a benign FNA
positive TPO antibody and basal CT in repeated samples 42.92, 38.15,
diagnosis (Bethesda II), the overall malignancy rate (false negative rate) was 10%
and
33.99 pg/ml respectively. The patient was euthyroid. Plasmatic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
metanephrines and PTH were in normal ranges. The thyroid ultrasound
elusive. In a previous work, we described that the injection of several hTRa
showed an isoechoic nodule 6 mm in size with a punctate calcification in the
variants in zebrafish eggs caused a marked reduction of circulating
left lobe and two hypoechoic nodes on the right lobe 19 and 9 mm in size,
erythrocytes at later stages of the erythropoiesis. To characterise the
with central and peripheral vascular signal. After a provocative test with
involvement of TRa during erythrocyte development, we analysed by qRT-
high dose Ca was performed, stimulated CT level was 96.6, 98.10 and
PCR and in situ hybridization
(ISH) the expression of different
82.10 pg/ml at 2, 5 and 10 min respectively. The patient underwent total
haematopoietic markers. We microinjected the zebrafish eggs at 1-2 cells
thyroidectomy. The histology showed multifocal medullary microcarci-
stage with 80pg/embryos of the purified mRNAs of several hTRa variants,
noma (max 5/5 mm in the left lobe), pTN: pT1a(m) Nx and positive
and from the 6-hpf, the injected embryos were treated with the control
immunohistochemistry for calcitonin. Postoperatively calcitonin level
vehicle, or with 20 mM-T3, added in the harvested water. By qRT-PCR, the
!0.2 pg/ml and CEA was negative. The mutations of RET protooncogene
expression of genes involved in the specification of lateral mesoderm (cdx4,
was tested, too.
bmp2b, smad5, chd), induction and proliferation of haematopoietic stem
Conclusion
cells (HSC) (tal1, lmo2, gata1, gata2) and proliferation of erythrocytes (zin,
We have to pay attention for patients with bCT O10 pg/ml and, a high-dose Ca
grx5, cia, cha) appeared significantly reduced in all hTRa-injected embryos.
test is reliable for the identification of MTC.
Consistent with previous results, the treatment with high T3 doses can
DOI: 10.1530/endoabs.49.EP1220
rescue the DN-activity of the missense variants D211G and A263V, whereas
the truncated receptors A382PfsX7, E403X and F397fs406X are unaffected
by TH treatment. Furthermore, we analysed the specification of HSC in
embryos at 8-somite stage, by ISH. The vast majority of the hTRa-injected
embryos showed a reduced or undetectable expression of early erythropoi-
esis markers, such as c-myb, pu.1, tal1 and gata1 in anterior or posterior
lateral mesoderm. At 36-hpf, we also observed a dramatic reduction of gata1
in the intermediated cell mass of hTRa-injected embryos. Therefore, our
EP1221
results highlight a relevant role for TRa during the early phases of the
primitive haematopoiesis, when the HSC start to proliferate and
Clinicopathological characteristics and outcomes of differentiated
differentiate.
thyroid carcinoma in children and adolescents
Research founding
Andrei Liviu Goldstein1, Iulia Andreea Chiriac1, Adina
Mariana Ghemigian1,2, Camelia Procopiuc1, Mircea Vasile Ghemigian1,
IAI-Ricerca Corrente RF-2011 05C102.
Daniel Brasoveanu1, Daniela Goldstein1, Mariana Purice1, Florin Alexiu1,
DOI: 10.1530/endoabs.49.EP1222
Gabriela Voicu1, Dumitru Ioachim1 & Iuliana Gherlan1,2
1‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.
Introduction
Differentiated thyroid carcinoma is a rare entity in pediatric population, with
particularities in diagnosis, management and outcomes.
Paediatric Endocrinology
Methods, aim
EP1223
Retrospective noninterventional study describing clinical presentation and
An interesting etiology in childhood choreoathetosis; autoimmune
outcomes of children with DTC.
hyperthyroiditis
Results
Ayca Torel Ergur1, Sevinc Odabasi Gunes1, Cihat Sanli2 &
Between 2011 and 2017 54 children and adolescents aged 7.8-18 years (mean age
Rabia Gundogan2
at diagnoses 14.4 years) with DTC were diagnosed/followed up in our Institution.
1Kirikkale University Faculty of Medicine, Department of Pediatric
The female to male ratio was 3.5:1. In 70% cases unilateral thyroid nodule was the
Endocrinology, Kirikkale, Turkey;2Kirikkale University Faculty of
first manifestation of the disease, in 25.9% cases the DTC was diagnosed during
Medicine, Department of Pediatric Cardiology, Kirikkale, Turkey.
the follow-up for chronic thyroid pathology, whereas in 3.7% cases cervical
lymph node enlargement was the first clinical sign. 29.6% patients had cervical
node involvement at diagnosis, 9.3% had pulmonary metastases. The initial
Introduction
tumour size (over 4 cm diameter), the diffuse sclerosing form of papillary cancer
Neurologic symptoms due to autoimmune encephalopathy related to autoimmune
were independent risk factors for initial metastasis. A total thyroidectomy was
hyperthyroidism (AEAH) cases are very rare in childhood. The reason why
performed in 58.5% cases, a total thyroidectomy with central neck dissection in
hyperthyroidism causes this situation is still unknown. In this case we discussed
41.5% cases. 57.4% patients were classifies as low risk, 18.6% as high risk
the diagnosis, treatment and follow-up of a case with choreoathetosis in the
patients. The follow-up period was between 1 and 98 month, with an average of
review of literature.
30.4 months. At the last visit 36.3% patients had a good response to therapy,
Case
28.5% were in complete remission of the disease and 9.5% had stable persistent
15 years old female admitted to hospital with the complaint of nervousness,
disease.
discomfort for last 3 weeks. There was not any particular feature in personal and
Conclusion
family history. In physical examination, heart rate was
110/min, goiter,
DTC in children and adolescents has good prognosis even in loco-regionaly
exophthalmos, dysarthria, involuntary hand-foot movements, and decrement of
advanced forms of the disease.
fine motor skills was observed. Laboratory results were sT3:
12.59 ng/dl,
DOI: 10.1530/endoabs.49.EP1221
sT4:3.6 ng/dl, TSH:0.007 mU/ml anti-TPO 591.4 595 IU/ml, ani-Tg:357.9 IU/ml,
TRAb: positive. In thyroid ultrasonography volume OC2S.D., and parenchymal
heterogeneity were observed. History of beta streptococcus infection was
negative, mitral valve prolapse and non-rheumatologic mitral regurgitation was
seen on echocardiography so Sydenham’s chorea was not considered. Lupus
antibodies were negative; C3, C4, cranial MR and MR spectrogram were normal.
Anti-thyroid and beta-blocker treatment were started. On the 14th day of the
treatment major recovery in patient’s walking and talking were observed.
Nuclear Receptors and Signal Transduction
Recovery of the fine motor skills was evaluated comparatively with weekly video
records. On the first month of the treatment fine motor skills were definitely
EP1222
normal.
The human TRa variants affect the specification of haematopoietic stem
Discussion
cells during zebrafish haematopoiesis
Cranial hypoperfusion due to cerebral vasculitis, autoimmunity specific to
Federica Marelli1, Giuditta Rurale2, Silvia Carra1 & Luca Persani1,2
cerebral tissues and primary demyelination secondary to neuronal dysfunction
1IRCCS Istituto Auxologico Italiano, Milan, Italy;2University of Milan,
were blamed in pathogenesis of AEAH. Plasmapheresis and corticosteroids are
Milan, Italy.
used in addition to anti-thyroid drugs in the treatment. The best aspect of is our
patient responded anti-thyroid drugs well. Our case is very challenging since it
reminds us the autoimmune thyroiditis in the etiology of major neurologic
Anaemia in RTHa patients correlates with documented abnormal
symptoms in children and adolescents.
erythropoiesis and reduced haematocrit in TRa-null or mutant mice, but
DOI: 10.1530/endoabs.49.EP1223
the underlying mechanisms and characterization of the defect remain
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1224
plasma T3 and GH concentrations at 1st, 3rd, 6th, 7th, 10th-15th and 18th
Thyroid pathology and breasts diseases in adolescent girls
and 19th year. The plasma T3 levels were positively correlated with plasma
Olga Gumeniuk & Yuriy Chernenkov
GH concentrations during infancy, pre-puberty, early and mid-puberty. The
Saratov State Midical University, Saratov, Russia.
concentrations of T3 and LGV were positively correlated at 1st, 3rd, 4th, 7-
15th and 18-20th year. The plasma concentrations of T3 were positively
correlated with LGV at infancy, pre-puberty, early and mid-puberty. In
conclusion, the present study shows negative correlations between T4 and
Several studies have noted that there is a connection between thyroid
GH and LGV and positive correlations between T3 and GH and LGV at
pathology and breast diseases.
infancy and mid-puberty.
Purpose
DOI: 10.1530/endoabs.49.EP1225
The study was undertaken to estimate the frequency of the breasts diseases in
adolescent girls with thyroid pathology.
Patients and methods
The study included 2371 girls
(aged
10-18 years). Thyroid diseases were
diagnosed on the basis of hormonal analysis and typical picture of examination
and thyroid ultrasound. Breast diseases were diagnosed on the basis of signs and
typical picture of breast ultrasound. We have identified the two groups: girls
EP1226
(nZ618) with thyroid pathology (group I) and girls (nZ30) without thyroid
pathology
(control group). Statistical analysis was performed using Mann-
Pediatric case of Autoimmune Polyglandular Syndrome type IIIC:
Whitney Test, P value of!0.05 were considered statistically significant. This
autoimmune thyroid disease and severe autoimmune thrombocytopenia
study has been carried out in accordance with the Helsinki Declaration.
Joanna Prokop1, Elzbieta Leszczynska3, Maryna Krawczuk-Rybak3 &
Results
Artur Bossowski2
The endemic goiter was diagnosed in every forth girls. Autoimmune thyroiditis
1Endocrinology Department, Centro Hospitalar Lisboa Central, Lisbon,
was found in 30 girls, nodul goiter in 4 and congenital hypothyroidism (later
Portugal;2Department of Pediatrics, Endocrinology, Diabetology with
form) in 2 adolescent girls. The investigation shows that every adolescent girl
Cardiology Divisions, University Children’s Clinical Hospital of Bialystok,
with thyroid diseases had breast disorders. Breast cysts (cystic dysplasia) was
Bialystok, Poland;3Department of Pediatric Oncology and Hematology,
diagnosed in 42% cases, fibrous mastopathy (dysplasia) - in 35%, adenosis
University Children’s Clinical Hospital of Bialystok, Bialystok, Poland.
mastopathy - in 18%, breast secretion - in 5% and fibroadenoma in 4 patients. All
girls with breast dysplasia and fibroadenoma complained of mastalgia. The
Introduction
average level on the visual analog pain scale in cases of mastalgia amounted
Association between autoimmune thyroid disease (AITD) and other autoimmune
6.9G2.1 points (in group I). The investigation shows that only 2 girls without
disorders is common and known as autoimmune polyglandular syndrome (APS).
thyroid pathology had breast diseases (predmenstrual mastalgia) (!0.001). The
It may involve hypoparathyoridism with Addison disease (AD) and mucocuta-
average level on the visual analog pain scale in control group was 3.8G1.4 points
neous candidiasis - APS type I, AD with Diabetes mellitus type 1 (DM1) or
(PZ0.02).
AITD- APS type II, AITD associated with other autoimmune diseases (excluding
Conclusions
AD): DM1- type IIIa, pernicious anemia- IIIb, or alopecia and/or vitiligo and/or
This study has shown a high frequency of the breast diseases among the
other autoimmune disorder- IIIc, any other combination being classified as APS
adolescent girls with thyroid pathology. Thyroid diseases are risk factor for breast
type IV. We report a case of a 15-year old patient diagnosed simultaneously with
disorders and show the necessity of for observation and examination of breast.
Graves disease (GD) and severe autoimmune thrombocytopenia (AIT).
DOI: 10.1530/endoabs.49.EP1224
Clinical case
A 15-year-old female patient was admitted to hospital with palpitations, weight
loss, petechiae on lower limbs, during menstruation. Physical examination
revealed tachycardia, goiter, thyroid bruit, fine distal tremor, petechiae of trunk,
upper and lower limbs. Abnormalities in laboratory studies: thrombocytopenia-
platelet count: 4.0!103/ul, clinical hyperthyroidism with positive TSH receptor
antibody. Myelogram: normal. Thyroid ultrasonography: enlarged thyroid gland,
colour Doppler: increased blood flow. She was treated with intravenous
EP1225
immunoglobulin (IVIG), platelets concentrate and started methimazole. During
Age and development stage dependent association between thyroid
follow-up she had 4 more episodes of severe thrombocytopenia, with good
hormones and growth hormone and linear growth velocity in boys
however temporary response to therapy with IVIG or intravenous corticosteroids.
between the age of 1 and 20 years
Meanwhile vitamin B12 deficiency was detected and vitamin B12 replacement
Afzaal Ahmed Naseem1, Mazhar Qayyum1, Maleeha Akram1,
therapy started. After normalization of thyroid function, maintaining low dose of
Zubaria Iqbal1, Faheem Tahir2, Sarwat Jahan3, Kiran Afshan3 &
methimazole, thrombocytopenia persisted (platelet countO20!103/ul). Anty-
Syed Shakeel Raza Rizvi1
glutamic acid decarboxylase(GAD) antibodies were tested: positive, without
1Department of Zoology, Pir Mehr Ali Shah Arid Agriculture University
hyperglycemia.
Rawalpindi, Rawalpindi/Punjab, Pakistan;2Reproductive Physiology,
Comments
Public Health Laboratories Division, National Institute of Health,
Although some autoimmune diseases may coexist, combination of AIT and GD is
Islamabad, Pakistan;3Department of Animal Sciences, Quaid-e-Azam
rarely reported. Moreover it was unusual because of juvenile onset, severity of
University, Islamabad, Pakistan.
thrombocytopenia, simultaneous diagnosis of GD, concomitant presence of GAD
antibodies and vitamin B12 deficiency. The patient needs to be monitored closely
for early detection of other autoimmune disorders or glandular failure and initiate
hormone replacement therapy if it is established.
During the time of puberty, thyroid hormones (THs), thyroxin (T4) and
DOI: 10.1530/endoabs.49.EP1226
triiodothyronine (T3), influence growth and developmental processes by
working in association with growth hormone (GH), insulin like growth
factor-I (IGF-1), glucocorticoids, insulin and gonadal steroids. THs have a
direct effect on GH secretion, which stimulates IGF system. It has been
suggested that THs control increase in bone length through synergy with
GH. This investigation determined age and developmental stage dependent
EP1227
association between circulating concentrations of T4, T3, GH and linear
Pediatric thyroid nodule: cytologic and histopathologic correlation
growth velocity (LGV). Blood samples were collected from 540 normal
Ana Miranda1, Sofia Pires2, Maria José Noruegas2, Cláudia Piedade2,
healthy boys (27 boys/age group) between 1 to 20 years of age and plasma
Manuel Ramos2, Joana Caetano2, Rita Cardoso2, Isabel Dinis2 &
concentrations of T4, T3 and GH were determined using specific ELISA;
Alice Mirante2
LGV was measured by calculating changes in height in cm/year. Data were
1Hospital Prof. Doutor Fernando Fonseca E.P.E., Amadora, Portugal;
analyzed using Student’s t test, ANOVA and Pearson correlation r. The
2Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra,
concentrations of T4 and GH were positively correlated at 3rd, 7-9th, 14-
Coimbra, Portugal.
16th and 18th and 19th year. T4 and GH concentrations were positively
correlated at pre-puberty and early and late puberty. The concentrations of
T4 and LGV were positively correlated at 3rd, 4th, 7th, 14-16th and 18-20th
Background
year. There were positive correlations between plasma T4 levels and LGV at
Thyroid nodule in the pediatric age group is rare, but the rate of malignancy is
pre-puberty and late puberty. There were positive correlations between
much higher than adult population. Fine needle aspiration biopsy (FNAB) is an
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
accurate test commonly used to determine whether thyroid nodules are malignant
EP1229
in adults. However, less is known about its diagnostic accuracy for this purpose in
Thyroid disorders and type 1 diabetes
children.
Ach Taieb, Hasni Yosra, Maaroufi Amel, Kacem Maha, Chaieb Molka &
Aim
Ach Koussay
To characterize the outcomes of FNAB of nodular thyroid disease at a pediatric
CHU Farhat Hached Sousse, Sousse, Tunisia.
tertiary-care institution and to correlate cytopathology with histopathology.
Materials and methods
Retrospective analysis to identify children who underwent FNAB of the thyroid
Introduction
between 2000 and 2016. Epidemiological, clinical, radiological, cytologic and
Type 1 Diabetes is an auto-immune disease caused by a disturbance of the
histopathologic data were analysed. The smears were categorized according to
immune system, damaging the Beta-cells. The association with other auto-
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) into six
immune diseases was frequently described, and dysthyroidism represents an
categories - Nondiagnostic, benign, atypia of undetermined significance/follicular
important part of these associations. In type 1 diabetes, the hormonal profile can
lesion of undetermined significance
(AUS/FLUS), suspicious for follicular
be disturbed regardless of auto-immunity. The goal of our study the thyroid
neoplasm (SFN), suspicious for malignancy (SM), and malignancy.
hormonal profile in type 1 diabetes, as well as the prevalence of auto-immune
Results
dysthyroidism associated with it.
Out of 32 cases, 87.5% were females. Patients ranged in age from 6.8 to 17.9
Material and methods
years (meanGS.D., 14.8G2.6 years). Seven individuals underwent more than one
This is a retrospective cross-sectional study based on the observation of patients
FNAB. Histological follow-up was available in
50%cases. The diagnosis
admitted for diabetes with insulin deficiency. The positivity of anti-pancreas
according to TBSRTC included 3 (9.4%) nondiagnostic, 22 (68.8%) benign,
antibodies testified to the auto-immune characteristic; anti glutamic acid
1
(3.1%) AUS/FLUS, 0SFN, 2 (6.3%) SM, and 4 (12.5%) malignancy cases. On
decarboxylase GAD and/or anti tyrosine phosphatase IA2. The goal is to
histological follow-up (nZ16), the rate of malignancy was 50%.There was no
determine the type 1 diabetic patients’ thyroid hormonal profile, and the auto-
difference in the ecografic size of the nodule of benign versus malignant lesions
immune dysthyroidism profile.
(PZ0.27) or diagnostic versus non-diagnostic lesions (PZ0.61). No difference
Results
was found in benign versus malignant lesions (PZ0.97) or diagnostic versus non-
Our series was conducted with 359 patients: 209 men and 150 women, aged
diagnostic lesions (PZ0.60), concerning mean age. Diagnoses at cytopathology
between 10 and 69 years with an average of 28.75 years. The clinical picture was
and surgical pathology were concordant in
9/14
(64%) nodules. Overall
ketotic in the majority of cases: 336 (93.6%), with inaugural ketosis in 313 cases
sensitivity of FNAB was 66.7% and specificity was 75%.
(87.2%). Insulin deficiency varied between one week an 36 months, with an
Conclusion
average of 3.75 months and a standard deviation of 6.8 months, exceeding 6
Due to the limited sample size our FNAB sensitivity and specificity are lower than
months achieving a slow form and a previous oral treatment in 24% of cases.
the previous reported on literature (90.6-100% and 76.2-100%, respectively). In
Regarding weight, the average BMI was 22 (extremes: 15 and 39), over 30 in 22
patients whose cytology was reported as inadequate or benign, is important to
patients. Upon admission, average blood sugar levels were 16.40 mmol/l with an
maintain follow-ups.
average glycosylated hemoglobin HbA1C of 12.32%. Average TSH levels were
DOI: 10.1530/endoabs.49.EP1227
of 3.23 mUI/l and the average T4 levelsZ12.43 pg/l in 242 patients who had
thyroid function tests. Auto-immune thyropathies were frequent: 54 patients (71%
of cases). Hashimoto’s disease dominated the etiologic profile and was confirmed
by the presence of anti-TPO antibodies found in 37 patients (48.6% of cases).
Basedow’s disease was found in 17 other patients (22.3% of cases) with positive
anti-TSH receptor antibodies.
Conclusion
Type 1 Diabetes is common in adults and children, and the association with auto-
immune diseases is frequent, hence the necessity of looking for these diseases
when patients are diagnosed with diabetes.
DOI: 10.1530/endoabs.49.EP1229
Thyroid (non-cancer)
EP1228
Thyroid autoimmunity in beta thalassemia minor
Sati Sena Yildiz1 & Ali Ramazan Benli2
1Department of Health and Social Services, Kayisdagi Darulaceze Ministry,
Istanbul Metropolitan Municipality, Istanbul, Turkey;2Department of
Family Medicine, Medikal Fakulty, Karabuk University, İstanbul, Turkey.
EP1230
Keep calm and put on the emergency list: total thyroidectomy for
refractory thyrotoxicosis
Background-aim
Ahmed Al-Sharefi1, Suhel Ashraff1, Wael Elasaify2 & Rasha Mukhtar1
Tendency to autoimmune diseases has been reported to be increased in beta
1Department of Diabetes and Endocrinology, The James Cook University
thalassemia minor (BTM). Our aim was to examine the prevalence of thyroid
Hospital, Middelsbrough, UK;2Department of Surgery, The James Cook
autoimmunity in BTM.
University Hospital, Middelsbrough, UK.
Method
Eighty six adults with BTM and 93 age and gender matched controls were
included in the study. The two groups were compared cross-sectionally in terms
The standard management for Grave’s thyrotoxicosis includes the use anti-
of anti-thyroid antibodies (anti-TG and anti-TPO) and thyroid hormones. Patients
thyroid drugs, surgery and radioactive iodine treatment. In certain
-
with known autoimmune disorders other than autoimmune thyroid disease were
situations,alternative methods including bile acid sequestrants and therapeutic
not included in the study.
plasma exchange (TPE) have proven effective especially when other treatment
Results
modalities fail. We describe a case where conventional and alternative non-
In the BTM group, serum TSH, FT4, FT3 levels were statistically indifferent from
invasive measures failed to restore an euthyroid state and resorted to emergency
the control group. Serum anti-TG and anti-TPO antibody levels were found to be
thyroidectomy. A 49 years old female was referred signs and symptoms consistent
similar in the two groups. BTM and control groups were similar in terms of anti-
with Grave’s thyrotoxicosis. She was already started on pulse IV methylpredni-
thyroid antibody positivity prevalence. In the BTM group, anti-TG was 11.6%
solone for active thyroid eye disease. Her thyroid functions tests showed a
and anti-TPO was 14% positive, while these were respectively 14% and 12.9%
suppressed TSH of !0.05 mIU/l (0.27-4.2),free T4 of 52.7 pmol/l (10.0-21.0)
positive in the control group
(PZ0.806 and PZ0.989, respectively). The
and free T3 of 18 pmol/l (3.5-6.5). Her Thyroid receptor antibodies were high of
proportion of anti-TG and/or anti-TPO antibody positive subjects was found to be
O100 IU/l (1.0-1.8). She was started on anti-thyroid drugs which were stopped
20.9% in the BTM group, and 20.4% in the control group (PZ0.919). Ratios of
due to side effects. She had active thyroid eye disease so radioiodine was not
subjects with euthyroidism, hypertiroidism and hypothyroidism were similar in
appropriate and surgery considered the best option. She failed to block on
both group.
Potassium iodide, and surgery was cancelled due to hyperthyroidism. She was
Conclusion
started on Steroids and Cholestyramine but failed to respond with worsening
Because thyroid autoimmunity prevalence in the BTM group is not increased
symptoms and biochemistry. As a last resort, therapeutic plasma exchange was
compared to the control group, we consider that there is no necessity for routine
initiated with improvement in her thyroid biochemistry but no resolution despite
anti-thyroid andibodies and thyroid hormone testing in subjects with BTM.
seven sessions. An emergency total thyroidectomy was rearranged as the final
DOI: 10.1530/endoabs.49.EP1228
resort with steroid and B-blocker cover. Fortunately, the surgery was uneventful
and she made an uneventful recovery with subsequent improvement in her thyroid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
functions and clinical symptoms. This case demonstrates how Graves’s
EP1233
thyrotoxicosis can pose a clinical challenge when it is refractory to all medical
Risk factors associated with the severity of Graves’ ophthalmopathy
therapies including plasma exchange. Total thyroidectomy remains the best and
Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Karima Khiari,
only option, a comprehensive multidisciplinary approach involving an
Nadia Mchirgui & Néjib Ben Abdallah
endocrinologist, a surgeon and an anaesthetist is crucial to optimize the outcome
Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.
and reduce the risk of thyroid storm.
DOI: 10.1530/endoabs.49.EP1230
Introduction
Graves’ ophthalmopathy (GO) is an autoimmune disorder affecting the retro-
orbital tissues. It represents the main extra- thyroidal expression of Graves’
disease (GD). Its onset and progression are influenced by several factors that
are potentially modifiable. The aim of this study was to identify risk factors for
severe GO.
Methods
EP1231
Patients with GD were enrolled into a retrospective study. We compared possible
Screening with TSH and anti-TPO antibodies of patients with vitiligo
risk factors and various clinical findings between patients with mild to moderate
Anca E Chiriac1, Anca Chiriac2 & Doina Azoicai1
GO and those with a severe form.
1University of Medicine and Pharmacy ‘Grigore T Popa’, Iasi, Romania;
Results
2Nicolina Medical Center, Iasi, Romania.
Of 90 participants with GD, 59 patients (65.8%) presented with GO. Their mean
age was 35.15G12.25 years and their M/F ratio was 31/28. GO was the
Aim
circumstance of discovery of GD in 11% of cases. Its clinical manifestations range
The aim of the study was to evaluate the relation of vitiligo with thyroid
from mild findings such as tearing (25.6%), conjunctival injection (16.7%), gritty
autoimmunity.
eyes (10%) and photophobia (8, 9%) to more significant findings including
Materials and methods
exophthalmos (65.6%), eyelids retraction (41.1%), palpebral edema (18.9%),
A cross sectional study was done on 75 patients clinically diagnosed (old and
Oculo-palpebral asynergy (17.8%), exposure keratopathy (7.8%), diplopia (6.7%),
new) with different types of vitiligo. Patients with known thyroid disease were
reduced visual acuity (5.6%) and strabismus (2.2%). GO was mild in 64.4%,
excluded from the study. Serum TSH and anti-TPO antibodies were measured in
moderate in 16.9% and severe in 18.6% of cases. On multiple logistic regression
all patients.
analysis, smoking status (PZ0.005) and male gender (P!0.001) were predictive
Results
factors associated with the severity of GO. Other factors such as age, initial free T4
The prevalence of anti-TPO antibody positivity was found in 23 of 75 patients
level, TSH-receptor antibodies and a history of diabetes were studied but were not
(30.6%).
predictive of severe GO.
Conclusion
Conclusion
Although none of vitiligo patients enrolled in the study had symptoms or signs of
Although various factors may influence the severity of GO, our study showed that
thyroid disease at the time of clinical examination anti-TPO antibodies proved to
smoking and male gender were the major and the more significant risk factors for
be positive and with high values in almost one third of the patients.
developing severe GO. Therefore it is important for patients with GD to stop
smoking.
Multidisciplinary approach for patients diagnosed with vitiligo and screening
with anti-TPO antibodies are strongly recommended.
DOI: 10.1530/endoabs.49.EP1233
DOI: 10.1530/endoabs.49.EP1231
EP1234
Determination of plasma cortisol levels in women with dysthyroidism
EP1232
Samira Akdader-Oudahmane, Zohra Hamouli-Said &
Clinical aspects of cardiothyreosis in patients with Graves’ disease
Fatma Hadj-Bekkouche
Rym Belaid, Ibtissem Oueslati, Wafa Mimita, Nadia Mchirgui,
University of Algiers, Algiers, Algeria.
Karima Khiari & Néjib Ben Abdallah
Department of Endocrinology, Charles Nicolle Hospital, Tunis, Tunisia.
Activation of the corticotropic axis seems to affect the thyroid axis at the central
level and/or by a direct effect on the thyroid gland. The aim of this study is to
Introduction
investigate a possible disruption of the adrenal cortical function that would cause
Cardiothyreosis
(CT) is the most frequent and dangerous complication of
dysthyroidism in a population of women by assaying plasma cortisol. The study
hyperthyroidism (HT). It is defined as an association of HT with severe heart
was carried out in a human population divided into three subpopulations
abnormalities such as: rhythmic troubles, heart and/or coronary insufficiency. The
according to plasma levels in TSH, FT4 and FT3: the subpopulation with
aim of our study was to describe the frequency and the clinical characteristics of
euthyroidism (control), the subpopulation with hyperthyroidism (Hyper) And the
CT in Graves’ disease (GD).
subpopulation with hypothyroidism (Hypo). Hormone levels were determined by
Methods
radioimmunoassays (FT3, FT4 and cortisol) and radioimmunometric (TSH).
Patients with GD were enrolled into a retrospective study. The prevalence and the
Variations in plasma cortisol content in subpopulations with dysthyroids have
clinical characteristics of CT were described.
been observed and are in favor of an interrelation between the two glands. These
Results
results could be explained by the fact that factors responsible for the activation of
Out of 90 participants with GD, 12.2% patients presented with cardiothyreosis.
the corticotropic axis are capable of causing structural and functional changes in
Their sex ratio (M/F) was 9/2 and their mean age was 46.72G15.11 years. CT was
the thyroid as a function of the nature of the stimulus, Its intensity and its duration.
the circumstance of discovery of GD in 2.2% of cases. Its clinical manifestations
Keywords: Glucocorticoids, thyroid, hyperthyroidism, hypothyroidism, cortisol.
were palpitation in 75.5%; dyspnea in 24.4% and anginal pain in 5.6%. Different
DOI: 10.1530/endoabs.49.EP1234
modes of presentation of CT were found: ten cases of atrial fibrillation (ACFA)
(90.9%); five cases of Heart failure
(45.45%) and three cases of coronary
insufficiency
(27.27%). Systolic blood pressure was on average
128G
11.6 mmHg and mean diastolic blood pressure was 76G19 mmHg. Mean heart
frequency was measured at 106G20 beats/min. Underlying mitral valvulopathy
was found in two cases. Six out of 11 patients presented anemia (54.5%) and
EP1235
90.9% had severe hyperthyroidism. Arrhythmia was reduced in 72.7% of the
Therapeutic plasma exchange in the treatment of hyperthyroidism
cases, after treating with betablocker.
Hamide Piskinpasa1, Meral Mert1, Ahmet Cem Dural2, Pinar Karakaya1,
Conclusion
Firuze Midi Kursat3, Yildiz Okuturlar3 & Bahar Ozdemir3
CT, although rare, remains a serious life-threatening complication of GD. The
1Department of Endocrinology and Metabolism, Bakirkoy Dr Sadi Konuk
ACFA is its most common clinical form and underlying cardiac disease is often
Education and Research Hospital, Istanbul, Turkey;2Department of General
present.
Surgery, Bakirkoy Dr Sadi Konuk Education and Research Hospital,
DOI: 10.1530/endoabs.49.EP1232
Istanbul, Turkey;3Department of Internal Medicine, Bakirkoy Dr Sadi
Konuk Education and Research Hospital, Istanbul, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Preoperative preparation of the hyperthyroid patient for thyroidectomy is
EP1237
imperative to avoid perioperative complications due to severe thyrotoxicosis.
Asymptomatic riedel thyroiditis presented in a patient with thyroid
24-years old woman was admitted at our clinic for uncontrolled Graves’ disease.
storm and polyglandular autoimmune disease
In our case, agranulocytosis introduced by propylthiouracil. Therefore, surgery
María Laura García1, Yamila Martinez Artola1, Marta Endelman1,
was the only chance of an effective therapy. In cases when the patient is
Sabrina Mayoni1, Daniel Santiago García1 & Noelia Rella1,2
unresponsive to medical therapy or when such therapy is contraindicated,
1Hospital Méndez, Buenos Aires, Argentina;2Hospital Británico, Buenos
therapeutic plasma exchange (TPE) could be useful for preparing patients for
Aires, Argentina.
surgery. After 13th TPE, our patient both FT4 and FT3 levels remained above the
normal limits but the sign and symptoms of thyrotoxicosis improved In the
literature, number of plasmapheresis sessions done were usually less than 13
Riedel Thyroiditis is a rare form of infiltrative and fibrotic disease of the thyroid
except a case of Jod Basedow with 17 sessions We observed a moderate decrease
that is characterized by compressive symptoms resulting from a rapidly enlarging
in FT3
and at least decrease in FT4
levels after thirteen session. Total
goiter. The association with Graves Thyroiditis and autoimmune diseases is very
thyroidectomy was performed successfully. In cases when the patient is
rare. The aim of this presentation is to report a patient with asymptomatic Riedel
unresponsive to medical therapy or when such therapy is contraindicated, TPE
Thyroiditis associated with Thyroid Storm and Polyglandular Autoimmune
could be useful for preparing patients with thyrotoxicosis for surgery. It is still
Disease. A 54-year-old female patient with recent diagnosis of Grave’s Disease
unclear why some patients achieve the maximum benefit from TPE, regardless of
was admitted to our hospital with congestive heart failure, abdominal pain,
their etiology. Our patient both FT4 and FT3 levels remained above the normal
vomiting and diarrhea. Her medical history was remarkable for dilated
limits but the sign and symptoms of thyrotoxicosis improved and maybe reduced
myocardiopathy, cholecystectomy and precocious ovarian failure. At physical
the risk of thyroid storm in the perioperative period. We continued to use the
examination ascites, bilateral pleural effusion and a 50 g goiter with a 19 mm
b-blocker and systemic steroid therapy in order to avoid thyroid storm during the
nodule were present. Thyroid Storm was diagnosed according to Burch-Wartofsky
operation and a few days after surgery. These findings suggested that TPE
Score. A 10 miCu I131 dose was administrated given the impossibility to prescribe
ameliorates the clinical symptoms of thyrotoxicosis rather than thyroid hormone
antithyroid drugs because of severe liver disease associated. Due to persistent
status. It is unclear which elements are responsible for determining patient
hyperthyroidism a second dose of
12 miCu I131 was administrated. After
response to TPE.
achieving euthyrodism on L-thyroxine treatment a hepatic biopsy was indicated
due to chronic intrahepatic cholestasis with negative antibodies and confirmed a
DOI: 10.1530/endoabs.49.EP1235
stage 2 Primary Biliary Cirrhosis. Later on the patient presented impaired fasting
glycaemia. A pancreatic, adrenal and ovary autoimmune panel was asked and only
GADA resulted positive. Histocompatibility study showed HLA DQ9 and DQ4.
Three fine needle aspirations (FNA) were performed during follow up due to
changes in the vascular flow of the nodule. After a negative first result the second
FNA leads to III Bethesda diagnosis. Given the insufficient material obtained
during the third a total thyroidectomy was indicated. Histopathological
examination revealed a
1.5 cm Follicular Adenoma surrounded by Riedel
Thyroiditis. To our knowledge asymptomatic Riedel Thyroiditis associated with
Thyroid Storm and Polyglandular Autoimmune Disease has not been described.
DOI: 10.1530/endoabs.49.EP1237
EP1236
Adult outcome of congenital hypothyroidism
Najoua Lassoued, Selmane Ouannes, Hbib Soua, Hachmi Ben Hammouda
& Mohamed Taher Sfar
Pediatric Department, Taher Sfar University Hospital, Mahdia, Tunisia.
EP1238
Congenital hypothyroidism in children with down syndrome
Najoua Lassoued, Salmane Ouannes, Sobhi Ghanmi, Hachmi
Introduction
Ben Hammouda, Hbib Soua & Mohamed Taher Sfar
It is because of the heavy somatic and especially intellectual impact of congenital
Pediatric Departement, Taher Sfar Unversity Hospital, Mahdia, Tunisia.
hypothyroidism that its systematic screening from birth has been proved to be
essential. Numerous publications have already reported the considerable
improvement in the prognosis of this condition but still few relate to adults.
Introduction
This preliminary work proposes to report the adult outcome in a cohort of 12
Congenital hypothyroidism is 30 times more frequent in newborns with Down
patients followed for congenital hypothyroidism.
syndrome (DS) than in the population of healthy children. Mild isolated TSH
Patients and methods
elevation with normal thyroxine (T4) levels is the most commonly seen pattern of
Descriptive study of 12 patients, seven girls and five boys, followed for congenital
thyroid dysfunction in these children.
hypothyroidism in the pediatric department of Mahdia and who reached an age of
Patients and methods
18 years.
A retrospective study was carried out on eleven patients with DS in the pediatric
Results
department of Mahdia who were followed for congenital hypothyroidism.
The mean age at diagnosis was 4.5 months. The average term was 38 SA. The
Results
mean birth size was 49.5 cm. The mean birth weight was 3700 g. Regarding
The average age of diagnosis of hypothyroidism was 3 months. Trisomy 21 was
statural development: the average final size was
153.5 cm (128-174). The
free in 10 patients and secondary to a translocation (46, XY, t rob (14;21),C21) in
difference between final size and target size was -0.7 DS. The last average BMI
a single patient. Four patients had interventricular communication, 3 patients had
was 21.35 kg/m2 (16-27). Regarding pubertal development: In girls, the onset of
atrial septal defects, 2 patients had arteriovenous communication and only one
breast development (S2) appeared at the average age of 9 and a half years, the
patient had cleft palate. Renal ultrasound was normal in all patients except one
average age of menarche was 12 years. In boys, the onset of increased testicular
patient who had a moderate left pyelocalicial dilatation. Thyroid hormone tests
volume (G2) appeared at the average age of 13 years, the onset of pubic hair (P2)
were done after the discovery of an umbilical hernia in one patient and a neonatal
at
12 years. For the school curriculum: in primary school, all children were
jaundice in 3 patients; the thyroid assessment was then requested before the
admitted to the normal age of 6 years. Only one patient redoubled in primary.
genetic confirmation of trisomy 21 by the karyotype. For the remaining 7 patients,
Four patients redoubled in secondary, only nine patients reached the baccalauréat
hypothyroidism was discovered during a biological assessment requested as part
and three left the high school.
of the systematic follow-up of these patients. The mean TSH value was
Discussion
13.72 mU/ml. Hypothyroidism was subclinical in 4 patients (with normal T4
An improvement in the results is still possible by acting on the different
value). Cervical ultrasound showed a thyroid gland in place in all patients. No
prognostic factors: age at onset of treatment, higher dose of thyroxine in the
patients developed goiter. The initial mean dose of L-thyroxine was 7.25 mg/kg/d.
neonatal period, psychological monitoring with appropriate aids if necessary and
After 3.25 years of follow-up, hypothyroidism proved to be transient in one
above all compliance in adolescence.
patient while it was permanent in the others.
Conclusion
Conclusion
It is impossible to draw definitive conclusions from this study, given the small
Newborns with DS have often subclinical hypothyroidism at birth. Systematic
number of patients studied. This is a preliminary study of work to be continued in
screening at birth and subsequent repeat screening is necessary because L-
the adult sector. For this these patients were oriented in the service of adult
thyroxine administration will improve growth, hypotonia and psychomotor
endocrinology.
functions in these patients.
DOI: 10.1530/endoabs.49.EP1236
DOI: 10.1530/endoabs.49.EP1238
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1239
Conclusion
In non-diabetic patients, IR and thyroid dysfunction have strong correlations with
Retrospective audit: To investigate the long-term outcome of fixed
NAFLD. The role of thyroid autoimmunity in this relationship needs further
dose 300 MBq of radioiodine (131-I) treatment for Autonomous
assessment.
Toxic Thyroid Nodule
Vikram Lal & Richard Quinton
DOI: 10.1530/endoabs.49.EP1240
Royal Victoria Infirmary, Newcastle, UK.
Introduction
Radioiodine (131-I) treatment for benign thyroid disease has a 70 year history.
Among the radioactive isotopes, (131-I) can be used successfully. The intention
of radioiodine treatment is primarily to induce a euthyroid or hypothyroid state,
EP1241
but in the case of large multinodular goitres, shrinkage represents a secondary aim
of therapy. The optimal method for determining iodine-131 treatment doses for
Two pseudomalabsorbtion cases successfully treated with parenteral
Toxic Thyroid nodule is unknown, and techniques have varied from a fixed dose
levothyroxine
Seher C¸ etinkaya Altunta¸, Mehtap Evran, Murat Sert & Tamer Tetiker
to more elaborate calculations based upon gland size, iodine uptake, and iodine
Cukurova University Medical Faculty, Department of Internal Medicine,
turnover. Historically, UK prescribing has varied widely according to local
Division of Endocrinology, Adana, Turkey.
custom and practice. The range of activities currently prescribed varies between
200-800 mega Becquerel (MBq), with the majority of patients receiving 400-
600 MBq. Toxic adenoma, usually mild hyperthyroidism required 500 MBq of
Hypothyroidism is a common endocrine disorder which is easily treatable by an
131-I radioiodine.
appropriate thyroid hormone replacement therapy in the majority of patients. In
Data/Method
some patients, hypothyroidism is refractory to oral levothyroxine substitution.
We collected data from nuclear medicine department and hospital electronic and
Common causes of lack of response to levothyroxine replacement comprise non-
paper patient records. In this retrospective audit we had total 10 patients (8-female
compliance and impaired absorption. We report a case of pseudomalabsorption of
and 2 male) who received a single fixed dose radioiodine (131-I) for autonomous
levothyroxine. Here, we report two female patients with hypothyroidism who had
toxic thyroid nodule in the 10-year period from 2007-2016. Patients’ age were
multinoduler goiter and thyroid papillary carcinoma with total thyroidectomy,
between 20 to 75 years. All patients had suppressed TSH at!0.05 nmol/l, with
despite the use of levothyroxine sodium at very high doses (800 mcg/day to
mildly raised thyroid hormones, and thyroid antibodies (TPO and TR) were
1100 mcg/day). Desired blood TSH and fT4 levels were reached soon after the
negative which tended to excluded thyroid immune disorders.
days of administration of levothyroxine by parenteral routes(intramusculer-
Results
intravenosus) to the patient who had malabsorption but no detectable etiology. By
We checked their Thyroid function tests at 3, 6, 12 and 24 -month periods. There
investigation during hospitalization in the endocrinology department. Symptoms
were significant improvements in thyroid function tests, with
4/10 patients
of the patients have declined. Clinical and laboratory improvement in pollinic
achieving results within the euthyroid range and
6
patients becoming
follow-ups continued in these two patients. With these findings, these two patients
hypothyroid. All nodules shrank down to become non-palpable and no patient
were diagnosed as pseudomalabsorbtion.
required a repeated dose of 131-I.
DOI: 10.1530/endoabs.49.EP1241
Recommendations
Though,
500MBq of 131-I radioiodine is recommended for toxic thyroid
adenoma in the UK, our data showed that a smaller fixed dose is 100% effective
and probably associated with lower rate of hypothyroidism (60%) at 2 years. Ref;
Radioiodine in the management of benign thyroid disease Clinical guidelines,
Royal College of Physicians, UK.
DOI: 10.1530/endoabs.49.EP1239
EP1242
Follow-up observations on nodular goiter in Japanese - Progression and
related factors
Takao Kunori, Noriko Nemoto, Nanako Fujikawa, Satoru Shiraso,
Hiroshi Yoshida, Akihiko Hashimoto, Shinya Kawaguchi & Fumiaki Shinya
EP1240
Iwaki-kyoritsu Hospital, Iwaki-shi, Fukushima-ken, Japan.
Assessment of thyroid functions, thyroid autoimmunity and insulin
resistance in non-diabetic patients with non-alcoholic fatty liver disease
Nodular goiter (ND) is increasingly found by image analysis. The long-term
Maha Assem1, May Fawzi1, Alhosaeyn Ibrahim2 & Aasem Saif1
course of ND, however, is not necessarily clear and may differ in locality. The
1Faculty of Medicine, Cairo University, Cairo, Egypt;2Ahmed Maher
present study analyzed the changes of ND in Japanese, taking iodine-rich foods,
Hospital, Cairo, Egypt.
during follow-up periods.
Patients and methods
Patients (nZ4,229) were followed up to 28 years (3.4G5.8 years). Volume of
Introduction
nodules (VOL) by ultrasonography (US) and laboratory data, including thyroid
Non-alcoholic fatty liver disease (NAFLD) is a common cause of impaired liver
hormones (TH), thyroglobulin (Tg), autoantibodies (Ab) and thyroid stimulating
functions. It is associated with hepatic and adipose tissue insulin resistance (IR) as
hormone (TSH), were examined. Increase rates of VOL (VIR, start from 100%)
well as decreased whole-body insulin sensitivity. Thyroid hormones are important
and Tg were compared in 5 periodic intervals; B-period (!2 years), C (2- yrs),
for the intrahepatic metabolism of lipids. Thyroid disorders have been associated
D (3- yrs), E (5- yrs) and F (10- yrs).
with IR due to various mechanisms such as altered insulin secretion and lipid
Results
levels.
1) VIR in 5 periods: In 6 scales (K50% to 400%-), NOD (%) of VIR!150%,
Aim
clinically ‘unchanged’, decreased in A (81%) to F (43%), while NOD (%) of
The aim of our study was to assess thyroid functions, thyroid autoimmunity and
VIRO200%, ‘visible enlargement’ increased; A (11%) to F (46%). 2) Analysis in
IR in non-diabetic patients with NAFLD.
solitary nodules (nZ1,314): a) VIR increased; B (119G82%) to F (176G140)
Material and methods
(P!0.05). b) Serum Tg showed mild increase; B (105G82%) to F (134G131). c)
The study was conducted on 90 non-diabetic subjects (60 patients with NAFLD
US detected fluids, ‘cystic’, more in F (78%) than in B (32%). 3) Pathology: VIR
and
30
subjects with normal liver). Both groups were sex matched.
of adenomatous goiter (AG) was 15% higher than that of non-AG (P!0.05).
Ultrasonography was used to categorize the study subjects into NAFLD and
4) Factors related to VIR: Initial VOL, Abs and length of follow-up periods were
normal liver groups. Thyroid functions and thyroid peroxidase antibody (TPO-
significantly related to VIR. Use of ethanol or TH-drugs also influenced VIR.
Ab) were assessed in all subjects. Homeostatic model assessment (HOMA-IR)
5) Late surgery (after 2 years): VIR of surgical cases (nZ24, 159G133%) was
was used to assess IR in the study population.
higher than that of non-surgical cases (nZ572, 129G96%, PZ0.14).
Results
Conclusions
Our study showed a highly-significant positive correlation between NAFLD and
NOD remained unchanged (VIR!150%) in 40% of patients over 10 years.
IR (P!0.001). It also showed a significant positive correlation between NAFLD
Progression of NOD seemed to be associated with pathology, TSH and Abs. Late
and thyroid functions with higher prevalence of subclinical thyroid dysfunction in
surgery tended to be performed in patients with higher VIR.
NAFLD patients (PZ0.02). Thyroid functions didn’t show any statistically
significant correlations with IR, but TPO-Ab showed significant positive
DOI: 10.1530/endoabs.49.EP1242
correlation with IR (PZ0.02) within the total study population.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
9,0
EP1243
8,5
Aggravation of thyroid dysfunction in a case of thyroid hormone
8,0
resistance after near total thyroidectomy for multinodular goiter
7,5
7,0
Ilkay Kartal & Gonca Tamer
6,5
Medeniyet University Goztepe Training and Research Hospital, Istanbul,
6,0
Turkey.
5,5
5,0
4,5
4,0
Introduction
3,5
Resistance to thyroid hormone
(RTH), a syndrome reduced end-organ
3,0
responsiveness to thyroid hormone.
2,5
Case report
2,0
1,5
A 42 year old woman underwent near total thyroidectomy due to her enlarged
1,0
thyroid with multiple nodules. At that time she had sligthly elevated values of
0,5
MedianA
plasma FT4, FT3 and normal TSH values and had no sign and symptoms of
0,0
25%-75%
-0,5
Min-Max
thyrotoxicosis or hypothyroidism. After thyroidectomy she recieved L-T4
TSH PRE TSH 3M TSH 6M TSH 12M TSH 24M
treatment but her TSH levels remains elevated although FT4 was high. She
Figure 1
was reffered endocrinology polyclinic when she began to have symptoms of
hypothyroidism like fatique, fibromyalgia. The results were FT4: 1.93 ng/dl (n:
0.61-1.12), FT3: 2.2 pg/ml (n: 2.5-3.9) TSHO100 uIU/ml (n: 0.27-4.2) under
Limitations
150 mcg L-T4 treatment. There were no detectable anti-thyroid autoantibodies.
This study is a retrospective review and did not employ controls, blinding, or
Alpha subunit of TSH level was 0.8 IU/l (n: 0-0.8) normal. No pituitary adenoma
randomization. Additionally, the thyroid antibodies did not evaluate.
was determined in pituitary MRI. She has no family history of thyroid disease.
Conclusion
Genetic test is not available in our hospital. We performed TRH stimulation test
Weight loss after the gastric bypass improved and normalized thyroid hormone
after taken off levothyroxine for 14 days and TSH diluted up to 20 times during
levels. More studies are required to clarify the reason of decrease in serum TSH.
test. After intravenous bolus injection of TRH
(200 mcg) serum TSH
concentration increased from
269 uIU/ml
(basal value) to a peak of
DOI: 10.1530/endoabs.49.EP1244
1330 uIU/ml at 30 min. As a result RTH was considered and LT4 initiated
again. After L-T4 titrated up to 175 mcg a day L-T3 added 12.5 mcg two times a
day. Six weeks after this treatment FT4:
2.58 ng/dl
(n:
0.61-1.12), FT3:
3.99 pg/dL (n: 2.5-3.9), TSH: 14 uIU/ml sn: 0.27-4.2). Her complaints were
reduced. Blood pressure was 120/80 mmHg, pulse 74/min. She was clinicaly
better.
EP1245
Conclusion
Correlation between serum nitrite (NO2) levels, TQ7 and GHQ12
Treatment with L-T3 would be more appropriate for reducing goitre size than
questionnaire scores in treatment-naïve hypothyroid patients
attempting thyroidectomy in that patient. In patients with RTH thyroid gland
Zoran Gluvić1, Vladimir Samardzi
´1, Jelena Tica Jevti
´1, Marina Vujovi
´1,
ablation tends to aggravate thyroid dysfunction and multinodularity. Large glands
Milena Lačković1, Vesna Popović-Radinović1, Saša Radenkovi
´2,
have been successfully treated by administration of a single high dose of L-T3
Violeta Mladenovi
´3, Emina Sudar-Milovanovi
´4, Milan Obradovi
´4 &
given every other day. Symptoms of thyrotoxicosis usually respond to the
Esma R Isenović4
administration of the beta bloker, atenolol.
1Division of Internal medicine, Department of Endocrinology, Zemun
DOI: 10.1530/endoabs.49.EP1243
Clinical Hospital, School of Medicine, University of Belgrade, Belgrade,
Serbia;2Clinic for Endocrinology and Diabetes, Nis Clinical Centre, School
of Medicine, University of Nis, Nis, Serbia;3Center for Endocrinology and
Diabetes, Clinical Centre Kragujevac, Faculty of Medical Sciences,
University of Kragujevac, Kragujevac, Serbia;4Lab for Molecular
Endocrinology and Radiobiology, Institute for Nuclear Sciences ‘Vin
ˇa’,
University of Belgrade, Belgrade, Serbia.
EP1244
Thyroid function and weight loss after Roux-en-Y gastric bypass:
Introduction
observational study
Primary hypothyroidism, as a clinical syndrome caused by insufficiency or
Gisah Amaral de Carvalho, Cleo Mesa Junior, Rodrigo Strobel &
inefficacy of thyroid hormones, significantly influences on patients’ quality of life
Paula Carolina Dambros Granzotto
(QoL). Accelerated atherosclerosis induces increased cardiovascular morbidity
Clinical Hospital of The Federal University of Parana, Curitiba, Brazil.
and mortality rates in hypothyroid patients. Serum NO2 levels, the stable NO
metabolites, are among well-known markers for endothelial dysfunction and
atherosclerosis in hypothyroidism. We examined the correlation between serum
Background
NO2 levels and QoL questionnaires scores (TQ7 and GHQ12) in treatment-naïve
TSH seems to be positively related to the degree of obesity and weight loss seems
hypothyroid females.
to induce a reduction in the TSH levels and T3Total. TSH is the first regulatory
Material and methods
mechanism of total energy expenditure and T3 regulates energy metabolism and
Cross-sectional study involved 82 females, divided into three groups according to
thermogenesis (1)
TSH and fT4 levels: latent (22) and overt (22) hypothyroid, and euthyroid (38)
Objective
group, respectively. Initially, after informed consent was signed, serum NO2
The aim of this study was to investigate the association between thyroid function
levels were measured and TQ7
and GHQ12 questionnaires were fulfilled.
and body mass index (BMI) in obese population. And evaluate the influence of
Obtained data were analysed with appropriate statistical methods. Statistical
weight reduction after gastric by-pass on thyroid hormone levels.
significance was 0.05.
Design
Results
Retrospective observational study
Overall mean of NO2 level was 11.2 mmol/l (0.9-79.0 mmol/l) and didn’t differ
Setting
between groups. Mean overall TQ7 and GHQ12 scores were 14 (5-40) and 12 (1-
A single center study in Curitiba, Brazil.
32) respectively, and statistically differ between groups (P!0.01). Correlation
Methods
between serum NO2 levels and TQ7 and GHQ12 scores didn’t significantly differ
We studied 215 obese patients (BMI 35-58.5 kg/m2), age between 18-65 years,
(rNO2/TQ7ZK0.241, rNO2/GHQ12ZK0.141; PO0.05).
baseline,
3,
6,
12,
24 months after laparoscopic Roux-en-Y gastric bypass
Conclusions
(RYGBP). Participants with thyroid disorders were excluded.
Decreased serum NO2 levels in hypothyroid groups pointed out to lowered NO
Results
bioavailability and therefore endothelial dysfunction. Otherwise, thyroid disease
Baseline TSH concentration was not associated with baseline BMI
(Pear-
specific questionnaire score determined hypothyroid patients in moderately
sonZ0.003; PZ0.971). There were a significantly decrease in serum TSH after
stressed cluster. A simultaneous use of NO2 levels and QoL scores can alleviate
RYGBP until 24 months (PZ!0.001) (Figure 1), but did not correlate with
decision to introduce the l-thyroxin management in hypothyroid patients,
weight loss (PearsonZ0.08; PZ0.303). Subclinical hypothyroidism prevalence
presumably in latent ones.
was 9.3% (nZ20) before RYGBP. At 12 months, 8.7% (nZ17) of this patients
had TSH!4.5 (PZ0.003).
DOI: 10.1530/endoabs.49.EP1245
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1246
especially NAC, in orbital fibroblasts. Some of the actions are exclusive to
Vitamin D levels in Graves’ disease (GD) are lower than in general
GO fibroblasts. These observation have important clinical implication, in
population but do not correlate with laboratory and clinical parameters
that some of these antioxidants could be tested in patients with GO.
in GD or SNPs associated with GD
DOI: 10.1530/endoabs.49.EP1247
Tereza Planck1,2, Bushra Shahida1, Johan Malm1,3 & Jonas Manjer1,4
1Lund University, Department of Clinical Sciences, Malmo, Sweden;
2Department of Endocrinology, Skåne University Hospital, Malmo,
Sweden;3Department of Clinical Chemistry, Skåne University Hospital,
Malmo, Sweden;4Department of Surgery, Skåne University Hospital,
Malmo, Sweden.
EP1248
Introduction
Intrathyroidal and peripheral venous blood lymphocyte subset patterns
The role of vitamin D in GD is poorly understood. The aim was to compare
in patients with Graves disease
vitamin D levels in newly diagnosed patients with GD with the general population
Margarita Dudina1,2, Dogadin Sergey1,2, Savchenko Andrey3,
and to correlate vitamin D levels at diagnosis with laboratory and clinical
Mankovsky Vladimir2 & Borisov Alexander3
parameters in GD. Moreover, we examined genetic variation in genes involved in
1Krasnoyarsk state Medical University named after prof. V.F. Voyno-
the vitamin D metabolism and their association with GD.
Yasenetsky, Krasnoyarsk, Russia;2Krasnoyarsk region clinical hospital,
Material and methods
Krasnoyarsk, Russia;3Institute for Medical problems of the North, Russian
Levels of vitamin D were compared in 292 patients with newly diagnosed GD and
Academy of Medical Science, Siberian division, Krasnoyarsk, Russia.
2305 controls. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor
(VDR), vitamin D binding protein (DBP) and 1-alpha-hydroxylase (CYP27B1)
Graves’ disease (GD) is an autoimmune disease with genetic predisposition. The
were examined for association with GD and/or Graves’ ophthalmopathy (GO) in
link with the major histocompatibility complex determines the complexity of
708 patients and 1178 controls.
the excess thyroid hormones molecular action on immune system that may cause
Results
the divergence of autoimmune process in GD, functioning not only in peripheral
Patients with GD had significantly lower levels of vitamin D compared to general
immune cells, but also in the thyroid. Objective: to study the phenotypic
population (55.0G23.2 vs 87.2G27.6 nmol/l, P!0.001). In patients with GD
composition of T- and B-lymphocyte subset patterns in peripheral blood and
(nZ219), there was no association between the levels of vitamin D and the levels
thyroid tissue in patients with GD. Materials and methods. The study included 43
of free thyroxine
(fT4), free triiodothyronine
(fT4), thyrotropin receptor
women with GD, mean age 39.95G14.38, who were performed the epifascial
antibodies (TRAb), GO at diagnosis, or relapse after terminating treatment with
thyroidectomy. Phenotypic composition of T
- and B-lymphocytes was
anti-thyroid drugs. Two SNPs in VDR were associated with GD, rs10735810 (OR
investigated by flow cytometry. Analysis of stained cells was performed on a
1.36, 95% CI 1.02-1.36, PZ0.02) and rs1544410 (OR 1.47, 95% CI 1.03-1.47,
flow cytometer FC-500 (Beckman Coulter, USA). Each sample was analyzed at
PZ0.02). However, there was no difference in mean vitamin D levels between
least
50,000 lymphocytes. Results. The median level of thyroid stimulating
genotypes in either rs10735810
(AA 55.9 nmol/l, AG
56.1 nmol/l, GG
hormone
(TSH), free thyroxine and autoantibodies to TSH receptor was
54.1 nmol/l, PZn.s.) or rs1544410
(AA 56.6 nmol/l, AG 57.5 nmol/l, GG
respectively
1,9
(0,9;
2,9) umol/ml,
16,8
(13,2;
19,0) and
15,8 (9,4;
24,2)
54.8 nmol/l, PZn.s.).
IU/ml. In peripheral blood of GD patients compared with healthy controls
Conclusion
identified the increased in 9.2% the relative number of total T lymphocytes
Patients with GD have lower vitamin D levels compared with general population;
(CD3C, P!0.001) and in 5.8% relative level of T-helper cells (CD3CCD4C,
however, the levels of vitamin D do not affect the laboratory or clinical
PZ0.019), but decreased content of T-regulatory cells
(CD3CCD4C
parameters of the disease. SNPs in the VDR influence the risk of GD through
CD127LowCD25High, PZ0.048) and total activated T cells
(P!0.001),
mechanisms other than reducing the vitamin D levels.
T-helper cells (CD3CCD4CCD25C, PZ0.045) and cytotoxic T-lymphocytes
DOI: 10.1530/endoabs.49.EP1246
(CD3CCD8CCD25C, PZ0.041). It is revealed that in the blood of GD patients
increased in 35.9% the relative number of B2-lymphocytes (CD19CCD5C,
PZ0.003), while reducing the amount of activated total B cells (CD19CCD23C,
P!0.001), B2 cells (CD19CCD5K, P!0.001), B2K simplet (CD19CCD5-
CD27K, P!0.001) and B2-memory (CD19CCD5KCD27C, P!0.001) cells.
In a comparative analysis of the phenotypic composition of T
- and
B-lymphocytes in peripheral blood and thyroid tissue revealed that in the tissues
EP1247
is 2.3 times higher relative content of total activated T cells (CD3CCD25C,
PZ0.037), in 5.1 times more of activated cytotoxic T-lymphocytes (PZ0.023),
Action of several bioavailable antioxidants in orbital fibroblasts from
1.7
times increased the percentage of B2-memory (CD19CCD5KCD27C,
patients with Graves’ Orbitopathy (GO): a new frontier in GO
treatment?
PZ0.028) cells. Conclusions. The reduction of activated T - and B-lymphocytes
Giovanna Rotondo Dottore1, Giamberto Casini2, Stefano
content in peripheral venous blood of patients with GD is determined by the
Sellari Franceschini3, Marco Nardi2, Paolo Vitti1, Claudio Marcocci1 &
migration of immune cells in thyroid tissue.
Michele Marinò1
DOI: 10.1530/endoabs.49.EP1248
1Department of Clinical and Experimental Medicine, Endocrinology Units,
University of Pisa and University Hospital of Pisa, Pisa, Italy;2Department
of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I,
University of Pisa and University Hospital of Pisa, Pisa, Italy;3Department
of Surgical, Medical and Molecular Pathology, ENT Unit I, University of
Pisa and University Hospital of Pisa, Pisa, Italy.
EP1249
Oxidative stress plays a crucial role in the pathogenesis of Graves’
No impact of subclinical hypothyroidism on cognitive functions among
Orbitopathy
(GO), supporting the use of antioxidants in GO patients.
the elderly
Selenium has a beneficial effect, but other antioxidants have not been
Harleen Kaur1,2, Nitin Malhotra2 & Jubbin Jacob1,2
investigated. Here we evaluated several antioxidants in primary cultures of
1Endocrine & Diabetes Unit, Christian Medical College and Hospital,
orbital fibroblasts from GO patients and control subjects. The following
Ludhiana, Punjab, India;2Department of Medicine, Christian Medical
substances were tested: Vitamin C (Vit-C), N-Acetyl-l-Cysteine (NAC),
College and Hospital, Ludhiana, Punjab, India.
melatonin (Mel), retinol (Ret), beta-carotene (bCar), Vitamin E (Vit-E).
Cells were treated with H2O2, which induced oxidative stress (increased
Background
glutathione disulfide). Pre-incubation with non cytotoxic concentrations of
Most recent cross sectional and longitudinal studies have failed to find an
all substances in GO, and with Vit-C, NAC and Mel in control fibroblasts,
association between cognitive dysfunction and subclinical hypothyroidism. A
prevented oxidative stress. H2O2 caused increased proliferation, which was
recent paper from our country however suggested a significant association.
reduced by Vit-C, NAC and bCar in GO, but not in control fibroblasts. H2O2
Objectives
did not affect HA release, which was however reduced by NAC and
This study was undertaken to determine the prevelance of cognitive impairement
melatonin in GO, and by all substances except for Vit-E in control
among educated, elderly Indian patients (O60 years) with and without subclinical
fibroblasts. Our findings show an antioxidant actions of several compounds,
hypothyroidism.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Materials and methods
1Sanatorio Méndez, Buenos Aires, Argentina;2Hospital Británico, Buenos
This study was conducted on educated, elderly patients admitted to the in-patient
Aires, Argentina;3CEBBAD, Universidad Maimonides, Buenos Aires,
department of Christian Medical College, Ludhiana. One hundred patients with
Argentina.
subclinical hypothyroidism an equal number of controls with normal thyroid
functions were interviewed after taking informed consent. Subclinical hypothyr-
oidism was defined as serum TSH level more than 4.0 mIU/L with serum fT3 and
fT4
in the normal reference range. Cognitive function was assessed by
Thyroid storm (TS) is a rare and life threatening condition that requires a
Hindi/English Mini mental status examination (MMSE) and clock drawing test
prompt recognition and treatment. The clinical features may overlap with
(CDT).
other acute medical conditions. Currently both Akamizu Criteria (JTA) and
Results
Burch and Wartofsky Scale (BW) are helpful diagnostics tools.
Objective
The cases (nZ100) had a mean age of 68.2 years, were 59% males and had a
To evaluate TS patients according to currently available criteria and to identify
mean body mass index of 25.5 kg/m2 compared to controls (nZ100) who had a
the clinical features and outcomes.
mean age of 69.9 years (P-0.09), were 64% male (P-0.5) and had a mean BMI of
Methods
25.3 kg/m2.All other baseline variables including co-morbidities, family history
A single center retrospective study covering a 6 year period was performed.
of dementia, head injury, smoking, alcohol use, fruit and vegetable intake, daily
Results
newspaper reading, education and exercise regularity were comparable in both
Fifteen cases were identified, resulting in four cases of TS per 10 000 admitted.
groups. The cases had mean MMSE of 26.1 and controls of 25.9 (P-0.68)
Mean age 49.8G17.3 years (range:
31-86). Male/Female:
3/12. Etiology:
respectively The cases had mean CDT of 2.19 and controls 2.18 (P-0.95).
autoimmune (nZ8), factitious (nZ3), amiodarone-induced (nZ3), undetermined
Conclusions
(nZ1). Manifestations at admission: cardiovascular
(nZ8), fever
(nZ3),
There is no difference in cognitive function in elderly with subclinical
delirium (nZ2), diabetic ketoacidosis (nZ1) and hypokalemic paralysis (nZ1).
hypothyroidism in comparison with elderly population having normal thyroid
Eleven had previous history of thyroid disease. Precipitating factors were found in
function.
12
cases. Thyroid hormone levels did not correlate with the severity of
Keywords: Subclinical, Hypothyroidism, Biochemical, Cognitive functions,
thyrotoxicosis. Mortality rate was 6.6%: 1 patient died from sepsis. Late hospital
Elderly
discharge was found in
4 patients
(PZ0.01): 3 required antithyroid drugs
DOI: 10.1530/endoabs.49.EP1249
withdrawal and the other received a heart transplant. The table resumes patients
according to BW and JTA. JTA fails to detect 4 patients with impending TS (st0),
one of which later on developed st1 (p8).
Conclusions
Ours results shows discrepancies between the two diagnostic systems. BW
appears to select a higher percentage of patients for aggressive therapy than JTA.
This presentation provides useful information for the management of TS, a rare
EP1250
and acute disease that requires high clinical suspicion in order to improve patient
Prolonged iodine excess due to hysterosalpingography in a pregnant
survival.
woman
Abbas Ali Tam, Sevgul Faki, Didem Ozdemir, Cevdet Aydin, Reyhan Ersoy
& Bekir C¸ akir
p1
p2
p3
p4
p5
p6
p7
p8
p9
p10
p11
p12
p13
p14
p15
Yildirim Beyazit University School of Medicine, Endocrinology and
Metabolism Diseases, Ankara, Turkey.
BW
35
40
40
75
60
55
35
35
55
35
35
80
65
65
35
JTA st0
st0
st2
st1
st1
st2
st1
st0
st1
st2
st2
st1
st1
st1
st0
Introduction
Hysterosalphingography (HSG) is the radiographic examination of uterine cavity
and fallopian tubes. It is generally used during evaluation of infertility and
DOI: 10.1530/endoabs.49.EP1251
radioopaque contrast is injected through cervical duct during the procedure.
Lipiodol which is the most commonly used contrast media in HSG is a fatsoluble
iodinated contrast media. This iodine is progressively cleared from the body in a
period ranging from a few weeks to a few months. Here, we present a 6 week
pregnant woman who underwent HSG 9 months ago and has very high urinary
iodine excretion.
Case
EP1252
A 31 years old woman at the 6th week of pregnancy was consultated for high
blood glucose. She was evaluated for infertility for 2 years, and HSG was
The role of FNDC5 gene expression in irisin level changes
performed
9 months before conception. There was no history of drug or
accompanying thyroid pathologies
nutritional supplement use that has high iodine content and that might affect
Ariadna Zybek-Kocik1, Nadia Sawicka-Gutaj1, Miroslaw Andrusiewicz2,
iodine status. Iodine excretion was 10087 mcg/L (100-700 mcg/L) in random
Joanna Waligórska-Stachura1, Piotr Bialas2, Jerzy Skrobisz3 &
urine sample and O450 ug/L in 24 hour urine. Her serum TSH was 2.19 uIU/ml,
Marek Ruchala1
fT4
was 1.32 ng/dl and fT3
was 1.32 pg/ml. Thyroid autoantibodies were
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan
negative and thyroid ultrasonography was normal.
University of Medical Sciences, Poznan, Poland;2Department of Cell
Conclusion
Biology, Poznan University of Medical Sciences, Poznan, Poland;
The optimal time for normalization of body iodine stores after exposure of
3Department of General Surgery and Multiple Trauma, with Division of
iodinated contrast media is not known exactly. Thyroid dysfunctions in the form
Gastroenterological and Endocrine Surgery, Provincial Hospital, Poznan,
of both hypothyroidism or thyrotoxicosis can develop in euthyroid subjects after
Poland.
use of iodinated contrast media during HSG. In our case, thyroid functions were
normal but urinary iodine was very high even several months after HSG. This
suggests that females at reproductive age who underwent HSG might have excess
Irisin is a recently reported, widely discussed new adipo-myokin secreted
iodine concentration for a prolonged time and should be carefully evaluated for
mainly by muscle tissue. It is a cleaved and secreted part of fibronectin type
development of thyroid dysfunctions.
III domain containing
5, encoded by the FNDC5 gene. Some of the
DOI: 10.1530/endoabs.49.EP1250
previously published studies claim that alterations of irisin levels in patients
affected by thyroid diseases may be connected mainly with accompanying
myopathy. However, to date it has not been evaluated, whether the changes
in expression of FNDC5 may play a role in irisin level alterations. The aim
of the presented study is to assess the expression of FNDC5 gene in thyroid
EP1251
tissue of subjects with Graves’ disease, multinodular benign goiter, toxic
goiter and papillary thyroid cancer. The group of 80 patients with above
The challenge of diagnosing thyroid storm: a comparison of the
mentioned thyroid pathologies were involved. All included subjects
Japanese Thyroid Association Criteria to de Burch Wartofsky
underwent total thyroidectomy for reasons unrelated to the study.
Point Scale
Quantitative RT-PCR was used to analyze the FNDC5 gene expression.
María Laura García1, Gabriela Szuman1, María Florencia Scoscia1,
As a result, the expression of FNDC5 was noted in all analyzed samples. No
Susana Bacigaluppi1, María Victoria Panebianco3 & Noelia Rella1,2
statistical difference between FNDC5 expression in benign and malignant
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
changes, as well as conditions associated with hyperthyroidism and
needed 1200 mg/day of Propylthiouracil. She delayed surgery for 2 weeks,
euthyroid state were found. Statistically significant overexpression of
then the dosage required for euthyroidism was 1800 mg/day for three weeks.
FNDC5 in patients with toxic goiter in comparison with tissues affected by
The goitre had 1.2 kg, from mandible angle to the supraclavicular region;
Graves’ disease, papillary thyroid cancer (tumor staged pT1 or pT2) and
she did not develop hypoparathyroidism or palsy of recurent laringeal nerve.
controls was observed. In conclusion, toxic goiter may be associated with
Second patient, 47 years old,with Graves’s disease, Addison disease, came
FNDC5 overexpression in thyroid tissue, in comparison with Graves’
with class III heart failure and severe asthma, She required 1800 mg of PTU
disease, papillary thyroid cancer staged pT1 or pT2 and controls. The
before surgery and had persistent hypoparathroidism. Third patient, 60 years
FNDC5 overexpression, on the other hand, is not directly associated with
old had severe cardiomyopathy at the beginning, left ventricle ejection
hyperthyroid state, as well as thyroid malignancy development. Hence, the
fraction 15%, atrial fibrillation that nedeed Cordarone both intravenously
changes in FNDC5 expression probably do not play the role in irisin
and orally. The dosage was progressivly increased from 60 to 180 mg/day
concentration changes associated with thyroid pathologies.
Thyrozol until safely opperated. Patient did not tolerate Propylthiouracil due
DOI: 10.1530/endoabs.49.EP1252
rash. Ejection fraction became 30% postopperatively and no complications
occurred.
DOI: 10.1530/endoabs.49.EP1254
EP1253
Long term effects of the less than total thyroidectomy: The experience of
a tertiary care center
EP1255
Georgios Boutzios1, Zoe Garoufalia2, Krystallenia Alexandraki1,
Postpartum thyrotoxicosis - a diagnosis, sometimes, postponed
Gregory Kaltsas1, Grigorios Kouraklis2 & Gerasimos Tsourouflis2
Alexandra Novais Araújo, José Marçalo, Cristiana Costa, Ana Wessling &
1Endocrine Unit, Department of Pathophysiology, Laiko University
Maria Joa˜o Bugalho
Hospital, Medical School, University of Athens, Athens, Greece;
Centro Hospitalar Lisboa Norte, Lisboa, Portugal.
2Second Department of Propedeutic Surgery, Laiko University Hospital,
Medical School, University of Athens, Athens, Greece.
Postpartum thyroid dysfunction occurs in 5-10% of women in the general
Background and aims
population within one year of delivery. The prevalence of postpartum
Less than total thyroidectomy (lobectomy, partial or subtotal thyroidectomy) is
Graves’ disease is estimated at 0.54%. Postpartum thyroiditis is much more
used mainly to treat thyroid nodules, and/or hyperthyroidism. The aim of the
common. Differential diagnosis is essential for an adequate treatment.
study was to investigate the long term effects of less extensive surgical
Radioactive iodine uptake can be useful to establish the etiologic diagnosis,
procedures. such as re-appearance of nodules and the need of thyroxin
but is contraindicated during lactation. Elevated titers of antithyrotropin
supplementation, or re-operation.
receptor antibodies (TRAbs) are suggestive of Graves’s disease but may be
Material and methods
measurable in approximately 10% of patients with painless thyroiditis and
Retrospective study in a tertiary Academic medical center. The study population
their titers can be low in the early phase of Graves’ disease. Therefore,
comprised initially 76 patients. Of whom 67 patients (ageGS.D.: 64.1G13.3, 58
the evolution of thyroid function and TRAbs’ titers may be needed to
(86.5%) females) who underwent lobectomy, partial thyroidectomy or subtotal
distinguish both pathologies. We present the case of a
25-year-old
thyroidectomy with benign histology and a follow-up equal or longer to 5 years
Caucasian woman who presented to the Emergency Department, 4 months
were included (9 excluded). None the patients appeared post-surgery permanent
after giving birth and still breastfeeding, complaining of palpitations,
iatrogenic hypoparathyroidism or recurrent laryngeal nerve injury.
anxiety, fatigue and insomnia with 1 week of duration and referring a 15 kg
Results
weight loss postpartum. She mentioned that her mother had Graves’ disease.
Mean follow up was 22.1G10.8 years. Patients who underwent lobectomy, partial
There was no ophthalmopathy; her heart rate was
140 bpm and the
thyroidectomy and subtotal thyroidectomy were 24 (35.8%), 9 (13.5%) and 34
electrocardiogram confirmed sinus tachycardia. Thyroid examination
(50.7%), respectively. Patients received thyroxin replacement were 62 (92.5%).
showed a painless tender and slightly enlarged gland. Blood tests - TSH
Relapse as defined by re-appearance of nodules or recurrence of hyperthyroidism
0.011 uU/nl (0.3-4.2), FT3O20 pg/ml (2.3-4.2) and FT4 5.33 ng/dl (0.93-
in total population was in 39 (58.2%) patients: 70.8% (17/24) in lobectomy group;
1.7). She was referred to the Endocrinology Department under treatment
77.8%
(7/9) in partial thyroidectomy, and
44.1%
(15/34) in subtotal
with methimazole and propranolol. Further testing revealed positive anti-
thyroidectomy group, respectively. Re-operation underwent 7 patients (10.4%)
thyroid peroxidase and thyroglobulin antibodies and TRAbs within ‘grey
of total or 17.9% of the recurrence cases. Univariate analysis showed that the type
zone’. Thyroid function was monitored with slowly tapering of methimazole
of operation and the length of follow up were predictors for relapse (OR: 1.81,
dosage. Eight months postpartum, despite low methimazole dosage (2.5 mg
95%CI: 1.03-3.19, PZ0.038 and OR: 0.92, 95%CI: 0.87-0.97, PZ0.002,
id) she presented with asymptomatic hypothyroidism (TSHO100 uU/ml).
respectively). Multivariate analysis showed that the length of follow up was
Anti-thyroid antibodies remained positive but TRAbs were negative.
superior independent factor predicting relapse (OR: 0.92, 95%CI: 0.87-0.98,
Methimazole was suspended and levothyroxine 25 mcg id initiated. At
PZ0.006).
last follow-up, the patient remains asymptomatic and in euthyroidism.
Conclusions
Diagnosis of postpartum thyroiditis was assumed. Monitoring thyroid
The majority of patients received thyroxin replacement. The length of follow-up
function and TRAbs levels for several months might be necessary to allow
and the type of operation have an impact on relapse, but mostly the length of
the differential diagnosis.
follow up. Treatment with total thyroidectomy could eventually avoid a relapse
DOI: 10.1530/endoabs.49.EP1255
and a possible need for re-operation.
DOI: 10.1530/endoabs.49.EP1253
EP1256
EP1254
Clinical characteristics of painless thyroiditis
Severe hyperthyroidism imposes large amounts of antithyroid
Yonghyun Kim, Jeonga Choi & Donghyun Shin
compounds
Daejin Medical Center, Seongnam, Republic of Korea.
Adina Mazilu1, Cristina Spiroiu1 & A E Ranetti1,2
1Central Military Emergency Hospital, Romania, Romania;
Background
2National Institute of Endocrinology, Romania, Romania.
There are a lot of painless thyroiditis cases without symptoms diagnosed on health
check up or thyroid hormone screening, but there is a few data about it compared
to much data about painful subacute thyroiditis. So, we collected data about
We present three cases of females with low body weight that needed large
diagnostic routes, laboratory and clinical characteristics of painless thyroiditis.
amounts of anti-thyroid drugs - 4-5 mg/kg Thiamazole and 50 mg/kg of
Method
Propylthiouracil. First patient, aged 32, weight 45 kg, had Graves’s disease
Painless thyroiditis patients diagnosed between 2010 and 2016 were reviewed.
evolving for more than five years. She has been proposed surgery and
We defined painless thyroiditis as disease with typical clinical courses of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
thyrotoxicosis and sequential hypothyroid phase and decreased uptake on thyroid
Introduction
scan.
Brittle hypertyroidism is a term used for the clinical situation characterized by
Result
hypo-hyperthyroidism with antithyroid drugs, despite good compliance and
Total 191 patients (139 female, 52 male) were involved. The diagnostic routes
follow-up. Here, we presented five patients suggested to have Brittle Graves.
were classified under four entry. First, health check up: 47 patients, 24.6%.
Case-1
Second, patients evaluated with thyroid function test because of nonspecific other
Thyrotoxicosis was observed in a 57-year-old female patient and Graves was
symptoms or routine check up of inpatient: 68 patients, 35.6%. Third, patients
diagnosed after laboratory and imaging examinations 25 months after initiation of
evaluated with thyroid function test because of thyrotoxic symptoms or signs
propylthiouracil 50 mg/day, she developed hypothyroidism and the drug was
(fatigue, palpitation, tremor, goiter etc): 59 patients, 30.9%. Fourth, patients
discontinued. Thyrotoxicosis recurred in 3 months and the patient underwent
associated with postpartum: 17 patients, 8.9%. Permanent hypothyroidism was
thyroidectomy. The histopathological diagnosis was lymphocytic thyroiditis.
not uncommon (7/191; 3.7%). Higher peak TSH level (P value below 0.001) was
Case-2
related with permanent hypothyroidism. 11.5% (22/191) experienced recurrence.
Graves was diagnosed in a 22-year-old female patient with Down syndrome.
Lower peak TSH (P value 0.018) and short duration of thyrotoxicosis phase
After 15 days of propylthiouracil treatment, serum TSH was 100 IU/ml and
(P value 0.001) was associated with recurrence.
hyper-hypothyroid periods recurred despite appropriate treatment and thyroid-
Discussion
ectomy was offered.
More than 50% of painless thyroiditis was diagnosed on health check up or
Case-3
accidental thyroid function test without typical thyrotoxic symptoms. Many
Thyrotoxicosis was observed in a 48-year-old female patient with a history of
patients with heterogenous parenchymal echogenecity on sonography finding
levothyroxine use for 10 years. She had positive TSH receptor antibody and
without history of thyroid disease could be go for that cases. Higher peak TSH
ophthalmopathy. Methimazole was started because thyrotoxic state persisted
was related with permanent hypothyroidism. In contrast, lower peak TSH was
despite discontinuation of levothyroxine, but hypothyroidism developed in a short
associated with recurrence and short duration of thyrotoxicosis phase was also
time and thyroidectomy was offered.
related with recurrence.
Case-4
DOI: 10.1530/endoabs.49.EP1256
A 67-year-old male patient with a diagnosis of Graves disease has used
methimazol for 14 months and the drug was discontinued due to hypothyroidism.
Recurrent periods of hyper-hypothyroidism developed in follow-up and BTT
(bilateral total thyroidectomy) was performed.
Conclusion
Hyper-hypothyroid fluctuations can be observed in patients with Graves disease.
This clinical manifestation overlap with hashitoxicosis. “Brittle Graves” seems to
be a better definition for such cases.
EP1257
DOI: 10.1530/endoabs.49.EP1258
The effectiveness of parathyroidectomy in children with primary
hyperparathyroidism
Nazira Rikhsieva
Tashkent Paediatric Medical Institute, Tashkent, Uzbekistan.
Objective
To Evaluate the effectiveness of parathyroidectomy in children with primary
hyperparathyroidism.
Materials and methods
Under our observation in the period 2014-2015, were 46 patients with primary
EP1259
hyperparathyroidism at the age of 11-16 years. To assess the effectiveness of
parathyroidectomy a questionnaire was used and table PAS (Parathyreoidectomy
The role of an ultra-sensitive fourth-generation TSH assay in the
Assessment of symptoms- table of symptoms in primary hyperparathyroidism to
management of subclinical hyperthyroidism
assess the effectiveness of parathyroidectomy).
Emily Austin1, Steve Peacey2 & Andrew Bates1
The results of the study
1Heart of England NHS Foundation Trust, Birmingham, UK;
Evaluation of the effectiveness of parathyroidectomy with regard to the
2Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
elimination of most symptoms in primary hyperparathyroidism table PAS
revealed a statistically significant reduction of symptoms and complaints. The
amount of symptoms in the preoperative period was 445, a month after surgery
The management of endogenous subclinical hyperthyroidism is largely guided by
decreased to 350, 3 months later 200, with certainty P!0.01. Indicators of the
perceived risk, including the presence of cardiovascular disease, atrial fibrillation
sum of symptoms after 1 year was 155, which represents a dramatic difference
or osteoporosis. We have utilised a fourth-generation TSH assay, providing a
compared to the preoperative period. While decrypting the received data of the
10-fold increase in sensitivity compared to third-generation assays, to determine
questionnaires, it became evident a significant reduction of complaints and
whether patients with subclinical hyperthyroidism can be differentiated from
symptoms of primary hyperparathyroidism which undoubtedly attests to the
those with overt hyperthyroidism, based on their now measurable TSH levels.
effectiveness of the operation.
Two groups of patients were identified using thyroid function tests measured with
Conclusions
a traditional third-generation assay (Roche). The first (Group 1) had normal free
Parathyroidectomy is undoubtedly the most effective treatment of primary
thyroid hormone levels and the second (Group 2) had elevated free thyroid
hyperparathyroidism in children today. We recommend you to use the
hormone levels. Both had a suppressed TSH (!0.02). The samples were then
questionnaire on the table as PAS in the outpatient setting and in hospitals.
re-analysed using a fourth-generation assay (Olympus AU3000i) and the values
This way complaints will allow you to suspect primary hyperparathyroidism in
compared. All results are given as median and interquartile range. Group 1
patients. Early detection of pathology of the parathyroid gland, and operative
(nZ23, M:F 4:19), free T4 17.5 pmol/l (15.8-19.9), free T3 6.1 pmol/l (5.5-6.3);
intervention are essential to early recovery of patients and their wellbeing.
Group 2 (nZ54, M:F 14:40) free T4 32.3 pmol/l (25.7-54.9), free T3 pmol/l 10.7
DOI: 10.1530/endoabs.49.EP1257
(7.9-13.0). Group 1 fourth-generation TSH 0.009 mU/l (0.007-0.014); Group 2
0.004 mU/l (0.003-0.008) (P!0.001, Mann-Whitney U). Whilst group 1 has a
significantly greater fourth-generation TSH than group 2, comparison of the
interquartile ranges confirms significant overlap. In group 1 12/23 patients had
fourth-generation TSH values above the upper limit of the interquartile range of
those with overt hyperthyroidism (group 2). Thus, the measured fourth-generation
TSH may be of value in determining the need for treatment. Those in group 1 with
EP1258
TSH values falling within a comparable range to those with overt hyperthyroid-
Fluctuating thyroid hormones in Graves disease: a case series of
ism should be considered for treatment, whilst those with greater TSH values
brittle Graves
could be monitored for progression. Our data suggest that a fourth-generation
Muhammet Cuneyt Bilginer, Sevgul Faki, Cevdet Aydin, Didem Ozdemir,
TSH assay is of value in assessing which patients with subclinical
Abbas Ali Tam, Reyhan Ersoy & Bekir Cakir
hyperthyroidism should be treated and those who should be monitored.
Ankara Yildirim Beyazit University School of Medicine, Department of
DOI: 10.1530/endoabs.49.EP1259
Endocrinology and Metabolism, Ankara, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1260
still suppressed
(fT4
13.7 pmol/l; fT3
4.71 pmol/l; TSH
0.01 mIU/l). We
concluded that severe thyrotoxicosis in our patient was due to malabsorption of
Non-thyroidal illness syndrome in chronic renal failure and oxidative
thyrosupressive drugs caused by Crohn’s disease and thyrotoxicosis itself. In such
stress: preliminary data on triiodothyronine relationships with
cases alternative therapy options should be considered.
extracellular superoxide-dismutase
Antonio Mancini1, Nicola Panocchia2, Giuseppe Martino1, Carmine Bruno1,
DOI: 10.1530/endoabs.49.EP1261
Sonia Silvestri3, Patrick Orlando3, Fabio Marcheggiani3, Luigi Tazza2,
Luca Tiano3, Giovanni Gambaro2 & Alfredo Pontecorvi1
1Catholic University of the Sacred Heart, Operative Unit of Endocrinology,
Rome, Italy;2Fondazione Policlinico Gemelli, Nephrology Division, Rome,
Italy;3Polytechnic University of Marche, Department of Life and
Environmental Sciences, Ancona, Italy.
EP1262
Congenital disorders in children of the mothers with thyroid
malfunctioning at pregnancy
Non-thyroidal-illness syndrome (NTIS) is present in chronic renal failure and
Saba Akbar1, Rubina Mansoor2 & Muhammad Irfan1
considered an adaptive mechanism. However oxidative stress is linked to NTIS in
1Department of Zoology, Pir Mehr Ali Shah, Arid Agriculture University,
a vicious circle, due to deiodinases alteration and negative effect on antioxidant
Rawalpindi, Pakistan;2Chemical Pathology, Rawalpindi Medical College,
levels or activity. One key antioxidant, protective toward ROS-mediated tissue
Rawalpindi, Pakistan.
damage, is extracellular superoxide-dismutase (ec-SOD), present in extracellular
matrix and with a role in mediating nitric oxide-induced signaling. ec-SOD is
specifically released from endothelium by heparin injection, allowing the
In the present study we hypothesized that maternal thyroid disorders may be
determination of ec-SOD activity in vivo without affecting Cu,Zn-SOD or
associated with maternal and foetal morbidity and mortality. The present study
Mn-SOD. No data are reported on ec-SOD in renal failure and its relationship
included 136 pregnant women selected randomly in first trimester and observed
with thyroid function. Therefore we have studied 12 hemodialysis patients (9
throughout the pregnancy till birth. The assessment of thyroid hormones showed a
males and 3 females, mean age 67 ys), evaluating thyroid hormones and ec-SOD
total of 33.08% (nZ45) pregnant ladies were having thyroid disorders; 17.65%
activity after enoxaparin administration. Blood samples were obtained at the
(nZ24) with hypothyroidism and 15.44% (nZ21) with hyperthyroidism. The
starting of hemodialytic session, 5 and 10 min after 1000-4000 U enoxaparin and
mothers with hypothyroidism were significantly (P!0.05) heavier than normal
at the end of the session. SOD activity was measured by a modified nitrite method.
mothers while the mother with hyperthyroidism were significantly (P!0.05)
Superoxide generated by hypoxanthine and xanthine oxidase was changed by
lighter than normal and those with hypothyroidism. The hyperthyroidism
hydroxylamine to nitrite ion which was measured spectrophotometrically at
increased the odds (OR: 6.80; 95% CI: 1.65-28.09) of miscarriages significantly
550 nm by the use of a chromogen. The amount of SOD required to inhibit 50%
(P!0.05). Maternal hypothyroidism increased the gestational period signi-
nitrite ion generation was defined as 1 U SOD activity. Six patients exhibited low
ficantly
(P!0.05) and hyperthyroidism decreased the gestational age signi-
fT3 values (1.8G0.1 pg/ml); the others had normal fT3 (2.5G0.2 pg/ml); fT4 and
ficantly (P!0.05). Maternal hypothyroidism may lead to significantly (P!0.05)
TSH values were normal. Basal eC-SOD did not differ between the two groups,
increased birth weight and maternal hyperthyroidism may decreased the birth
but the percentual increase after heparin was significantly correlated with T3
levels
(rZ0.24, P!0.05). These preliminary data suggest that low T3 can
weight significantly (P!0.05). The maternal hypothyroidism may lead to a
negatively influence endothelial antioxidant defenses. The relationships of this
statistically significant (P!0.05) decrease in the size of skull and brain weight in
datum with cardiovascular complications and prognostic usefulness remain to be
neonates. Furthermore, the hypothyroidism and hyperthyroidism increased the
established.
odds of webbed neck neonates (OR: 5.87; 95% CI: 1.22-28.30 & OR: 11.73 95%
CI: 2.64-52.06, respectively. The data exhibited that the maternal hyperthyroid-
DOI: 10.1530/endoabs.49.EP1260
ism increased the odds (OR: 10.47; 95% CI: 1.78-61.78) of eyes defects in
neonates. The maternal hypothyroidism increased the risk (OR: 18.00; 95% CI:
1.91-169.10) of neonatal congenital heart defects.
DOI: 10.1530/endoabs.49.EP1262
EP1261
Therapeutic options in severe thyrotoxicosis with malabsorption
Mirjana Stojkovic1,2, Slavica Savic1, Biljana Nedeljkovic-Beleslin1,2,
EP1263
Jasmina Ciric1,2, Tanja Nisic1 & Milos Zarkovic1,2
Psychometric evaluation of the newly developed hypoparathyroidism
1Clinic of Endocrinology, Diabetes and Metabolic diseases, Clinical Center
symptom diary
of Serbia, Belgrade, Serbia;2School of Medicine, University of Belgrade,
Theresa Coles1, Kristina Chen2, Lauren Nelson1, Nimanee I Harris1,
Belgrade, Serbia.
Montserrat Vera-Llonch2 & Susan Martin1
1RTI Health Solutions, Research Triangle Park, NC, USA;2Shire Human
Abstract
Genetic Therapies, Inc., Lexington, MA, USA.
A 55-year-old woman was admitted to our hospital due to severe hyperthyreosis.
She started to feel symptoms of hyper-metabolism four months prior to
Objective
hospitalization. At that time she was admitted in regional hospital and had
The purpose of this study was to evaluate the psychometric properties of a novel,
gastroenterological examination because of diarrhea. Crohn’s disease was
patient-reported outcome
(PRO) measure, the Hypoparathyroidism
(HPT)
diagnosed and therapy started. At the same time, thyrosupressive therapy started.
Symptom Diary (HPT-SD), using data collected during a cross-sectional,
She had a history of hyperthyreosis thirteen years ago, duodenal hemorrhage
noninterventional, observational study. The HPT-SD, developed according to
ulcer, hypertension, cerebral vascular insult and myopericarditis. Despite
the US Food and Drug Administration PRO guidance, addresses the severity of
maximal dose of thiamazole, on admission she was highly hyper-metabolic.
key symptoms (muscle cramping, tingling and muscle spasms/twitching, fatigue,
Hormonal analysis revealed severe thyrotoxicosis (fT4 O100.0 pmol/l; T4O
cognition, emotions) and impacts on sleep, ability to exercise, ability to work, and
320.0 nmol/l; TSH!0.005 mIU/l) with increased TRAb (13.9 IU/l), and negative
family relationships.
TPOAb (!28.0 U/ml) and TgAb (!15.0 IU/ml). Stool analysis was positive for
Methods
muscle fibers, fat and carbohydrates indicating maldigestion and malabsorption.
Individuals who self-reported HPT were recruited to participate in a paper-based
Because of multiple comorbidities, we decided to prepare a patient for radioactive
survey collecting demographic and HPT-related clinical and treatment
iodine treatment (RAI). We concluded that at this hyper-metabolic state, it could
information, patient global impression of severity (PGIS), the HPT-SD, and
lead her in thyroid storm and that her thyroid hormones should be decreased at
three supporting measures: Functional Assessment in Cancer Therapy-Cognitive
safer levels prior to RAI. After admission, we started with intrathyroidal
Function
(FACT-Cog), Functional Assessment of Chronic Illness Therapy-
dexamethasone injections with initial decreasing of thyroid hormones. The
Fatigue Scale (FACIT-Fatigue), and the Hospital Anxiety and Depression Scale
procedure wasn’t continued because of gastric pain she started to feel (history of
(HADS). Item- and scale-level internal consistency reliability, discriminating and
ulcer). We replaced thiamazole for PTU, and started with therapeutic plasma
construct validity were evaluated. A scoring algorithm was developed based on
exchange
(TPE). After TPE, we observed a significant decrease in fT4
psychometric and qualitative results.
(54.5 pmol/l), T4 (139.0 nmol/l) fT3 (8.5 pmol/l) T3 (2.27 nmol/l) levels. Clinical
Results
improvement was achieved. Patient underwent RAI treatment safely, and after
Participants rated their HPT as moderate (34.6%) or severe (32.7%). Participants
two months, her thyroid hormones were in the normal referent range with TSH
did not endorse the most severe response choices (e.g., ‘Very severe’) for 4
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
muscle-related symptom items. Inter-item correlations revealed a pattern of
Background
moderate to strong relationships among symptom (rZ0.3-0.8) and impact items
Optimal management of hypothyroidism prior to and after conception is
(rZ0.5-0.7), providing evidence for two HPT-SD subscales: symptoms and
associated with improved pregnancy outcomes. Compliance with existing
impacts. Construct validity correlations supported a priori convergent validity
management guidelines in Australia and New Zealand is unknown.
hypotheses (jrj O0.5) between HPT-SD subscales and the FACT-Cog, FACIT-
Methods
Fatigue, and HADS. The HPT-SD demonstrated discriminating ability between
A validated electronic survey was distributed to endocrinologists, obstetricians
patients who reported mild versus severe HPT on the PGIS (P!0.05 for 12 out of
and general practitioners via their specialty professional bodies and results were
13 items).
analysed.
Conclusions
Results
The HPT-SD is an appropriate measure of HPT-related symptoms and impacts.
There were 394 survey respondents: 80.5% (317) from Australia and 19.5% (77)
Severe muscle-related symptoms were reported during qualitative development;
from New Zealand. They comprised 263 Obstetrics and Gynaecology doctors
all HPT-SD response choices were retained to capture severe symptoms. Future
(OG), 69 Endocrinology doctors (E) and 58 General Practitioners (GP). Four
studies should assess the HPT-SD measurement properties using longitudinal
respondents were excluded as they did not meet inclusion criteria. Over half of
study designs.
respondents (57.4%) had more than 10 years of specialty experience. 95.2% of
DOI: 10.1530/endoabs.49.EP1263
respondents (375/394) completed the clinical questions as the remainder were not
involved in managing hypothyroidism in pregnancy or in women of reproductive
age. On confirmation of pregnancy, 68.3% of respondents (nZ233) reported
checking thyroid function tests (TFTs) before adjusting thyroxine dose. 27.7% of
respondents reported increasing thyroxine dose by 30-50% or by 2 tablets per
week as soon as pregnancy is confirmed as recommended by guidelines. 85.2% of
respondents reported adjusting thyroxine dose during pregnancy to recommended
EP1264
TSH targets of TSH ! 2.5 mIU/l in the 1st trimester and ! 3 mIU/l in the 2nd
Early diagnosis of primary biliary cirrhosis during follow-up for
and 3rd trimesters (46.7%Z155/332) or to TSH and free T4 trimester specific
Graves’ disease
ranges for their laboratory
(38.5%Z128/332). 75.9% of respondents would
Sevgul Faki1, Muhammet Cuneyt Bilginer1, Cevdet Aydin1,
appropriately treat pregnant women with thyroxine if TSH was O 2.5 mIU/l
Didem Ozdemir1, Husniye Baser2, Osman Ersoy3, Reyhan Ersoy1 &
(36.0%Z112/311) or above trimester specific ranges for their laboratory
Bekir Cakir1
(39.9%Z124/311).
1Department of Endocrinology and Metabolism, Yildirim Beyazit
Conclusions
University, School of Medicine, Ankara, Turkey;2Department of
Reported practice in management of hypothyroidism prior to and during
Endocrinology and Metabolism, Ataturk Education and Research Hospital
pregnancy in Australia and New Zealand varies significantly from recommended
Education and Research Hospital, School of Medicine, Ankara, Turkey;
guidelines. These findings have significant implications for pregnancy outcomes.
3Department of Gastroenterology, Yildirim Beyazit University, School of
Further education is needed for all medical practitioners involved in treating
Medicine, Ankara, Turkey.
women of reproductive age.
DOI: 10.1530/endoabs.49.EP1265
Introduction
Hepatic dysfunction in hyperthyroidism may occur due to high thyroid hormones,
medications or associated autoimmune liver disease. Autoimmune hepatitis or
primary biliary cirrhosis (PBC) has rarely been reported in Graves’ disease. We
report a patient presenting with pruritus and diagnosed as accompanying PBC and
Graves’ disease.
Case
A 50 years old female patient applied with progressive pruritus for at least 4
months. Laboratory investigations showed normal alanine aminotransferase and
aspartate aminotransferase. Serum alkaline phosphatase
(ALP) was 125 IU/l
EP1266
(%105 IU/l), gamma glutamyl transferase (GGT) was 132 IU/l (%42), and total
Analysis of cardiovascular changes in Graves disease and their dynamic
serum bilirubin and conjugated bilirubin were within normal ranges. She had low
during the treatment
TSH (!0.005 U/l) and high serum free T4 (4.6 ng/dl) and free T3 (14.71 pg/ml).
Arina Frolova, Tatiana Rodionova, Marina Orlova & Marina Chuvashova
Thyroid peroxidase antibody and thyroid stimulating hormone receptor antibody
Saratov State Medical University, Saratov, Russia.
were also positive. She was afebrile and had regular pulse rate of 110/min and
normal blood pressure. There was no exophthalmus, goiter, hepatomegaly or
splenomegaly in physical examination. Ultrasonographically, the thyroid gland
Objectives
was enlarged with increased vascularity. Technetium-99m scintigraphy showed
Estimate the prevalence of of cardiovascular symptoms, to identify the main
increased activity throughout the gland with cold nodules in an enlarged thyroid
changes in echocardiography at Graves disease (GD) and their dynamic during
gland. She was started on methimazole and propranolol. After a week of
treatment.
treatment, her ALP and GGT levels raised to 160 and 151, respectively that we
Methods
discontinued methimazol. Serology tests for viral hepatitis, human immuno-
Investigated 86 patients with GD. The functional class (FC) chronic heart failure
deficiency virus and cytomegalovirus were negative; laboratory tests excluded
(CHF) was determined according to the New York Heart Association (NYHA).
copper, iron-related metabolic disorders and autoimmune liver diseases. Anti-
All patients underwent echocardiography before treatment and after 3 months of
mitochondrial antibody was found positive and PBC was diagnosed with clinical
euthyroid state.
and laboratory findings. She was started on ursodeoxycholic acid and underwent
Results
bilateral total thyroidectomy.
At baseline 32.6% patients had no symptoms of CHF, I FC had 19.7%, II FC -
Conclusion
34.9% and III FC - 12.8%. Tachycardia was presented in 87.2% patients,
PBC is often associated with other autoimmune diseases. When a cholestatic
shortness of breath - 67.4%, arrithmias - 58.1%, pain in the chest - 26, 7%.
pattern of liver enzymes is observed during follow-up for Graves’ disease, PBC
Patients without CHF and with 1 FC showed no significant differences in the
should be considered in the differential diagnosis.
echocardiological parameters compared with the control. Patients with 2 FC
observed a higher left ventricular ejection (LVE) (P%0.05), left ventricular
DOI: 10.1530/endoabs.49.EP1264
posterior wall thickness
(LVPWT) (P%0.05) and interventricular septum
thickness (IVST) (P%0.05). Patients with 3 FC characterized by an increase of
size of the left (P%0.05) and right atrials (P%0.05), end-diastolic dimension of
left ventricle
(EDD LV) (P%0.05), EDD of left (r%0.05) and right atrial
(P%0.05). Clinically 3 months after reaching the euthyroid state at 48.8% were
EP1265
maintained complaints of palpitations, at 20.9%- shortness of breath. In patients
Survey on the management of hypothyroidism during pregnancy by
with FC 2 maintained high LVE, LWPWT, IVST. Among patients with FC 3 also
general practitioners, endocrinologists and obstetricians in Australia
were signs oh heart cavities diliatation.
and New Zealand
Conclusions
Danijela Dravec3, Bernard Champion1,2, Jack Wall1 & Emily Hibbert1,4
Cardiovascular symptoms frequently encountered in GD, and some may be stored
1University of Sydney - Sydney Medical School Nepean, Sydney, Australia;
on reaching euthyrosis. For patients with CHF FC 2 is characterized by left
2Macquarie University, Sydney, Australia;3Specialists on Derby, Kings-
ventricular hypertrophy and myocardial hyperfunction that persist over time
wood, Australia;4Nepean Hospital, Kingswood, Australia.
during treatment. At 3 FC showed signs of heart cavities diliatatation combined
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
systolic dysfunction, which are only partially reversible with normalization of
EP1269
thyroid function.
Effectiveness of radioiodine treatment for autonomous toxic node
DOI: 10.1530/endoabs.49.EP1266
Ana Sofia Osório1, Ana Filipa Martins1, Vânia Gomes1, Raquel Vaz de
Castro1, Ema Nobre1, Mickael Antoine Ferreira3, Guilhermina Cantinho2
& Maria João Bugalho1
1
Serviço de Endocrinologia, Diabetes e Metabolismo, Hospital de Santa
Maria, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal;2Instituto de
Medicina Nuclear da Faculdade de Medicina de Lisboa, Lisboa, Portugal;
3
Statistical Independent, Lisboa, Portugal.
EP1267
Prevalence of the thyroiditis in childbearing age women
Objective
Mohammed El Amine Amani1 & Farida Chentli2
The aim of this study was to evaluate the treatment outcomes in patients with
11st November 1954 University Hospital, Oran, Algeria;2Bab-el-oued
autonomous toxic nodule (ATN) that received a radioiodine treatment (RAIT)
University Hospital, Algiers, Algeria.
and to determine the influence of age, gender, nodule size and iodine activity.
Methods
Background and aims
We performed a retrospective study of all RAIT done for hyperthyroidism
It has been demonstrated that the thyroid autoimmunity, during pregnancy,
(nZ149) in our hospital during 2014 and 2015. Patients with ATN submitted to
adversely affects the course of the pregnancy. The anomalies may be prior to the
RAIT were selected to analysis. We studied 58 patients (mean age 59.6G13.98
conception, hence the interest of studying the women during the genital activity
years), a total of 59 treatments, corresponding to 39.6% of all RAIT. Treatment
period. Our objective was to determine the prevalence of the thyroiditis in
success was analysed according to demographic (age and gender) and clinical
childbearing age women.
data (thyroid function tests 1 year after RAIT, iodine activity administered and
Materials and methods
nodule size). Activities of 5 or 10 mCi were the most used. Treatment success was
Prospective study, on 270 childbearing age women. Study protocol: clinical
defined as achieving euthyroidism or hypothyroidism 1 year after the last RAIT.
examination, thyroid stimulating hormone
(TSH), free thyroxine
(FT4) and
For statistical data analyses was used a 95% confidence interval (sig!0.05).
thyroid antibodies. Statistics tests: collection of data on EPI INFO 5.1.
Results
Results
The cure rate was 84.6%. Hypothyroidism was observed in 25.6% (10 patients).
Data expressed as mean (270 women), age: 30.3G0.4 years, weight: 65.9G
Only 6 patients remained in hyperthyroidism. Age and nodule size did not
0.9 kg, body mass index: 24.7G0.3 kg/m2, TSH: 2.4G0.2 mIU/l and FT4: 14.8G
influence the outcome. Additionally, no correlation was found between gender
0.2 pmol/l. The positivity of the antithyroperoxidase antibodies
(TPO-ab)
and iodine activity in therapeutic effectiveness. Although not statistically
concerned 38/270 women (14.1%), the antithyroglobulin antibodies (Tg-ab)
significant, the cure rate was higher with
10 mCi (92.6%) comparing with
42/270 women (15.6%) and one of the two antibodies (TPO-ab and / or Tg-ab)
5 mCi (72.7%).
54/270 women (20.0%). The mean TSH of the women with thyroiditis was 4.39G
Conclusion
4.93 mIU/l vs 1.89G1.06 mIU/l for those without it (P!0.0001). The mean FT4
There is a trend for a higher effectiveness with 10 mCi than with 5 mCi. The cure
of the women with thyroid autoimmunity was 14.38G1.08 pmol/l vs 14.87G
rate with 10 mCi is similar to those described in the literature for 15 and 20 mCi,
with a lower rate of hypothyroidism.
2.05 pmol/l for those with negative antithyroid antibodies, NS. Of the 54 women
with thyroiditis, 35/54 were in euthyroidism (64.81%) and 19/54 of them were in
DOI: 10.1530/endoabs.49.EP1269
hypothyroidism (35.19%), 9/54 in subclinical hypothyroidism (16.67%) and
10/54 in overt hypothyroidism (18.52%).
Conclusion
In our study, 20.0% of the women had thyroiditis and their mean TSH was
significantly higher vs those with negative antithyroid antibodies. In the subgroup
of women with thyroiditis, 64.81% were in euthyroidism.
EP1270
DOI: 10.1530/endoabs.49.EP1267
Endemic goiter in Xinjiang, Northwestern China
Yoichi Izumi1, Yuji Kasamaki1, Yukio Ozawa2 & Hirosi Kawamura2
1
Department of Medicine, Himi Municipal Hospital, Kanazawa Medical
University, Himi, Toyama, Japan;2Blood Pressure Center,
MJG Cardiovascular Institute, Saitama, Japan.
EP1268
Background
Prevalence and etiology of the hypothyroidy in childbearing age women
Endemic goiter occurs frequently in iodine deficient areas. Our past medical
Mohammed El Amine Amani1 & Farida Chentli2
survey revealed that goiter was endemic in Xinjiang, Northwestern China,
11st November 1954 University Hospital, Oran, Algeria;2Bab-el-oued
because, several elderly Uygur subjects had goiter. In the present study, several
University Hospital, Algiers, Algeria.
medical parameters were compared between subjects with and those without
goiter.
Methods
Background and aims
Elderly Uygur (age, 65-70 years nZ99) and very old Uygur subjects (age, O90
The hypothyroidism may be prior to the conception, hence the interest of studying
years nZ111) were hospitalized, requested to provide blood and urine samples,
women during the genital activity period. Our objective was to determine the
and underwent 24 h-ambulatoly blood pressure monitoring. Goiter was not
prevalence and the etiologies of the hypothyroidism in childbearing age women.
identified in Hun and Kazakh participants.
Materials and methods
Results
Prospective study, on 270 childbearing age women. Study protocol: clinical
No subjects had any symptoms attributable to abnormal thyroid function. The
examination, urinary iodine, thyroid stimulating hormone (TSH), free thyroxine
goiters identified ranged in size from that of the walnuts to the fist. Body mass
(FT4) and thyroid antibodies. Statistics tests: collection of data on EPI INFO 5.1.
index of the subjects with goiter (GOC) was slightly but significantly lower than
Results
Data expressed as mean (270 women), age: 30.3G0.4 years, weight: 65.9G
that of the subjects without goiter (GOK). There were no significant differences
0.9 kg, body mass index: 24.7G0.3 kg/m2, urinary iodine: 225.6G5.8 mg/l, TSH:
in blood pressure, heart rate, urinary catecholamine levels, insulin sensitivity, and
2.4G0.2 mIU/l and FT4: 14.8G0.2 pmol/l. The iodine deficiency was found in
serum levels of free thyroxin, thyroid stimulating hormone, triglycerides, or low-
19/270 women (7%). The hypothyroidism involved 31/270 women (11.5%),
density lipoprotein and high-density lipoprotein cholesterol, between GOC and
the subclinical form in 19/270 (7.1%) and the overt form in 12/270 (4.4%). Of the
GOK participants. The prevalence of goiter in women was 6 times that of men.
31 hypothyroid women, the etiology of the hypothyroidism was related to the
The iodine content in the salt extracted from the study area was 0 parts per million
autoimmune thyroid disease in 19/31 women (61.3%) and to the iodine deficiency
(ppm) while in that obtained from the market was 29.1 ppm.
in only one case (3.23%).
Conclusion
Conclusion
The results suggest that prevalence of goiter in Uygur might have been caused by
In our study, 11.5% of women of childbearing age were in hypothyroidism (overt
intake of iodine-free salt. Individuals with goiter would live safely and come
and subclinical forms). The etiology of the hypothyroidism was dominated by the
today. The higher prevalence of goiter among women suggests that hormones
thyroiditis.
might play a role in the development of thyroid disease.
DOI: 10.1530/endoabs.49.EP1268
DOI: 10.1530/endoabs.49.EP1270
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1271
EP1273
How does overt and subclinical hypothyroidism due to thyroiditis of
Evaluation of circulating irisin levels in patients with never treated
Hashimoto affect lipid parameters
overt hyperthyrodisim
Gergana Tosheva1, Mira Siderova1, Kiril Hristozov1, Yana Bocheva2 &
Asena Gokcay Canpolat, Mustafa Sahin, Demet Corapcioglu, Rıfat Emral &
Mila Kostova1
Ali Rıza Uysal
1University Hospital ‘St Marina’ Clinic of Endocrinology, Varna, Bulgaria;
Ankara University Faculty of Medicine, Ankara, Turkey.
2University Hospital ‘St Marina’ Central Clinical Laboratory, Varna,
Bulgaria.
Aims
Because of an increased metabolic activity and thermogenesis in hyperthyroid-
Aim
ism, we aimed to evaluate the association of serum irisin with thyroid hormones.
The aim of this retrospective study is to assess the lipid disturbances in patients
Methods
with autoimmune thyroiditis.
A total of 25 hyperthyroid patients and 24 age- and gender-matched healthy
Methods
controls were enrolled. Serum irisin levels, thyroid hormones and body
1380
patients with autoimmune thyroiditis, hospitalized in Endocrinology
compositions were analyzed.
department of ‘St. Marina’ Hospital, Varna for the period of 2004-2015 year,
Results
participated in the study. After excluding conditions influencing lipid profile, 771
Serum irisin levels were significantly higher in hyperthyroid group (P!0.001).
patients remained for analysis (36 men and 735 women, mean age 49.81G13.98
Distribution of fat free mass and muscle mass was similar between study groups.
years). They are divided in three groups according to TSH values - group A (0.4-
Serum irisin level has a negative correlation with TSH level (P!0.001), %fat
4 mU/l), group B (4.01-10 mU/l), group C (TSH R10.01 mU/l). Group B is
mass (PZ0.021) and positive correlation with TSH receptor antibody (TRAB)
divided into two subgroups - B1 - patients with negative thyroperoxidase
level (PZ0.002).
antibodies (TPO Ab) and B2 - patients with positive TPO Ab. We evaluated
Conclusion
thyroid ultrasound data, laboratory tests of TSH, free T3 (FT3), free T4 (FT4),
Our results showed that increased serum irisin levels in hyperthyroid patients
TPO-Ab, total cholesterol (TC), triglycerides (TG), LDL - and HDL-cholesterol
might be associated with the effects of TSH.
levels.
Keywords: Hypertyroidism; irisin; TSH receptor antibody
Results
DOI: 10.1530/endoabs.49.EP1273
With the increase of TSH value, we observe elevation in serum triglycerides
(group A-TG 1.34 mmol/l, group B-1, 44 mmol/l, group C-1, 69 mmol/l); as well
as in LDL-c values (group A-3, 41 mmol/l; group B- 3, 53 mmol/l; group C-4,
19 mmol/l). The comparison of the two subgroups B1 and B2 find out increasing
levels of TC, TG, LDL-c and a decreasing of HDL-c. A significant difference in
EP1274
TG between patients in group A and C is observed (P 0.001). Statistical
significance in LDL-c level is achieved in group A and C (P 0.000), group B and
Is there a correlation between serum selenium level and the severity of
C (P 0.000), in group B2 and C (P 0.001). 16.9% of the patients from group B and
Graves’ orbitopathy?
17.1% from group C had already coronary heart disease and/or cerebrovascular
Iwona Palyga1, Danuta Gasior-Perczak1, Klaudia Gadawska-Juszczyk1,
disease.
Estera Mikina1, Monika Piwowar1, Monika Szymonek1, Tomasz Trybek1,
Conclusions
Agnieszka Walczyk1, Ryszard Mezyk1, Urszula Majewska2 &
Autoimmune thyroiditis as one of the main reasons for hypothyroidism is
Aldona Kowalska1,2
associated with lipid abnormalities and increased cardiovascular risk, which are
1Holycross Cancer Centre, Kielce, Poland;2The Faculty of Health Sciences,
more pronounced in overt than in subclinical hypothyroidism.
Jan Kochanowski University, Kielce, Poland.
DOI: 10.1530/endoabs.49.EP1271
Introduction
Selenium (Se) deficiency is a known risk factor for autoimmune thyroid diseases
including Graves’ orbitopathy (GO).
Objective
EP1272
To determine the concentration of Se in serum and to determine the dependency
of Se concentration on known markers of disease severity: the TRAB levels and
Primary hypothyreosis in cobalt intoxication
the CAS (clinical activity score) in patients with GO.
Dagmar Langova
Material
IK IPVZ, KNTB as, Zlín, Czech Republic.
64 patients (50 women, 14 men; average age- 54.5 years) with active, moderate to
severe GO who have not received prior selenium supplementation and were
Most common causes of primary hypothyreosis are destruction of thyroidal
qualified to i.v. metylprednisolone treatment according to the EUGOGO scheme,
parenchyma by the autoimmune antibodies, interventions on the gland (surgery,
at a single site in the years 2014-2016.
radioiodine treatment) and external actinotherapy
(hematologic and ENT
Method
malignancies). Drug induced thyroidal impairment is well-known too (amio-
Set average and median concentrations of Se, TRAB and CAS in the group of
darone, lithium, interferon). Our case demostrates the primary hypothyreosis
patients and determined the correlation coefficients between serum Se and TRAB
caused by cobalt. The source was Co-Cr hip prostehis after its rupture (PHACT).
and CAS.
A 55 old man was reffered to endocrinologist in 2011 with enlargement of thyroid
Results
gland (volume 84 ml) and signs of primary hypothyreoidism (TSH 76 mU/l). No
Selenium deficiency was found in 15 patients, in 27 the concentration was normal,
elevation of antibodies levels was present, family history of thyroid disease
in 22- the Se level was above the upper limit of normal. There was no correlation
negativ. Thyroxin substitution treatment resulted in both normalisation of thyroid
between Se and CAS or TRAB revealed.
function and thyroid gland volume (TSH 1.3 mU/l, 18 ml).
Conclusions
Personal history
1) The severity of OG expressed by well known indicators: CAS and TRAB were
Hyperlipoproteinema, smoking. The man also underwent implantation of right
not dependent on the concentration of Se.
2) It seems that it should be
hip prosthesis after an injury in 2002. The course was complicated by deep venous
recommended to measure the concentration of selenium before starting the
thrombosis of the right leg and massive pulmonary embolism requiring
supplementation of Se because of low frequency of Se deficiency in this group of
thrombolysis treatment. The prosthesis was damaged in 2010 because of necrosis
patients.
and replaced with the Co-Cr type. Since 2010 the patient was examined by
DOI: 10.1530/endoabs.49.EP1274
multidisciplinary specialists because of polymorhpic atypical complaints
(arrhytmias - considered cardiomyopathy, atypical neuropathy, hypacusis). In
2014 patient was admitted to hospital with atypical back and pelvis pains.
Following RDG imaging of the right trochanter and acetabulum a diagnosis was
finally obtaned showing pathology - local osteal reaction. The puncture of the
affected spot revealed dark fluid with high levels of cobalt and chromium. The
EP1275
defficient prosthesis was then removed. PHACT id.e prosthetic hip-associates
Nicotinamide phosphoribosyltransferase expression in thyroid glands of
cobalt toxicity. The symptoms are atypical - arrhytmias, different neurological
patients with Graves’ disease
symptoms, changes of thyroid gland functions, deafnes, eye disorders.
Nadia Sawicka-Gutaj1, Miroslaw Andrusiewicz2, Agata Czarnywojtek1,3,
Joanna Waligorska-Stachura1, Maciej Biczysko4, Jerzy Skrobisz4,
DOI: 10.1530/endoabs.49.EP1272
Jerzy Sowinski1 & Marek Ruchala1
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Poznan University of Medical Sciences, Department of Endocrinology,
EP1277
Metabolism and Internal Medicine, Poznan, Poland;2Poznan University of
Hypothyroidism - once a week treatment option in young- and
Medical Sciences, Department of Cell Biology, Poznan, Poland;3Poznan
middle-aged adults
University of Medical Sciences, Department of Pharmacology, Poznan,
Satish Chander Wasoori1, Manoj Naik2, Deepak G Pande1 &
Poland;4Department of General Surgery and Multiple Trauma, with
Chetan Bhardwaj1
Division of Gastroenterological and Endocrine Surgery, Provincial Hospital,
1Park Hospital, Gurgaon, Haryana, India;2Sunjeevan Hospital, Thane,
Poznan, Poland.
Maharashtra, India.
Abstract
Objective
Nicotinamide phosphoribosyltransferase (NAMPT) overexpression was reported
To evaluate the effectiveness and compliance to L-thyroxine in the treatment of
in many autoimmune diseases. We have also found NAMPT overexpression in
Hypothyroidism in a weekly dose of 7 times of normal dose as an alternative to
leukocytes of patients with Graves’ orbitopathy. Therefore, we aimed to analyze
daily dosing in young and middle aged adults.
NAMPT expression level in thyroid gland of patients with Graves’ disease with
Methods
orbitopathy and without orbitopathy, and in healthy thyroid gland. We have
A randomized prospective observational study on 180 patients (female:male)
analyzed 80 thyroid tissue samples of patients who underwent thyroidectomy.
ratio of 5:1 aged between 18 and 55 years with an established diagnosis of
Among these, there were 41 patients with Graves’ disease (20 patients with
Hypothyroidism were assigned a weekly dose of seven times of normal dose. The
orbitopathy and 21 patients without orbitopathy), and 39 samples of healthy
patients were randomized in 3 groups G1, G2 and G3. Group 1 (G1): 60 patients
thyroid tissue. NAMPT overexpression was found in thyroid glands of patients
with established diagnosis of Hypothyroidism with TSH value of 4.2 or less,
with Graves’ orbitopathy (P!0.000001). NAMPT expression in patients with
currently on daily dose. The subjects were assigned weekly dose of L-thyroxine
Graves’ disease without orbitopathy was similar to healthy controls. Our results
which was 7-fold of normal dose. Group 2 (G2): 60 patients with established
suggested that NAMPT might be involved in the inflammatory cascade in Graves’
diagnoses of Hypothyroidism with TSH value of more than 4.2. The subjects were
orbitopathy.
assigned weekly dose of L-thyroxine which was 7-fold of normal dose, the dose in
DOI: 10.1530/endoabs.49.EP1275
this group was individualized as per the body weight and TSH value. Group 3
(G3): 60 patients newly established diagnoses of Hypothyroidism with TSH value
of more than 4.2. The group was started with a weekly dose which was
individualized as per the body weight and TSH value. All subjects in all the
groups were screened for malabsorption and were not receiving any drugs which
interfere with the absorption of L-thyroxine. The minimum to maximum dose
used in this study was 175-1050 mcg.
Results or case presentation
We achieved complete restoration of euthyroidism in all 59 subjects in the group
1
(G1) at 12 weeks and it continued to 24 weeks. We had to withdraw it in a
EP1276
55-year male patient because of hyperthyroid symptoms. In group 2 (G2), we
Associations between thyroid and kidney functions
achieved complete euthyroidism in 52 subjects at 12 weeks and it increased to
Lina Zabuliene1,2, Modesta Petraviciute3, Birute Pauliukiene4 &
55 subjects with some dose adjustment at 24 weeks. We could not achieve
Jurgita Urboniene5
euthyroidism in 5 subjects at 24 weeks. This may be attributed to other metabolic
1Clinics of Rheumatology, Traumatology - Orthopaedics and Reconstruc-
disorders like diabetes and obesity. In (G3) we achieved complete euthyroidism in
tive Surgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania;
54 subjects at 12 weeks and it increased to 59 subjects with some dose adjustment
2Karoliniskiu Outpatient Clinic, Vilnius, Lithuania;3Faculty of Medicine,
at 24 weeks. 1 subject shifted to another city and so did not complete the study.
Vilnius University, Vilnius, Lithuania;4Antakalnio Outpatient Clinic,
Conclusion
Vilnius, Lithuania;5Centre of Infectious Diseases, Vilnius University
Once weekly dose of L-thyroxine as an alternative to daily dosing regimen was
Hospital Santariskiu Klinikos, Vilnius, Lithuania.
shown to be efficacious and safe for the treatment of hypothyroidism to treat non-
compliant hypothyroid young- and middle-aged adults. The results show that it
can be started in newly diagnosed hypothyroid patients. For patients who find it
difficult to adhere to a rigorous treatment regime it is a valid therapeutic option
Two-way interactions between thyroid and kidney functions are known. Chronic
and can also be considered as a first line therapy in young and middle aged
kidney disease
(CKD) is accompanied by changes in synthesis, secretion,
working adults facing impaired absorption due to early breakfast (no need to wait
metabolism, and elimination of thyroid hormones, increased risk of hypothyroid-
30-45 min for breakfast).
ism, rarely subclinical hyperthyroidism, whereas thyroid dysfunction affects
physiology of the kidney, renal blood flow, glomerular filtration rate (GFR),
DOI: 10.1530/endoabs.49.EP1277
tubular function, metabolism of water and electrolytes, and kidney structure. The
aim of the study was to examine associations between thyroid stimulating
hormone (TSH) level and kidney function.
Methods
We analysed retrospective data of
781 adult patients, referred for routine
EP1278
simultaneous testing of TSH and serum creatinine in 2015 in Vilnius Antakalnio
Effect of subclinical hypothyroidism and autoimmunity on adverse
outpatient clinic. GFR was estimated by the simplified Modification of Diet in
pregnancy and neonatal outcome in our population
Renal Disease equation. Linear regression was used to evaluate the association
Cristina López-Tinoco, Begon˜a Sánchez-Lechuga, Almudena Lara,
between TSH and estimated GFR.
Julia Barcala, Laura Larrán, Daniel Medina & Manuel Aguilar-Diosdado
Results
Endocrinology Department, Cádiz, Spain.
Mean TSH concentration was 2.58G4.19 mIU/l, mean serum creatinine 72.72G
22.32 mmol/l and mean estimated GFR 83.12G24.91 ml/min/1.73 m2. 45.3% of
patients had stage 2 CKD, 16.0% - stage 3 CKD, 1% - stage 4 or end stage CKD.
Patients with CKD of any stage were older than those with normal kidney
The effect of subclinical hypothyroidism (SH) and thyroid autoimmunity on
function (mean age 66.98G11.20 vs 50.96G15.42 years, P!0.0001) and their
adverse pregnancy and neonatal outcome, are still subject of interest and
TSH was higher (2.86G5.07 vs 2.12G1.93 mIU/l, PZ0.004). 12.9% of patients
controversy. Nowadays, guidelines recommend establishing reference
had thyroid dysfunction:
7.9% had subclinical hypothyroidism
(TSH 4.69-
values of local thyroid hormones that allow definition of the SH in a
10 mIU/l), 1.3% overt clinical hypothyroidism (TSH O10 mIU/l) and 3.7%
specific population. The objective of this study was to assess the effect of SH
subclinical hyperthyroidism
(TSH !0.465 mIU/l).
12.8% of patients with
and autoimmunity in early pregnancy on adverse pregnancy and neonatal
estimated GFR !60 ml/min/1.73 m2 had subclinical hypothyroidism, 1.5% -
outcome in our population. The reference range of thyrotropin (TSH) was
overt clinical hypothyroidism. Lower estimated GFR was associated with higher
3,86 mUI/ml, in our Cádiz-San Fernando area, in Spain. 438 pregnant
TSH level (BZK0.72 (95% CI K1.13 - K0.30), PZ0.001).
women with HS (defined according to our reference values) in the first
Conclusions
trimester of gestation were recruited. Women were classified into two
Thyroid dysfunction is relatively common among persons with CKD: 14.3% of
groups according to thyroid function and anti-TPO results. The mean age
patients with moderate, severe and established kidney failure have hypothyroid-
was 31,32G5,5 years, BMI was 24.5G5.3 kg/m2. Twenty-four percent of
ism. Reduction in estimated GFR is independently associated with increased TSH
the patients had a family history of Thyroid disease and 23% of miscarriage.
levels.
The mean of levels of TSH at diagnosis were 5,1G1,3 mUI/l with a final
DOI: 10.1530/endoabs.49.EP1276
mean dose of levothyroxine 64.9 mcg/day and levels of TSH 2.5G1.2 mIU/l
at the end of pregnancy. Sixteen percent of the deliveries were by cesarean
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
section, and 20% had complications (premature rupture of membranes,
Aim and objective
preeclampsia, preterm delivery, small for gestational age). Thirteen percent
The aims of this study were to determine the incidence of breast cancer molecular
had anti-TPO positive. Comparing anti-TPO positive/negative groups with
subgroups, to investigate the relationship between autoimmune thyroid disease
obstetrics and perinatal outcomes, no statistically significant differences
and prognostic and predictive factors in patients who were diagnosed with breast
were found. We concluded that in our area, patients with HS, defined
cancer.
according to our local reference values, have a low rate of adverse
Materials and methods
pregnancy and neonatal outcome. Also, if we consider the presence of anti-
One hundred one patients who were followed up with the diagnosis of breast
TPO positive, there are no differences. Further studies will be needed to
cancer at our Endocrinology and Medical Oncology Departments were included.
determine the relationships between HS and autoimmunity and adverse
Patients are divided into subgroups based on the molecular classification. Patients
pregnancy and neonatal outcome.
with high serum levels of thyroid peroxidase antibody
(anti-TPO) were
DOI: 10.1530/endoabs.49.EP1278
considered as autoimmune thyroid disease. Prognostic and predictive parameters
such as tumor size, axillary involvement, histological grade, lymphovascular
invasion, hormone receptor status, HER2 overexpression were collected. The
relationships between autoimmune thyroid disease and tumor’s prognostic and
predictive factors were studied.
Results
The prevalence of thyroid autoimmunity was 23.8% (nZ24) among with our
study group. Patients with autoimmune thyroid disease had a significant lower
rate of axillary involvement (37.5% vs 61% [PZ0.043], respectively). Other
parameters did not differ between patients with and without autoimmune thyroid
disease.
EP1279
Conclusions
We found a favorable association between autoimmune thyroid disease and
Metastatic differentiated thyroid carcinoma: cumulative doses of
axillary involvement which is crucial and strongly prognostic parameter of breast
adjunct 131i-iodide therapy
cancer prognoses. This supports the idea of thyroid autoimmunity being a
Patrícia Gouveia1, Teresa Pereira2, Ana Amado2, Ricardo Teixeira1,
favorable prognostic parameter in breast cancer. Further studies are necessary to
Antonio Costa3, André Carvalho2, Cláudia Freitas2 & Fátima Borges2
investigate the reasons of protective or predictive effect of high anti thyroid
1Department of Nuclear Medicine, Centro Hospitalar do Porto, Porto,
peroxidase levels in breast cancer patients.
Portugal;2Department of Endocrinology, Centro Hospitalar do Porto, Porto,
Portugal;3Department of Surgery 2, Centro Hospitalar do Porto, Porto,
DOI: 10.1530/endoabs.49.EP1280
Portugal.
Introduction
131I-iodide therapy (RIT) is an important treatment modality for patients with
differentiated thyroid carcinoma (DTC). However, despite the overall excellent
outcome, some DTC patients with poor prognosis may require multiple doses of
radioactive iodine.
Aim
The purpose of our study was to evaluate the efficacy of cumulative doses (CDs)
of RIT in metastatic DTC patients.
EP1281
Material and methods
Subacute Thyroiditis with an atypical clinical course and thyroid
A retrospective study was conducted on a cohort of 84 metastatic DTC patients
99mTc uptake
(mean age 46.6G17.4 years) who received a CDs R300 mCi of RIT, between
Deniz Sema, Maktav Celikmen & Ali Ozdemir
January 1956 and December 2016. A disease-free status was established as:
Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey.
undetectable TSH-suppressed Thyroglobulin levels, whole body imaging scan
without local-regional uptake or distant metastases and negative cervical
ultrasound or thoracic CT scan.
Background
Results
Subacute thyroiditis (SAT) is a transient inflammatory, probably viral disease of
Eighty-four patients, 58 females and 26 males, who completed more than one RIT
the thyroid gland. It is clinically characterized by pain, fever, increased
with a CD R300 mCi, were followed up for 15.0G8.8 years. At the time of
erythyrocyte sedimentation rate
(ESR) or other markers of inflammation,
diagnosis 62 (73.8%) patients had local cervical metastases and 22 (26.2%) had
transient thyrotoxicosis, and has a tendency to recur. In most cases, in addition
distant metastases. Papillary carcinoma sub-type was present in 75 (89.3%) of
to the clinical features, scintigraphy and ultrasound may support the diagnosis of
patients. Seventeen out of 84 patients (20.2%) achieved a disease-free status. No
SAT. However, in the present case, SAT with an atypical thyroid99mTc uptake
patient with CDs higher of 450mCi has reached a disease-free status. Patients with
and a nodule formation in ultrasound lead to diagnosis difficulties.
evidence of brain or bone metastases (7 out of 94) did not achieve the disease-free
Case presentation
status, regardless of the CDs received.
A 31-year-old woman with the clinical suspicion of SAT was observed.
Conclusion
Thyrotoxicosis was present and the tests for anti-thyroid peroxidase, anti-
Twenty percent of patients who received a CDs R300 mCi of RIT achieved a
thyroglobulin and TSH receptor antibodies were negative. Thyroid scintigraphy
disease-free status. Quality of life and the disease progression rate are important
with99mTc demonstrated decreased uptake in the right but a normal uptake in the
aspects that were not addressed in our study. The decision of further treatment
left lobe. Four weeks after clinical and laboratory remission she developed a
with RIT should be carefully evaluated and made on a case-by-case basis.
painful palpable nodule of the left thyroid lobe. Increased erythyrocyte
Furthermore, this study seems to indicate that brain or bone metastases may not
sedimentation rate above 100 mm/h and elevated C reactive protein were present.
respond to higher CDs.
Ultrasonographic examination showed an enlarged left lobe and area of low
DOI: 10.1530/endoabs.49.EP1279
echogenicity with shaded margins and microcalcifications. The lesion showed a
contrast uptake in contrast-enhanced magnetic resonance imaging (MRI). The
second scintigraphy demonstrated a bilateral, heterogeneous uptake with a
suspected hipoactive nodular image of the left thyroid lobe. Fine-needle
aspiration biopsy from the nodule revealed multinuclear giant cells consistent
with SAT.
EP1280
Conclusion
Autoimmune thyroid disease may affect prognosis of breast cancer
In most cases, the diagnosis of SAT can be made based on the physical and
Selim Yalcin1, Ramazan Cosar2, Aydin Cifci2, Askin Gungunes3 &
laboratory findings of the patient and the clinical course of the disease. Findings
Senay Arikan Durmaz3
of thyroid scintigraphy and ultrasound that are not consistent with subacute
1Department of Oncology, School of Medicine, Kirikkale, Turkey;
thyroiditis do not exclude the diagnosis of SAT. For definitive diagnosis of an
2Department of Internal Medicine, School of Medicine, Kirikkale, Turkey;
atypical SAT and exclusion of thyroid malignancies, fine-needle aspiration
3Department of Endocrinology and Metabolism, School of Medicine,
biopsy may be required.
Kirikkale, Turkey.
DOI: 10.1530/endoabs.49.EP1281
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1282
EP1284
Weak numeracy is common problem in patients with thyroid diseases
Percutaneous ablation of benign thyroid nodules: specific simulators for
Ewa Wawak1, Pawel Basinski1, Malgorzata Gasiorek1 &
practicing enolization and laser procedures
Krzysztof Marczewski1,2
Teresa Jiménez, Pablo Vidal-Ríos, Antonio Rodríguez, Laura Villas &
1Department of Nephrology and Endocrinology Pope John Paul II Regional
Sebastian Vidal-Ríos
Hospital, Zamosc, Poland;2Faculty of Health Sciences University of
Coruna Endocrinology Center, La Coruna, Spain.
Economy and Innovations, Lublin, Poland.
Introduction
Ethanol and laser ablation of benign thyroid nodules is bursting rapidly in
In modern medicine, we expect from patients numeracy skills. Starting with the
clinical practice because of its efficacy, safety and economy. However, these
correct dosage of drugs up to understand the principles of risk assessment of
techniques require some manual operator training. In order to facilitate this
alternative treatments. These skills, however, are probably rarely checked. Just as
hands-on training, we propose two homemade, cheap and specific simulators
the skills of reading, where we entrust signature ‘read and understood’. That is
to practice these clinical procedures.
why we want to introduce our observation.
Material and methods
Method
Two models were optimized: Gel-Phantom Coruna VR16 (gelatine and
Subsequent patient, outpatient endocrinological clinic, we have proposed making
plantago-ovata with inlays of different objects simulating pure and mixed
two tests to assess numeracy: Schwartz test (max. 3 points) and Berlin Numeracy
cysts) and Proteon-Phantom Coruna VR17 (pork loin with inlays of different
Test (max. 4 points).
objects simulating solid nodules (homogeneous, heterogeneous and with
Results
microcalcifications). For enolization, pure ethanol and a 2-way device (Device
We investigated 112 patients (101 women) in age 17 to 85 years (average 55G15).
Coruna VR15, poster 94, 58th Congress Malaga, Spain, SEEN 2016) were
No one person became maximal possible results, and 11 (10%) had not answered
used for sequential ethanol-NSS instillation (to reduce irritation of the capsule
any question. The results of other patients indicate significant problems with
upon withdrawal of the needle). For laser ablation, a 1064 nm Nd-YAG
simple counting. 2 person rejected Schwartz test, and 1 person rejected BNT test.
laser through a thin optic fiber of
300um obtained from an EchoLaser
From others 36 person became 0 points in Schwartz test, 43 patients 1 point, 23
generator (Elesta, Florencia-Italy) was used. Monitoring was performed with
patients 2 points and only 8 maximally possible 3 points. Similar or even worse are
the Acusson
2000
Hellix ultrasound platform
(Siemens, Forchheim-
the results in BNT 29 person became 0 points, 56 1 point, 22 2 points, only 3 3
Germany). The assessment was performed among different operators
point and no one maximal possible
4 points. We did not find significant
(nZ12), especially those attending the Coruna Workshop on Laser Ablation.
correlations between the results of the tests, and the sex, age and TSH.
Results
Conclusion
For cystic nodules simulation and practicing ethanol sclerosis, the most
Weak numeracy is a common problem in patients with thyroid diseases.
valued simulators were: fluid on a knotted glove (pure cyst), grapes or
DOI: 10.1530/endoabs.49.EP1282
dwarfish tomatoes (mixed cyst), piece of wet sponge wrapped in knotted
kitchen plastic (‘sponge’ cyst) and anchovy stuffed olive (hyperechoic nodule
with hypoechoic center). For solid-state nodules simulation and practicing
laser ablation, the most valued were: beef liver wrapped in knotted plastic
(solid isoechoic nodule), cooked yolk wrapped in knotted plastic (hyperechoic
solid nodule), raisins and water wrapped in knotted plastic (heterogeneous
nodule), and raisins, water and eggshells
(heterogeneous nodule with
‘microcalcifications’).
Conclusion
In summary Gel-Phantom Coruna VR16 and Proteon-Phantom Coruna VR17
EP1283
simulators were surprisingly useful for practicing percutaneous ethanol and laser
A case of levothyroxine tablet malabsorption associated with gastric
ablation procedures. In addition, we highlight their low cost and easy preparation.
neuroendocrine tumour corrected with gel capsule formulation
DOI: 10.1530/endoabs.49.EP1284
Olivera Boskovic1, Ranko Lazovic1,2, Brigita Smolovic1,2 &
Mirha Hasanbegovic2,3
1Clinical Center of Montenegro, Podgorica, Montenegro;2Medical Faculty,
University of Montenegro, Podgorica, Montenegro;3General Hospital
Pljevlja, Pljevlja, Montenegro.
EP1285
Improved diagnostics with increased treatment of hypothyroidism
Multiple dose adjustments can sometimes be inefficient in reaching
during pregnancy - a 10 year study of Finnish pregnant women
eumetabolic state in patients with hypothyroidism treated by levothyroxine
Suvi Turunen1,2, Tuija Männisto3,5, Anna-Liisa Hartikainen3, Mika Gissler4,
sodium tablets. We report a case of 44-year-old female who has been on
Anna-Maria Lahesmaa-Korpinen4, Marja Vääräsmäki1,3 & Eila Suvanto1,3
levothyroxine sodium tablet replacement therapy since 2004 without ever
1Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland;
reaching eumetabolic state, presented as outpatient one year ago. As sellar
2Medical Research Center Oulu (MRC Oulu), Oulu, Finland;3University of
MRI ruled out pituitary adenoma, investigation targeting malabsorption was
Oulu, Oulu, Finland;4Institute of Health and Welfare, Helsinki, Finland;
initiated. Antibodies to gliadin and transglutaminase were in normal range.
5Nordlab, Oulu, Finland.
Absorption test with
300 mcg levothyroxine was positive in aspect of
presence of selective levothyroxine malabsorption. Initial endoscopies
revealed chronic atrophic gastritis without excluding possibility for tumor
presence. Serum CgA level was 521 mcg/l. The final third endoscopy was
Thyroid diseases affect up to 4% of all pregnancies. Several evidence-based
successful in detecting the gastric submucosal change, confirmed by
recommendations have been created to observe and treat thyroid diseases in
endoscopic ultrasound as submucosal lesion no larger than 12 mm located in
pregnant women. We studied whether the diagnostics and treatment of
the upper part of anterior gastric wall. Histological analysis of biopsy
hypothyroidism among pregnant women have improved in the course of
specimen confirmed lesion to be neuroendocrine tumor grade 1. Further
time. Data consisted of all singleton pregnancies (NZ571785) during 2004-
imaging excluded its metastatic spreading, so the indication for surgical
2013 in Finland, collected from the Finnish Medical Birth Register (MBR).
removal was established. Patient could not undergo surgery with TSH levels
Data on maternal thyroid diseases were obtained from the MBR and the
exceeding 100 mmU/l and free T4 lower than 5 pmol/l despite being on
Hospital Discharge Register, and combined with the Special Refund
300mcg of levothyroxine daily substitution regimen. Changing to a gel
Entitlement Register and the Register on Reimbursed Drug Purchases
capsule formulation taken once a day at dose of 100 mcg lead to a rapid TSH
consisting data on medication purchases during the index pregnancy.
decreasement and thyroid hormones normalization, so the patient was
Women with thyroid diseases other than hypothyroidism were excluded
surgically treated as eumetabolic. On reviews thereafter she remained
(NZ4561), rendering a final study population of
567 224
singleton
euthyroid, without complaints of previously reported fatigue and loss of
pregnancies. Pregnancies were divided into four categories: mothers with
appetite. This case suggests that gastric chronic inflammatory processes and
diagnosed hypothyroidism treated with levothyroxine (NZ8893), mothers
neuroendocrine tumors as well may affect levothyroxine absorption where
treated with levothyroxine without a recorded hypothyroidism diagnosis
gelatine capsules appear to be effective treatment option.
(NZ6788) (mostly treated in the primary care), mothers with diagnosed
DOI: 10.1530/endoabs.49.EP1283
hypothyroidism but without levothyroxine treatment (NZ683) and mothers
without thyroid diseases or thyroid medication
(NZ550 860). In 2004
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
approximately 1% of pregnant women had diagnosed hypothyroidism and
mild swelling of extraocular muscles. She was diagnosed with Graves’
were treated with levothyroxine. By 2013 this prevalence had more than
ophthalmopathy too. After that, it was decided thyroidectomy. In addition,
doubled up to 2.4%. The prevalence of women receiving levothyroxine
oligoamenorrhea appeared and ultrasound and magnetic resonance of the
treatment without recorded hypothyroidism diagnosis was 0.2% in 2004 but
abdomen and pelvis detected an
11!11!9 cm solid-cystic mass in right
12-fold higher (2.5%) in 2013. The increase in prevalence of diagnosed
ovarian. The patient underwent right salpingo-oophorectomy. Histology revealed
hypothyroidism and levothyroxine treatment has been steady over time.
a benign SO. Immediately, ocular disease and hyperthyroidism improved.
Surprisingly, the prevalence of pregnant women with hypothyroidism and
Subsequently, total thyroidectomy was performed, which showed GD and benign
no recorded levothyroxine treatment has been constant between 0.1 and
thyroid nodules.
0.2%. Our study shows that the diagnoses of hypothyroidism and use of
Conclusions
levothyroxine treatment among pregnant women have increased markedly
The diagnosis of functioning SO in presence of GD may be a challenge and it may
during the past 10 years. This suggests that clinical recommendations have
be difficult to determine the precise cause of hyperthyroidism. When a patient has
improved the awareness on the risks of hypothyroidism on pregnancy and
increased thyroid uptake of technetium in the scan, an ectopic hormone
the threshold to treat hypothyroidism during pregnancy seems declining.
production is not suspected. When SO is surgically removed and subsequently
DOI: 10.1530/endoabs.49.EP1285
the hyperthyroidism and ocular disease improve considerably, the diagnosis of
functioning SO is quite likely.
DOI: 10.1530/endoabs.49.EP1287
EP1286
EP1288
Radiofrequency ablation for benign thyroid nodules: 450 patients -
three years follow-up
Clinical characteristics and outcomes of patients with myxedema coma:
Viacheslav Solovov, Aleksandr Makhonin, Mikhail Vozdvizhenskiy &
a 15-years experience of a tertiary care center in Thailand
Andrew Orlov
Suwanna Pitchaiprasert1, Patinut Buranasupkajorn1,
Samara Oncology Center, Samara, Russia.
Sompongse Suwanwalaikorn1,2, Sarat Sunthornyothin1,2,
Weerapan Khovidhunkit1,2 & Thiti Snabboon1,2
1Department of Medicine, Faculty of Medicine, Chulalongkorn University,
Purpose
Bangkok, Thailand;2Excellence Center for Diabetes, Hormone and
The objective of this study was to evaluate the efficacy and safety of ultrasound
Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
(US)-guided radiofrequency ablation
(RFA) for treating of benign thyroid
nodules.
Material and methods
Background
The retrospective analysis included the results of treatment of 450 patients with
Myxedema coma is an uncommon but life-threatening condition of severe and
benign tumors of the thyroid gland in the Samara Oncology Center. 91 (20.2%)
decompensated hypothyroidism requiring early recognition and prompt treat-
patients had autonomously functioning thyroid nodules and 359 (79.8%) had
ment. The aim of this study is to describe the clinical features and identify factors
symptomatic ones. The mean volume of nodule was 33.5 (4.1-179.5).
associated with mortality of our patients diagnosed myxedema coma over the past
Results
15 years.
RFA reduced nodular volume by 70% after 6 months, 84% after 36 months and it
Materials and methods
was an effective method for treating nodule-related clinical problems and hot
Retrospective chart review of patients diagnosed and treated at King
nodules. 47 (10.4%) patients with big nodule volume underwent 2-6 sessions of
Chulalongkorn Memorial Hospital for myxedema coma during 2002-2016 was
RFA. Cosmetic results were excellent in 96% of patients in the RFA group. No
performed. Their demographic data, clinical features, precipitating factors and
serious complications such as thyroiditis, voice change, and hematomas were
treatment outcomes were analyzed. We also compared different scoring systems
observed in RFA patients.
including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health
Conclusion
Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA)
RFA was effective and safe for treating benign thyroid nodules. RFA might be
score and Wartofsky myxedema coma score to predict the outcomes.
recommended for treating benign thyroid nodules as the first-line treatment.
Results
A total of 13 cases, 9 females and median age of 79 years ranged between 60-94
DOI: 10.1530/endoabs.49.EP1286
years, were recruited. All of them had primary hypothyroidism. Seven patients
(54%) were newly diagnosed hypothyroidism at the time of presentation of
myxedema coma. Six patients (46%) died and sepsis was the major cause of
death. Lower FT4 level was only parameter significantly different between the
patients who survived and those who died (PZ0.04). On analyzing the various
scoring systems, they did not demonstrate a significant difference between
EP1287
survivors and non-survivors; however, a Wartofsky myxedema score below 90
Coexistence of Graves’ disease and unilateral benign struma ovarii:
was associated with a better outcome.
A case report
Conclusions
Rosa Marquez-Pardo, Lourdes Garcia-Garcia-Doncel, Mgloria
Myxedema coma still carries a high mortality rate even with the appropriate
Baena-Nieto, Manuel Cayon-Blanco, Rosario Lopez-Velasco &
diagnosis and treatment. With a high proportion of undiagnosed hypothyroid
Isabel Torres-Barea
patients in our study, it should be alert clinicians to beware of this preventable
Jerez Hospital, Jerez de la Frontera, Cadiz, Spain.
condition in an appropriate clinical context. Thyroid hormone levels and
Wartofsky myxedema score may be applied as clinical prognostic parameters.
DOI: 10.1530/endoabs.49.EP1288
Introduction
Struma ovarii (SO) is a rare ovarian teratoma composed predominantly (more
than 50%) or entirely of thyroid tissue. It constitutes 2% to 4% of ovarian
teratomas. This tumor is often asymptomatic and discovered incidentally. Only
8% of patients present clinical hyperthyroidism.
Case report
EP1289
A 42-year-old woman presented palpitations, anxiety, sweating, emotional
Evaluation of interrelationships between thyroid function,
lability and weight loss for several months. Physical examination revealed goitre,
autoimmunity, insulin resistance and lipid profile in Graves’ disease
tachycardia and slight tremor. Laboratory tests confirmed hyperthyroidism:
António Carujo1, Celestino Neves2, Joa˜o Sérgio Neves2, Sofia Castro
thyrotropin (TSH) 0.01 mcU/ml (0.3-5), serum-free thyroxine 5.21 ng/dL (FT4)
Oliveira2, Oksana Sokhatska3, César Esteves2, Miguel Pereira2,
(0.9-2.1), serum-free triiodothyronine
(FT3)
22.5 pg/ml
(2.57-4.43) and
José Luís Medina1, Luís Delgado3 & Davide Carvalho1,4
thyrotropin receptor antibody
(TRAb)
21.78 U/l
(positive O2). Thyroid
1Faculty of Medicine, University of Porto, Porto, Portugal;2Endocrinology
ultrasound identified a multinodular goitre with a dominant nodule of 14 mm in
Service, São João Hospital, Faculty of Medicine, University of Porto, Porto,
left lobe. Technetium thyroid scan showed diffuse uptake. She was diagnosed as
Portugal;3Immunology Department, São João Hospital, Faculty of
having Graves’ disease (GD) and started on thiamazole and propranolol. Several
Medicine, University of Porto, Porto, Portugal;4Instituto de Investigação e
months later, she remained hyperthyroid and appeared proptosis, lid retraction
Inovação em Saúde, Faculty of Medicine, University of Porto, Porto,
and ocular chemosis. Magnetic resonance of the orbits demonstrated bilateral
Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
EP1291
Thyroid hormones modulate the lipoprotein and glucose metabolisms. In
Trans-axillary endoscopic thyroidectomy - technique
hyperthyroidism, insulin resistance is a frequent finding.
Jaime Vilaça, Susana Graça & Paula Mendes
Aim
Tiroide Center, Porto, Portugal.
To assess interrelationships between thyroid function, autoimmunity, lipid
profile, glucose metabolism and other cardiovascular risk factors in patients
with Graves’ disease.
Introduction
Methods
Trans-axillary surgery is an emerging technique for cervical approach with
We recorded free T3 (FT3), free T4 (FT4), TSH, TSH receptor antibodies
fantastic cosmetic result. With more than 50 cases treated by our group, we
(TRAB), parameters of the lipid profile, glucose metabolism [including insulin
developed our technique with specific safe methodologies.
resistance marker Homeostasis Model Assessment for Insulin Resistance
Aims
(HOMA-IR)], C reactive protein (CRP) and homocysteine in 126 patients with
To present step-by-step technique of trans-axillary endoscopic thyroidectomy.
Graves’ disease in the first cycle of treatment with methimazole (93% females,
Material and methods
mean age 44.8G15.2 years). Patients were divided in subgroups according to:
This is a video surgery that uses three trocars and a harmonic scalpel for
TRAB (positive (nZ57) or negative (nZ69)) and thyroid function (normal
dissection and ligation. Incisions are made in the armpit and areolar border.
(nZ74), subclinical (nZ29) or clinical hyperthyroidism (nZ22)). Spearman
Results
correlations, T-tests and Mann-Whitney tests were performed for statistical
Technique is described in 10 steps: (i) trocars and patient position; (ii) dissection;
analysis.
(iii) landmarks (sternal notch, ECM anterior border, thyroid cartilage); (iv) omo-
Results
hyoid muscle dissection; (v) split strap muscles; (vi) upper pole dissection and
Comparing TRAB- and TRABC groups, significantly lower apolipoprotein B
ligation; (vii) ligation of the middle thyroid vein and recurrent laryngeal nerve
(80.3(73.2-87.4) vs 89.7(83.5-95.8)mg/dl, PZ0.047) and TSH (0.180(0.002-
(RLN) visualization; (viii) inferior pole ligation; (ix) lobectomy; (x) specimen
1.080) vs 1.020(0.235-2.055]mUI/ml, P!0.001) were found in the TRABC
removal and haemostasis; Three auxiliary techniques are used to increase safe and
group. Comparing with the normal thyroid function group, patients in the
to reduce complications:
clinical hyperthyroid group presented significantly lower apolipoprotein B
1. Intra-operative ultrasound
(70.9(57.2-84.6) vs
89.7(83.7-95.8)mg/dl, PZ0.007) and higher fasting
2. Neuromonitoring of the RLN
glucose
(96.0(83.0-109.0) vs
86.4(83.8-89.0)mg/dl, PZ0.019), insulin
3. Indocyanine green (ICG) fluorescence for parathyroid vascular assessment
(10.4(6.2-15.8) vs
7.5(4.8-9.7)mUI/ml, PZ0.021), HOMA-IR
(2.09(1.29-
Conclusions
4.53) vs 1.55(0.95-2.13), PZ0.023) and CRP (0.57(0.20-0.93) vs 0.20(0.07-
Cervical scar-less surgery is very appealing for the patient. For the surgeon with
0.38)mg/l, PZ0.005). No significant differences were found between the
advanced laparoscopic skills this is a feasible and reproducible technique, with
subclinical hyperthyroid group and the remaining groups. There was a negative
excellent results. Security techniques can have great value in more demanding
correlation between TSH and TRAB (rZK0.386, P!0.001). Apolipoprotein B
cases.
was positively correlated with TSH (rZ0.236, PZ0.016), and negatively with
DOI: 10.1530/endoabs.49.EP1291
TRAB (rZK0.211, PZ0.030). Both FT3 and FT4 were positively correlated
with fasting insulin (rZ0.268, PZ0.008 and rZ0.226, PZ0.025, respectively)
and HOMA-IR (rZ0.258, PZ0.010 and rZ0.259, PZ0.010, respectively).
FT4 was also positively correlated with fasting glucose (rZ0.269, PZ0.008).
Conclusion
In patients with Graves’ disease, the interrelationships between thyroid function,
autoimmunity, insulin resistance and lipid profile may contribute to the increased
cardiovascular risk.
EP1292
DOI: 10.1530/endoabs.49.EP1289
Trans-axillary endoscopic thyroidectomy - scarless surgery of the neck:
our experience
Jaime Vilaça, Susana Graça & Paula Mendes
Tiroide Center, Porto, Portugal.
Introduction
Endoscopic techniques are uprising in the cervical field mainly because of the
exceptional cosmetic results. These surgeries are frequent in the far east Asia but
still rare in Europe. We started these approach on November 2014. This paper is a
review of our experience.
EP1290
Aims
Successful radioiodine treatment of Graves disease for a patient with a
To present a series of trans-axillary endoscopic thyroidectomy.
history of «iodide allergy»
Material and methods
Nesrine Cheikhrouhou, Intidhar Elbez, Kaouthar Limem, Aida Mhiri,
This is a cohort study of
50 consecutive patients treated by trans-axillary
Bechir Ltaeif & Faouzi Ben Slimene
endoscopic thyroidectomy. Patients are selected using the following indications:
Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.
benign or suspicious nodules until 35 mm, micro papillary cancer, lobes until
65 mm. Interventions are video recorded and time, recurrent laryngeal nerve
Introduction
identification and parathyroid identification are registered. Laryngoscopy is
Graves’s disease is the most common cause of hyperthyroidism. There are three
performed at the end of the procedure. Morbidity data are collected during
current therapeutic options: anti-thyroid medication, surgery, and radioactive
surgery, on the day after, 2 weeks, 2 months and one year after the operation. All
iodine (I 131). There are few data in the literature regarding the effects of
the pathological reports are reviewed.
radioiodine therapy.
Results
Case report
Among the series, 78% were women with an average of 48 year old. All patients
We describe a 47-year-old patient who had Grave’s disease resistant to anti
had normal thyroid function at the time of the operation and 95% were low-risk
thyroid medication. Radioactive iodine was indicated. The patient was reluctant
anaesthetic candidates (ASA1 or 2). Half complained of goitre. All but 2 were
because she had a history of anaphylactic reaction to computed tomography (CT)
submitted to lobectomy. There was no conversion to open surgery. No dead was
contrast agent. We explicated to the patient that the implication of iodine has
registered. There were 5 cases of morbidity: 2 seromas, 2 skin burn and 1 transient
never been demonstrated during allergic hypersensitivity reactions due to
recurrent laryngeal nerve palsy. All cases of lobectomy were discharged home on
iodinated drugs. She successfully underwent treatment with 12 mCi (444 MBq)
post-operative day 1.
radioactive iodine.
Conclusions
Conclusion
Endoscopic cervical approach is difficult to implement among surgeons without
Asking a patient if he/she is ‘allergic to iodine’ is a question that should be
advanced laparoscopic skills.The technique revealed to be safe and reproducible
avoided because its significance is null. A diagnosis of drug allergy, essentially
with potential to enlarge indications. The use of neuromonitoring, ICG
relying on clinical symptoms, biological tests and cutaneous tests, is required to
fluorescence and intra-operative ultrasound are tools already tested by the
take adequate preventive measures.
group with a benefit in safety.
DOI: 10.1530/endoabs.49.EP1290
DOI: 10.1530/endoabs.49.EP1292
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1293
EP1295
TSH oscillations in young patients with type 1 diabetes may be due to
Treatment of toxic multinodular goiter with 131 radioactive iodine -
glycemic variability
effects in volume reduction, thyroid function and autoimmunity
Giuseppe Bellastella1, Ofelia Casciano1, Lorenzo Scappaticcio1,
Catarina Roque1, Francisco Sousa Santos1, Tania Pilli2 & Furio Pacini2
Dario Giugliano1, Maria Ida Maiorino1 & Katherine Esposito2
1Endocrine Unit, Hospital de Egas Moniz, C.H.L.O. E.P.E., Lisbon,
1Endocrinology and Metabolic Diseases Unit, Department of Medical,
Portugal;2Endocrine Unit, University of Siena, Siena, Italy.
Surgical, Neurological, Metabolic Sciences and Aging, University of
Campania, L. Vanvitelli, Naples, Campania, Italy;2Diabetes Unit,
Abstract
Department of Medical, Surgical, Neurological, Metabolic Sciences and
Radioiodine is a definite treatment option for toxic goiter. We have evaluated
Aging, University of Campania, L. Vanvitelli, Naples, Campania, Italy.
volume reduction, function and autoimmunity outcomes with a 15 mCi fixed
regimen. Patients with at least one US evaluation before and after Iodine-131
therapy and with at least one year of follow-up were included. TSH, free-T4,
A link between thyroid dysfunction and diabetes mellitus exist. Uncertainties on
antibodies and goiter volume before and yearly after Iodine-131 treatment were
the role of glycemic variability on thyroid hormones and TSH concentrations still
analysed for the length of the entire follow-up. The total 151 patients, 72.6%
persist. We want to evaluate the influence of glycemic variability on thyroid
females, had a mean follow-up of 6.2 (1-12) years. At the time of treatment, the
hormones and TSH concentrations in patients with type 1 diabetes (T1DM). 77
mean age was 68.8 years and the initial goiter volume 48.9 (8-255.7) ml, with no
patients with T1DM on insulin therapy without thyroid dysfunction and 100
statistical difference between sexes. Increased volume was observed in 96.5%
healthy controls were evaluated for basal glucose concentrations, HbA1c, thyroid
females and 91.7% males and there were 10.6% in hyperthyroidism and 89.4% in
hormones and TSH levels. Glucose variability was investigated through the
subclinical hyperthyroidism. The mean percentage volume reduction in the first
standard deviation of blood glucose (BGSD) readings and through the mean
year was 29.8% which represents 14.7 ml with a Pearson coefficient of correlation
amplitude of glycemic excursions (MAGE) and continuous overlapping net
with initial volume of 0.058. During the following years mean reductions of 19.7,
glycemic action (CONGA), the low (LBGI) and high (HBGI) blood glucose
15.8,
9.7,
5.8
and 1.4% were observed. Absolute volume reductions were
indices. The links between TSH, thyroid hormones, glycemia and HbA1c were
maximal at the 3rd and 4th years representing mean reductions of 50 and 52%.
studied in patients and in controls, whereas those between TSH, thyroid hormones
Initial volume, TSH and age could not produce an explicative model for the
and indices of glucose variability only in patients. All subjects had TSH, thyroid
percentage of reduced volume. Euthyroidism was achieved in 60.9% patients,
hormones and thyroid antibodies in the normal range. No correlations were found
subclinical hyperthyroidism in 8.6% and hypothyroidism in 26.5% of which
in T1DM patients between free thyroid hormones and glycemic values, HbA1c
23.8% were subclinical. Hypothyroidism was related significantly with initial
and indices of glucose variability, while an inverse correlation was observed
volume (P!0.001) and maximal percentage of reduction (PZ0.012). The
between TSH levels and glycemic values (rZK0.4; PZ0.02), CONGA index
development of new detectable anti-thyroid antibodies was identified in 5 patients
(rZK0.3; PZ0.04) and HBGI (rZK0.3; PZ0.05) but not with HbA1c
(6.9%), the result being above cut-off in none of them. New anti-TSH-receptor
(rZK0.1; PZ0.47). No significant correlations of TSH and thyroid hormones
antibodies developed in 4 (5.5%) patients 1-3 years post-treatment. With 15 mCi,
with glycemia and HbA1c were observed in controls. In T1DM patients was
all patients experienced volume reduction in the first years after treatment,
found an inverse correlation between TSH and glycemic variability with direct
achieving means above 50% at the 3rd year, most were rendered euthyroid and
action of glycemic excursions on TSH secretion disengaged from variations
developed no auto-immunity.
of thyroid hormone concentrations. The study of thyroid function
(TSH
DOI: 10.1530/endoabs.49.EP1295
concentrations) in these patients should be made by multiple samples on patients
in euglycemic state to avoid underestimation or overestimation of thyroid
dysfunction due to a misdiagnosis of euthyroidism or dysthyroidism with
consequent inappropriate therapy.
DOI: 10.1530/endoabs.49.EP1293
EP1296
Four out of five patients with acute kidney injury have thyroid
dysfunction
Manpreet Choulia1, Jasmine Das2, Maria Ghosh3 & Jubbin Jacob
1
Endocrine and Diabetes Unit, Department of Medicine, Christian Medical
College and Hospital, Ludhiana, Punjab, India;2Department of Nephrology,
Christian Medical College and Hospital, Ludhiana, Punjab, India;
EP1294
3Department of Biochemistry, Ludhiana, Punjab, India.
May erythrovirus (parvovirus) B19 trigger autoimmune thyroid
diseases?
Objectives
Serdar Ucgun1, Kevser Onbasi1 & Nilgun Kasifoglu2
This study was undertaken to ascertain the prevalence of thyroid dysfunction(TD)
1Dumlupinar University, Kutahya, Turkey;2Eskisehir Osmangazi
in patients with Acute Kidney Injury(AKI) and assess the prognostic implications
University, Eskisehir, Turkey.
of TD in AKI patients.
Materials and methods
Consecutive adult patients (O18 years) admitted with AKI to the departments of
Erythrovirus (EVB19) can recognize auto-antigens by using molecular mimicry
Nephrology & Medicine were recruited if they met AKIN classification criteria
mechanisms. EVB 19 is accused in the pathogenesis of many autoimmune
for AKI after
48 h of admission
(1). Patients were screened for thyroid
diseases. Especially EVB19 is very important in the pathogenesis of autoimmune
dysfunction with serum sampling of Thyroid stimulating hormone, Free T3 and
thyroid diseases. Thus in some case presentations; it was shown that EVB19
Free T4 after taking informed consent. Prognosis of TD in AKI patients was
might be related with Hashimoto’s thyroiditis. Although etiopathogenesis of
assessed in terms of: 1) Duration of hospital stay, 2) Need for Renal Replacement
Graves’ disease and Hashimoto’s thyroiditis is not known exactly; they are
Therapy (RRT), 3) In-hospital mortality.
thought to occur as a result of interaction of genetic and environmental factors.
Results
Infections are one of the environmental factors, which were alleged to be involved
147 patients with AKI (93M:54F) with a mean age of 57.8 years were recruited
in the pathogenesis, but this was not proved. Parvovirus B19 (EVB19) is an
and TD was noted in 114 patients(77.5%). Of these, 74(64.91%) patients had
unproven viral agent, which was thought to play a role in pathogenesis. In this
Non-thyroidal illness (NTI), 10(8.77%) had primary hypothyroidism, 17(14.91%)
study; the prevalence of EVB19 was studied in autoimmune thyroid patients. This
had subclinical hypothyroidism,
4(3.51%) had primary hyperthyroidism,
study was conducted on patients who were followed-up in the Endocrinology and
7(6.14%) had subclinical hyperthyroidism and 2(1.75%) had central hyperthyr-
Internal Medicine Polyclinics and who agreed to participate in the study. Total 90
oidism. A trend to longer duration of hospitalisation for AKI patients (O7 days)
individuals were counted in this study including 30 patients with Hashimoto’s
was seen in 65(75.58%) patients with TD compared to 17(62.96%) patients
thyroiditis, 30 patients with Graves’ disease and 30 control individuals who were
without TD (PZ0.09). RRT requirements (56.36 vs 59.38%) (PZ0.84) and
compatible in terms of age. EVB19 IgG-IgM was studied manually using
in-hospital mortality
(31.58 vs 33.33%) (PZ0.84)of AKI patients with and
immunological ELISA method and values were read in spectrophotometer.
without TD were similar. However, a trend of increasing mortality was seen in
According to results of this study; there was no significant difference for
AKI patients with NTI (PZ0.059).
Parvovirus B19 IgG-M levels between patients with autoimmune thyroid disease
Conclusions
and the control group.
Four out of five patients with AKI had some form of thyroid dysfunction, of which
DOI: 10.1530/endoabs.49.EP1294
majority of them had NTI. However, presence of TD did not significantly affect
prognosis of these patients.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Reference
physician to visually differentiate between necrotic or destroyed tissue (which
(1) Lopes JA, Jorge S. The RIFLE and AKIN classification for acute kidney
shows absent or very low uptake of the radiopharmaceutical) from hypermeta-
injury: a critical and comprehensive review. Clin Kidney J 2013 6 8-14.
bolic cells (with increased uptake).
DOI: 10.1530/endoabs.49.EP1296
Case report
A 72-year-old male with atrial fibrillation treated with amiodarone for 10 years
was sent to our Endocrinology outpatient clinic for new-onset asymptomatic
subclinical hyperthyroidism (FT3 2.56 pg/ml (2.00 4.40); TT3 85 ng/dl (80-200);
FT4 1.59 ng/dl (0.93-1.70); TT4 10.0 (5.1-14.1); TSH 0.03 mU/l (0.27-4.20)).
He had a history of euthyroid benign nodular disease. We admitted AIT type 2,
but considering the mild thyroid dysfunction, we chose to pursue further
EP1297
evaluation with
99mTc sestamibi scintigraphy, in order to initiate targeted
The assessment of influence vitamin D deficiency on the Hashimoto’s
therapy. Scintigraphic images showed initial uptake by the thyroid gland with
thyroiditis activity
rapid washout, a pattern described in literature as corresponding to AIT type 3.
Katarzyna Lizis-Kolus1, Alicja Hubalewska-Dydejczyk2, Anna
The patient’s thyroid hormones normalized before starting any medication and he
Sowa-Staszczak2, Anna Skalniak2, Aldona Kowalska1,3 & Pawel Lizis4
is currently on follow-up.
1Department of Endocrinology, Holycross Cancer Center, Kielce, Poland;
Conclusion
2Department of Endocrinology, Jagiellonian University Medical College,
This case report is illustrative of the possible role of
99mTc sestamibi
Krakow, Poland;3The Faculty of Health Sciences of the Jan Kochanowski
scintigraphy in diagnosis and management of thyroid disfunction induced by
University, Kielce, Poland;4Holycross College, Department of Education
amiodarone. However, more expertise is further needed.
and Health Protection, Kielce, Poland.
DOI: 10.1530/endoabs.49.EP1298
The observed increase in the incidence of Hashimoto’s thyroiditis (HT) requires
research on factors that may affect its development. One of them may be vitamin
D deficiency which is an epidemiological problem all over the world.
Aim
The assessment of influence vitamin D deficiency on the HT activity.
EP1299
Material and methods
Effect of vitamin D supplementation on patients with Graves disease
310 people were enrolled in the study: 155 patients with HT (a-TPO and/or a-TG
Maram Maher, Nermin Sheriba, Abeer Elewa, Ahmed Mohamed
positivity)-144 women (93%), 11 men (7%) and 155 healthy volunteers-139
Bahaa Eldin, Nesma Ali Ibrahim & Dina Marawan
(90%) women and 16 men (10%); mean age: 49G18, 58G17, 49G17 and 56G
Ain Shams University, Cairo, Egypt.
16 years respectively. For analysis purposes the HT group was divided into two
subgroups: without (E) and with l-thyroxine treated hypothyroidism (H): 45
patients aged
50G14 and 110 patients aged
50G17 respectively. Serum
Multiple factors contribute to the etiology of Graves disease(GD), including
25OHD3, TSH, a-TPO, a-TG, 25OHD3 levels were measured in all subjects.
genetic and environmental factors.vitamin D is well known in calcium
Vitamin D deficiency was defined as 25OHD3! 30 ng/ml.
metabolism and has also been shown to be a modulator in innate and adaptive
Results
immunity. There is a well-established link between vitamin D deficiency and
In HT patients 25OHD3 level was lower than in the control group: 23.2 ng/ml
various autoimmune diseases. The prevalence of vitamin D deficiency was
(Q1-Q3: 18.6-29.0) vs 25.6 ng/ml (Q1-Q3: 21.0-31.4; PZ0.006). There is no
reported to be common in patients with GD. Whether vitamin D deficiency has a
difference between 25OHD3 concentration in subgroup E and control group (28.7
causal relationship with GD remains controversial.Aim:to evaluate the effect of
vs 25.6 ng/ml; PZ0.4) but 25OHD3 level was significantly lower in subgroup H
vitamin D supplementation in patients with GD with and without opthalmopathy
than in subgroup E (21.5 ng/ml; Q1-Q3: 17.8-27.3 vs 28.7 ng/ml; Q1-Q3: 21.4-
methods: A randomized prospective study was conducted on 60 adult patients
33.2; P! 0.001). The study showed higher 25OHD3 level in a-TPO negative than
with GD.
in a-TPO positive patients (32 ng/ml; Q1-Q3: 25.6-37.7 vs 22.1 ng/ml; Q1-Q3:
Group 1
18.1-28.4; P!0.001); the same was observed in a-TG negative and a-TG positive
20 patients with GD receiving 30 mg of methimazole daily.
subjects
(28.7 ng/ml; Q1-Q3:
23.2-32.7
vs
20.2 ng/ml; Q1-Q3:
15.4-23.6;
Group 2
P!0.001). In subgroup E 25OHD3 level was similar independently of a-TPO
40
patients with GD receiving same dose of methimazole and vit. D3
or a-TG positivity.
200 000 IU/month. Patients were followed up for 3 months.
Conclusions
Results
Evidence of a link between increased level of antithyroid antibodies in
40% of patients in group 1 and 72.5% in Group 2 were vit. D deficient,Vit. D was
hypothyroid patients with HT and 25OHD3 deficiency may suggest that this
significantly correlated with thyroid volume and degree of exophthalmos. Gp 2
group is particularly prone to the vitamin D deficiency and can benefit from its
had significant lower thyroid volume and better effect on degree of exopthalomos.
alignment.
Conclusion
DOI: 10.1530/endoabs.49.EP1297
Vit. D suuplementation for GD has a favourable effect on thyroid volume and
degree of exophthalmos.
DOI: 10.1530/endoabs.49.EP1299
EP1298
The role of 99mTc-sestamibi in amiodarone-induced
thyrotoxicosis - Case report
EP1300
Margarida Victor, Ana Gonçalves Ferreira, Susana Carmona, Henrique
Primary hyperparathyroidism coexisting with Graves’ disease in a
Vara Luiz, Maria Carlos Cordeiro, Jorge Portugal & Ana Isabel Santos
patient with vitamin D deficiency
Hospital Garcia de Orta, Almada, Portugal.
Panagiotis Athanassiou1, Ifigenia Kostoglou-Athanassiou2 & Eleni Pantazi3
1Department of Rheumatology, St Paul’s Hospital, Thessaloniki, Greece;
2Department of Endocrinology, Red Cross Hospital, Athens, Greece;
Introduction
3Department of Endocrinology, Alexandra Hospital, Athens, Greece.
Amiodarone is an antiarrhythmic iodine-rich drug, known to induce thyroid
dysfunction both due to its high iodine content and through amiodarone-induced
thyrotoxicosis (AIT), being this latter process classified into three different types.
Primary hyperparathyroidism is known to coexist with thyroid cancer and breast
Type 1 is associated with increased thyroid hormone synthesis; type 2 is a
cancer. However, primary hyperparathyroidism coexisting with Graves’ disease
destructive process with thyroid hormone release and type 3 is thought to be a
is extremely rare. The aim was to describe the case of a patient with Graves’
mixture of the former two. Since treatment options are different, there has been
disease causing severe hyperthyroidism who in the course of the disease
a growing need for a diagnostic method that could accurately distinguish these
developed vitamin D deficiency and primary hyperparathyroidism. A patient,
types and therefore allow targeted therapy. 99mTc-sestamibi scintigraphy has
female, aged
49
years, presented with severe hyperthyroidism causing
been gaining a specific role in this matter: with recognized increased uptake by
tachycardia, palpitations and weight loss. TSH receptor antibodies were positive
epithelial cells that show high mitochondrial concentration, it allows the
in the context of Graves’ disease. She was treated with methimazole and
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
propranolol and the disease went into remission. A year later treatment with
Introduction
methimazole was discontinued and 4 months later the patient had a relapse of
The incidence of depressive type psychoaffective disorders is significantly
hyperthyroidism. Laboratory tests revealed hyperthyroidism along with vitamin
increased in patients with chronic autoimmune thyroiditis.
D deficiency and elevated PTH levels. Vitamin D was administered along with
Objectives
methimazole and propranolol. During follow up, despite normal vitamin D levels,
The study of thyroid autoimmunity correlated with serum levels of TSH, FT4 and
PTH levels remained extremely elevated and blood calcium levels in the upper
depression degree.
normal range. Ultrasound of the thyroid and parathyroid glands revealed a
Methods
parathyroid adenoma adjacent to the left thyroid lobe. The adenoma was visible in
The study comprised 70 patients (64 women and 6 men), aged between 18 and 66
a scan with 99mTc-sestamibi. The patient is being followed up and prepared for
years, divided in 4 groups. All study groups were analyzed according to the
surgical treatment of both hyperthyroidism and primary hyperparathyroidism.
degree of depression and serum TSH, FT4, thyroid peroxidase antibody(TPOAb)
The extremely rare case of a patient with concurrent Graves’ disease causing
,thyroglobulin antibody(TGAb). There were calculated the average values,
severe hyperthyroidism and primary hyperparathyroidism along with vitamin D
standard deviation, incidence and statistical significance of p value !0.01. Beck
deficiency is presented. This case further illustrates that primary hyperparathyr-
depression test was used to determine the level and severity of depression.
oidism may be diagnosed in the context of severe vitamin D deficiency, being
Results
aggravated by vitamin D administration and that primary hyperparathyroidism
Absence of depression was associated with elevated TSH (6.49G3) and low
may coexist with thyroid disorders.
FT4(10G6); TPOAb values (199G12) and TGAb values (358G8). Minimum
DOI: 10.1530/endoabs.49.EP1300
depression was correlated with elevated TSH (6.6G3) and normal FT4 (14.8G
9.8); TPOAb values
(247G18) and TGAb values
(385G22). Moderate
depression has been associated with normal TSH (4.2G2) and normal FT4
(18.5G15); TPOAb values (253G26) and TGAb values (422G16). Severe
depression was accompanied by slightly elevated TSH (4.3G3) and normal
FT4(15.5G8.7); TPOAb values (336G18) and TGAb (425G22).
Conclusions
It was revealed a high incidence of depressive disorders among the pacients with
EP1301
chronic autoimmune thyroiditis with a distribution of medium and severe forms of
Primary underdosed hypothyroidism - parodontal implications
depression predominantly in women without any evidence of thyroid hormonal
in adults
level involvement.The study shows a heterogeneity of thyroid autoimmunity
Razvan Circo, Seila Ibadula & Eduard Circo
regarding the effect of antithyroid antibodies in generating psycho-emotional
Clinical Endocrinology Department, SCJU ‘Sf. Apostol Andrei’, Constanta,
processes commonly found in these patients.
Romania.
DOI: 10.1530/endoabs.49.EP1302
Introduction
Dento-maxillary system changes associated to thyroid disorders are constantly
present. Differentiated impairment, depending on the period of evolution of the
disease, explains the high percentage of over 60% of cases with parodonthopathy.
Aim of the study
Evaluating the oro-maxillo-facial changes in patients with underdose treated
EP1303
hypothyroidism.
Frequency and prognostic factors of non-diagnostic cytology in
Methods
ultrasound guided thyroid fine needle aspiration biopsy: a 2-year single
The study group comprised 154 patients with hypothyroidism, 132 women and 22
centre experience
men. The examination included the assessment of oral cavity under parodontal
Vasileios Chambidis, Athanasios Siolos, Zoe Efstathiadou, Albana Sykja,
status, the quality of dentition, changes of dento-maxillary dynamics.
Thomas Georgiou, Eleni Chambidou, Athanasios Panagiotou,
Results
Fotini Adamidou & Marina Kita
Facial and lip changes were present in 28.4% of cases; macroglossia 13%; mucoid
‘Hippokration’ General Hospital of Thessaloniki, Thessaloniki, Greece.
infiltration of lingual mucosa and oral submucosa K76%; gingivitis and chronic
marginal periodontitis K98%; pathological tooth mobility - grade 1(73%) and
grade 2 (15%); 12 patients (9.16%) required periodontal abscess drainage - 2
Aim
cases of upper premolars (14%) - 10 cases of lower molars (36,5%). Modification
Ultrasound-guided Fine Needle Aspiration Biopsy (USg-FNAB) is the most
of occlusion by changing maximum pressure points - 72 patients (52%). A total
accurate modality for distinguishing malignant or possibly malignant from benign
of 61 patients (46.5%) presented vestibular pockets - 23 periodontal (17.5%), 25
thyroid nodules. However, a certain amount of specimens turn out to be non-
palatal
(19%) and 13 with lingual localization (10%). The average time of
diagnostic or inadequate. Several factors contribute to this outcome such as the
evolution of hypothyroidism with subdosed treatment was 4.3G1.2 months.
examiner’s experience, characteristics of the nodule and patient’s compliance.
Dental cavities were present in 77% of patients; partial edentation - in 89.3%;
Understanding these factors could contribute to reduction of non-diagnostic
total edentation - 9.16%.
results.
Atrophied prosthetic field
Methods
Four cases (3%); 8 cases (6%): osteophitic hyperostosis. The average time of
All nodules examined by USg-FNAB between Jan 2014 and Nov 2015 at the
evolution of hyperthyroidism: 7.4G1.5 months. The specific dento-parodontal
thyroid clinic of our department were reviewed (nZ682 patients with 987
and prosthetic treatment previously assumes the control of the thyroid hormone
nodules). Patient demographic characteristics
(sex and age), nodule charac-
deficiency.
teristics (size, location, previous FNAB) and the experience of the examiner were
Conclusions
recorded.
Periodontal changes are almost constantly found in hypothyroidism. The extent of
Results
the disease without a normal substitution is directly proportional to the severity
The only factor that exhibited a significant positive association with non-
and a high incidence of complications.
diagnostic cytology on USg-FNA was the age of the patient (P ! 0.01). Nodule
DOI: 10.1530/endoabs.49.EP1301
size was marginally negatively associated (PZ0.054). No other factor emerged as
a predictor of non-diagnostic cytology.
Conclusions
The present study indicates that patient age is a prognostic factor for non-
diagnostic cytology on USg-FNA. This might be attributed to the fact that older
patients usually present with nodules baring morphologic characteristics such as
cystic composition and peripheral calcifications that are associated with non-
diagnostic cytology. On the other hand, the marginally negative association with
EP1302
nodule size, seems justified by the fact that small nodules are technically more
Assessment of the degree of depression in patients with chronic
difficult to biopsy. It is of note that the examiner’s experience has not emerged as
autoimmune thyroiditis depending on the serum autoantibodies and
a prognostic factor, possibly due to the fact that nodules which are not easily
thyroid hormone levels
accessible are usually biopsied by more experienced staff.
Seila Ibadula, Olesea Scinic & Eduard Circo
DOI: 10.1530/endoabs.49.EP1303
Spitalul Judetean de Urgenta ‘Sf.Apostol Andrei’, Constanta, Romania.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1304
EP1306
Juvenile hypothyroidism-particularities in the development of the
Audit of utility of radio-isotope scan in the investigation of
dento-maxilary system
thyrotoxicosis or subclinical hyperthyroidism and timing of
Razvan Circo, Seila Ibadula & Eduard Circo
anti-thyroid medication
Spitalul Judetean de Urgenta ‘Sf. Apostol Andrei’, Constanta, Romania.
Satish Artham, Heather MacFarlane, Nishwa Ali & Andy James
Royal Victoria Infirmary, Newcastle, UK.
Introduction
Juvenile hypothyiroidism shows various complications depending on the
Thyrotoxicosis is one of the most common clinical problems in patients referred
correctitude of substitutive treatment.
to endocrine clinic. TRAb is specific for graves disease (GD) and radioisotope
Aims of the study
scan (RIS) is useful diagnostic test in the investigation of thyrotoxicosis. RIS is
To identify the massive facial changes with occlusive disorders, dental
commonly used when TRAb is borderline or negative to exclude thyroiditis.
malpositions, altered chronology of dental eruption, periodontal changes in
Aims and methods
terms of absence of thyroid replacement therapy or drug sub-dosing.
To look at the use of RIS in the investigation of thyrotoxicosis and sub-clinical
Methods
hyperthyroidism (SCH), and use of anti-thyroid medication (ATM) in these
The study group comprised 24 children, 15 girls and 8 boys; 4 cases of congenital
conditions. Retrospective audit, data collected from electronic pathology and
myxedema;19 cases of earned hypothyroidism and the mean age was 9G2.4
radiology system, and clinic letters over 11months (Jan 15 to Nov 15).
years- that presented in their evolution periods of underdosed substitutive
Results
thyroxine treatment.
nZ66, of which 63 (95.5%) were sub-clinical hyperthyroidism or thyrotoxicosis.
Results
FemaleZ52(82.5%). Mean age: 54.07 years. 60 (95%) patients had TRAb
Facial changes: infiltrated facial skin and lips; widened transverse diameter of the
checked and 3 (5%) patients not. (nZ1 SCH, planned for radio iodine, nZ1 on
skull; microretrognathia - 12 cases (52%). pale and infiltrated lingual and jugal
carbimazole and planned for radioiodine, nZ1
TRAb requested but not
mucosa, 14 children (60.8%) - lingual fungal detritus; 8 children (34.7%) -
processed). All patient with TRAb Kve and 5 patients with TRAb Cve had
‘geographic’ tongue. Occlusive disorders: frontal malocclusion in the sagittal
RIS. 23 (36.5%) were diagnosed with graves disease. 3 patients with negative
plane - 19 children (80%); front reverse occlusion - 8 cases (34.7%); open bite -
TRAb who were later diagnosed with GD on RIS were commenced on
4 cases (17.4%); lower proalveolodentition with interdental spacing - 17 children
carbimazole before diagnosis. 17 (27%) were diagnosed with thyroiditis, of which
(68%). Dental malpositions:reverse overlap - 11 cases (47.8%), eruption of
4
(23.5%) were commenced on carbimazole before diagnosis.
central upper incisors in vestibular position - 1 case (4.3%); bilateral ectopic
Conclusion
canine - 1 case (4.3%); dentoalveolar incongruence - 1 case
(4.3%). The
This audit shows appropriate use of RIS in all patients in the investigation of
chronology of dental eruption: late eruption - 19 patients (78.2%); prolonged
thyrotoxicosis and SCH. 5 patients with positive TRAb had RIS as TRAb was
mixed dentition - 14 patients (60.8%); taurodontism - upper molars-1 case
borderline and history was not typical of graves disease.
7 patients were
(4.3%); accelerating the teeth eruption when introducing thyroxine therapy
commenced on ATM before diagnosis of GD. All these patients had mild to
between 6 and 8 months. Periodontal changes: pathological dental mobility,
moderate thyrotoxicosis. These patients could have been started on b-blockers
pathological diastemas, gingival recession, real periodontal pockets - 8 cases
rather than ATM as they are associated with side effects of agranulocytosis which
(34.7%).
can risk life threatening infections.
Conclusions
DOI: 10.1530/endoabs.49.EP1306
In hypothyroid child prevail the disorders of occlusion and chronology of
eruption. Early diagnosis and a well conducted thyroxine treatment requires the
prophylaxy of dento-maxillary complications in children.
DOI: 10.1530/endoabs.49.EP1304
EP1307
Thyroid autoimmunity and frequency of malignant or suspicious for
malignancy thyroid nodule cytology
Athanasios Siolos, Vasileios Chambidis, Zoe Efstathiadou,
Thomas Georgiou, Athanasios Panagiotou, Fotini Adamidou & Marina Kita
‘Hippokration’ General Hospital of Thessaloniki, Thessaloniki, Greece.
EP1305
Introduction
Thyrotoxic periodic paralysis
Thyroid autoimmunity has been associated with the diagnosis of differentiated
Ahmet Kaya & Mustafa Kulaksizoglu
thyroid (DTC) cancer in surgical series. However, this finding has not been
Division of Endocrinology and Metabolism, Meram Medical Faculty,
consistent in Fine Needle Aspiration Biopsy (FNAB) cytology series.
Necmettin Erbakan University, Konya, Turkey.
Aim
We aimed to investigate the association between thyroid autoimmunity and DTC
in patients who underwent ultrasound-guided FNAB.
Thyrotoxic periodic paralysis (TPP) is due to a fall in potassium levels and threat
Methods
life if it effects respiratory muscles. Men are more effected than women, and
A retrospective analysis of patients who had undergone ultrasound-guided FNAB
lower extremeties are more prone to involvement. Serum potassium in
between Jan 2014 and Nov 2015 was performed. Patients were classified into two
hyperthroidism is usually normal, but NaC/KC ATP’ase sensitivity is increased
groups, according to the presence of thyroid auto-antibodies
(ATA): ATA
and extracellular potassium rapidly passes to the intracellular space. Beta
negative (ATA K) and ATA positive (ATAC) patients. In ATAC patients,
blockers, small dose potassium replacement and hyperthyroidism treatment
either one or both antibody types
(anti-thyroid peroxidase abs or anti-
blocks this shift and TPP can be treated. Achieving euthyroidism is essential for
thyroglobulin abs) were positive. Patient demographic characteristics, the
the cure of TPP. Although hyperthyroidism effects mainly females, TPP is seen
presence of risk factors for thyroid cancer and nodule size were recorded.
more in males especially in the second and fourth decades. Periodic paralysis is
Cytology reports were classified, according to the Royal College of Pathologists
seen only in 2% of thyrotoxic patients which is characterized by hypokalemia,
guidance, as negative for malignancy
(Thy2), possible neoplasm
(Thy3),
proximal muscle weakness and acute onset. We present four cases of male
suspicious for malignancy
(Thy4) and malignant
(Thy5). Non-diagnostic
patients aged between 28 and 36 years old. Their complaints were, fatique,
cytology reports (Thy1) were excluded. The frequency of possible neoplasm,
weakness and difficuilty in walking. Two patients had known Graves’ disease and
suspicious or malignant (Thy3, Thy4, Thy5) was estimated in the two patient
two patients were diagnosed as new onset Graves’ disease. They did not have
groups (ATAK, ATAC).
predisposing factors such as alcohol intake, using diuretics or laxatives. On
Results
phsical examination, they all had proximal muscle weakness and diminished
During the study period 673 nodules of 466 patients were biopsied. Thyroid
lower extremity deep tendon reflexes. Their potassium levels were 2.7-2.3-2.1-
autoimmunity was present in 41.8% of patients. The frequency of suspicious or
1.9 mEq/l respectively. Their thyroid antibodies were positive, TSH levels were
malignant (Thy3, Thy4, Thy5) cytology reports was comparable in the two patient
supressed and free thyroid hormones were elevated. Patients were treated with
groups (5.8% in ATAC patients vs. 4% in ATAK patients; PZ0.303).
potassium replacement and antithyroid drugs and lower extremity weakness and
Conclusion
paralysis were disappeared. HPP is a genetic disorder but rarely it can be due to
In the present study, no association between the presence of thyroid autoimmunity
thyrotoxicosis. Although TTP is more commonly seen in Graves disease, it is free
and suspicious or malignant findings in thyroid nodule cytology was found.
of disease duration and severity.
DOI: 10.1530/endoabs.49.EP1307
DOI: 10.1530/endoabs.49.EP1305
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1308
EP1310
Clinical experience with glucocorticoid therapy in patients with
Relapsing Graves’ hyperthyroidism in a male patient with central
endocrine ophthalmopathy
hypothyroidism after surgery of craniopharyngioma: case report
Irina Bourko1, Halina Korolenko2, Olga Bourko3, Oksana Dudich1 &
Anisoara Bumbu, Yawa Abouleka, Louis Potier, Ronan Roussel &
Viktoria Krasilnikova1
Michel Marre
1Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus;
Universitary Hospital Bichat Claude-Bernard, Paris, France.
210th Clinical Hospital, Minsk, Belarus;3Republican Scientific and
Practical Center of Cardiologz, Minsk, Belarus.
Introduction
Graves’ disease is an autoimmune thyroiditis, less common in men but with
Objective
relapse of hyperthyroidism significantly more frequent in men than in women
To evaluate the efficacy, safety and to determine the criteria for the glucocorticoid
after anti-thyroid medications’ withdrawal. Craniopharyngioma is a rare brain
therapy scheme: intravenous pulse therapy followed by tablet form in prolonged
tumor which arises in the pituitary stalk and project into the hypothalamus. The
regime in the treatment of active phase of endocrine ophthalmopathy (EOP).
distribution by age is bimodal with a slight male predominance and a poor
Materials and methods
survival rate for older than 65 years. The association of these pathologies is
28 patients of both sexes (52 eyes) with endocrine ophthalmopathy in the active
extremely rare.
phase were included in the study. The average age - 43.4G10.6 years. The
Observation
duration of the disease ranged from 3 to 12 months. The activity of disease was
We report the case of a 67 years-old patient who presented a severe thyrotoxicosis
evaluated according to a scale of clinical activity of EOP - Clinical Activity Score
due to a relapse of a Graves’ disease in remission since 2009. At the moment of
(CAS), and thickening of the extraocular muscles based on MSCT of the orbits.
presentation the patient was in treatment with levothyroxine for a central
Results
hypothyroidism secondary of a craniopharingyoma surgery. Clinically he
One month after the start of pulse therapy there was a significant reduction of EOP
presented tachycardia, weight loss, confusion, anorexia and biologically he had
activity and severity in all patients, which was confirmed by an increase in vision,
low TSH value and very high FT4 (100 pmol/l) and FT3 (50 pmol/l) values which
a decrease in the level of intraocular pressure, reduction in the amount
were increasing 5 days after stopping the levothyroxine. TSH receptor antibodies
exophthalmus at 0.8G0.02 mm (P !0.05) and the frequency of diplopia. 3
were positives (2.8 U/l) and the I-123 scintigraphy found an intense and uniform
months after the start of glucocorticoid therapy in 100% of cases a transition to the
fixation confirming the relapse of Graves’ disease. A treatment with carbimazole
inactive phase of the disease was determined. Reoccurrence of the disease after 12
60 mg per day was started with a strictly surveillance of hepatic enzymes. There
months was diagnosed in 3 patients (10.7%).
was a decrease of thyroid hormones and hepatic enzymes and also symptoms in 2
Conclusions:
weeks. A thyroidectomy is to discuss, because of the relapse and the severity of
i) Intravenous pulse therapy with high doses of methylprednisolon followed by
the symptoms, after achieving the euthyroid status.
oral administration in prolonged regime is effective and safe; it contributes to the
Conclusion
rapid achievement of clinical effect and stable remission of the disease. ii) A
We described here, for the first time, an association of a relapsing Graves’ disease
thickening of the extraocular muscles is the criteria for the start of glucocorticoid
in patient with hormonal supplementation for central hypothyroidism after
therapy.
surgery of craniopharyngioma, with a favorable evolution after treatment with
DOI: 10.1530/endoabs.49.EP1308
anti-thyroid medications.
DOI: 10.1530/endoabs.49.EP1310
EP1309
Thyroid storm presenting in the context of recent influenza vaccination
and untreated Graves disease
Neil Kelly, Dushyant Sharma & Reza Zaidi
EP1311
Royal Liverpool University Hospital, Liverpool, UK.
TSH normalization and negative anti-TSH receptor
antibodies - Predictive value for remission in Graves’ disease
Catarina Roque, Francisco Sousa Santos, Ricardo Capita˜o, Carlos Bello,
Introduction
Catia Ferrinho & Carlos Vasconcelos
Thyroid Storm is a life-threatening but rare (incidence 0.2 per 100 000) disease
Endocrine Clinic, Hospital de Egas Moniz C.H.L.O. E.P.E., Lisbon,
state which presents as an extreme form of thyrotoxicosis. A hyper-metabolic
Portugal.
state resulting from excessive thyroid hormone release which can be precipitated
by both thyroidal and non-thyroidal illness.
Case
Graves’ disease is the most common cause of hyperthyroidism in non-endemic
In this case we discuss a 72 year old female with previously treated Graves
areas and antithyroid drugs are the preferred first-line therapy in many centers.
disease who presented in thyroid storm one week after annual flu vaccination. On
The aim of this retrospective investigation was to verify the association of
initial presentation, she was in overt heart failure with bilateral pleural effusions
remission with the achievement of normal TSH and free-T4 during the first 18
and a community acquired pneumonia, atrial fibrillation at a rate of 170 beats per
months of treatment and to compare it with negative anti-TSH-receptor antibodies
minute and acute confusion with significant agitation. The decision to treat
at 18 months, a marker with known prognostic value. All patients diagnosed with
initially with beta blockers was complicated by her being in heart failure with
Graves’ disease from 2008 to 2015 were selected. Those with more than 2 years of
significant pulmonary oedema and a rapid ventricular rate precipitating a peri-
follow-up and with synchronous determination of TSH, free-T4 (fT4), free-T3
arrest state. The guidance of the cardiologists to give amiodarone to chemically
and anti-TSH-receptor antibodies (TRAb) performed at our clinic were included.
cardiovert conflicted with her thyrotoxic state. Relevant Data includes a Thyroid
We compared TRAb titer, TRAb positivity, TSH and fT4, between the group that
stimulating hormone of !0.05 mIU/l and a T4 of 96.5 pmol/l. A biochemically
achieved remission and the one that did not, for the length of treatment and follow
euthyroid state was eventually achieved using propathyaurocil, intravenous
up. We obtained 71 patients with mean age of 47 years of which 76% were
hydrocortisone, Lugols Iodine and Bile salts. Beta blockers and amiodarone were
females. The mean follow-up after remission was 2 years. Remission was
used with caution in the context of heart failure/suspected thyrotoxic
achieved in 28% patients after 18 months of treatment. There were no significant
cardiomyopathy and a thyrotoxic state respectively. Further investigation showed
differences in sex or age among the 2 groups. No association was found between
the patient had previously been treated for Graves and this was a late presentation
the development of hypothyroidism during therapy and remission. Negative
recurrence seven years after completing block and replace therapy.
TRAbs at 18 months associated with remission significantly (P!0.001) with a
Discussion
strength of association of 0.86. A non-supressed TSH accompanied by normal fT4
We present this case because it highlights a rare case of thyroid storm presenting
levels achieved during therapy was associated significantly with remission (P !
seven years following initial block and replace therapy had discontinued. The
0.001) with a strength of association of
0.74. Logistic regression with this
temporal relationship between presentation and the administration of the flu
parameter could explain 59.8% of remissions after initial therapy with P!0.001.
vaccination mean this must be considered as a potential non-thyroidal precipitant.
This profile of thyroid function was associated with negative TRAbs significantly
The presentation in fast atrial fibrillation is also significant as the treatment of
(P!0.001). Achieving a non-suppressed TSH in the presence of normal fT4,
choice was amiodarone and this could have potentially exacerbated her
during the first 18 months of therapy, associates with TRAb negativization and
underlying thyrotoxicosis.
could predict remission in approximately 60% of patients.
DOI: 10.1530/endoabs.49.EP1309
DOI: 10.1530/endoabs.49.EP1311
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1312
6
months).
44% would recommend routine neck US, and
19.3% would
recommend routine DEXA. In a case of thyrotoxicosis due to 3 cm toxic nodule
Treatment choice and patient satisfaction in thyrotoxicosis
tirads 4a most endocrinologists (70%) would refer to RAI ablation, 46.4% without
Helen Conaglen, Jade Tamatea, Mark Swarbrick, John Conaglen &
FNA and 23.7% with FNA. No significant difference was found in correlation
Marianne Elston
with gender, years of board certificate, or work environment.
Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand.
DOI: 10.1530/endoabs.49.EP1313
Background
Thyrotoxicosis may be associated with considerable patient morbidity. Graves’
disease (GD) and toxic multinodular goitre (TMNG) are the most common causes
of thyrotoxicosis. Therapeutic options include anti-thyroid medication or
definitive treatment by radioiodine or surgery. Efficacy, quality of life and cost-
effectiveness are among the outcomes that have been compared between these
EP1314
two therapies. However, there is still no clear consensus as to which treatment
option offers a better outcome.
Case report: identification and characterization of interference by
IgM anti-streptavidin antibody in a patient with spurious thyroid
Aims
function tests
The aim of this study was to assess quality of life amongst patients who received
Leo Lam3, Warwick Bagg1,2, Julie Lim4, Martin Middleditch5 &
anti-thyroid medication, radioiodine or surgery and to assess patient satisfaction
Campbell Kyle3,6
with the treatment modality selected.
1Department of Endocrinology, Auckland District Health Board, Auckland,
Method
New Zealand;2Medical Programme Directorate, Faculty of Medical and
Participants in a prospective study with new onset thyrotoxicosis were invited to
Health Sciences, The University of Auckland, Auckland, New Zealand;
participate. Those who agreed to be involved completed a questionnaire detailing
3Department of Chemical Pathology, LabPlus, Auckland City Hospital,
factors involved in treatment choice, quality of life (ThyPRO) and satisfaction
Auckland, New Zealand;4Department of Physiology, School of Medical
with their treatment.
Sciences, New Zealand National Eye Centre, The University of Auckland,
Results
Auckland, New Zealand;5Auckland Science Analytical Services,
Of those eligible for the study
146 patients completed the questionnaires,
University of Auckland, Auckland, New Zealand;6Department of
representing a return rate of 73%. GD was the cause of the thyrotoxicosis in 84%
Biochemistry, Labtests, Auckland, New Zealand.
and TMNG in 16%. Fifty-eight percent of patients had received anti-thyroid
medication, 19% radioiodine, and 22% thyroid surgery, the latter two groups
usually following a period of medical therapy. The impact of treatment on
Introduction
recovery time, activities of daily living, possibility of depression or anxiety, and
Falsely high FT4 and FT3 with concurrent falsely low TSH have been reported in
doctor’s recommendations were identified as the most important factors in
patients taking biotin and in a few case reports of patients with IgG anti-
choosing a treatment. Satisfaction levels were high across all three treatment
streptavidin antibody. However, other isotypes and effects on other immunoas-
types. There was no difference in quality of life between the treatment types apart
says have not been reported.
from a higher score for cosmetic concerns in the surgical group.
Case
Conclusions
A 77 year female presented with worsening fatigue with a background of
These results indicate that overall patient satisfaction with treatment and quality
hyperthyroidism on carbimazole. Clinically she appeared hypothyroid. Her
of life are comparable across all three treatment options. Therefore, factors such
results on Roche Cobas platform were: TSH 0.75 mIU/l (R.I. 0.27-4.2), FT4
as patient preference and resource availability may be more important than
12 pmol/l (12-22) and FT3 8.1 pmol/l (3.9-6.8). However, tests repeated on
treatment type.
Siemens Centaur platform were: TSH 37 mIU/l (0.3-4.0), FT4 7 pmol/l (10-20)
DOI: 10.1530/endoabs.49.EP1312
and FT3 3.0 pmol/l (3.0-6.5), suggesting Cobas results were falsely low for TSH
and falsely high for FT4 and FT3. To identify the cause of interference a second
sample from the patient was preincubated with streptavidin microparticles. After
incubation TSH on Cobas platform increased from 0.2 to 0.7 mIU/l, while FT4
reduced from 28 to 16 pmol/l, and FT3 from 9.0 to 4.7 pmol/l. Siemens results
were unchanged. Elution of streptavidin microparticles with 0.1M citric acid
identified a 75 kDa band on reducing SDS-PAGE. Purification and sequencing of
peptide fragments by LC-MSMS of this band identified this protein as IgM heavy
EP1313
chain. This demonstrates IgM anti-streptavidin antibody as the cause of
Management of relapsing Graves: a clinical survey among
interference. The patient’s hypothyroid symptoms resolved when carbizamole
endocrinologists in Israel
was stopped. The effect of preincubation with streptavidin microparticles was also
Shlomit Koren1, Miriam Shteinshnaider1,4, Karen Or1,4, Dror Cantrell1,3,
tested on Roche Cobas immunoassays for FSH, LH, oestradiol and testosterone in
Carlos A Benbassat1,4 & Ronit Koren1
this patient’s serum. Sandwich immunoassays were falsely low and competitive
1Endocrine Institute, Assaf Harofeh Medical Center, Zerifin, Israel;
immunoassays were falsely high. Oestradiol exhibited the largest difference,
2Department of Internal Medicine A, Assaf Harofeh Medical Center,
at 240 pmol/l initially but becoming undetectable following incubation.
Zerifin, Israel;3Department of Internal Medicine C, Zerifin, Israel;
Conclusions
4Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
This is the first case describing IgM anti-streptavidin antibody as the cause of
interference on thyroid function tests and also shows its effects on other
immunoassays.
Background
DOI: 10.1530/endoabs.49.EP1314
The management of relapsing Graves’ disease is controversial. Previous surveys
from different regions in the world demonstrated variations in the clinical
practices of patients with Graves’ disease relapse.
Methods
To determine management pattern among endocrinologists in Israel an electronic
questionnaire was e-mailed to all members of the Israeli Endocrine Society.
Questionnaires included demographic data and clinical scenarios with questions
regarding the treatment and follow up of patients with relapsing Graves’ disease.
Results
EP1315
We received 98 responses from Israeli endocrinologists. 42 (43%) males and 56
Severe Grave’s dermopathy and acropachy discording with moderate
(57%) females. 41.8% had board certificate for more than 10 years. 72.4%
ophtalmopathy: (a case report)
responders work in hospital environment and 26.5% work in community clinics.
Dhiyaeddine Bellarbi, Hafsa Si Youcef & Noura Soumeya Fedala
61.2% see more than 10 thyroid patients in clinic per week. When managing
Endocrine and Metabolic Diseases Department, Bab El Oued Hospital,
Graves’ relapse following ATD treatment in a young male, 68% would restart
Algiers, Algeria.
ATD (98% mercaptizol) and 32% would refer to RAI treatment. Interestingly,
endocrinologist who treat more thyroid patients (more than 10/week) tend to
choose ATD over RAI (PZ0.04). In case of recurrent Graves’ and ophtalmopaty
Introduction
50% would continue ATD, 22.4% would recommend RAI treatment and 27.6%
Pretibial Myxedema(PM) and acropachy(AP) are rare extrathyroidal mani-
surgery. Most endocrinologists (56%) would continue ATD for 12-24 months.
festations of Graves’ disease observed only in
0.5-4% of all cases. These
75% would monitor CBC and liver function (39% for the first month and 36% for
extrathyroidal manifestations are generally associated to severe ophtalmopathy.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Only few cases of severe thyroid dermopathy and achropachy occurring with
Aim
moderate ophtalmopathy were reported.
There are studies showing that Hashimoto’s thyroiditis (HT) progresses more
Observation
rapidly, thyroid echogenicity is lower and thyroid autoantibodies are higher titer
We present a 60years old female patient who developed grave’s disease on a pre-
positive in immunoglobulin G4 (IGg4) positive patients.But a small number of
existing goiter associated to extrathyroidal manifestations. Physical examination
studies that do not support this data have also been published.We planned this
revealed; some signs of hyperthyroidism, moderate exophthalmos measured by
study to evaluate the findings of IgG4 (C) Hashimoto’s thyroiditis cases.
hertel’s exophtalmometer at 20 for right eye and 19 for Left eye, bilateral severe
Materials and methods
PM manifested by elephantiasis, severe AP manifested by clubbing and finger
New diagnosis without treatment of thyroid 92 patients with HT and 60 healthy
deformations, compressive goiter with 3 palpated nodules (a 5 and 4 cm nodules
volunteers were included fort he study between October 2015 and October 2016.
occupying the totality of the right and left lobe respectively, and a 2 cm left lobo-
After 8 hours of fasting, basal thyroid function tests and serum IgG4 level were
isthmic nodule) which were confirmed by ultrasound of the neck that showed
analyzed in the whole of the individual and thyroid ultrasonography was
hypervascularization of the normal parenchyma. Thyroid function tests before
performed all of them.HT patients were divided into subgroups with IGG4 (group
treatment showed FT3 predominating hyperthyroidism: TSHus!0.005, FT4Z
1) and without IgG4 (group 2).
4.11 ng/dl (N:0.7-1.4), FT3O30 pmol/l (N:3.0-8.3 pmol/l). Anti-thyroid per-
Findings
oxidase antibodies were positive 149.6 UI/ml (N:!12 UI/ml). Total thyroid-
Mean IgG4 levels were similar between patient group and healthy volun-
ectomy was performed after normalization of thyroid function under 60 mg of
teers.There were 22 patients in group 1 and 70 patients in group 2. Mean age
neomercazol, and this goiter was benignant on pathology. PM was stabilized after
values of two groups were similar.Statistically men patients were more in group 1
surgery and management of hypothyroidime by levothyroxine.
(PZ0.009). There was no statistically significant difference was detected between
Conclusion
two groups in terms of mean thyroid stimulant hormone (TSH), free T4, free T3,
PM and AP are very rare. They reflect the severity of autoimmunity and long
anti-TPO and anti-Tg antibodies, thyroid volume, thyroid nodule quantity and
duration of hyperthyroidism. These signs are often observed in severe
thyroid parenchyma echogenicity.
hyperthyroidism and are constantly associated to ophtalmopathy which is
Results
generally severe. Infiltration corresponds to the accumulation of GAG in the 3
There are publications in the literature that, IgG4 positive HT is more often
conditions. Moderate ophtalmopathy occurring with severe PM(elephantiasis)
detected in younger age and men patients, it is related lower echogenity
and AP(clubbing and deformations) is not habitually reported.
ultrasonographically and higher titre thyroid autoantibodies. However in our
DOI: 10.1530/endoabs.49.EP1315
study, among IgG4 positive HT patients, statistically meaning difference was not
detected in terms of parameters examined, except more men numbers. We have
thought that, these results arised because of the premise of working and IgG4
positive case number scarcity.
DOI: 10.1530/endoabs.49.EP1317
EP1316
The importance of the study of several immunoregulatory cytokines in
the manifest hypothyroidism
Marina Orlova, Arina Frolova, Tatiana Rodionova, Irina Badak &
Tatiana Baitman
Saratov State Medical University named V.I. Razumovsky, Saratov, Russia.
The research goal was to study serum concentration of immunoregulatory
EP1318
cytokines
(IL-1ß, IL-6ß, IL-8ß, IL-10ß) in
80
patients with manifest
TRAB positive thyroid dysfunction associated with Alemtuzumab
hypothyroidism at the age of
21-50.
48
patients suffering from chronic
treatment for MS: A case series
autoimmune hypothyroidism and 32 patients with postoperative hypothyroidism
Aoife Garrahy, Sulaiman Ali, Siobhan McQuaid & Maria M Byrne
were examined. It was revealed that autoimmune hypothyroidism effects balance
Department of Endocrinology, Mater Misericordiae Hospital, Dublin,
disturbance of cytokine-producing activity Th1 and Th2 types, this plays an
Ireland.
important role in development of autoimmune state, chronization and disease
progress. The research goal was to study kidneys’ function in conditions of
thyroid hormone deficit. Estimation of kidneys’ function included study of daily
Alemtuzumab is a monoclonal antibody directed against CD52 licenced for the
microalbuminuria; serum concentration of creatinine and rate calculation of
treatment of relapsing remitting multiple sclerosis (MS). Thyroid dysfunction
glomerular filtration with MDRD formula; examination of urea level; potassium
occurs in one third of patients, likely secondary to lymphocyte reconstitution.
and natrium in blood serum; urinary excretion of chemokines: monocyte
Case 1
chemoattractant protein-1 (MCP-1) and Regulated on Activation, Normal T-cell
A 36 year old female, treated with alemtuzumab 15 months prior, presented to
Expressed and Secreted. In both groups of patients with hypothyroidism is
antenatal clinic at 12 weeks gestation with symptoms of thyrotoxicosis. fT4 was
established a significant decrease of glomerular filtration rate, tubular
83.7 pmol/l (RR 12-22), TSH suppressed, TRAB positive. She was treated with
reabsorption, and increase sodium excretion in the urine, indicating a violation
carbimazole and remains on antithyroid medication at 30 weeks gestation; TRAB
of tubular functions in form of decrease sodium reabsorption in the proximal
titer has risen to O40 IU/l (RR 0-1.5).
tubule, and was accompanied by a decrease in median serum sodium levels below
Case 2
the normal range. Level of proinflammatory cytokines IL-1ß, IL-6ß, IL-8ß and
A 36 year old male, treated with alemtuzumab 18 months prior, was admitted for
anti-inflammatory cytokine IL-10ß; vascular endothelial growth factor in blood
investigation of weight loss and functional decline. fT4 was 37.9 pmol/l, TSH was
serum of 80 patients with clinical hypothyroidism and 50 healthy persons were
suppressed and he had a large smooth goiter. TRAB was 18.9 IU/l. He was treated
studied. Our data are the evidence of increase in patients with autoimmune
with carbimazole and is undergoing rehabilitation.
hypothyroidism of IL-6 level of blood serum and urea excretion level of anti-
Case 3
inflammatory cytokine MCP-1, decrease of IL-10 production in patients with
A 39 year old female, treated with alemtuzumab 2 months prior, was referred to
clinical hypothyroidism in their second age period. Healthy persons aged over 35
the endocrine clinic with fT4 of 60.2, suppressed TSH and TRAB 24 IU/l. She
demonstrate increase of level of anti-inflammatory cytokine IL-10
on a
was asymptomatic and became hypothyroid four weeks later (fT4 !5.2 pmol/l,
background of gently cut cue of proinflammatory cytokines IL-1ß, IL-8ß.
TSH 58 mU/l). Twelve months on, she is euthryoid on L-thyroxine 100 mg daily.
DOI: 10.1530/endoabs.49.EP1316
In this case series we demonstrate three cases of alemtuzumab induced thyroid
disease, occurring 2-18 months post treatment, all of which are TRAB positive.
Case 1 highlights that women of child-bearing age treated with alemtuzumab
should be counseled regarding the risk of thyroid dysfunction in future pregnancy.
TRAB should be monitored in each trimester and close monitoring for foetal
thyrotoxicosis is required. Case 3 highlights that TRAB positivity is not specific
EP1317
for Graves disease and in this case is associated with overt hypothyroidism. This
The position of immunoglobuline G4 positive in Hashimoto’s thyroiditis
case series illustrate the unpredictable clinical course of thyroid dysfunction in
Zeynep Cetin1, Bulent Can1, Merve Catak1, Ozden Ozdemir Baser1,
patients treated with alemtuzumab; long-term monitoring of thyroid function is
Dilek Berker1 & Serdar Guler2
recommended.
1Numune Training and Research Hospital, Ankara, Turkey;2Liv Hospital,
DOI: 10.1530/endoabs.49.EP1318
Ankara, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1319
controls (PZ0.04). However, fT3 levels were similar statistically between groups
(PZ0.347), free T4 was significantly lower in the patient group (PZ0.01). Mean
Serum levels of insulin-like growth factor 1 in patients with
native thiol and total thiol levels were significantly higher in the patient group
hyperthyroidism or euthyroidism
compared to the control group (PZ0.04 and PZ0.036, respectively). There were
Fen-Yu Tseng1, Yen-Ting Chen2, Yu-Chao Chi2, Pei-Lung Chen1,3 &
not any statistically significant differences between groups regarding calculated
Wei-Shiung Yang1,2
disulphide/native thiol (-S-S-/-SH), disulphide /total thiol (-S-S-/-SHC-S-S-),
1Department of Internal Medicine, National Taiwan University Hospital,
native thiol/total thiol (-SH/-SHC-S-S-) ratios. The association between acute
Taipei, Taiwan;2Graduate Institute of Clinical Medicine, National Taiwan
phase reactants and thiol-disulphide parameters were evaluated and no significant
University, Taipei, Taiwan;3Department of Medical Genetics, National
correlation was found. Similarly, there was no significant correlation between
Taiwan University Hospital, Taipei, Taiwan.
antibody positivity and thiol-disulphide parameters.
Conclusion
Background
To our knowledge, our study is the first one that evaluated the association between
Insulin-like growth factor 1 (IGF1) has molecular structure similar to insulin. As
HT and thiol-disulphide status according to Erel and Neselioglu method. In
an important mediator of growth hormone, IGF-1 plays roles in growth of
conclusion native and total thiol levels were detected to be increased in euthyroid
children and anabolic effects of adults. We evaluate serum levels of IGF-1 in
HT patients, these results were not consisted with the literature data using
patients with hyperthyroidism or euthyroidism.
different methods.
Subjects and methods
DOI: 10.1530/endoabs.49.EP1320
In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid
individuals (EU group) were recruited. The patients of HY group were treated
with anti-thyroid regimens as clinically indicated, whereas no medication was
given to EU group. The demographic characteristics, anthropometric and
laboratory data of both groups at baseline and at the 6th month were compared.
Associations between levels of IGF1 and free thyroxine (fT4), TSH, or log
transformation of TSH (logTSH) were analyzed.
Results
At baseline, the HY group had significantly higher serum IGF1 levels than the EU
group (median (Q1, Q3): 305.4 (257.4, 368.1) vs 236.7 (184.6, 318.8) ng/ml,
EP1321
P!0.01). The serum IGF-1 levels of the HY group decreased after anti-thyroid
Hashimoto Encephalopathy with polymorphic neuropsychiatric signs:
regimens, but still were higher than that of the EU group at the 6th month (299.5
a case report
(249.9, 397.9) vs 222.1 (190.2, 305.4) ng/ml, P!0.01). At the baseline, the serum
Diana Simoniene1,2, Raimonda Klimaite1,2, Greta Mikelaityte2 &
levels of IGF1 in all patients were positively associated with fT4 (bZ29.02,
Evalda Danyte1,3
P!0.01) and negatively associated with TSH (bZK31.46, PZ0.04). The
1Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,
associations between serum levels of IGF1 with fT4 or TSH became insignificant
Kaunas, Lithuania;2Lithuanian University of Health Sciences, Kaunas,
at the 6th month. However, the serum IGF1 levels were persistently negatively
Lithuania;3Institute of Endocrinology, Lithuanian University of Health
associated with logTSH both at baseline (bZK29.04, P!0.01) and at the 6th
Sciences, Kaunas, Lithuania.
month (bZK26.65, PZ0.02).
Conclusions
In comparison to EU group, patients with hyperthyroidism had higher serum IGF1
Hashimoto encephalopathy (HE) is a rare and steroid responsive encephalopathy
levels, which decreased after anti-thyroid regimens. The serum IGF1
associated with autoimmune thyroiditis (1). Patients with Hashimoto encephalo-
concentrations were negatively associated with logTSH in patients with
pathy may present with a variety of neuropsychiatric signs (2). 68-year old
hyperthyroidism or euthyroidism.
woman was admitted to the Neurology Department, of Hospital of Lithuanian
University of Health Sciences, Kauno klinikos (HLUHS KK), due to disorder of
DOI: 10.1530/endoabs.49.EP1319
consciousness of uncertain aetiology in August
2016. The signs of motor
dysfunction, generalized rigidity, and disorientation, with several episodes of loss
of and recurrent episodes of psychosis with hallucinations were observed since
2011. She had hospitalisations in neurology units of several hospitals and was
discharged with different diagnoses and modes of treatment. She developed
cerebral oedema with abundant myoclonic seizures in extremities in August 2016.
The possibility of ischemic, neurodegenerative or neuro-inflammatory disease
was ruled out in LUHS KC. Irregular activity of slow range waves was observed
in EEG. Brain CT showed no signs of ischemia. High protein concentration was
EP1320
found in lumbar aspirate. Brain MRI SI T2W revealed changes characteristic of
HE. Laboratory tests: FT4 6.7 pmol/l (normal 9-21), TSH 17.71 mU/l (0.4-3.6),
Evaluation of oxidative stres by means of thiol-disulphide homeostasis
antiTPO 270 kU/l (0-2), and signs of chronic thyroiditis in thyroid ultrasound
in patients with euthyroid Hashimoto’s thyroiditis
made possible to diagnose autoimmune thyroiditis with hypothyroidism and HE.
Merve Dirikoc1, Oya Topaloglu2, Cevdet Aydin2, Ahmet Dirikoc2,
The treatment with L-thyroxine
50 mg/d, and
3-day bolus therapy of
Sefika Burcak Polat2, Ozcan Erel3, Reyhan Ersoy2 & Bekir Cakir2
Methylprednisolone
1 g/d was started with rapid regression of clinical
1Department of Internal Medicine, Ataturk Education and Research
neurological signs. Prednisolone per os followed, with gradually reduced dose.
Hospital, Ankara, Turkey;2Department of Endocrinology and Metabolism,
The patient’s condition improved significantly and she was discharged. During
Yildirim Beyazit University School of Medicine, Ankara, Turkey;
follow-up appointment after 3 months, her neurological state and psychiatric
3Department of Biochemistry, Yildirim Beyazit University School of
condition were deemed stable, thyroid hormones in normal range on L-thyroxine
Medicine, Ankara, Turkey.
50 mg/d. MRI HE changes have regressed. Patients with unexplained
encephalopathy, progressive cognitive impairment, polymorphic neuropsychia-
Aim
tric should be considered to rule out HE, MRI and test of antiTPO levels should be
In this study we aimed to evaluate the oxidative stress via evaluating changes in
performed.
dynamic thiol-disulphide status in euthyroid patients with Hashimoto’s thyroiditis
DOI: 10.1530/endoabs.49.EP1321
(HT).
Methods
Fifty euthyroid patients with HT and 50 healthy individuals were enrolled in this
study. Thyroid function tests (free triiodothyronine (fT3), free thyroxine (fT4),
thyrotropin
(TSH)), acute phase reactants
(C-reactive protein
(CRP), high
sensitive CRP (hs-CRP)) and thiol-disulphide parameters were evaluated. Native
thiol
(-SH), total thiol
(-SHC-S-S-), disulphide
(-S-S-) levels, calculated
disulphide/native thiol (-S-S-/-SH), disulphide /total thiol (-S-S-/-SHC-S-S-),
native thiol/total thiol (-SH/-SHC-S-S-) ratios were compared between groups.
EP1322
Results
Cardiothyreosis: prevalence and risk factors
Mean age was 38.3G10.4 years in the patient group and 37.2G10.1 years in the
Meriem Yazidi1,2, Mélika Chihaoui1,2, Hiba Oueslati1, Ons Rejeb1,2,
control group. There were 43 (86%) females and 7 (14%) males in the patient
Sana Ouali1,2, Salsabil Rejaibi1, Fatma Chaker1,2 & Hédia Slimane1,2
group while there were 39 (78%) females and 11(22%) males in the control group.
1Faculté de médecine de Tunis, Université de Tunis El Manar, Tunis,
Median TSH level was significantly higher in the patient group compared to
Tunisia;2Hôpital La Rabta, Tunis, Tunisia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Background
1Faculté de médecine de Tunis, Université de Tunis El Manar, Tunis,
Cardiothyreosis (CT) or thyrotoxic heart is associated with higher morbidity and
Tunisia;2Hôpital La Rabta, Tunis, Tunisia.
mortality than the other forms of hyperthyroidism. Its risk factors have been
investigated in a limited number of studies. The aim of our study was to identify
Subclinical hypothyroidism (SCH) is a common disorder and indications of
risk factors of CT in patients with hyperthyroidism.
treatment are still being debated. The aim of our study was to describe the
Methods
therapeutic and evolutionary characteristics of SCH.
We identified 538 patients with a hospital discharge diagnosis of hyperthyroidism
Methods
from January 2000 to December 2015. Thirty five patients were diagnosed with
We undertook a longitudinal retrospective study in 110 patients with SCH
CT. Their demographic, clinical and biological characteristics were retro-
biologically defined by increased serum thyroid-stimulating hormone (TSH)
spectively studied and compared with those of 72 controls randomly selected,
levels (O4 mIU/l) and normal FT4. Pregnancy, age less than 18 years, personal
using univariate and multivariate analysis.
history of partial thyroidectomy or radioactive iodine therapy were exclusion
Results
criteria.
The prevalence of CT in patients hospitalized for hyperthyroidism was 6.5%. The
Results
cardiac complications were atrial fibrillation (AF) in 33 cases (6.1%) and cardiac
Sixty-one (55.5%) patients were put under L-thyroxine therapy. The TSH level of
heart failure (CHF) in 11 cases (2%). The risk factors of CT were age greater than
treated subjects was significantly higher than that of untreated subjects (8.1 mIU/l
50 years (ORZ13.1 (95% CI, 4.9-34.4)), low socioeconomic status (ORZ2.8
vs 5.9 mIU/l, P!0.001). Thyroid peroxidase antibodies were more frequently
(95% CI, 1.2-6.7)), low educational level (ORZ3.1 (95% CI, 1.2-8.3)), history
positive in treated subjects (93% vs 7%, P!0.001). The dose of L-thyroxine
of hypertension (ORZ3.5 (95% CI, 1.1-11.2)) and a multinodular toxic goiter as
which allowed the normalization of the TSH level was on average 63.9 mgG
the etiology of hyperthyroidism (ORZ4.6 (95% CI, 1.6-13.9)). After multi-
39.4 mg/day. There was no significant difference between the results of the
variate analysis, age greater than 50 years was the only independent risk factor of
metabolic parameters (weight, blood pressure, fasting glucose, total cholesterol,
CT (adjusted ORZ11.6 (95% CI, 2.7-49.5)). Severe biological hyperthyroidism
triglycerides and HDL cholesterol) before and after normalization of TSH level.
(FT4O 3 times normal) was associated with a lower risk of CT (adjusted ORZ
In untreated patients, spontaneous TSH normalization occurred in 27% of cases
0.2
(95% CI, 0.1-0.9)).
after an average time of 3.5G3.1 months.
Conclusions
Conclusion
The prevalence of CT in patients with hyperthyroidism was 6.5%. The two types
L-thyroxine replacement in patients with SCH concerned almost half of our
of cardiac disease observed were CHF and AF with a clear predominance of the
patients. Higher TSH level and positive thyroid peroxidase antibodies were more
latter. Advanced age was the only independent risk factor of CT.
frequently associated with L-thyroxine requirement. Spontaneous TSH normal-
DOI: 10.1530/endoabs.49.EP1322
ization was relatively frequent (one quarter of untreated patients); hence repeating
measurement of FT4 and TSH is necessary before starting L-thyroxine therapy.
DOI: 10.1530/endoabs.49.EP1324
EP1323
Takotsubo cardiomyopathy associated with thyrotoxicosis
Helena Vitorino, Joana Costa, Filipa Moleiro, Cláudia Jesus, Ana Afonso,
Nadine Monteiro, Sofia Santos, Eduarda Comenda & Helena Cantante
EP1325
Hospital Lusíadas Lisboa, Lisboa, Portugal.
The manner of performing the thyroid ultrasound examination and the
reliability of assessment of the thyroid size in school-aged children
Background
Arkadiusz Zygmunt1, Zbigniew Adamczewski1, Malgorzata
Takotsubo cardiomyopathy is a rare, acute, nonischemic cardiomyopathy causing
Karbownik-Lewinska2 & Andrzej Lewinski1
transient systolic disfunction of the apical and/or mid segments of left ventricle
1Department of Endocrinology and Metabolic Diseases, Medical University
and is commonly associated with emotional and physical stress. Thyrotoxicosis is
of Lodz, Lodz, Poland;2Department of Oncological Endocrinology, Lodz,
a rare cause of this condition, resulting from direct and indirect action of thyroid
Poland.
hormones on the cardiovascular system.
Case presentation
A 43-year-old woman presented at emergency room with chest pain, shortness of
Goitre incidence in school-aged children evaluated by the use of ultrasonography
breath, palpitations, nausea, anxiety, slurred speech and myalgia. Two months
(US), apart from reflecting urine iodine concentration and percentage of
earlier she had been admitted in another hospital with chest pain and a diagnosed
households consuming iodized salt, is an essential indicator for assessing iodine
Takotsubo cardiomyopathy, based on normal cardiac catheterization and
intake in a given area. The position in which the US examination is being
compatible echocardiographic changes. At admission, diagnosis of recurrent
performed can also be an important problem in terms of its result interpretation.
Takotsubo cardiomyopathy in the context of thyrotoxicosis was assumed (TSH !
The aim of the study was to examine what is the difference between the thyroid
0.05 mm/l, fT4
65 mg/dl). Further evaluation confirmed Graves’ disease.
volume measured in the supine and sitting position and to determine the
Recomended treatment was started and follow-up at
5
weeks revealed
coefficients of variation between measurements performed by the same observer
improvement of cardiac function and near normalization of thyroid hormone
(intra-observer variation), between two (2) observers (inter-observer variation)
and between two different positions
(inter-position variation). The survey
levels.
included 87 children (56 girls and 31 boys, aged 7-13 years). The US tests
Conclusions
were carried out by two (2) examiners (AZ and ZA). Thyroid volume measured in
Takotsubo cardiomyopathy could be the presenting manifestation of thyroid
a sitting position was significantly lower than in the supine position. The intra-
storm. Awareness of this possible association is important in establishing the
observer variations equalled 9.7% (CI - 8.1-11.13) for ZA and 9.56% (CI - 7.66-
diagnosis and institution proper management.
11.45) for AZ. The inter-observer variations amounted to 34.53% (CI - 31.9-
DOI: 10.1530/endoabs.49.EP1323
37.1) and 35.7% (CI - 32.5-38.9) for measurements performed in the supine and
the sitting position, respectively. We have concluded that the size of the thyroid
gland depends on the position in which it is examined. The manner the US
evaluation is being performed is important for the analysis of the results. It is
crucial to aim at the smallest value of inter-observer variation, which can be
achieved by strictly defining the methods of measurement of the thyroid and
comparing one’s measuring techniques with the reference technique. Con-
EP1324
clusions: The use of standards in US evaluation performed in the supine position,
Therapeutic and evolutionary characteristics of subclinical
as well as those without a strict determination of the study method, including body
hypothyroidism
position during examination, can lead to erroneous conclusions.
Meriem Yazidi1,2, Imed Mezghani1, Fatma Chaker1,2, Ons Rejeb1,2,
DOI: 10.1530/endoabs.49.EP1325
Mélika Chihaoui1,2 & Hédia Slimane1,2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1326
processed with the chi-square test. Pearson and spearman correlation analysis
were performed for normally and non-normally distributed data, respectively.
Which cytologic or architectural characteristics are associated with
Results
malignancy in AUS/FLUS cytologies according to subgroups?
There was an inverse correlation between baseline serum vitamin D levels and
Oya Topaloglu1, Aysegul Altinboga2, Fatma Neslihan Cuhaci1,
thyroid volume, TRAb, fT3 and PTH levels (PZ0.02, rZK0.31; PZ0.005,
Cevdet Aydin1, Husniye Baser3, Omer Yazicioglu4, Afra Alkan5,
rZK0.36; PZ0.04, rZK0.26; PZ0.02, rZK0.32; respectively). Thyroid
Reyhan Ersoy1 & Bekir Cakir1
volume was also correlated with serum fT4, fT3, TRAb and TPOAb (PZ0.001,
1Department of Endocrinology and Metabolism, Yildirim Beyazit
rZ0.426; PZ0.001, rZ0.50; PZ0.04, rZ0.26; PZ0.001, rZ0.42; respect-
University Faculty of Medicine, Ankara, Turkey;2Department of Pathology,
ively). Low vitamin D and high TgAb levels were independently associated with
Ataturk Education of Research Hospital, Ankara, Turkey;3Department of
thyroid volume in logistic regression analysis (PZ0.03, OR:18.7, CI 95% 1.34-
Endocrinology and Metabolism, Ataturk Education of Research Hospital,
260.91 and PZ0.04, OR: 16.6, CI 95% 1.07-255.64; respectively).
Ankara, Turkey;4Department of General Surgery, Ataturk Education and
Conclusion
Research Hospital, Ankara, Turkey;5Department of Biostatistics, Yildirim
Baseline serum vitamin D levels are inversely related with thyroid volumes, fT3
Beyazit University Faculty of Medicine, Ankara, Turkey.
and TRAb levels in new-onset Graves disease. In addition to several advantages,
optimization of vitamin D levels would also be beneficial in the surveillance of
Aim
these patients. However larger scale studies are required in order to make further
Atypia/follicular lesion of undetermined significance(AUS/FLUS) is a category
suggestions.
of thyroid cytology with features that are neither definitely benign or malignant.
DOI: 10.1530/endoabs.49.EP1327
We aimed to determine whether specific cytologic or architectural features are
associated with malignancy in AUS/FLUS category of Bethesda system
according to subgroups.
Methods
The specimens of patients who underwent surgery with preoperative thyroid fine
neeedle aspiration (FNA) biopsies of Bethesda Category III (AUS/FLUS) were
reanalyzed. An experienced cytopathologist who blinded to original cytology and
EP1328
final histopathology was reevaluated the specimens and numerated the cytology
A novel mutation in thyroid hormone receptor-beta gene causing
from 1 to 7 according to Bethesda system as follows; Group 1: cells producing
resitance to thyroid hormone in a tunisian female
microfollicles, Group 2: containing predominantly Hurthle cells with rare cells
Ons Rejeb, Melika Chihaoui, Meriem Yazidi, Ibtissem Oueslati,
and colloid, Group 3: difficulty in evaluation of atypia due to smear artifacts,
Fatma Chaker & Hedia Slimane
Group 4: cellular smears containing benign Hurthle cells, Group 5: focal cells
University of Tunis El Manar, Faculty of Medicine of Tunis, La Rabta
with nuclear changes like papillary carcinoma but generally benign appearance,
Hospital, Department of Endocrinology, Tunis, Tunisia.
Group 6: cells with atypic features but generally benign appearance, Group 7: rare
follicular cells with nuclear enlargement and frequently apparent nucleoli.
Results
Introduction
Specimens of one hundred and ninety five patients (153 females, 42 males) with a
The syndrome of resistance to thyroid hormone is a rare inherited disorder
mean age of 47.87G12.18 years were included to the study. Of these 195 patients,
characterized by elevated circulating thyroid hormones, failure to suppress
148 had AUS and 47 had FLUS cytology. Nuclear groove formations are found as
pituitary thyroid stimulating hormone
(TSH) and variable tissue target
higher in malignant group in overall study population and in also AUS subgroup
hyposensitivity to thyroid hormone action. We reported the case of a RTH
(PZ0.005 and PZ0.023, respectively), but not in FLUS subgroup (PZ0.164).
syndrome with a novel mutation.
Nuclear enlargement, overlapping, elongation, inclusions, and papilleroid
Case report
features were similar between malignant and benign groups in all patients,
A 15-year-old girl was investigated for visual hallucinations and behavior
AUS and FLUS subgroups. Furthermore cytologic groups distributions are
disorders. Her medical history was unremarkable except for a learning disability
similar between benign and malignant groups in all patients, and in AUS and
and a hyperactivity disorder in childhood. There was no family history of thyroid
FLUS subgroups (PO0.05, for all).
diseases and she was not taking any regular medication. She was found to have
Conclusion
abnormal thyroid function tests with increased plasma free T3, free T4
of
Patients in Bethesda Category III particularly in AUS subgroup with cytologic
2.51 ng/dl
(reference range:
0.71-1.85 ng/dl) with non-suppressed TSH of
interpretation of nuclear grooves are at higher risk of malignancy and should
7.7 mUI/ml (referance range: 0.12-3.4 mUI/ml). On examination, weight was
undergo surgery.
48 kg, height was 141 cm, blood pressure was normal and pulse rate was 92
DOI: 10.1530/endoabs.49.EP1326
beats/min. She had clinical symptoms of thyroid hormone excess: moist skin,
insomnia and agitation. She had no goiter or dysthyroid eye disease. Repeated
thyroid function tests confirmed previous findings. Thyroid antibodies (anti-
peroxydase and anti-TSH receptor) were negative. The level of TSH a-subunit
was normal 0.54 mUI/ml (range: 0.05-0.9) and the ratio TSH a-subunit/TSH was
less than 1. TSH-secreting tumor was ruled out by normal pituitary magnetic
resonance imaging (MRI). Genetic analysis yielded a novel mutation in the THRb
gene, c.1369 GOA in exon 10, due to a base pair substitution of glutamic acid by
lysine in position 457.
EP1327
Discussion
Relationship between thyroid volume and baseline vitamin D levels in
We reported a novel mutation in the THRb gene that has not been previously
new-onset graves disease
described and discussed the clinical presentation of the thyroid hormone
Gulsah Y Yalin1, Fuat Cenik2, Huseyin Celik1 & Abdulbaki Kumbasar2
resistance syndrome according to the different mutations.
1Department of Internal Medicine, Division of Endocrinology and
DOI: 10.1530/endoabs.49.EP1328
Metabolic Diseases, Kanuni Sultan Suleyman Research and Training
Hospital, Istanbul, Turkey;2Kanuni Sultan Suleyman Research and
Training Hospital Department of Internal Medicine, Istanbul, Turkey.
Introduction
Serum 25(OH) vitamin D levels are shown to be significantly lower and
associated with lower remission rates in Graves disease. In this study we aimed to
EP1329
investigate the impact of baseline vitamin D levels on thyroid volume in patients
Succesfull treatment of hyperthyroidism with plasmapheresis
with new-onset Graves disease.
Ozden Ozdemir Baser1, Derya Koseoglu2, Merve Catak1, Zeynep Cetin1 &
Materials and methods
Dilek Berker1
This is a monocenter cross sectional study with a total of 61 new-onset Graves
1Ankara Numune Education and Research Hospital, Ankara, Turkey;
disease patients (n:61, F: 40, M:21) who were divided into two groups according
2Hitit University Hospital, Corum, Turkey.
to baseline serum vitamin D levels, as Group-1 (D vit !20; n:42) and Group-2 (D
vit R20; n:19). Plasma fT4, fT3, TRAb, TPOAb and PTH levels were analysed
and thyroid volume (ml), isthmus thickness (mm) were measured by the same
Introduction
physician with thyroid ultrasonography at the time of diagnosis for each patient.
Hyperthyroidism is the condition that occurs due to excessive release of thyroid
The results were compared between the two groups. Categorical variables were
hormone by the thyroid gland. Anti-thyroid drugs are usually the first choice of
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
the treatment but surgery and radioactive iodine can also be used in treatment of
method is more reliable for ATG detection and how a result of ‘ATG positive’
hyperthyroidism. Plasmapheresis is a rapid and effective treatment option in cases
actually influences the Tg measurement.
where immediate euthyroidism is needed to be obtained due to complications of
thyrotoxicosis and major side effects of antithyroid drugs.
DOI: 10.1530/endoabs.49.EP1330
Material and method
Between January 2012 and December 2016, we evaluated patients who received
plasmapheresis to provide immediate euthyroidism due to severe hyperthyroid-
ism or side effects of anti-thyroid drugs or urgent non-thyroid surgery were
included to the study.
Results
Eighteen patients were included the study, of whom 11 were female and seven
EP1331
were male. The mean age was 52.44 years. Seven patients had TDG (%38.9), two
patients had TDMNG (%11.1), two patients had TA (%11.1), four patients had
Reference range determination of TSH during the first trimester of
TMNG (%22.2) and one patient had amiodarona induced thyrotoxikosis (%5.6).
pregnancy and the impact of its future implantation in the South
Additionally, plasmapheresis was performed to achieve euthyrodism before non-
area of Seville
Guillermo Martínez de Pinillos Gordillo, Carmen Carretero Marín, José
thyroid surgery in two patients (11.1%). The mean plasmapheresis sessions was
Álvaro Romero Porcel, María del Mar Viloria, María Dolores Hidalgo,
5.22. The mean sessions was 3.62 for patients with TDG and TDMNG, whereas it
Rufina Carrasco, Joaquín Bobillo, Mariana Tomé Fernández-Ladreda &
was 6.43 for patients with TA and TMNG (P:0.029). The decrease of mean fT4
María Victoria Cózar León
and fT3 were 48% and 65%, respectively (P!0.0001). Anaphylaxis was seen
Hospital de Valme, Sevilla, Spain.
only in one patient due to fresh frozen plasma. So treatment was changed to
albumin.
Conclusions
Objectives
Although plasmapheresis is not commonly used for the treatment of the
Different scientific societies recommend performing screening for clinical
hypertyroidism, it is a reliable and effective treatment option for patients who can
primary hypothyroidism during the first trimester of pregnancy using local
not use antithyroid drugs or hyperthyroidism can not resolve with these drugs
normality ranges of TSH and just in the lack of these, should the American
before total thyroidectomy, RAI or non thyroid emergency surgery.
population reference levels be used. Our objective is to determinate the reference
DOI: 10.1530/endoabs.49.EP1329
range of TSH during the 1st trimester of pregnancy in our healthcare area and the
impact of its implantation.
Material and methods
Prospective study where women selected had no history of thyroid pathology nor
where taking any drugs that may disrupt thyroid function. TSH, FT4 and anti-
thyroid antibodies (TPOab, TGab, TRab) were determined between week 9 and
11. TSH O5 mU/ml, positive thyroid autoimmunity or any condition that may
EP1330
interfere were excluded
(final nZ282). Reference levels were defined by
Measurement of anti-thyroglobulin antibodies, a matter of equipment?
calculating the confidence interval between p2.5 and p97.5 of the distribution.
Ricardo Capita˜o1, Susana Prazeres2, Ana Font2, Conceição Godinho3,
Tests for hypothyroidism screening in the last two years were reviewed and
Isaura Rodrigues3, Frederico Cerveira4, Grac¸a Belo1, João Viana1 &
variations on the diagnosis of hypothyroidism depending on the TSH reference
Deolinda Madureira5
level used was analysed.
1Hospital Egas MonizCentro Hospitalar Lisboa Ocidental, Lisboa, Portugal;
Results
2Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa,
New local reference level for the 1st trimester: TSH 0.17-4.39 mU/ml; T4L 0.97-
Portugal;3Centro Hospitalar Lisboa Central, Lisboa, Portugal;4Centro
1.88 ng/dl. Screening tests in the last 2 years (1/12/2014 to 30/11/2016) nZ6032.
Hospitalar do Baixo Vouga, Aveiro, Portugal;5Sociedade Portuguesa de
Diagnosis of hypothyroidism using American standard reference levels (TSHO
Endocrinologia Diabetes e Metabolismo, Lisboa, Portugal.
2.5 mU/ml):
35.8% (2181
women). Diagnosis of hypothyroidism with our
reference levels (TSH O4.39 mU/ml): 8,6% (524 women). Total number of TSH
R 10 mU/ml: 0.6% (37 women).
Introduction
Conclusions
The presence of anti-thyroglobulin antibodies (ATG) can induce falsely lower
Reference levels for TSH in our study are similar to others in different Spanish
thyroglobulin
(Tg) values. The methods characteristics used for ATG
areas and differ significantly from the American reference range, those standard
measurement vary according to the equipment/reagent used. ATG at our centre
ranges imply an unacceptable rate of diagnosis of hypothyroidism (one out of
is measured by Unicap.
three women), even more if a universal screening strategy is carried out.
Objective
Determination and implementation of locally assessed reference levels would
To assess if patients with negative ATG by Unicapw have different results with
avoid overdiagnosis, unnecessary treatment and follow-up.
other equipment.
Methods
DOI: 10.1530/endoabs.49.EP1331
A cross-sectional retrospective study was conducted in February-March of 2016,
in which blood samples from patients followed at our Centre, with negative ATG,
were selected and separated into three groups: 1) differentiated thyroid carcinoma
(DTC), total thyroidectomy, Tg!0.2 ng/ml; 2) without DTC and positive TPO;
3) without DTC and negative TPO. ATGs were measured by Immulitew, Cobasw,
Architectw and Adviaw. ATG’s classification was based on the cut-off of each
manufacturer. Q-Chrocan test was used to calculate the p-values (P!0.05 were
considered statistically significant).
EP1332
Results
Iodine content of iodized salt in Spain
A total of 141 samples were analysed. The results are described in the table
Vanessa Arosa1, Maider Sánchez Goitia1, Mercedes Espada2,9,
below: high significant differences were found between the various methods in all
Luis Irigoyen1, Gonzalo Maldonado1, Juan José Arrizabalaga1,9,
groups. The Architect and the Immulite had the highest and lowest rate of ATG
Piedad Santiago3,9, María Orosia4,9, Edelmiro Menéndez5,9, Lluís Vila6,9,
positives, respectively, compared to Unicap.
Silvia Wengrowicz7,9 & Sergio Donnay8,9
Discussion
1Endocrinology and Nutrition Department, Hospital Universitario Araba,
ATG results depend on the equipment used. This can influence the follow-up
Vitoria-Gasteiz, Spain;2Unidad de Química Clínica, Laboratorio Normativo
strategy of patients with DTC. These results also raise the question of which
de Salud Pública, Departamento de Sanidad y Consumo del Gobierno
Vasco, Derio, Spain;3Endocrinology and Nutrition Department, Complejo
Hospitalario de Jaén, Jaén, Spain;4Endocrinology and Nutrition Depart-
Table 1
ment, Hospital Royo Villanova, Zaragoza, Spain;5Endocrinology and
Positive ATG
Q test
Nutrition Department, Hospital Central de Asturias, Oviedo, Spain;
6Endocrinology and Nutrition Department, Hospital de Sant Joan Despí
Group
N Unicap Immulite Cobas Architect
Advia
c2
P
Moisès Broggi, Sant Joan Despí, Spain;7Instituto Catalán de Endocrino-
(A) DTCC/Tg!0.2
88
0
1
(1%)
3
(3%)
23
(26%)
6
(7%)
70.0
!0.001
logía, Barcelona, Spain;8Endocrinology and Nutrition Department,
(B) DTCK/TPOC
28
0
2
(7%)
8
(29%)
26
(93%)
11
(39%)
67.2
!0.001
Fundación Hospital Alcorcón, Alcorcón, Spain;9Área de Conocimiento del
(C) DTCK/TPOK
25
0
0
1
(4%)
6
(24%)
2
(8%)
17.7
0.001
Tiroides de la Sociedad Espan˜ola de Endocrinología y Nutrición, Madrid,
Total
141
0
3
(2%)
12
(9%)
55
(39%)
19
(14%)
152.7
!0.001
Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
Optimization of iodine intake aims to prevent the irreversible damage that iodine
deficiency (ID) can cause in the central nervous system during its development,
as well as thyroid disorders that can be induced by both ID and excessive
micronutrient intake. The Spanish legal regulation stipulates that iodized salt (IS)
must contain 60 mg of iodine per kg of salt (60 ppm), allowing a tolerance of
G15%. The aim of this study is to address the iodine content of different
commercially available IS in Spain.
Methods
Reference
162 different IS lots from 51 different product presentations were collected from
1) van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJ, Brouwer E,
Spanish food stores in Andalusia, Aragon, Asturias, Balearic Islands, Catalonia,
Codreanu C, Combe B, et al. EULAR definition of arthralgia suspicious for
Madrid and Basque Country between 2014 and 2016. Iodine concentration in
progression to rheumatoid arthritis. Annals of the Rheumatic Diseases. 2016
these samples was assessed by HDL-chromatography (HPLC).
October 6.
Results
2) Radu L, Groppa L, Vudu L. Musculoskeletal impairement in primary
The mean (S.D.) and median (P25-P75) iodine concentration for these 162
hypothyroidism. Rev Med Chir Soc Med Nat Iasi. 2016 April-June; 120 244-251.
samples was 61.2
(19.7) and
59
(50-70) mg I/g salt, respectively. Iodine
3) Jorge Cárdenas Roldán, Jenny Amaya-Amaya, Juan Castellanos-de la Hoz,
concentration dispersion was mainly attributable to iodide-fortified IS (nZ67).
et al., Autoimmune thyroid disease in rheumatoid arthritis: a global perspective,
The analysis of these fortified IS revealed that 67.2% of them had iodine levels
Arthritis, 2012. doi:10.1155/2012/864907
out of the legal threshold (51-69 mg I/g salt), whereas only 43.2% of the iodate-
4) Amr H Sawalha, Susan Kovats. Dehydroepiandrosterone in systemic lupus
fortified IS (nZ95) were outside this limit (P!0.05).
erythematosus. Current Rheumatology Reports. 2008 August 10 286-291.
Conclusions
5) Ernestam S1, Hafstrom I, Werner S, Carlstrom K, Tengstrand B. Increased
IS, having an average 60 mg I/g salt, is an important alimentary source of iodine in
DHEAS levels in patients with rheumatoid arthritis after treatment with tumor
Spain. The use of iodate instead of iodide for the fortification of the salt allows a
necrosis factor antagonists: evidence for improved adrenal function. Journal of
greater proportion of IS with iodine concentration within the legal limits. Public
Rheumatology. 2007 July; 34 1451-1458.
Health and Consumer Affairs authorities should closely monitor IS production
processes and eventually check IS sale points in order to homogenize the iodine
content of commercially available IS packages and thereby optimize their intake
DOI: 10.1530/endoabs.49.EP1333
by the population.
DOI: 10.1530/endoabs.49.EP1332
EP1334
A thyroid storm in a context of diabetic ketoacidosis: case report
Ghizlane El Mghari, Loubna Oukit & Nawal El Ansari
Endocrinology Department, CHU Mohammed VI, Marrakesh, Morocco.
EP1333
Low DHEAS levels predict rheumatism in primary hypothyroidism:
preliminary data from tertiary hospital
Introduction
Ravindra Shukla, Praveen Sharma, Vikram Singh & Gopal Vohra
The association of a thyroid storm and diabetes ketoacidosis is relatively rare.
AIIMS, Jodhpur, Jodhpur, India.
We report two cases.
Observations
The first one is a 20 years old woman, with no history of diabetes, who came with
Introduction
ketoacidosis, a history of non medicated thyrotoxicosis, and she was complaining
DHEAS is weak androgen with specific role in human physiology illdefined.
about fever, a thyrotoxicosis syndrome, a vascular goiter, and exophtalmos. Her
Various studies have implicated role of DHEAS in autoimmune arthritis
general condition had improved significantly after the treatment in emergency and
including SLE and RA. Recently EULAR consensus statement has approved
under maintenance therapy. The second one is a 54 years old female, with a case
CSA (clinically significant arthralgia) for incipient RA.
of diabetes mellitus, who presented a ketoacidosis. But despite the control of this
Methods and material
situation, the patient’s consciousness level became disturbed and she presented
34 follow up patients of primary hypothyroidism rated their symptom score on
hyperthermia. The thyroid function tests revealed hyperthyroidism. Thus, thyroid
CSA (clinically suspect arthralgia) as given by EULAR(1) Their DHEAS levels
storm was evocated and managed. The patient finally passed away despite the
were divided into quartiles while CSA was graded from 100 sensitivity (when one
prompt medical care.
component is positive) to 100 specificity (when all seven component are positive).
Discussion
Kendal tau test of correlation was run using SPSS 21. ROC curve for DHEAS to
In these two cases, a thyroid storm, associated with Graves’ disease covered by
predict at least one symptom of CSA was run. SPSS version 20 used for analysis.
diabetic ketoacidosis was the final diagnostic. Thereby, for patients having
Results
diabetic ketoacidosis one should seek an eventual thyroid storm, and vice versa:
Anti TPO Ab were available for 19 subjects, out of which 16 were Anti TPO AbC.
in fact, there are some symptoms in common. But there are scores to help
25(OH) vitamin D levels were available for only seven patients hence excluded
systematize the diagnosis. The management is controlled, acutely based on
from analysis. Kendal’s tau correlation test yieldedstrong negative correlation
antithyroid drugs in high doses, betablockers and corticosteroids. We should not
between DHEAS levels at the time of presentation and CSA score.{P!0.01;
disregard the search for and treatment of precipitating factors: ketoacidosis in our
r K0.512}.
cases. And identify the thyroid underlying disease: most commonly Graves’
Discussion
disease.
This the first study evaluating role of DHEAS in rheumatism of primary
DOI: 10.1530/endoabs.49.EP1334
hypothyroidism. Musculoskeletal abnormalities arecommon in primary auto-
immune thyroid disease (AITD); 2) AITD is also associated with rheumatoid
arthritis
(RA); 3) There has been recent acknowledgement of role of local
androgen in molecular pathogenesis of autoimmune arthritis; 4) We found inverse
correlation between serum DHEAS and rheumatism. The serum DHEAS levels
seemed to predict grade of rheumatism in these patients. The finding and strength
of association is significant and opens further avenues for research regarding role
EP1335
of DHEAS in musculoskeletal manifestations of AITD. DHEAS supplementation
Hyalinizing trabecular adenoma of the thyroid
has been evaluated in SLE (4) but not in hypothyroidism. Although association
Ozen Oz Gul1, Soner Cander1, Pinar Sisman2 & Canan Ersoy1
between Rheumatoid arthritis (RA) and DHEAS is not well defined, improvement
1Uludag University Medical School, Department of Endocrinology and
in RA is associated with increase in DHEAS levels
(5) Does DHEAS
Metabolism, Bursa, Turkey;2Kars State Hospital, Department of
supplementation early in RA or pre -RA alters its natural history, in background
Endocrinology and Metabolism, Kars, Turkey.
of hypothyroidism? Well designed studies are needed.
Conclusion
Introduction
Rheumatism as evaluated by CSA criteria bears strong inverse correlation with
Hyalinizing trabecular adenomas (HTA) of the thyroid gland is a rare neoplasm of
DHEAS. Further trials examining role of DHEAS in such group of patients can be
follicular cell origin. HTA can be present as a thyroid nodule or incidental finding
explored.
in a thyroidectomy specimen. HTA is generally accepted to be a benign tumor,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
but their cytological features can be similar to those of papillary thyroid
autoimmune mechanism leading to absolute insulin deficiency. In patients
carcinoma (PTC).
with an autoimmune endocrine disease, there is a high risk of development of
Case report
another autoimmune endocrine disorder. The purpose of our work is to assess the
A 59 year old woman, who had cholangiocellular carcinoma, admitted to our
prevalence of thyroid autoimmunity among our LADA patients.
institution with a solitary thyroid nodule and cervical lymphadenopathy. Fine
Patients and methods
needle aspiration biopsy of the cervical lymphadenopathy revealed suspicious for
Our study has included 17 patients followed for LADA. Thyroid status and
carcinoma metastasis. Her serum free thyroxine (fT4), free triiodothyronine (fT3)
thyroid autoimmunity were ordered in all patients.
and TSH levels are 1.42 ng/dl, 2.82 pg/ml, and 0.486 mIU/ml. Ultrasonography
Results
of the thyroid gland showed a 1.4 cm sized, regularly marginated, hypoechoic,
The mean age of patients was 46.7 years and the mean age of discovery was 40.5
calcified thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule
years. The sex ratio was 1.4 with a female predominance. The average BMI was
revealed suspicious for PTC. Total thyroidectomy were perfomed. The final
24.5 kg/m2. The TPO antibodies were positive in five of our patients (29.4% of
pathology was 1.0-cm sized hyalinizing trabecular adenoma. Histologically, the
cases), including four women. The rate of anti-GAD antibodies was higher in the
tumor showed tumor cells arranged in trabeculae and a prominent hyaline stroma.
LADA group with positive anti TPO antibody compared to the group with
The neoplastic cells were focally immunoreactive for thyroglobulin and negative
negative anti TPO (345.6 mUI/l vs. 250.4 mUI/l).
for calcitonin and chromogranin. After surgery L-thyroxine replacement therapy
Discussion
was started. Cervical metastasis was thought to be associated with cholangio-
The prevalence of thyroid antibodies in patients with LADA varies between 20
cellular carcinoma. The patient referred to the Oncology department for the
and 30%. The association has been explained by the sharing of a common genetic
treatment of metastatic cholangiocellular carcinoma.
material, but also by a deficit in the immune regulation or a poor ability to develop
Conclusion
tolerance to auto antigens.
Ultrasonografic features of HTA similar to malign thyroid lesions and frequently
Conclusion
misdiagnosed as papillary carcinoma on fine-niddle aspiration cytology. The most
Thyroid autoimmunity is frequently observed in LADA diabetes, identifying a
recent and controversial debate surrounding HTA concerns its potentially
particular phenotype of patients with higher titer of anti GAD antibodies, and
malignant behavior and the possible relationship to PTC. Although cases of
eventually, a poor glycemic control where the interest of its systematic screening.
malignant HTA have been recorded, HTA should be considered a benign
DOI: 10.1530/endoabs.49.EP1337
neoplasm or, at most, a neoplasm of extremely low malignant potential. In this
report we present and discuss an unusual case of a patient who had a hyalinizing
trabecular adenoma and cholangiocellular carcinoma.
DOI: 10.1530/endoabs.49.EP1335
EP1336
Amiodaron induced hyperthyreosis and recurrent ventricular
tachycardia
Roman Kołodziejczak1, Alicja Łuczyn´ska-Kołodziejczak1 &
Anhelli Syrenicz2
EP1338
1Ragional Hospital, Gorzow Wlkp., Poland;2Pomeranian Medical
Thyroid and metabolic disorders in patient with kidney injury
University, Szczecin, Poland.
undergoing renal biopsy
Joanna Sztembis, Aneta Kołodziej-Kł
˛k, Agnieszka Gala-Bł
˛dzin´ska &
Grzegorz S´ wider
52 years old man medicated with amiodaron
12 months, with laboratory
Department of Internal Medicine, Nephrology and Endocrinology,
confirmed hyperthyroidism, in us-examination 45 ml Basedow goiter, TRAb
St. Queen Jadwiga Clinical Hospital No. 2, Rzeszow, Poland, Rzeszow,
positive; ventricular tachycardia 180/min intermittent with sinusal tachycardia
Poland.
120/min, thiamasol 120 mg i.v./daily, hydrocortisone 400 i.v. daily, crystalloids,
beta blockers, diazepam, albumin. J131
scintigraphy
- no iodine uptake.
natriumperchlorate 1500 mg daily initially, continued next month 900 mg coused
There are a several known interactions between kidney functions, thyroid and
iodine uptake 17%. Finally -radioiodine 20 mCi, followed with thiamazole and
metabolic balance. Hypothyroidism is associated with reduced GFR and
steroids. After
4
weeks
- euthyroid.
32
years old woman after many
hyperthyroidism results in increased GFR and increased RAA activation. Chronic
hospitalizations because of ventricular tachycardia. Clinical, ultrasound and
kidney disease is characterized by low T3
syndrome, increased primary
laboratory parameters of Basedow disease. Medication: thiamasole, cortisone and
hypothyroidism and subclinical hypothyroidism. The hyperthyroidism increases
Irenat prepared to the radioiodine therapy. After three times of 20 mCi I131
CKD progression while hypothyroid state lowers it. Proteinuria, especially in
hypothyroid, 100 mg thyroxin. 48 years old man with hypertrophic cardiomio-
nephrotic syndrome, often results in urinary loss of thyroid hormones bound to the
pathy, after over 6 months use of amiodaron lack of effect and recidive of
various binding proteins which results in reduction in the serum total thyroid
ventricular tachycardia. Lab. - thyreotoxicosis, in ultrasound left lobe tumor 27
hormone levels. Isolated cases of hyperthyroidism have been associated with
ml, biopsy benign. Initially cured with thiamazole 60 mg, followed with irenat
tubulointerstitial nephritis. Thyroid dysfunction is also associated with
900 mg daily and after iodine uptake recurrence
-20mCi radioiodine
131,
glomerulonephritis by a common autoimmune etiology. There are known several
euthyreosis after 3 months.
mechanisms like the presence of circulating immune complex among patients
Cases demonstrate problematic situation of amiodaron cured patients, thyroid
with thyroid disease, the association of Hashimoto’s thyroiditis and membranous
dysfunction may occur during amiodaron therapy and in some patients is
nephropathy with immune complex deposition in the glomerular as well as
dangerous. Hyperthyroidism is difficult to cure if caused by amiodaron but in this
thyroid epithelial basement membrane. There is also common occurrence of
patients should be radical, it is necessary to have available perchlorat for this
thyroid and renal disease in association with other autoimmune diseases such as
cases and rodioiodine therapy.
type 1 diabetes mellitus. We retrospectively analyzed the data (thyroid function,
DOI: 10.1530/endoabs.49.EP1336
metabolic syndrome occurrence, type of diabetes) of 126 patient hospitalized in
our clinic from 2013 to 2016 who underwent renal biopsy (52 women, 62 men and
6 children). The most common indications for renal biopsy were nephrotic
syndrome in 47 patients
(37.3%), non-nephrotic proteinuria in
31 patients
(24.6%), worsening renal function in
22 patients
(17.5%), coexistence of
proteinuria with hematuria in 16 patients (12.7%), nephritic syndrome in 9
EP1337
patients (7.1%) as well as an isolated hematuria in 1 patient (0.8%). Membranous
Autoimmune thyroiditis in patients with latent autoimmune diabetes of
glomerulonephritis was the most common histological diagnosis observed in
adults (LADA)
biopsies, and was diagnosed in 19 patients (15.1%). Our analysis proved higher
El Ansari Nawal, Fatima Zahra Zaher & Ghizlane Elmghari
occurrence of hypothyroidism
(8.7%), hyperthyroidism
(2.38%) and goiter
Department of Endocrinology, Diabetes, Metabolic Diseases and Nutrition,
(3.17%) in comparison to general population. Interestingly there was no higher
Mohammed VI University Hospital, Marrakesh, Morocco.
occurrence of obesity and overweight (40.4%) and type 1 and 2 diabetes, but
many patient had steroid-induced diabetes (16%). It is important to monitor every
Introduction
patient with renal dysfunction due to higher prevalence of thyroid pathology.
Latent autoimmune diabetes in adults
(LADA) is an endocrine disorder
DOI: 10.1530/endoabs.49.EP1338
characterized by a progressive destruction of pancreatic beta cells by an
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1339
relative contribution of each nosological entity. Nevertheless, the clinical
presentation, the EMG and the prompt response to levothyroxine, favor
Reversible thyrotoxic pulmonary hypertension with heart failure:
hypothyroidism as the main cause.
2 cases
Aftab Khattak1, Eleanor Wong1, George Mak1 & James A O’Hare1,2
DOI: 10.1530/endoabs.49.EP1340
1University Hospital Limerick, Limerick, Ireland;2University of Limerick,
Limerick, Ireland.
Introduction
Heart failure is a complication of thyrotoxicosis. We present 2 unusual cases
presenting with pulmonary hypertension with isolated right heart failure that
reversed after treatment.
Case description
EP1341
Case 1: A 55-year-old man presented with weight loss, dyspnoea and leg
Is Levothyroxine requirement the same for tablet and soft gel
swelling. HR: atrial fibrillation
51/min. He had a raised JVP, tricuspid
formulation in postsurgical hypothyroidism?
regurgitation and severe pitting oedema. Pro-BNP:
4995 pg/ml, TSH:
Vincenzo Di Donna1, Rosa Maria Paragliola1, Chiara De Waure2,
0.06 mU/l, FT4:
54.1 pmol/l, FT3:10.5 pmol/l. TSH receptor antibodies
Annapina De Rosa1, Giampaolo Papi1, Alfredo Pontecorvi1 &
(TRAb) were positive. CTPA: no pulmonary embolism. Echo: PAP 45 mmHg,
Salvatore Maria Corsello1
LVEF preserved. Carbimazole, diuretics, ACE inhibitors and Apixaban were
1Endocrinology, Università Cattolica del Sacro Cuore, Rome, Italy;
commenced. Right heart catheterization showed non-obstructive coronary artery
2Institute of Public Health, Università Cattolica del Sacro Cuore, Rome,
disease and pulmonary hypertension. Repeat ECHO 7 months later revealed
Italy.
normal right heart pressure and size when euthyroid. Tricuspid regurgitation and
Pulmonary Hypertension were resolved.
Background
Case 2: A 34-year-old male presented with oedema, elevated JVP, tricuspid
In a previous publication we identified the major predictive factors of
regurgitation and atrial fibrillation. Pro-BNP: 2064 pg/ml TSH: 0.05 mU/l, Free
levothyroxine (LT4) requirement and proposed an efficient nomogram to calculate
T4: 72.6 pmol/l, TRAb positive. CTPA negative for PE. ECHO: PAP 60 mmHg.
LT4 substitutive starting dose after total thyroidectomy for benign disease. The
Right cardiac catheterisation when euthyroid demonstrated a RVSP of 32 mm Hg,
aim of this study was to assess whether the LT4 requirement differs between the
pulmonary artery systolic pressure of
27 mmHg and a wedge pressure of
tablet and the soft gel capsules formulations.
14 mmHg indicating a resolution of his RHF.
Methods
Learning point
One hundred and three consecutive patients submitted to total thyroidectomy for
Selective right heart failure may occur in thyrotoxicosis perhaps due to altered
benign disease and were receiving substitutive therapy with LT4 were enrolled.
metabolism of pulmonary vasodilators resulting in raised pulmonary vascular
All patients received the LT4 tablet formulation. The specific substitutive starting
resistance.
dose was calculated using the previously described nomogram and was aimed at
DOI: 10.1530/endoabs.49.EP1339
achieving normal TSH levels
(0.4-2.5 mU/L). Exclusion criteria were:
malignancy at histological examination, symptoms or signs of malabsorption,
assumption of drugs or habits interfering with LT4 absorption, impaired renal
function, pregnancy, poor compliance with drug administration. TSH, FT4, and
FT3 were assessed three months after the switch from tablet to soft gel capsule
formulation at the same dose of LT4. Mean and standard deviation (SD) were used
for quantitative variables. The paired t-test was applied in order to compare the
thyroid function tests with different formulations of LT4.
Results
Serum TSH was significantly lower during treatment with soft gel capsules
EP1340
[1.3 mU/L (SD 0.9) and 1.8 mU/L (SD 1.2) respectively, PZ0.02]. There were no
Peripheral neuropathy in hypothyroidism - about a clinical case
statistically significant differences for FT3 and FT4.
José Marçalo, Alexandra Araújo, Carolina Faria, Ana Wessling,
Conclusions
Maria Raquel Carvalho, Ema Nobre & Maria João Bugalho
Levothyroxine substitutive dose is not significantly different between soft gel
Hospital de Santa Maria, Lisbon, Portugal.
capsules and tablets in patients without malabsorption but TSH is significantly
lower with the first one. This datum must be considered in clinical practice,
particularly for patients with TSH at limits of the therapeutic range or if a strict
Introduction
Hypothyroidism can affect the nervous system, commonly causing mono and
therapeutic goal is needed.
polyneuropathies which show a variable frequency and pattern. Its mechanisms
DOI: 10.1530/endoabs.49.EP1341
are not fully understood. Symptoms usually correlate better with the duration of
the dysfunction rather than with its severity and typically improve significantly
after medical therapy.
Case report
A 58-year-old woman was admitted at our hospital with a one-year history of
progressive weakness of both lower extremities, more evident on her left limb.
The patient reported a
20-year history of hypothyroidism medicated with
levothyroxine 25mcg id and type 2 diabetes medicated with metformin 1000mg
EP1342
bid, without proper follow-up. She denied other relevant long-term medication or
addictions. Fifteen days prior to admission, she was paraparetic and had lost her
Immune reaction to food antigens in Graves’disease (GD) patients:
ability to walk. No other relevant personal or familial medical history was found.
role of gliadin and other food antigens
Neurological examination showed painless sensorimotor polyneuropathy and
Danila Covelli1, Giuseppe Colucci1, Mario Salvi1, Ulrike Kaiser2,
lower muscular strength on both legs. Laboratory results revealed hypothyroid-
Anja Eckstein2, Maria Cristina Burlacu3, Chantal Daumerie3, Gez Richell4,
Petros Perros4, Mohd Shazli Draman5, Marian Ludgate5, Giulia Masetti6 &
ism: TSH 37.1mU/L and FT4 0.5ng/dl. Serologic studies were negative and
Filippo Biscarini6
B12-deficiency was excluded, as well as other common causes of peripheral
1Graves’ Orbitopathy Centre, Endocrinology, Fondazione IRCCS Cà
neuropathy. Lumbar MRI did not show spinal cord compression and
Granda, and University of Milan, Milan, Italy;2Center for Ophthalmology
cerebrospinal fluid analysis was inconclusive. Bilateral carpal tunnel syndrome
University Clinic, Essen, Germany;3Médecin spécialiste hospitalier Service
and sensorimotor polyneuropathy, without criteria of Guillain-Barré syndrome,
d’Endocrinologie, Diabétologie et Nutrition Cliniques universitaires St-Luc
were found on electromyography
(EMG). Furthermore, myopathic aspects
(UCL), Bruxelles, Belgium;4Diabetes & Endocrine Royal Victoria
compatible with muscular necrosis were detected, despite normal creatine kinase
Infirmary, Newcastle Upon Tyne, UK;5Division of Infection and Immunity
levels. Few weeks after progressively increasing levothyroxine dose, laboratory
School of Medicine, Cardiff University, Cardiff, UK;6PTP Science Park,
studies showed: TSH 10.2mU/L, FT4 1.27ng/dl, Anti-TPO 66U/mL. Unsatisfac-
Lodi, Italy.
torily controlled hyperglycemia persisted (HbA1c 10.2%). Paraparesis signi-
ficantly improved and sensorimotor dysfunction subsided.
Conclusion
As known, an imbalance of the gut microbiota is associated with a higher risk for
In general, sensorimotor peripheral neuropathy is common in diabetes and
autoimmune diseases. Moreover the increased rates of autoimmunity reported in
occasional in hypothyroidism. In the described case, it is difficult to ascertain the
urban residential areas worldwide suggest a possible influence of diet. We report
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
on the antibody response to food antigens in GD patients. Since 10% of celiac
Methods
patients develop an autoimmune thyreopathy we focused on gliadin (DGP),
The primary method used for the analysis of QoL was the own orginal combined
transglutaminases
(tTG) and
40
other food antigens
(FA). Commercially
questionnaire. Statistical methods from Excel
2010
were used in results
available ELISA assays were performed according to the manufacturer’s
evaluation.
instructions. 105 and 108 sera from 5 European endocrine centres have been
Results
tested for IgG and IgA to tTG and DGP. Results have been compared to
There were 214 patients in the examined group: 34 patients with hyperthyreosis
epidemiological data. 71 sera have also been tested for IgG to FA and compared
(10 men, 24 women) - group A, and 180 patients with hyperthyreosis (25 men,
to 25 healthy controls. 6 out of 105 sera (5.7%) showed positive tTG; 16 and 7
155 women) - group B. QoL was evaluated on numeric scales from 0 - the worst
out of 108 (15 and 6.5%) positive DGP-IgA and IgG, respectively; a higher
to 10 - the best. Present level of QoL was 6.4 vs 7.25, when in the time of
prevalence compared to the worldwide prevalence of celiac disease (1%) (chi-
diagnosis it was 4.6 vs 6.0, in the time without disease - 7.6 vs 8.3 and in the time
squared test; p-value ! 0.001). Prevalence of smokers and ocular involvement
excellent health - 8.0 vs 9.2. The average duration of disease was 6.5 vs 11.30
was not higher in patients with positive sera compared to negative. 23 out of 71
years and the duration of symptoms before diagnosis was 0.74 vs 0.99 years.
(32.3%) GD sera showed sensitivity against a food antigens, compared to 25% (6
Patients were very satisfied with the level of information about their disease: 4.6
out of 24) positive results among healthy controls (chi-squared test; P-valueZ
vs 4.3, with medical care - 4.8 vs 4.7 and with nursing care4.8 vs 4.7 (1- the worst,
0.4). Interestingly, some antigens (cow’s milk, egg white, wheat, yeast) are more
5- the best). Disability of work was 0.8 vs 4.9 days in employed patients (19 in
frequently positive than others. The distribution of antibodies against TSH
group a and 79 in group B) per year. Patients visited endocrinologic outpatients
receptor
(TRAb) values was not different in positive or negative sera. In
department 5.1 vs 2.2 times per year. Willingness to pay was 55 vs 48 V
conclusion, the prevalence of positive tTG antibodies is higher in GD patients
per month.
than worldwide. Even though autoantibodies to DGP and tTG were equally
Conclusions
distributed between all 5 centres we observed the highest percentage of positive
Hyperthyreosis and hypothyreosis had a significant impact on patients’s QoL
responses to other food antigens in Cardiff, suggesting that diet may contribute to
mostly hyperthyreosis. There are a significant differences in duration of disease
the increased sensitivity. More studies are needed to confirm these data.
and symptoms, disability of work and professional visits - hyperthyreosis had
DOI: 10.1530/endoabs.49.EP1342
greater impact. Information about the disease, evaluation of medical and nursing
care and willingness to pay had no statistical differences.
DOI: 10.1530/endoabs.49.EP1344
EP1343
Neutrophil/lymphocyte (N/L) ratio should not be used as an indicator of
inflammation in hyperthyroid patients
Murat Dagdeviren1, Tolga Akkan2, Dilek Celiker2, Serdar Karakaya2,
Derun Taner Ertugrul1 & Mustafa Altay1
1Kecioren Education and Research Hospital, Endocrinology and Metab-
olism, Ankara, Turkey;2Kecioren Education and Research Hospital,
EP1345
Internal Medicine, Ankara, Turkey.
Broken heart by thyroid? A rare case of Graves’ disease associated to
Takotsubo cardiomiopathy
Introduction
Georgiana Constantinescu1,2, Carmen Plesoianu1,3, Cezara Raileanu1,3,
Neutrophil/lymphocyte
(N/L) ratio is considered as a sign of systemic
Iuliana Ardeleanu1,3, Mihaela Negru2, George Zmau1,2,
inflammation in recent years. In our study, we aimed to investigate N/L ratio in
Catalina Arsenescu-Georgescu1,3 & Carmen Vulpoi1,2
hyperthyroid patients and healthy control group.
1Gr. T Popa University, Iasi, Romania;2Saint Spiridon Clinical Hospital,
Material & methods
Iasi, Romania;3Prof. Dr. George Georgescu Institute for Cardiovascular
A total of 121 hyperthyroid patients (71 patients with Graves’ disease and 50
Disease, Iasi, Romania.
patients with other causes of hyperthyroidism) and 40 healthy volunteers were
enrolled. Complete blood count was obtained from both group and thyroid
Introduction
function tests were obtained from hyperthyroid patients.
Takotsubo disease is a non-ischemic, reversible form of cardiomyopathy,
Results
triggered by intense emotional or physical stress. Characterized by normal
There was no significant difference between hyperthyroid patients and control
coronaries and a particular ventricular contraction, it is also known as ‘apical
group in terms of gender, leukocyte and lymphocyte count. There was a
ballooning syndrome’. Thyrotoxicosis, especially Graves’ disease, has been
statistically significant difference between groups in terms of neutrophil count and
associated with Takotsubo cardiomyopathy.
N/L ratio (PZ0.003 and P!0.001). Surprisingly, neutrophil count and N/L ratio
Case report
were significantly lower in Graves’ patients. We also find a significant negative
We report the coexistence of Takotsubo cardiomyopathy in a 37 year old female
correlation between serum free T3 levels and neutrophil count
(rZK0.28,
patient presenting with thyroid storm secondary to untreated Graves’ disease.
PZ0.01).
Addressed to the emergency unit with suspicion of acute coronary syndrome,
Conclusion
signs of lateral inferior apical ST-segment elevation were noticed on the ECG. At
N/L ratio was lower in Graves’ patients than in the control group. Slowing of
clinical examination: pale wet teguments, tachycardia, visible goiter and bilateral
granulopoiesis, shortening of the life span of circulating neutrophils, and the
exophtalmia. According to the Burch Wartofsky criteria for thyrotoxicosis the
development of anti-neutrophilic antibodies in autoimmune thyroid diseases may
patient had a score of 70, highly suggestive for thyreotoxic crisis, sustained by the
be responsible for this condition. N/L ratio should not be used as an indicator of
biological data (high free T4 5.27 ng/dl and free T3 7.47 pg/ml levels with
inflammation in hyperthyroid patients.
inhibited TSH
0.008 uUI/ml). She also associated anemia, inflammatory
DOI: 10.1530/endoabs.49.EP1343
syndrome and important hepatocytolisis. Echocardiographic she presented a
severely impaired left ventricular systolic function (ejection fraction 15%) with
apical ballooning and elevated left ventricular end diastolic pressure. Coronary
angiography revealed non-obstructive coronary atheroma. The final diagnosis of
Takotsubo cardiomyopathy was made on the basis of cardiac computer
EP1344
tomography. At the 7 weeks follow up, under antithyroid drugs there was an
improvement of thyroid hormone levels. Moreover, consistent with Takotsubo
Quality of life in patients with hyperthyreosis and hypothyreosis in
cardiomyopathy, at re-evaluation there was a cardiac function recovery with
slovak republic
normal ejection fraction (66%).
Jan Bielik1, Emilia Slavikova2 & Vladimir Melus1
Conclusions
1Trencin University of Alexander Dubcek, Trencin, Slovakia;
Thyrotoxicosis is associated with multiple implications in cardiovascular system.
2Faculty Hospital Trencin, Trencin, Slovakia.
Pathologically high levels of thyroid hormones cause exaggerated chronotropic
and inotropic response to cathecolaminee. One possible explanation could be the
Objectives
upregulation of beta adrenergic receptors by thyroid hormones in many tissues,
The prevalence of thyreoid diseases eg hyperthyreosis and hypothyreosis in
including cardiac.
Slovak Republic is about 240 000 patients. The objective of this study was to find
DOI: 10.1530/endoabs.49.EP1345
out the level of quality of life (QoL) in patients and other relevant characteristics
of diseaseas.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1346
Conclusion
Decrease in the disulfide/thiol ratio after levothyroxine sodium treatment in
The association of gene polymorphisms with the clinical outcome of
hypothyroidism may suggests that treatment plays a role in reducing both
Graves’ disease
oxidative stress and free radical mediated damage to the functional groups of
Dalia Dauksiene1, Narseta Mickuviene2 & Albertas Dauksa3
proteins. Thus, it may be possible to avoid the complications caused by oxidative
1Institute of Endocrinology, Medical Academy, Lithuanian University of
stress. As a result disulfide/thiol ratio may contribute to the management of
Health Sciences, Kaunas, Lithuania;2Behavioral Medicine Institute,
treatment in hypothyroid patients.
Medical Academy, Lithuanian University of Health Sciences, Palanga,
Lithuania;3Institute for Digestive Research, Medical Academy, Lithuanian
DOI: 10.1530/endoabs.49.EP1347
University of Health Sciences, Kaunas, Lithuania.
The aim
Of this study was to investigate the association between two common CTLA-4
gene SNPs (49A/G in exon 1 and CT60 A/G in 3’UTR) and Graves’ disease
outcome in Lithuanian population.
EP1348
Methods
The role of vitamin D receptor gene FokI (rs2228570) polymorphism in
This case-control study was performed in the Hospital of Lithuanian University of
the pathogenesis of thyroid associated orbitopathy
Health Sciences. Graves’ disease patients (nZ105) were divided into remission
Adam Maciejewski1, Michal Kowalczyk2, Adam Czyzyk3,
and failed treatment groups according to the final outcome of the disease. The
Teresa Gasinska4 & Katarzyna Lacka1
remission group (nZ49) - patients with euthyroid status minimum 1 year after
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan
antithyroid drugs
(ATD) withdrawal. The failed treatment group (nZ56) -
University of Medical Sciences, Poznan, Poland;2Department of
patients submitted radioiodine therapy or surgery due to poor response to ATD
Dermatology and Venereology, Poznan University of Medical Sciences,
therapy. Genomic DNA was extracted from the peripheral blood leukocytes with
Poznan, Poland;3Department of Gynecological Endocrinology, Poznan
kit Qiagen GmbH, Hilden, Germany.
University of Medical Sciences, Poznan, Poland;4Department of Internal
Results
Diseases and Oncologic Chemotherapy, Silesian Medical University,
The patients in failed treatment group had significantly higher frequency of GG
Katowice, Poland.
genotype and a lower frequency of AA genotype than patients in remission group.
Patients with GG homozygous genotype had more than four-fold (OR 4.94, 95%
CI 1.38-17.65) and more than sixteen-fold (OR 16.91, 95% CI 1.83-156.62)
Introduction
increase in risk of ATD treatment failure compared to patients with homozygous
Vitamin D, known mainly as a calcium-phosphorus homeostasis regulator, turned
genotype AA for 49A/G SNP and for CT60 SNP, respectively. When association
out to play also a significant role in the immune system modulation. Vitamin D
of 49A/G and CT60 genotypes on the outcome of Graves’ disease was analyzed
deficiency has been reported in some autoimmune disorders. It is also suspected
separately it provided significant prognostic information but after multiple
that polymorphisms of vitamin D-related genes comprise a risk factor for different
logistic regression analysis these genetic markers were not independent of other
autoimmune diseases. Therefore the aim of our study was to assess vitamin D
factors. Only TRAb levels before treatment was independently associated with
receptor
(VDR) gene FokI polymorphism in thyroid associated orbitopathy
elevated odds of failure (OR 1.05, 95% CI 1.02-1.08).
(TAO) in comparison to the controls among the Caucasian-Polish population.
Conclusion
Patients
the data shows significant association of two polymorphisms (A/G at position 49
The group studied consisted of 100 subjects diagnosed with TAO (mean age 53.8)
and CT60 in 3’UTR) in the CTLA-4 gene with Graves’ disease in Lithuania and
and 142 healthy age and sex matched controls. TAO was diagnosed by clinical
suggest that these genetic markers may provide important information in
examination, TRAb assessment and orbit MRI or CT. TAO group was further
predicting high risk patients for failure to ATD therapy.
divided into: A- orbitopathy from the onset of Grave’s disease, B- later
DOI: 10.1530/endoabs.49.EP1346
development of TAO. In the control group both TAO and autoimmune thyroid
diseases were excluded by clinical examination and thyroid ultrasound.
Methods
FokI polymorphism of the VDR was studied by PCR-RFLP analysis, randomly
selected patients were additionally analyzed by direct sequencing. The statistical
significance of differences between the allele and genotype frequencies in TAO vs
controls, as well as in subgroups of TAO were evaluated by c2 or Fisher’s exact
test. A P-value of !0.05 was considered significant.
EP1347
Results
The impact of levothyroxine sodium treatment on dynamic
Observed allele frequencies were in Hardy-Weinberg equilibrium. C allele and
thiol/disulphide homeostasis in overt hypothyroidism
CC genotype were more frequent in TAO compared to the controls (59.50 vs
Cemile Bicer1, Ihsan Ates2, Murat Aydin3, Mustafa Altay2,
55.28% and 34.00 vs 31.69%, respectively), although differences were not
Canan Topcuoglu4, Salim Neselioglu1, Ozcan Erel1 & Fatma Meric Yilmaz1
statistically significant (PZ0.36 and PZ0.50). CCCCT genotypes (dominant
1Yildirim Beyazit University Medical Faculty, Ankara, Turkey;2Ankara
inheritance model) were more frequent in the subgroup A compared to B (89.70%
Numune Training and Research Hospital, Department of Internal Medicine,
vs 75.00%), PZ0.07.
Ankara, Turkey;3Namik Kemal University Medical Faculty, Department of
Conclusions
Biochemistry, Ankara, Turkey;4Ankara Numune Training and Resaerch
There is no statistically significant difference in allele or genotypes distribution of
Hospital, Department of Biochemistry, Ankara, Turkey.
VDR FokI polymorphisms between TAO and the control group among the
Caucasian-Polish population.
DOI: 10.1530/endoabs.49.EP1348
Objective
Thiols are organic compounds that contain sulphydryl group (-SH) and have
important role in preventing oxidative stress especially in cells. The aim of our
study is to investigate the relationship between hypothyroidism due to HT and the
thiol disulfide homeostasis, the effect of treatment on this homeostasis and to
demonstrate the utility of thiol/disulphide homestasis as a marker for assessing the
damage to functional group of proteins and the oxidative balance in this group of
EP1349
patients.
Lymphoid hyperplasia in Graves’ disease: about 2 cases
Design, patients and measurements
Faten Hadjkacem, Dorra Ghorbel, Fatma Mnif, Hamza Elfekih,
Thirty-five patients with a new diagnosis of hypothyroidism due to HT who were
Nabila Rekik, Houcem Mrabet, Mouna Ammar, Nadia Charfi &
not yet under treatment is enrolled in the study. Serum samples were taken prior to
Mohamed Abid
the treatment and 6 months after initiation of levothyroxine sodium treatment to
The Department of Endocrinology and Diabetology of Hedi Chaker
compare clinical and laboratory parameters of patients. Thiol/disulfide
Hospital, Sfax, Tunisia.
homeostasis is evaluated by Erel & Neselioglu method.
Results
After
6 months of treatment the native thiol and total thiol levels were
Introduction
significantly increased
(PZ0.001 and PZ0.001). The disulphide level, the
Graves’ disease GD is an autoimmune disease, which can manifest with a variety
disulphide/native thiol and the disulphide/total thiol ratios showed a significant
of extrathyroidal clinical syndromes. Though quite rare, this disease can also
decline (PZ0.001, PZ0.001, PZ0.001 respectively).
manifest with lymphoid hyperplasia.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Case report
Introduction
Two cases are reported in the department of endocrinology and diabetology of
Radioiodine treatment (RAIT) is an effective definitive treatment for Graves’
Hedi Chaker hospital in Sfax-Tunisia from 2006 to 2016 associated GD with
Disease (GD) and Toxic Nodular Goiter (TNG). The aim of this study was to
lymphoid hyperplasia reaction. The first case was a 32 years old male with history
analyze demographic and clinical factors affecting the outcome of RAIT in
of GD 6 years back treated with propylthiouracil and beta blockers. He was
patients with hyperthyroidism.
admitted with follow complaints: dyspnea and edema of the lower limbs. The
Methods
diagnosis of cardiothyrosis with dilated cardiomyopathy has been confirmed by
Retrospective review of patients treated with RAIT for hyperthyroidism. A fixed
echocardiography. Neck-chest computerized tomography (CT) has been made to
dose of 10 mCi was administered to patients with GD and 15 mCi to patients with
explore swallowing disorder wich showed the presence of no compressed
TNG. Treatment success was defined as euthyroidism or hypothyroidism
heterogeneous goiter with mediastinal polyadenopathy and bilateral suspect lung
(subclinical/overt hypothyroidism) 12 months after RAIT.
nodules. The body scan revealed the same results with other deep localization of
Results
lymph nodes. The infectious and inflammatory etiological investigations were
217 patients were included; 122 with GD and 95 with TNG (52 patients with toxic
negatives. A total thyroidectomy with biopsy of mediastinal lymph node under
multinodular goiter and 43 with Toxic Adenoma). RAIT was more effective in
mediastoscopy confirmed histologically the presence of lymphocytic thyroiditis
TNG than in GD (94.7% vs 71.3%, P!0.05). Gender, previous thyroid function
with a lymphoid hyperplasia. The second case was a 47 years postmenopausal
and thyroid volume were significantly as-sociated with an effective outcome in
female followed for Graves’s disease complicated with cardiothyreosis. We have
patients with GD (P!0.05). No clinical or demographic factors affected the
discovered incidentally deep lymph nodes
(mediastinal, coeliomesenteric,
outcome in patients with TNG, although a higher Tc99 uptake on scintigraphy
aortocave) with lung nodules. The biopsy of the lung was not conclusive. The
was associated with persistent hyperthyroidism. Hypothyroidism was more
stability of these lesions for 10 years argues for a reactive lymphoid hyperplasia.
common in GD (62.3% vs 41.1%, PZ0.001). Hypothyroidism was significantly
Conclusion
more frequent in smaller nodules (26G8 mm vs 32G11 mm, P!0.05) and in
Reactive lymphocyte proliferation remains a histological diagnosis. It is
lower thyroid volumes (24.3G14 ml vs 37.7G19 ml, P!0.05).
necessary to complete with exhaustive etiology investigation in front of this
Conclusion
clinical presentation.
Thyroid volume seems to have a significant influence on the development of
DOI: 10.1530/endoabs.49.EP1349
hypothyroidism after the treatment and, in patients with GD, the efficacy of RAIT.
In GD, larger goiters may need a greater dose and beneficiate from a calculated
dose of radioiodine instead of a fixed predefined dose. In TNG, a fixed dose of
15 mCi successfully cured hyperthyroidism in almost all patients although in
selective patients with smaller thyroid nodules or smaller goiters a lesser RAIT
dose may restore euthyroidism.
DOI: 10.1530/endoabs.49.EP1351
EP1350
Effects of hypothyroidism on nutritional status: which impact?
El Mghari Ghizlane, Naima Bouznad & Nawal El Ansari
Department of Endocrinology, Diabetology, Metabolic Diseases and
Nutrition. PCIM Laboratory, FMPM, Mohamed VI CHU, Marrakech,
Morocco.
Introduction
EP1352
Hypothyroidism is a common disease in Morocco because of the iodine
An unusual case of subacute thyroiditis after alemtuzumab treatment
deficiency frequency. The metabolic and nutritional effects of hypothyroidism are
Philippe Baltzinger, Alina Dumitrescu, Clothilde Wagner,
known in the literature. The hypothyroidism is classically described among the
Nicolas Collongues, Jérôme De Seze, Thibault Bahougne &
causes of secondary obesity. The aim of the study is to evaluate the nutritional
Nathalie Jeandidier
status and anthropometric parameters in patients having hypothyroidism.
University Hospital of Strasbourg, Strasbourg, France.
Patients and methods
Patients were recruited from the out-patients clinics. All the patients with the
diagnosis of hypothyroidism and not receiving yet the L-thyroxin were included.
Introduction
All the patients were examined by the dietitian and the clinical and laboratory
Alemtuzumab, a humanized monoclonal antibody against CD52, is effective in
evaluation were carried on in all patients.
the treatment of early relapsing-remitting multiple sclerosis (MS). Thyroid side-
Results:
effects such as Graves’ disease have been already described. We describe one case
A total of .. were included. The mean age was 41 years. The sex ratio is 6/1.
of unusual subacute thyroiditis after alemtuzumab treatment.
Weight gain was found in 67% of patients with a mean gain of 8kg. The mean
Clinical case
weight was 80 kg for men and 68 kg for women for an average ideal weight of 64
A 38 year-old-female was treated by alemtuzumab for 2 years. She was referred
and 54 kg respectively. The BMI was normal in 43, 30% of cases, 26.60% were
for hyperthyroidism with 10 kg weight loss, diarrhea and palpitations. Clinical
overweight and 23.20% were obese. Waist circumference was pathological in
examination found cervical pain and fever. Thyroid function tests revealed low
92% of women and 80% of men. The body fat percentage was high in 60% of
TSH at 0.0170 mUI/l (N 0.270-4.20), increased fT4: 71.4 pmol/l (N 12-23) and
female patients and 80% of male patients. The average daily caloric intake for
fT3: 18.2 pmol/l (N: 3.84-7.07). Thiamazol (20 mg bid) and propranolol (20 mg
women was 2138.77 Cal while the caloric intake was 1856.6 Cal in men. High
tid) were started with daily neutrophil evaluation. First hypothesis was Graves’
intake in macronutrients was found in all patients.
disease, since it is currently described with alemtuzumab. Blood tests revealed
Conclusion
increased CRP: 156 mg/l (N!4 mg/l) without increased leukocytes. Ceftriaxone
Hypothyroidism is responsible for an important increase in body fat leading to
was started in front of a urinary infection suspicion. Finally, bacteriological
overweight and obesity. The hormonal replacement is an efficient way to
analyses (blood and urine) were negative and ceftriaxone was discontinued. After
overcome these nutritional and metabolic changes. The nutritional evaluation is
3 days under thiamazol treatment, fT4 increased up to 100 pmol/l and fT3 up to
critical for any patient consulting for hypothyroidism.
26.5 pmol/l without clinical improvement. Thyroid ultrasonography showed
DOI: 10.1530/endoabs.49.EP1350
isolated heterogeneous parenchyma. Technetium scintigraphy showed no uptake;
allow us to make the diagnosis of subacute thyroiditis. Finally, anti TSH receptor,
thyroglobulin and thyroperoxidase antibodies results came back negative.
Thiamazol was resumed, prednisolone (1 mg/kg per day) started. After 1 week,
neck pain and fever disappeared and fT3, like CRP, were normalized. After 2
weeks, fT3 and fT4 were in the normal ranges.
Discussion
Although subacute thyroiditis is not known as an auto-immune disease, an
increase of its incidence rate is found after alemtuzumab or INF-alpha treatment
EP1351
suggesting an immune participation. Moreover, this rise is not found after
Outcome of radioiodine therapy in patients with hyperthyroidism
alemtuzumab therapy for chronic B cell leukemia
(suggesting a specific
Catarina Machado1, Patrícia Tavares1, Sara Monteiro1, Gustavo Rocha1,
background in MS patient). We describe here the case of unusual severe subacute
Fernando Silva2, José Manuel Oliveira2 & Maria João Oliveira1
thyroiditis after alemtuzumab treatment.
1Centro Hospitalar de Vila Nova de Gaia/Espinho, EPE, Vila Nova de Gaia,
DOI: 10.1530/endoabs.49.EP1352
Portugal;2HPP-MM-Lenitudes, Porto, Portugal.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1353
EP1355
Pattern of amiodarone-induced thyrotoxicoxis before and after
Perinatal outcome in graves-basedow disease during pregnancy
universal salt iodization
Snezana Mihajlovska & Marija Mihajlovska
Raluca Trifanescu1,2, Cristina Popa2, Andrei Goldstein2, Florin Alexiu2,
1Department of Nuclear Medicine, Clinical Center ‘D-R Trifun Panovski’,
Mariana Purice2 & Catalina Poiana1,2
Bitola, Macedonia;2Department of Endocrinology, General Hospital
1‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania;
‘8-MI Septemvri’, Skopje, Macedonia.
2‘C.I. Parhon’ National Institute of Endocrinology, Bucharest, Romania.
The purpose of this study is to assess the treatment outcome of pregnant patients
Background
with Graves-Basedow disease. In the period of 20 years 59 pregnancies in
Prevalence and type of amiodarone-induced thyroid dysfunction in a population
hyperthyroid patients were registered with Graves-Basedow disease in the
depend on geographical iodine intake.
Department of Nuclear Medicine in Clinical Hospital Bitola. Thyrostatic therapy
Aims
was applied in 29 (56.5%) pregnant patients divided into 2 groups. The first group
To assess differences in amiodarone-induced thyrotoxicosis pattern before and
were patients who used methimazole therapy (MMT) or 50-400 mg propiltiuracil
after iodine supplementation.
(PTU). Of this group, 19 were born healthy infants (74.3%), 2 (5.12) with low
Patients and methods
birth weight, 5 (12.8) were premature but with no fetal malformations. The second
84 patients (41M/43F) with amiodarone-induced thyrotoxicosis, aged 60.1G11.9
group were patients who were not regularly controlled and treated. Of them all
years, were retrospectively reviewed. 28 patients were resident in former iodine-
three babies were born with malformations (two newborns died shortly after birth
deficient areas. TSH, FT4 and total T3 were measured by chemiluminescence;
and one newborn died six months after birth).
2 h and 24 h radioiodine (131I) uptake and color flow Doppler were performed.
Conclusion
Results
Our study suggests that patients treated with Graves-Basedow disease during
Type 1 amiodarone-induced thyrotoxicosis (AIT) was diagnosed in 21 cases
pregnancy with a low dose of thyrostatic therapy, provides a significant reduction
(25%), type 2 in 26 cases (30.9%) and mixed type in 37 cases (44%). Before
of fetal complications. Our study also indicated no significant difference in the
universal salt iodization were diagnosed 38 cases (type 1 AIT in 12 cases - 31.6%,
effects of both drugs - PTU and MMT in these doses although preferably PTU
type 2 in 14 cases - 36.8% and mixed type in 12 cases - 31.6%); after universal
because of reduced transplancental passage compared to MMT. In our study
salt iodization were diagnosed 46 cases (type 1 AIT in 9 cases - 19.6%, type 2 in
observed complications and mortality in newborns of mothers with uncontrolled
12 cases - 26% and mixed type in 25 cases - 54.3%); Patients with type 1 AIT
or inadequate and irregular treated hyperthyroidism.
were significantly younger (62.5G9.6 years vs 56.1G12.8 years, PZ0.05), with
DOI: 10.1530/endoabs.49.EP1355
significantly higher radioiodine uptake at
24 h (median 7% vs median 1%,
PZ0.022) and had higher thyroid volume (29.9G14.8 ml vs 19.9G8.6 ml,
PZ0.015) than patients with type 2 AIT. Patients with type 1 AIT had higher total
T3 levels than patients with type 2 AIT (340.9G157.4 vs 246.7G135.9 ng/dl,
PZ0.06) and type 3 AIT (216.4G111.8 ng/dl, PZ0.003, respectively). There
were no statistically significant differences in body mass index, amiodarone
treatment duration, amiodarone cumulative dose, FT4 levels between AIT type 1,
2 and mixed type.
Conclusion
After universal salt iodization, AIT type 2 and mixed type prevailed in our
geographical area.
EP1356
DOI: 10.1530/endoabs.49.EP1353
TSH receptor stimulating immunoglobulins - performance of an
automated immunoassay
Patrícia Tavares1, Catarina Machado1, José Carlos Pedroso2, Joana Vieira2,
Gustavo Rocha1, Sara Monteiro1, Ana Margarida Sousa1, Pedro Rodrigues1,
Agostinho Lira2 & Maria João Oliveira1
1
Endocrinology Department, Centro Hospitalar Vila Nova de Gaia/Espinho,
Vila Nova de Gaia/Porto, Portugal;2Clinical Pathology Department, Centro
Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia/Porto, Poland.
Introduction
Graves’ disease (GD) hyperthyroidism is caused by autoantibodies against TSH
receptor (TRAb). Three varieties of TRAb are now recognized: stimulating (TSI),
EP1354
blocking and neutral antibodies. Current TRAb immunoassays detect and
They think it’s all ovar(ii)
quantify serum immunoglobulins that interact with the TSH receptor but without
Raj Tanday1, Bonnie Grant1, Premila Kollipara2, Edel Casey1 &
discriminating their function. An automated immunoassay for the detection and
Khash Nikookam1
quantification of TSI is available.
1Department of Endocrinology, King George Hospital, London, UK;
Objective
2Department of Obstetrics and Gynaecology, King George Hospital,
Our study objective was to determine the performance of TSI assay in patients
London, UK.
with thyroid autoimmune disease, nodular disease, and healthy individuals.
Methods
A 37 year old woman was referred to the endocrinology clinic from the
59 subjects were enrolled in the study: 37 samples of consecutive individuals
gynaecologists. She was awaiting an 8 cm left ovarian cyst removal and found to
referred to the endocrinology consultation with thyroid pathology and 22 healthy
be hyperthyroid (fT3 7.8 pmol/l, fT4 of 19.0 pmol/l, TSH !0.01 mU/l). She
subjects. The Immulitew 2000 TSI (Siemens) was used to measure TSI.
described
4 months of palpitations, change in bowel habit and menstrual
Results
irregularity. She had no tremor or tachycardia. She had no palpable goitre or eye
Of the 37 patients, 30 (81,1%) were female and 7 (18,91%) were male, with a
signs. She had a past medical history of asthma on inhalers. There was no family
mean age of 58 (G14) years. 18 patients were diagnosed with autoimmune
history of thyroid disease. Repeat bloods confirmed T3 toxicosis, negative TPO
thyroid diseases (10 with untreated GD and 8 with Hashimoto thyroiditis (HT))
and TSH receptor antibodies. She was commenced on carbimazole 10 mg od. She
and 19 with nodular thyroid disease (12 with non-toxic goiter and 7 with toxic
underwent a successful left salpingo-ooperectomy. Histology showed a multi-
adenoma). Healthy subjects and those with nodular thyroid disease had a negative
loculated cyst containing hyperplastic thyroid tissue and no evidence of
TSI assay but one patient with HT had a positive TSI assay (specificity 98%). Of
malignancy. Following surgery she reported resolution of symptoms and had
the ten patients with diagnosis of Graves’ disease 10 had positive TSI assay
normalisation of thyroid function. Her carbimazole was reduced. At recent clinic
(sensitivity of
100%) with a median value of 3.6 IU/L (maximum of 90.1,
review she is clinically and biochemically euthyroid off carbimazole. Struma
minimum of 1.2). There was a positive correlation between the value of TSI assay
Ovarii is a rare finding of ectopic thyroid tissue in an ovarian teratoma. This case
and the amount of the free fractions of thyroid hormones.
illustrates the importance of checking thyroid function prior to gynaecological
Conclusion
surgery and to consider rarer causes of thyrotoxicosis.
This easy to perform assay method of TSI revealed high sensitivity and specificity
in the diagnosis of Graves’ disease.
DOI: 10.1530/endoabs.49.EP1354
DOI: 10.1530/endoabs.49.EP1356
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1357
not used as a mode of achieving euthyroid status with hyperthyroidism, though it
is often used in thyroid crisis.
Genetic variation in NFE2L2 and SEPS1S associated with increased
risk of Hashimoto’s thyroiditis
DOI: 10.1530/endoabs.49.EP1358
Liliana R Santos1,2, Cecila Dura˜es1,3, Ana Pestana1,3, César Esteves4,
Celestino Neves3,4, David Carvalho3,4, Manuel Sobrinho Simo˜es1,3 &
Paula Soares1,3
1Institute of Molecular Pathology and Immunology of University of Porto
(IPATIMUP), Porto, Portugal;2Internal Medicine Department, Hospital de
Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal;3Faculty of
Medicine of the University of Porto, Porto, Portugal;4Department of
Endocrinology, Hospital of S. Joa˜o, Porto, Portugal.
EP1359
A slow but continuous growth: Case study of a thyroid nodule
Hashimoto’s thyroiditis (HT) is the most common chronic autoimmune thyroid
David Veríssimo, Vitória Pires, Dolores Passos, Filipa Serra, Joa˜o Silva,
disease, which is characterized by alteration of the thyroid function. HT is a
Luís Lopes, João Jácome de Castro & Mafalda Marcelino
multifactorial disorder and several candidate genetic loci have been identified as
Hospital das Forças Armadas, Lisboa, Portugal.
contributing to HT. The transcription factor Nrf2, encoded by the NFE2L2 gene,
is an important regulator of the cellular protection against oxidative stress. The
Thyroid nodules are a common clinical finding, with an estimated prevalence of
relevance of selenoproteins in follicular thyroid cell physiology and in molecular
palpable thyroid nodules to be approximately 5% in women and 1% in men. The
physiology have pointed to a putative role of the interaction of Nrf2
with
clinical importance of thyroid nodules rests with the need to exclude thyroid
selenoproteins in the pathogenesis of autoimmune thyroid diseases. In order to
cancer. The prevalence of malignancy reported for palpable thyroid lesions ranges
evaluate the role of a promoter variation in NRF2 and SEPS1 in the risk for
from 5.0% to 6.5%. Patients with benign thyroid nodules are unlikely to suffer
developing Hashimoto’s thyroiditis (HT), we performed a case-control study
morbidity or mortality due to thyroid cancer. A 53 aged man presented with a
comprising 997 individuals (HT patients and unrelated controls). Genetic variants
20-year history of a slow-growing nontender neck mass. He denied any
were discriminated by real-time PCR using TaqMan SNP genotyping assays.
compressive symptoms, such as dysphagia, dyspnea or hoarseness. On physical
Three polymorphisms (- 653A/G: rs35652124; - 651G/A: rs6706649 and -
examination of the thyroid, the patient had a right-sided soft, elastic nodule larger
617C/A: rs6721961 SNPs) in the NRF2 gene promoter were studied and no
than
10 cm of diameter. TSH, T4l were within normal range and thyroid
significant difference were found between HT patients and controls with regard to
antibodies were negative. CT scan of the neck indicated a solitary dominant
genotypic or allelic frequencies of the three NFE2L2 SNPs (PO0.05). The joint
nodule of the right thyroid lobe measuring 140!78!84 mm without invasion of
effect of genetic polymorphisms in NFE2L2 and SEPS1 was assessed considering
adjacent structures. A minor compression and tracheal deviation to the left was
the high-risk genotypes of NF2L2 and SEPS1. Our findings suggest that the risk to
also reported. Thyroid ultrasound indicated a large, heterogeneous nodule, solid
develop Hashimoto’s thyroiditis is not associate to a single NFE2L2
with some cystic component and well-defined contours, occupying the entire right
polymorphisms but increases with the combined effect of the number of risk
lobe of the thyroid gland. Left lobe also had a 1.4 cm solid nodule. FNAB of both
alleles in NFE2L2 and SEPS1. Individuals carrying two high-risk genotypes
nodules were benign. The patient remained asymptomatic throughout. Natural
present a significant increased risk for HT.
growth behaviour of thyroid nodules is controversially discussed. In our clinical
DOI: 10.1530/endoabs.49.EP1357
case, the slow progression and the absence of compressive signs was suggestive
of a benign lesion. However, the large dimensions and the progressive growth of
the nodule might also be indicative of malignancy. There are few studies about
long-term prognosis of thyroid nodules, including their malignant transformation.
Although well established that approximately 90% of non-functioning thyroid
nodules are benign, even in slow growth big nodules with benign FNAB, surgery
is crucial to the final diagnosis.
DOI: 10.1530/endoabs.49.EP1359
EP1358
Safety and efficacy of cholestyramine in the adjuvant management of
Graves thyrotoxicosis
Taimur Gulfam & Sath Nag
James Cook University Hospital, Middlesbrough, UK.
Introduction
EP1360
Graves’s disease is an autoimmune condition both cell and antibody-mediated,
which is associated with thyrotoxicosis and extra thyroid features.
Mirela Tirnovan1, Anamaria Bursuc1, Alina Daniela Belceanu1,
Case report
Adina Manolachie1, Ioana Armasu1, Iulia Crumpei1, Georgiana
A 35-year-old female presented with symptomatic hyperthyroidism due to graves
Constantinescu1, Luminita Apostu2, Carmen Vulpoi1
thyrotoxicosis. She developed adverse reactions, including severe dermatitis and
Mirela Tirnovan1, Anamaria Bursuc1, Alina Daniela Belceanu1,
hepatotoxicity, to two of the thionamide drugs (carbimazole and propylthiouracil).
Ioana Armasu1, Iulia Crumpei1, Adina Manolachie1, Luminita Apostu2 &
Eventually we decided for definitive treatment in the form of a total
Carmen Vulpoi1
thyroidectomy, as it appeared to be the only option in a mother of a young
1Department of Endocrinology, U.M.F. ‘Grigore T. Popa’, Iasi, Romania;
child, which precludes radioiodine therapy. Unfortunately, we were unable to
2Department of Biochemistry, Iasi, Romania.
treat her with a beta-blocker due to her history of severe Raynaud’s disease. We
arranged for her to undergo rapid thyroid blockade 10 days prior to her surgery
Introduction
with Lugol’s iodine. After she had Lugol’s iodine, she exhibited a paradoxical
Many causes of malabsorbtion of levothyroxine
(LT4) in patients with
increase in her thyroid hormone levels, which was unusual and necessitated
hypothyroidism have been thoroughly described in literature. Pseudomalabsorp-
cancellation of her surgery. It appears she did not go through the Wolff-Chaikoff
tion, poor compliance of the patient is most common cause of failure of LT4
effect but instead showed Jod-Basedow effect, resulting in a significant rise in free
and/or liothyronine (LT3) treatment.
T4. We have agreed to commence her on cholestyramine 2 g three times a day and
Case report
prednisolone 40 mg once a day in order to improve her thyrotoxicosis. Eventually
27 years old woman, normopondeal, presented from the age of 11 years for short
she became euthyroid after a few weeks of starting the treatment and then
stature. Further investigations found pluritrope pituitary insufficiency (somato-
underwent total thyroidectomy.
trophic, gonadotroph, corticotroph and tireotroph) and substitutive treatment was
Comments
started (GH-treated off 17 years, actual height 168 cm, cortisol, esoprogestative
Thionamides are widely used as anti-thyroid drugs in the management of
and thyroid hormones). MRI described a small pituitary. Despite of increasing
hyperthyroidism but unfortunately they are also associated with serious adverse
dose of LT4, ulterior in association with LT3, and vitamic C for better absorption,
effects which was exhibited by this patient. In our case we have successfully used
THS remained high (13 mUI/ml, reference 0.4-4 mU/L) with constantly low fT4.
adjunct treatment including steroids and cholestyramine to achieve euthyroid
Celiac disease, pernicious anemia, gastrointestinal, liver, pancreatic, heart disease
state and making patient ready to undergo thyroidectomy. Although steroids are
or pregnancy were excluded by laboratory and imagistic investigations, also were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
excluded drugs and dietary interactions; To evaluate the hypothesis of
TSH (0,38-5,33 uUI/ml)
pseudomalabsorption, the patent was submitted to rapid LT4 absorption test.
After an overnight fasting, it was administreted 1000 mg LT4; We measured fT4 at
300 , 2, 4, 6 h.Immediately fT4 serum increase, with the maximum serum level
after
2 h (basal fT4Z0.56 ng/dl,
2 hZ1.72 ng/dl, peak fT4O2.5). The test
showed a normal absorption of LT4 and malabsorption was excluded.
34.02
Conclussion
30.76
28.44
27.39
Our case showed an inadequate thyroid hormone supplementation (3.3 mg/kg);
26.08
the literature suggested that after excluding organic cause or drug interaction, is
19.9
useful to make a malabsorption test, which confirms the diagnostic pseudoma-
16.9
16.1
labsorption; based on his historical attempts to stop the treatment, a psychological
10.7
counseling may be necessary. Once weekly oral thyroxine treatment, supervised,
can be a safe, well-tolerated, and effective therapy for patients with non-
2.1
3.2
2.3
2.6
2.7
compliance.
2.3
DOI: 10.1530/endoabs.49.EP1360
0
60
120
180
240
the graphic below. The patient remained with normal heart rate and normotensive
along LAT. The results showed a normal absorption of LT4, so pseudo-
malabsorption was proven. Based on this diagnosis was prescribed 1 mg of LT4
EP1361
weekly to improve therapeutic compliance. Nowadays, patient present normal
Oxidative profiles in patients with autoimmune thyroid diseases
TSH and FT4 serum levels. In conclusion, pseudo-malabsorption is an important
Fatma Mnif, Hamza Elfekih, Mouna Elleuch, Faten Hadjkacem,
differential diagnosis in persistent hypothyroidism to achieve therapeutic success
Houcem Elomma Mrabet, Nabila Rekik, Dorra Ghorbel, Mouna Mnif &
and LAT is a simple, secure and useful tool in this cases.
Mohamed Abid
Hedi-Chaker University Hospital, Sfax, Tunisia.
DOI: 10.1530/endoabs.49.EP1362
Introduction
Autoimmune thyroid diseases are known to be associated with oxidative stress.
Objectives
We studied the oxidative profiles in plasma and thyroid tissue of 82 patients
having Graves’ disease (GD) or Hashimoto thyroiditis (HT) or hashitoxicosis
(HTX) vs 65 healthy controls in order to evaluate the antioxidant enzymes’
activity and the lipid peroxidation.
Results
The lipid peroxidation was objected with a significant higher level of
EP1363
Malondialdehyde (MDA) in the plasma of our patients vs healthy controls
Serum irisin level in different thyroid dysfunction states and its relation
(P!0.01 for HT, P!0.001 for GD and HTX). A very low antioxidative activity
to markers of muscle dysfunction
of Glutathione peroxidase (GPx) was found in our patients vs healthy controls
Mohamed Reda Halawa, Mona Mohamed Abdelsalam,
(P!0.001 for HT and HTX, P!0.01 for GD). The Selenium which is GPx-
Bassem Mourad Mostafa & Amira Galal Ahmed
cofactor and the Catalase were found to be reduced as well. For the proteins
Ain Shams University, Cairo, Egypt.
oxidation, we found a higher level in Carbonyl-group, MDA and a lower level of
thiol-group in our patients vs healthy controls. Similar results were found in the
thyroid tissue samples.
Introduction
Conclusion
Irisin is a myokin secreted by myocytes responsible for transmission of signals
This study shows clearly the presence of an oxidative stress in both plasma and
from muscles to other body tissues. It improves systemic metabolism by
thyroid tissue in patients with autoimmune thyroid diseases.
increasing energy expenditure and has a significant influence on the body
DOI: 10.1530/endoabs.49.EP1361
metabolism and thermogenesis. Thyroid disorders are characterized by a
disrupted thermo-metabolic state and muscular damage, and the underlying
mechanisms still not clear.
Aim
To evaluate serum Irisin levels in patient with hypothyroid and hyperthyroid
disease and its relation to creatinine kinase (CK) a marker of muscle damage.
Method
90 subjects participated in the study. They were divided into three groups: Group
1: 30 hyperthyroid patients, Group 2: 30 hypothyroid patients, Group 3: 30 normal
persons. They were submitted to history, medical examination (Weight, Height
EP1362
and BMI) and measurement of fasting serum Irisin, TSH, Free T3, Free T4, CK.
Levothyroxine absorption test in the management of a patient with
Results
persistent hypothyroidism
Irisin hormone level was lower in hypothyroid patients (16.60G4.07) Pg/ml than
Joana Monteiro, Marta Ferreira, Miguel Pires, Alexandra Vieira,
hyperthyroid patients (26.83G7.95) Pg/ml and controls (25.70G5.29) Pg/ml
Daniela Guelho, Teresa Pereira, Fernanda Pinhal & Célio Fernandes
(P!0.01). However, it was higher in hyperthyroid than (PO0.05). Creatine
Centro Hospitalar de Leiria, Leiria, Portugal.
kinase (CK) level decreased in hyperthyroid patients (33.80G1.49) m/l than
hypothyroid patients (196.26G4.53) m/l and controls (62.86G1.63) m/l (P!0.01).
However, creatine kinase increased in hypothyroid patients (196.26G4.53) m/l in
Nonadherence to levothyroxine therapy is one cause of persistent hypothyroid-
comparison with control
(62.86G1.63) m/l
(P!0.01). There is a negative
ism. To distinguish nonadherence from malabsorption, a levothyroxine
correlation between Irisin, TSH, Weight, BMI and CK (P!0.01), and a positive
absorption test (LAT) is sometimes required. The authors report a case of a
correlation with freeT3 and free T4 (P!0.01) in hyperthyroid patients.
60-year-old female patient suffering from hypothyroidism resistant to oral
Conclusion
levothyroxine (LT4) substitution after radioiodine therapy for Graves’ disease.
Lower Irisin hormone level was found in patients with hypothyroidism which
Despite the continuous increases of LT4, over 10 years, to a maximum of
might be explained by muscles destruction demonstrated with high CK levels,
1 mg/day, she remained with high thyrotropin (TSH) and low free thyroxine
however the higher level of Irisin in hyperthyroidism might explained by
(FT4). Extensive investigation excluded disease of the small bowel, liver and
hypermetabolic state.
pancreas as well us drugs interactions. After careful consideration was decided to
conduct a LAT. Serum levels of TSH, FT4 and free triiodothyronine (FT3) were
DOI: 10.1530/endoabs.49.EP1363
drawn at 0, 60, 120, 180 e 240 min after 1mg of LT4. The results are presented in
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1364
supplementation as the first line of treatment. However, many of the symptoms
are unrelated to the failing thyroid function, but seem to be connected to the
Iodine deficiency is still prevalent in pregnant women from Romania
autoimmune disease, remain. Literature has reported on many of the
after universal salt iodization
environmental triggers of autoimmune response, however patients do not have
Monica Livia Gheorghiu1,2, Horea Ioan Ursu1,2, Irina Dumitrascu3,
a unified way to record, document, measure and understand their experiences and
Ionela Pascanu4, Carmen Georgescu5, Dan Mihu5, Corina Elena Delia6,
share them with their healthcare practitioners.
Geanina Mirela Toma6, Mihaela Stanciu7, Dragos Popescu7,
Objective
Corina Lichiardopol8, Mihaela Vlad9, Ramona Aldea10,
We aim to build a mobile phone application that would allow patients to record
Stefania Tudorache8, Mihaela Vasile8, Claudia Podia Igna11,
and overview their symptoms as well as their compliance to medication.
Mariana Purice1 & Adina Ghemigian1,2
Design
1C.I. Parhon National Institute of Endocrinology, Bucharest, Romania;
The app is build on a combination of thus far biomedical knowledge of symptoms
2C. Davila University of Medicine and Pharmacy, Bucharest, Romania;
related to Hashimoto’s as well as information gathered from interviewing
3Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania;
individuals diagnosed with Hashimoto’s. It enables individuals to record their
4University of Medicine and Pharmacy, Tirgu Mures, Romania;
experience on daily-weekly and monthly basis. No data are collected, the system
5I. Hatieganu University of Medicine and Pharmacy, Cluj Napoca,
is decentralized, and the recorded data are stored only on patient’s phones.
Romania;6Alessandrescu Rusescu National Institute for Mother and Child
Results
Care, Bucharest, Romania;7L. Blaga University, Faculty of Medicine,
Patient’s needs could be easily served through a mobile phone app, according to
Sibiu, Romania;8University of Medicine and Pharmacy, Craiova, Romania;
the first results. It could help the patients implement lifestyle changes that would
9V. Babes University of Medicine and Pharmacy, Timisoara, Romania;
serve as a first line of defence against non-thyroid related Hashimoto’s symptoms.
10Campulung Hospital, Campulung, Romania;11Astra Clinic, Sibiu,
Conclusion
Romania.
Smart phone apps have a great value and potential in collecting a large pool of
worldwide data, however they need to be co-developed with biomedical scientists
Introduction
and healthcare professionals in order to fully serve to patients, medical healthcare
Even mild to moderate maternal iodine deficiency during pregnancy is associated
professionals as well as the research.
with impaired child cognition. Iodine deficiency is especially problematic in
DOI: 10.1530/endoabs.49.EP1365
pregnant women, who have a higher iodine requirement (250 mg/day) than non-
pregnant women (150 mg/day).
Objective
To assess iodine status (median urinary iodine concentration, UIC) in pregnant
women from multiple endemic or non-endemic areas in Romania, 13 years after
implementation of the Universal Salt Iodization (25-40 mg iodine/kg salt).
Subjects and methods
Median UIC in the morning urine was evaluated by spectro-photometry in 409
pregnant women in the third trimester from seven geographical regions in
Romania (age range 16-44 years, median age 29 years, none treated with
thyroxine, 80% from endemic regions, 59% from urban regions). Data regarding
iodized salt intake, bread intake (usually containing 6-9 mg iodine/slice) and
EP1366
iodine supplements were assessed. The study was approved by the local Ethics
Committee.
Dynamic risk stratification for predicting recurrence in patients with
Results
differentiated thyroid cancer treated without radioactive iodine
Iodized salt was consumed by 87% of women, iodine supplements during
remnant ablation therapy
pregnancy by 48% of women. Median UIC in the study group was 131 mg/l,
Suyeon Park, Won Gu Kim, Eyun Song, Hye-Seon Oh, Mijin Kim,
reflecting iodine deficiency during pregnancy (normal values R150 mg/l). Lower
Hyemi Kwon, Min Ji Jeon, Tae Yong Kim, Young Kee Shong &
median UIC (mg/l) were recorded in the endemic regions of Transilvania (92),
Won Bae Kim
Oltenia (114), Moldova (129) and Muntenia (149) as compared to Bucharest area
Department of Internal Medicine, Asan Medical Center, University of Ulsan
(206) and other non-endemic regions (206.6), except Timis (140); 55.7% of
College of Medicine, Seoul, Republic of Korea.
women had values below 150 mg/l, 13% below 50 mg/l, 1.7% had values over
500 mg/l. Higher median UIC was recorded in women with a daily intake of R5
Background
slices of bread, 166 vs 111 mg/l, P!0.01. Similar UIC were found in women
Increased incidence of small differentiated thyroid cancer (DTC) has emphasized
taking prenatal vitamins containing iodine and in those with no supplements. In
the need for risk stratification and individualized disease management for these
Transilvania region there is a discrepancy between schoolchildren
(normal
low risk DTCs. The aim was to validate a new dynamic risk stratification (DRS)
median UIC) and pregnant women (low median UIC). Urinary iodine/creatinine
system for prediction of structural recurrent/persistent disease in patients with
ratio was not significantly different from urinary iodine levels.
DTC treated without radioactive iodine (RAI) remnant ablation therapy.
Conclusions
Methods
Mild iodine deficiency is still prevalent in Romanian pregnant women from
This historical cohort study included
357 patients with DTC treated with
historical endemic regions after 13 years of universal salt iodization. Iodine
lobectomy or total thyroidectomy without RAI therapy. We stratified patient
supplementation during pregnancy should be encouraged in these regions.
response to initial treatment as excellent, indeterminate, biochemical incomplete,
DOI: 10.1530/endoabs.49.EP1364
and structural incomplete according to the DRS system.
Results
During a median 8.6 year of follow-up, 3.6% patients had structural recurrent
DTC. The response was excellent in 71.7% patients, indeterminate in 18.5%,
biochemical incomplete in 8.4%, and structural incomplete in 1.4%. There were
significant differences in disease-free survival among the DRS groups (P!0.001).
The hazard ratio (HR) of recurrent/persistent disease was significantly higher in
biochemical incomplete group (HR Z20.8, P!0.001) and structural incomplete
group (HR Z243.3, P!0.001) compared with the excellent group. However, the
tumor node metastasis
(TNM) staging system and the American Thyroid
EP1365
Association (ATA) initial risk classification did not effectively predict recurrence
The potential of smartphone applications in management and
of DTC.
compliance to recommended lifestyle in Hashimoto’s patients
Conclusions
Vedrana Hogqvist Tabor & Mikael Hogqvist Tabor
The new DRS system was effective for predicting risk of recurrent/persistent
Boost by VLM Health UG, Berlin, Germany.
disease in patients with DTC who underwent lobectomy or total thyroidectomy
without RAI remnant ablation.
DOI: 10.1530/endoabs.49.EP1366
Background
Hashimoto’s thyroiditis
(HT), a chronic autoimmune disease caused by an
interaction between genetic factors and the environmental is treated by thyroid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1367
EP1369
Association between lymph node metastasis and patients’ age in
Differential diagnosis between Anaplastic Thyroid Cancer and
papillary thyroid microcarcinoma
Primitive Lymphoma of the Thyroid gland: A 66-cases study
Hye-Seon Oh, Min Ji Jeon, Suyeon Park, Mijin Kim, Hyemi Kwon,
Florence Kohler, Marie-Christine Vantyghem, Bruno Carnaille,
Eyun Song, Won Gu Kim, Young Kee Shong, Won Bae Kim &
Emmanuelle Leteurtre, Samuel Boury, Louis Terriou & Christine Do Cao
Tae Yong Kim
Centre Hospitalier Régional Universitaire de Lille, Lille, Nord, France.
Internal Medicine, Asan Medical Center, Seoul, Republic of Korea.
A rapidly growing neoplastic mass of the neck can either be caused by an
Background
anaplastic thyroid cancer (ATC) or a primitive lymphoma of the thyroid gland
Recent studies presented that younger patients with papillary thyroid
(PLT). These two malignancies share the same clinical features but vary widely in
microcarcinoma
(PTMC) had poorer clinical outcomes compared to older
their treatment and outcome. Only histologic criteria through biopsy can provide a
PTMC patients. The aim of this study is to investigate the impact of patient’s age
definitive diagnosis. The aim of this study was to assess biological and
on the lymph node metastasis (LNM) status of PTMC, a risk factor for recurrence
radiological differences between ATC and PLT in order to hasten differential
and poor clinical outcome of PTMC.
diagnosis. Sixty-six patients were included, 33 ATC and 33 PLT, diagnosed
Methods
between January 2000 and February 2016. Biological status (blood count, TSH,
The study evaluated 2068 PTMC patients who underwent thyroid operation with
antithyroid peroxidase antibodies, CRP, b2 microglobulin and LDH) and imaging
lymph node (LN) dissection from 2001 to 2009. All patients were allocated into
evaluation (Ultrasound (US) and computed tomography (CT) scanning) were
five groups by age; Group A (%35 years), Group B (35 !age%45), Group C
compared. ATC patients were all from Lille University Hospital. PLT being less
(45!age%55), Group D (55!age%65), and Group E (65!age). LNM status
common, 16 patients were included from Lille and 17 from other hospitals in
was divided into three groups by the number of metastatic LNs: no LNM, low
France. ATC was associated with higher leucocytes and neutrophils counts: over
volume LNM (%5 metastatic LNs), high volume LNM (O5 metastatic LNs). We
10000/ml and 7500/ml with positive predictive values (PPV) of 77.3 and 75%,
evaluated the correlation between patient’s age and high volume LNM in this
respectively. Neutrophils-to-lymphocytes ratio over 3,8 was noted in 77 and 48%
study.
of ATC and PLT patients, respectively. Thyroid tumor macrocalcifications and
Results
jugular vein thrombosis were found more frequently in ATC patients than in PLT
High volume LNM was found in 199 (8.9%) patients among whole study subjects
patients with PPV for ATC of 93 and 77.8% respectively, regardless of the
and was the most frequently found in the young age group (A 17.3%, B 8.4%, C
imaging technique (US or CT scan). PLT was associated with a thyroiditis history
7.2%, D 8.4%, and E 7.1%, respectively). Young age (Group A), male gender,
and/or high antithyroid peroxidase antibodies (PPV for PLT of 83 and 76.5%
larger primary tumor (O0.5 cm), multifocality, and extrathyroidal extensions
respectively). We conclude that blood count, antithyroid peroxidase antibodies
were significant risk factors for high volume LNM in univariate and multivariate
measurement, search for tumor calcifications and jugular vein thrombosis provide
analysis. In multivariate analysis, odd ratio (OR) of Group A for high volume
basic and relevant information in the initial work-up of thyroid mass to
LNM was 3.49 (95% CI, 1.67-8.06; P-value 0.002) compared to the Group E.
distinguish between ATC from PLT.
When analyzed only in women, young age (Group A) was also a significant risk
DOI: 10.1530/endoabs.49.EP1369
factor for high volume LNM (OR 6.00, 95% CI 2.73-20.76, P value 0.001). But
when analyzed in men, there was no significant difference in the incidence of high
volume LNM by different age groups (A 25%, B 18.1%, C 20.2%, D 22.0%, and E
22.7%, respectively).
Conclusion
High volume LNM was more frequently found in young aged female and male
patients. For patients under 35 years or male patients, immediate diagnosis and
surgical treatment for PTMC might be needed.
EP1370
DOI: 10.1530/endoabs.49.EP1367
The role of preoperative serum thyroglobulin values in the diagnosis of
differentiated thyroid cancer
Blertina Dyrmishi1, Taulant Olldashi1, Ema Lumi2, Entela Puca3,
Dorina Ylli4, Majlinda Ikonomi1 & Thanas Fureraj4
1
Hygeia Hospital Tirana, Tirana, Albania;2Regional Hospital Korca, Korca,
Albania;3Neo Style Clinic, Tirana, Albania;4UHC “Mother Teresa”,
EP1368
Tirana, Albania.
Breast cancer and family history for breast cancer in patients with
differentiated thyroid carcinoma
Safak Akin, Esra Tutal, Erkam Sencar, Melia Karakose, Ozgur Ozcelik,
Introduction
Mahmut Apaydin, Muyesser Sayki Aslan, Ilknur Unsal, Bekir Ucan,
Thyroglobulin (TG) is the most important protein produced by the thyroid. TG is
Mustafa Ozbek & Erman Cakal
considered a reliable marker of recurrent disease in patient with differentiated
Dı¸kapı Research and Training Hospital, Ankara, Turkey.
thyroid carcinoma (DTC). Before surgery, high serum TG values may be due to
an abnormally large thyroid, excessive thyroid stimulation, or physical damage to
thyroid etc.
Background and aim
Methods
The risk for breast cancer in patients with thyroid cancer has been investigated in
We evaluated in the retrospective study 20 patients (mean age 49.6G12 S.D.,
previous studies, and has been found to be increased. In this study we, therefore
range from 25-73 years old), with a histological diagnosis of DTC. Clinical
present retrospective analysis of the patients with differentiated thyroid
diagnosis before surgery was: 20% (4) solitary nodule; 10% (2) hyperthyroidism;
carcinoma in respect to breast cancer and family history for breast cancer.
5% (1) thyroid cancer with lytic bone metastasis; 65%(13) non toxic multinodular
Methods
goiter.
We conducted a retrospective study involving 455 patients with a diagnosis of
Results
differentiated thyroid carcinoma between January 2009 and March 2016.
Histological diagnosis: 85% (17) papillary thyroid cancer, and 15% (3) cases with
Results
follicular thyroid carcinoma. 25% (5) cases with micro DTC and 75% (15) of
The majority of them were female (403, 88.6%). Mean age at diagnosis was
cases with DTC more than 1 cm. We excluded from study one case with large
45.5G12.8 (range 10-81) years. We detected that 0.7% patients with thyroid
lytic bone metastasis because the serum TG value was very high 11096 ng/ml.
cancer had breast cancer and 13.4% patients had a family history of breast cancer
Mean TSH values were 1.4G0.9 IU/ml and mean TG values was 88.1G67 ng/ml
within three generations of the proband. There was no significantly differences
(range 16.7-255 ng/ml). In 20% (4) of cases with DTC less than 1 cm TG values it
between family history of breast cancer and gender, age at diagnosis, pathologic
were in the normal range. In 14 patients with DTC bigger than 1 cm: 42% (6) of
types, and RAI therapy.
cases had TG values more than 2 fold of normal range, 28% (4) of cases had TG
Conclusion
values in the normal range and 28% (4) of cases had TG values between normal
In the literature, there are many clinical, epidemiological, and experimental
and two fold normal range.
studies that show an association between thyroid cancer and breast cancer. Our
Conclusions
study is the first report showing history for breast cancer and family history for
In our study TG are more sensitive to detect DTC macro carcinoma, but we need
breast cancer is 0.7 and 13.4% this particular group of Turkish differentiated
to evaluate more cases, to compare TG values in cases with negative biopsy and to
thyroid cancer patients.
evaluate even the TG antibodies.
DOI: 10.1530/endoabs.49.EP1368
DOI: 10.1530/endoabs.49.EP1370
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1371
EP1373
Is there an impact of the concurrent presence of chronic autoimmune
Unilateral Graves’ disease with papillary carcinoma of the
thyroiditis in differentiated thyroid cancer patients?
hyperfunctioning lobe
Sorina Martin1,2, Oana Budianu3, Oana Ion3, Andreea Grigore3,
Georgios Papadakis1, Elena Gonzalez Rodriguez1, Gilles Allenbach2,
Anca Sirbu1,2, Carmen Barbu1,2, Cosmin Giulea4,5, Adrian Miron4,5,
Marie Nicod Lalonde2, Francois Gorostidi3, Kishore Sandu3,
Florin Andrei6 & Simona Fica1,2
Massimo Bongiovanni4 & Gerasimos P. Sykiotis1
1Endocrinology Department, Carol Davila University of Medicine and
1Service of Endocrinology, Diabetes and Metabolism, CHUV, Lausanne
Pharmacy, Bucharest, Romania;2Endocrinology Department, Elias
University Hospital, Lausanne, Switzerland;2Service of Nuclear Medicine,
Hospital, Bucharest, Romania;3Carol Davila University of Medicine and
CHUV, Lausanne University Hospital, Lausanne, Switzerland;3Service of
Pharmacy, Bucharest, Romania;4Surgery Department, Elias Hospital,
Otorhinolaryngology, CHUV, Lausanne University Hospital, Lausanne,
Bucharest, Romania;5Surgery Department, Carol Davila University of
Switzerland;4University Institute of Pathology, CHUV, Lausanne
Medicine and Pharmacy, Bucharest, Romania;6Pathology Department,
University Hospital, Lausanne, Switzerland.
Elias Hospital, Bucharest, Romania.
Background
Background
Graves’ disease (GD) typically manifests as an autoimmune hyperfunction of
The association between differentiated thyroid carcinoma
(DTC) and auto-
both thyroid lobes. Less than 10 cases of unilateral GD have been described, and
immune thyroiditis (AT) has been reported in numerous studies, yet the impact of
the pathophysiology of unilateral GD remains unknown. Co-existence of
the concurrent presence of AT and DTC remains controversial.
malignancy has never been reported. We report a case of GD of the left lobe
Methods
with simultaneous discovery of a papillary carcinoma within the hyperfunctioning
We retrospectively analysed the files of 493 patients submitted to thyroidectomy
lobe.
in our surgery department between January 2012 and September 2015.
Case description
Results
A 49-year-old patient of Middle-Eastern origin was referred to our clinic in
A total of 86 patients with DTC were enrolled, mean age 53.99G13.91 years,
November 2016, one year after the diagnosis of symptomatic thyreotoxicosis,
83.7% females. 25 (29%) patients, all women, associated biochemical and/or
treated by carbimazole for the first
6 months. Subclinical hyperthyroidism
histopathological AT. We found no significant differences between patients with
recurred after treatment withdrawal. Thyroid isotope scanning with99Tc in
DTC and AT compared to patients without AT regarding the ultrasound
September 2016 showed diffusely increased uptake of the left lobe (with the
characteristics of the thyroid nodules: nodule diameter (PZ0.330), echogenicity
exception of a low uptake zone) and minimal uptake of the right lobe. In
(PZ0.572), halo presence (PZ0.528), microcalcifications (PZ0.347), vascular-
November 2016, the patient was asymptomatic and had subclinical hyperthyroid-
ization
(PZ0.199) and lymph nodes involvement
(PZ0.418), nor the
ism. Thyroid gland ultrasonography
(US) showed a slightly enlarged and
histopathological characteristics of the DTC: tumor subtype (PZ0.100), tumor
heterogeneous left lobe with clearly increased vascularity. The right lobe was
diameter (PZ0.726), the presence of multifocality (PZ0.829), TNM staging
smaller, homogeneous, with normal vascularity confined to its periphery. Based
(PZ0.672), vascular invasion
(PZ0.149), capsular invasion
(PZ0.617),
on the imaging results and positive thyrotropin receptor antibodies, unilateral GD
extracapsular extension
(PZ0.713) or the presence of local lymph nodes
was diagnosed. The low uptake zone in the left lobe corresponded to a hypoechoic
metastasis (PZ0.888).
nodule with suspicious US features (central calcification, possible infiltration of
Conclusions
the thyroid capsule). Fine-needle biopsy of this lesion revealed papillary
Although our data showed a high prevalence of AT in patients with DTC, we
carcinoma (Bethesda class VI). Total thyroidectomy will soon be performed.
found no significant differences regarding the ultrasound and histopathological
Conclusion and perspectives
characteristics of DTC in patients that concurrently had AT compared to patients
GD can rarely present with an asymmetric involvement of the thyroid lobes. Our
without AT.
patient is the first case associating unilateral GD and thyroid malignancy in the
DOI: 10.1530/endoabs.49.EP1371
ipsilateral lobe. Given that total thyroidectomy is indicated, complete
histological, biochemical and genetic evaluation of both lobes will allow us to
test current hypotheses on the pathophysiology of unilateral GD.
DOI: 10.1530/endoabs.49.EP1373
EP1372
20,000 euros for diagnosis of one thyroid cancer case: It is not too much?
Marek Maciejewski1, Agnieszka Sawicka1, Michal Slomian1,
Malgorzata Gasiorek1, Renata Budzynska-Nosal1 &
Krzysztof Marczewski1,2
1Pope John Paul II Regional Hospital, Zamosc, Poland;2University of
EP1374
Economy and Innovation, Lublin, Poland.
Trends in the clinicopathological features and clinical outcomes of
medullary thyroid carcinoma - an Israeli multicenter study
Introduction
Dania Hirsch1,8, Orit Twito2,8, Sigal Levy3, Gideon Bachar4,8,
Thyroid cancer is a major public health problem, and fine-needle biopsy is an
Eyal Robenshtok1,8, David J Gross5, Haggi Mazeh6 & Carlos Benbassat7,8
established method of its early detection. However, there are still some
1Institute of Endocrinology, Rabin Medical Center, Petach Tikva, Israel;
controversy about the indication for BACC depending on the clinical data and
2Institute of Endocrinology, Meir Medical Center, Kfar Saba, Israel;
the results of diagnostic imaging. An important role is also played by economic
3Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, Israel;
criteria, including socially acceptable, so-called equitable cost of obtaining
4Department of Otorhinolaryngology, Rabin Medical Center, Petach Tikva,
additional year of life, which in our country is determined to three times the
Israel;5Neuroendocrine Tumor Unit, Endocrinology & Metabolism Service,
average national income per capita.
Department of Medicine, Hadassah-Hebrew University Medical Center,
Results
Jerusalem, Israel;6Department of Surgery, Hadassah-Hebrew University
We analyzed the results of fine needle biopsy of thyroid nodules taken in the years
Medical Center, Jerusalem, Israel;7Endocrine Institute, Assaf Harofeh
2008-2016 in ambulatory patients. In most cases, these people were targeted due
Medical Center, Zerifin, Israel;8Sackler Faculty of Medicine, Tel Aviv
to changes in the ultrasound detected by examination performed for other
University, Tel Aviv, Israel.
indications, the so-called incidentalomas. The most common indication was
evaluating the patency of the carotid arteries. We have performed total of 5347
Background
biopsy of thyroid focal lesions which led to the diagnosis of eight cases of thyroid
The massive use of neck sonography has led to a dramatic increase in the
cancer. Average cost detection of a single cancer case amounted to approximately
incidence of thyroid cancer detection, predominantly small papillary carcinomas.
20 000 Euro.
However, changes in the presentation and course of medullary thyroid carcinoma
Conclusion
(MTC) over time remain unclear.
This cost does not exceed three times the annual GDP per capita, but is high.
Objective
Therefore, it seems reasonable to discuss the criteria for performing the BACC in
To evaluate trends in the presentation and outcomes of MTC.
case of incidental thyroid focal changes, particularly in regions with a lower
Methods
incidence of thyroid cancer.
Patients treated for MTC at four medical centers in Israel were divided into two
DOI: 10.1530/endoabs.49.EP1372
groups by year of diagnosis, 1963-2005 (period A) and 2006-2016 (period B),
and compared for clinicopathological variables.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Results
EP1376
The cohort included 189 patients (55% female) of mean age 48.9G18.6 years
Differentiated thyroid cancer in patients taking lithium for bipolar
followed for 10.1G9.4 years. Of these, 104 patients (55%) were diagnosed in
affective disorder: a case series
period A, and 85 (45%) in period B. No significant between-group differences
Abbas Ali Tam, Cevdet Aydin, Didem Ozdemir, Muhammed
were found in primary tumor size at diagnosis (26.2G18.5 and 23.7G17.6 mm,
Cuneyt Bilginer, Reyhan Ersoy & Bekir C¸ akir
respectively), proportion of micro-MTCs (!1 cm) (18/74, 24.3% and 19/75,
Yildirim Beyazit University School of Medicine, Endocrinology and
25.3%, respectively), or TNM staging. Period A was characterized by a higher
Metabolism Diseases, Ankara, Turkey.
rate of familial MTC (28/98, 28.6% vs 6/73, 8.2%; PZ0.001) and lower age at
diagnosis (45.2G18.6 years vs 53.7G17.7 years; PZ0.002). Cervical lymph
node dissection was more commonly performed in period B (58/81, 71.6% vs
Aim
68/80, 85%; PZ0.05), but no concomitant increase in the rate of metastatic
Lithium bicarbonate is a drug used in the initial treatment of bipolar disorders.
lymph node excision (46/64, 71.9% and 45/70, 64.3% respectively, PZ0.36).
Lithium is an element of alcali metal group and besides being a causative agent
There was no significant difference between groups A and B in disease-free-
for goiter and hypothyroidism primarily, it has also some antithyroid effects.
survival
(DFS) at one year after diagnosis (34/87, 39.1% and 35/70, 50%,
Rarely, lithium may cause hyperthyroidism secondary to thyroiditis or probably
respectively PZ0.2) or at last follow-up, comparing patients with similar
autoimmune mechanisms. The association between lithium and thyroid cancer is
surveillance periods (11/28, 39.3% and 36/75, 48%, PZ0.5).
very little known subject. In this case series, we presented differentiated thyroid
Conclusions
cancer in five patients using lithium for the treatment of bipolar affective disorder
Unlike differentiated thyroid cancer, most presenting features of MTC have not
Cases
changed in recent years. The most significant temporal change is a decreased rate
Three of patients were female and two were male. Three patients had
of familial MTC. Despite the use of more extensive surgical procedures and new
hypothyroidism and were using levothyroxine and two patients were euthyroid.
treatment modalities, there has not been significant improvement in disease-
There was a solitary thyroid nodule in two, while multiple nodules were present in
related outcomes.
others. Preoperatively, thyroid fine needle aspiration biopsy was performed in all
DOI: 10.1530/endoabs.49.EP1374
patients and cytological results were suspicious for malignancy in three, atypical
cells in one and atypia of undetermined significance in one subject.
Histopathologically, one patient had minimal invasive follicular carcinoma, two
had papillary thyroid carcinoma, and two had concomitant papillary thyroid
carcinoma and papillary thyroid microcarcinoma. All patients were given
radioactive iodine ablation treatment postoperatively.
Conclusion
Thyroid dysfunctions can be observed in patients using lithium due to various
mechanisms. Among these, thyroid cancers are the least known and patients with
nodular goiter on lithium therapy should be evaluated carefully for the risk of
EP1375
development of thyroid cancer.
Association of preoperative neutrophil lymphocyte ratio and platelet
DOI: 10.1530/endoabs.49.EP1376
lymphocyte ratio with clinical features of differentiated thyroid cancer
Bengur Taskiran1, Guven Baris Cansu1, Goknur Yorulmaz2 &
Ruya Mutluay1
1Yunus Emre State Hospital, Eskisehir, Turkey;2Osmangazi University,
Eskisehir, Turkey.
Introduction
EP1377
Platelets and neutrophils take part in proliferation of cancer cells, angiogenesis,
and metastasis. Studies on various cancer types showed relation between
Predictive value of CHAID Algorithm in the diagnosis of malignancy in
prognosis and absolute numbers of neutrophils, lymphocytes, and the ratio
thyroid nodules with Bethesda III (AUS/FLUS) cytology
in-between (NLR) and platelet/lymphocyte ratio (PLR). We aimed to evaluate
Reyhan Ersoy1, Cevdet Aydin1, Oya Topaloglu1, Didem Ozdemir1,
NLR and PLR and their relation with features of differentiated thyroid carcinoma
Husniye Baser2, Fatma Neslihan Cuhaci1, Abbas Ali Tam1, Berna Ogmen2,
(DTC).
Sefika Burcak Polat1, Fatma Dilek Dellal2, Ahmet Dirikoc1,
Materials and methods
Nagihan Bestepe2, Mehmet Kilic3, Aysegul Aksoy Altinboga4 &
Electronic data of 330 patient with pathologic diagnosis of thyroid carcinoma
Bekir Cakir1
were evaluated retrospectively. Two hundred and fifty five patients with other
1Department of Endocrinology and Metabolism, School of Medicine,
chronic diseases and medullary thyroid carcinoma and whose pathology reports
Ankara Yildirim Beyazıt University, Ankara, Turkey;2Department of
and preoperative CBC data were unavailable were excluded. Clinical and
Endocrinology and Metabolism, Ankara Ataturk Education and Research
laboratory features of 75 patients (63 female, 12 male) were analysed.
Hospital, Ankara, Turkey;3Department of General Surgery, School of
Results
Medicine, Ankara Yildirim Beyazıt University, Ankara, Turkey;
The most common subtype was conventional type papillary thyroid cancer
4Department of Pathology, Ankara Ataturk Education and Research
(nZ46). Mean age was 46G12 years. 50 tumours were unifocal, 25 multifocal.
Hospital, Ankara, Turkey.
Forty-two patients had tumour less than 1 cm in size, 33 had 1 cm or larger. Forty
patients underwent radioactive iodine therapy or remnant ablation (RAI dose:
Introduction
92G32 mCi). Preoperative and postoperative NLR and PLR were not different
‘Artificial intelligence’ is an information-processing technology developed and
according to age (younger than or older than 45 years, focality (uni/multi focal),
inspired by the information processing technique of human brain. Artificial
RAI history (absence/presence), tumour size (less than 1 cm or larger), invasion
intelligence applications are used with an increasing ratio in medicine;
(nZ11). When 2.5 was chosen as cut-off value for NLR, preoperative and
particularly in the fields of breast cancer, radiology, cardiology, health
postoperative PLR was significantly (PZ0.0001 and PZ0.046) different; age at
management and drug effects analysis. There is not any study concerning thyroid
diagnosis was also significantly different
(PZ0.002). There was a positive
diseases and artificial intelligence applications in the literature. In this study, we
relation between preoperative and postoperative PLR (rZ0.575, PZ0.0001) and
aimed to use an artificial intelligence application
- CHAID (Chi-Squaered
NLR values (rZ0.431, PZ0.004). NLR was also positively correlated with PLR
Automatic Interaction Detection) algorithm- to predict malignancy risk in thyroid
both in pre- and postoperative period. Postoperative thyroglobulin data were
nodules with Bethesda III -atypia of undetermined significance/follicular lesion
available in 55 patients. It was negatively correlated with preoperative NLR
of undetermined significance (AUS/FLUS)- cytology.
(rZK0.354, PZ0.008). Age was positively correlated with NLR (rZ0.245,
Methods
PZ0.345). Tumour size was negatively correlated with postoperative PLR
Data of 3300 patients (6863 nodules) evaluated by our multidisciplinary council
(rZK0.102, PZ0.048).
and operated between 2005-2016 were analysed retrospectively. There were 364
Conclusion
patients with 385 nodules with AUS/FLUS cytology in. 65 parameters including
Preoperative NLR and PLR does not predict clinical features of DTC. Association
clinical, laboratory, ultrasonographical, cytological and histopathological features
between pre- and postoperative PLR and NLR may be due to a continuum instead
of each nodule were evaluated. The diagnostic value of CHAID algorithm was
of causal relation. Unlike high NLR associated poor prognosis in other cancer
determined considering histopathological diagnosis as the reference method.
types, higher NLR was observed in cases with lower thyroglobulin levels. CBC
Results
has no effect on thyroid cancer with indolent nature.
There were 75 male (20.6%) and 289 female (79.4%) patients. Histopathological
DOI: 10.1530/endoabs.49.EP1375
diagnosis was benign in 282 (73.2%) and malignant in 103 (26.8%) nodules.
Analysis with CHAID algorithm revealed that presence of thyroiditis/chronic
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
thyroiditis ultrasonographically, and presence of nuclear groove and intranuclear
1University of Health Sciences Gazi Yasargil Education and Training
inclusions cytologically were predictive for malignancy. This algorithm had a
Hospital, Diyarbakir, Turkey;2Ege University Faculty of Medicine
sensitivity of
49.5%, specifity of
96.8%, positive predictive value of
85%,
Endocrinology Department, Izmir, Turkey;3Ege University Faculty of
negative predictive value of 16% and accuracy of 84.15%.
Medicine Department of Medical Biology, Izmir, Turkey.
Conclusion
The main issue in thyroid nodules is to differentiate benign and malignant lesions.
While doing this, clinician should try to avoid unnecessary ultrasonography
examinations, fine needle aspiration biopsy and surgical approach. Superfluous
Thyroid cancer is the most common malignant tumor of the human
interventions cause increased economical burden for both the patient and the
endocrine system. Recently, its incidence has increased significantly.
country. Use of artificial intelligence applications in clinical practice might help
Anaplastic cancer constitutes
2-4% of thyroid cancers and remains
aggressive. The life expectancy is 2-6 months. It is often beyond the
to reduce unnecessary diagnostic procedures and surgical interventions in thyroid
surgical margin. External radiation therapy or chemotherapy are the
nodules with AUS/FLUS. cytology.
treatment options. Therefore, new therapeutic approaches are needed.
DOI: 10.1530/endoabs.49.EP1377
Peroxisome proliferator-activated receptor
(PPAR) gamma is a DNA-
binding nuclear hormone receptor and regulates transcription effects in cell
energy metabolism. PPAR gamma agonists may inhibit tumor growth
through terminal cell differentiation induction, cell cycle arrest, apoptosis
induction and angiogenesis inhibition. PPAR gamma agonists show
significant antitumor activities against various cancers both in vitro and
in vivo. Metformin (1,1-Dimethylbiguanide) is the most widely used drug in
EP1378
treatment of type 2 diabetes patients. Preclinical data show its anticancer
Thyroid autoimmunity and risk of incidental thyroid microcarcinoma
effects. The molecular mechanisms of metformin in cancer cells is still
in non-toxic nodular thyroid diseases
unknown. In our study, we plan to evaluate effects of combination of
Dimitrios Askitis1, Eleni I Efremidou1, Michail A Karanikas1,
metformin and pioglitazone on AMPK/mTOR signal pathway, p53 and
Grigorios Tripsianis1, Alexandra Giatromanolaki2,
apoptosis in human anaplastic thyroid cancer cells. In C643 and SW1736
Alexandros Polychronidis1 & Nikolaos Lyratzopoulos1
cell lines, IC50 doses of metformin and pioglitazone were found as 17.69
1First Surgical Department, University Hospital of Alexandroupolis, Faculty
and 11.64 mM, and 27.12 and 23.17 mM respectively. The combination of
of Medicine, Democritus University of Thrace, Alexandroupolis, Greece;
metformin and pioglitazone was determined as additive with isobologram
2University Pathology Department, University Hospital of Alexandroupolis,
analyses. Both of the compounds induce apoptosis separate or in
Faculty of Medicine, Democritus University of Thrace, Alexandroupolis,
combination. Consequently, we have evaluated the down regulation of the
Greece.
expression levels of oncogenic AKT3, CHUK, CDC42, EIF4E, HIF1A,
IKBKB, ILK, PIK3CA, PIK3CG, PLD1, PRKCA, RICTOR genes in MET
and PIO combination treated cells. Moreover, expression levels of tumor
Aim
suppressor DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8,
Thyroid cancer comprises the most common endocrine malignancy and a variety
GSK3B, MTOR, MYO1C, PTEN, ULK1, ULK2 genes were found to
of studies have investigated the role of thyroid autoimmunity as an independent
increase functionality. The results show that these agents can be used in the
risk factor for the manifestation of differentiated thyroid cancer in otherwise
treatment of thyroid cancer as novel therapeutic agents.
benign thyroid disorders. Objective of the current retrospective study is the
DOI: 10.1530/endoabs.49.EP1379
assessment of any possible correlation between thyroid autoimmunity, in terms of
elevated thyroid autoantibodies, and incidental thyroid microcarcinoma (ITC) in
non-toxic nodular thyroid diseases, subjected to total thyroidectomy (TT).
Patients and methods
In First Surgical Department between 1 January 2005 and 01 March 2010 a total
of 186 patients (146 females/40 males) underwent TT after referral for benign
non-toxic nodular thyroid diseases. Surgical specimens were evaluated in
University Pathology Department and the diagnosis of ITC was recorded.
Elevated thyroid autoantibody titers were assessed in patients without (group A)
and those with (group B) thyroid cancer. The results were also compared
EP1380
regarding preoperative diagnosis.
Vitamin D status and MPV changes in differentiated thyroid cancer
Results
Kevser Onbasi1, Turkan Pasalı Kilit1 & Aysenur Beyazıt Ucgun2
32 patients (17.2%) were diagnosed with microcarcinoma (females/males: 2.2/1),
1Dumlupinar University, Kutahya, Turkey;2Suleyman Demirel University,
while 154 patients (82.8%) were free of malignancy. 9/34 patients with solitary
Isparta, Turkey.
thyroid nodule (STN) and 33/152 subjects with multinodular goiter (MNG) had
biochemical signs of thyroid autoimmunity. 9/32 (28.1%) cancer patients had
elevated thyroid autoantibodies preoperatively. The prevalence of thyroid
autoimmunity was higher
(non-statistically significant) in the cancer-group
Thyroid cancer is the most common cancer in the endocrine system. Thyroid
compared to the non-cancer cohort (28.1% vs 21.4% respectively; PZ0.41).
follicular epithelial-derived cancers are papillary, follicular, and anaplastic
Furthermore, the prevalence of thyroid microcarcinoma was also higher (non-
cancer. Risk factors for differentiated cancers are radiation exposure, and
statistically significant) in the autoimmunity subgroup compared to the non-
family history. Possible risk factors like occupational and environmental
autoimmunity subgroup (21.4% vs 16%; PZ0.41). These differences were
exposures, increased parity, late age at first pregnancy, and hepatitis C-
manifested solely in the MNG group.
related chronic hepatitis are potential but not proven risk factors. In order to
Conclusions
evaluate other potential risk factors have we investigated the vitamin D
Thyroid autoimmunity does not seem to feature an independent risk factor
status and MPV (mean platelet volume) in thyroid cancer patients and in
associated with thyroid microcarcinoma in non-toxic nodular thyroid diseases.
other benign thyroid disorders. 25-OH vitamin D3 levels were low and MPV
However, a non-significant higher correlation is recognized in the subgroup of
euthyroid multinodular goiter. Further studies are required to investigate the
potential association between thyroid autoimmunity and carcinoma, as a helpful
Table 1 MPV values and 25-OH vitamin D3 levels in benign and malign
indication for surgical referral.
thyroid disorders
DOI: 10.1530/endoabs.49.EP1378
Hashimoto
Graves
Thyroid cancer
thyroiditis
disease
Healthy con-
(nZ47)
(nZ30)
(nZ30)
trols (nZ30)
P
Age (years)
45.96
(21-84)
41.43
(17K59)
42.37
(18-75)
45,37 (19K69)
K
Gender (male/
4/43
4/26
14/16
6/24
K
female)
EP1379
WBC (!109/l)
7.42G2.19
7.34G1.42
7.92G1.91
7.39G2.16
0.174
Hb (g/dl)
13.11
(9.3-
13.47
(11.1K
13.98
(10.9-
13.55
(8.50K
0.035*
Effects of combination of metformin and pioglitazone on AMPK/mTOR
16.8)
15.3)
17)
16.80)
signal pathway, p53 and apoptosis in human anaplastic thyroid
Platelets (!109/l)
279.14G81.98
293.43G66.27
272.8G67.90
266.57G61.10
0.145
cancer cells
MPV (femtoliters,fl)
8.22
(6-10.7)
8.41
(6.9K
8.38
(6.5-
8.56
(6.40K
0.001*
10.6)
11.2)
10.90)
Nilufer Ozdemir Kutbay1, Mehmet Erdogan2, Banu Sarer Yurekli2,
25-OH Vitamin D3
13.82G8.01
19.94G11.68
20.05G12.63
18.94G11.70
0.006
Cansu Caliskan Kurt3, Cumhur Gunduz3 & Cigir Biray Avci3
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
values have been found to be low. Low vitamin D may be a risk factor for
1Holycross Cancer Centre, Kielce, Poland;2Jan Kochanowski University,
thyroid cancer. Decreased MPV values may be used as a predictor of thyroid
Kielce, Poland;3Medical University of Silesia, Katowice, Poland.
cancer.
Background
DOI: 10.1530/endoabs.49.EP1380
A dynamic risk stratification with modified initial estimated risk based on
response to therapy and disease course is one of the crucial changes adopted
recently by the American Thyroid Association (ATA). The analysis of BRAF
status is not routinely recommended by ATA, although this finding may be
advantageous to individualized risk-adapted approach in papillary thyroid cancer
(PTC). The methods used to detect the BRAF V600E are known of variation in the
sensitivities, variable susceptibilities for DNA degradation, and possible
equivocal results with direct DNA Sanger sequencing (Seq), particularly. The
aim of this study was to examine the relation between the BRAF status of PTC
detected applying three methods and ATA response-to-therapy categories
(excellent, indeterminate, biochemical/structural incomplete), and recurrence
EP1381
identified after no evidence of disease (NED) or persistence disease.
BRAFV600E status and Stimulated Thyroglobulin at ablation time
Methods
increase prognostic value of American Thyroid Association (ATA)
Unselected 723 PTC cases with known BRAF status diagnosed 2000-2013,
classification systems for persistent disease in Differentiated Thyroid
actively monitored at single institution, and reviewed retrospectively up to
Carcinoma (DTC)
December 31, 2015. Genotyping of BRAF was implemented using the algorithm:
Andrea Repaci1, Valentina Vicennati1, Alexandro Paccapelo1,
Seq, followed by more sensitive allele-specific polymerase chain reaction (PCR),
Nicola Salituro1, Ottavio Cavicchi2, Fabio Monari3, Giovanni Tallini5,
and real-time PCR (quantitative PCR; qPCR). Considering various limitations of
Elisa Gruppioni4, Annalisa Altimari4, Michelangelo Fiorentino4 &
particular methods 639 specimens were available for the analysis by Seq, 638 by
Uberto Pagotto1
ASA-PCR, and 705 by qPCR.
1Endocrinology Unit, Department of Medical and Surgical Sciences,
Results
S. Orsola-Malpighi Hospital, Alma Mater University of Bologna, Bologna,
BRAF V600E was found in 51.6%, 67.7%, and 67% PTCs detected by Seq, PCR,
Italy;2Otolaringology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy;
and qPCR, respectively. The indeterminate response was significantly more
3Radiation Oncology Center, Department of Experimental, Diagnostic and
frequent in BRAF-positive PTCs identified by SDefault (PZ0.03), but not by
Specialty Medicine-DIMES, S. Orsola-Malpighi Hospital, Alma Mater
ASA-PCR (PZ0.07), and qPCR (PZ0.06). There was no significant relation
University of Bologna, S. Orsola-Malpighi, Bologna, Italy;4Laboratory of
between BRAF-positive cases and other not-excellent response-to-therapy
Oncologic Molecular Pathology, S.Orsola-Malpighi Hospital, Bologna,
categories, recurrences and persistent disease regardless of the method used.
Italy;5Anatomic Pathology-Molecular Diagnostic Unit AUSL of
Conclusions
Bologna,Department of Medicine (DIMES), Bologna, Italy.
The BRAF V600E mutation identified by high sensitive methods (ASA-PCR,
qPCR) did not significantly alter a response-to-therapy category and out-come of
PTC. However, an indeterminate response was more frequent in BRAF-mutated
Background
PTC detected by direct sequencing.
Stimulated Thyroglobulin levels measured at the time of remnant ablation (Htg-
A) and BRAFV600E mutation were shown to have prognostic value in predicting
DOI: 10.1530/endoabs.49.EP1382
persistent disease in DTC. The aim of this study was to evaluate the prognostic
role of Htg-A combined with BRAFV600E status in association with revised
American Thyroid Association (ATA) risk stratification.
Patients and methods
620 patients treated for a DTC were included in this study with median follow-up
duration of 6.1
year. All patients were submitted to a total thyroidectomy,
followed by radioiodine ablation. Patients with positive antibodies anti-Tg were
excluded. The predictive value of Htg-A was calculated by receiver operating
characteristic curve analysis. Cox proportional hazard regression modeling,
including BRAF status, Htg-A and ATA classification system, was assessed to
EP1383
evaluate existing persistent disease risk.
Results
Thyroid nodules ultrasound classification and the importance of the
BRAF status and Htg-A levels together improve ATA risk classification in all
endocrinologist clinical feeling
categories. In particular in Low risk ATA only BRAFV600ECHtg-AO8.9 ng/ml
Bruno Madeo1,2, Giulia Brigante1,2, Anna Ansaloni1,2, Erica Taliani1,2,
was associated with persistent disease (PZ0.001 HR 60.2 CI 95% 5.28-687. In
Manuela Simoni1,2 & Vincenzo Rochira1,2
Intermediate ATA risk BRAFwt C Htg-AO8.9 ng/ml was associated with
1Unit of Endocrinology, Department of Biomedical, Metabolic and Neural
persistent disease (PZ0.029 HR 2.71 CI 95% 1.106-6.670) and BRAFV600EC
Sciences, University of Modena and Reggio Emilia, Modena, Italy;
HtgO8.9 ng/ml was associated with persistent disease (PZ0.000 HR 5.001 CI
2Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
95% 2.318-10.790). In High risk ATA BRAFV600ECHtg-A!8.9 ng/ml was
associated with persistent disease (PZ0.042 HR 5.963 CI 95% 1.069-33.255)
Background and aim of the study
and BRAFV600ECHtg-AO8.9 ng/ml was associated with persistent disease
Several ultrasound (US) classifications for estimating thyroid nodules risk have
(PZ0.002 HR 11.564 CI 95% 2.543-52.576).
been proposed. Since most of them are hardly applicable in clinical practice, we
Conclusion
created a local tool, named Modena classification
(MC), considering US
BRAF status and Stimulated Thyroglobulin levels at ablation time improve the
characteristics and clinician subjective impression. The aim is to verify the
ATA risk stratification, so also Htg-A could be included in ATA risk
diagnostic accuracy of MC and to compare it to US classifications of American
classification.
Thyroid Association(ATA) (1) and British Thyroid Association(BTA) (2).
DOI: 10.1530/endoabs.49.EP1381
Methods
We prospectively enrolled 111 patients (33M, 78F; age 19-75; total 457 nodules)
with an indeterminate, suspicious for malignancy or malignant cytology. All the
patients underwent neck US before surgery and a score risk was assigned,
according to MC: low (not certainly nodular or not suspect); intermediate
(indeterminate); high
(suspect or very suspect). Then, we retrospectively
classified nodules according to ATA and BTA. The US pattern was related to
EP1382
hystology.
Results
High sensitivity of BRAF detection method does not alter response to
All the classifications had low sensitivity and positive predictive value (PPV), and
therapy of papillary thyroid cancer of known BRAF status
high specificity and negative predictive value (NPV) for low risk categories. For
Agnieszka Walczyk1, Aldona Kowalska1,2, Artur Kowalik1,
the intermediate risk category, BTA had the highest accuracy (68%). For higher
Janusz Kopczynski1, Iwona Palyga1, Danuta Gasior-Perczak1,
Estera Mikina1, Katarzyna Lizis-Kolus1, Dorota Szyska-Skrobot1,
risk categories, MC had good sensitivity (62%), high specificity (89%) and
Monika Szymonek1, Stefan Hurej1, Maciej Kajor3, Magdalena Chrapek2 &
accuracy (81%); ATA had high sensitivity (83%), low specificity (48%), accuracy
Stanislaw Gozdz1,2
58%; BTA had high sensitivity (88%), low specificity (44%), accuracy 57%.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusions
The present study assessed the feasibility of evaluating tumor invasion into the
A classification that considers the subjective impression of the clinician, in
RLN using ultrasonography (US) and computed tomography(CT).
addition to the known US characteristics, has highest accuracy and specificity
Materials and methods
compared to guidelines classifications, particularly if the nodule has suspect US
Of 7,916 patients with a PTC who underwent surgery at our hospital, 35 with
features.
preoperative tumors that were %10 mm, without distal metastasis or lymph node
References
metastasis, and with surgical findings of RLN invasion were included. The
(1) Haugen et al. Thyroid. 2016, 26: 1-133.
location of the tumor and the degree of contact with the thyroid capsule (DCTC)
(2) Perros et al. Clin Endocrinol (Oxf). 2014; 81 (Suppl 1):1-122.
were examined by US and CT.
DOI: 10.1530/endoabs.49.EP1383
Results
Ten of the 35 patients were treated by combined resection of the RLN, and 25
patients were treated by shaving the RLN. US revealed that the tumor was located
at the dorsal side of the thyroid in 31 patients (88.5%). In all patients who were
treated by combined resection of the RLN, the tumor was located at the dorsal
side of the thyroid. Among these patients, the DCTC determined by US was
R25% in nine patients and !25% in one. Among those who were treated by
RLN shaving, the DCTC was R25 and !25% in nine and 16 patients,
respectively (PZ0.003). The DCTC was R25% in all patients who were treated
combined resection and in 15 of the 25 patients who treated by RLN shaving
EP1384
(RZ0.018) according to CT imaging. The tumor was located 1-1.5 cm from the
Five-year follow-up of thyroid cold nodules with somatic oncogene
cricoid cartilage in most patients who were treated by combined resection.
mutations in Hungarian patients
Conclusions
Bálint Tobiás1,4, Bernadett Balla1,4, Petra Soltész1, János P Kósa1,4,
When a PTC is located at the dorsal side of the thyroid with R25% DCTC,
János Horányi2, Balázs Járay3, Eszter Székely3, Roland Istók3,
surgery should be selected for RLN invasion. Our results showed that the
Tamás Székely3 & Péter Lakatos1
accuracy of predicting recurrent laryngeal nerve invasion can be improved by
11st Department of Internal Medicine, Semmelweis University, Budapest,
combining US with neck CT.
Hungary;21st Department of Surgery, Semmelweis University, Budapest,
DOI: 10.1530/endoabs.49.EP1385
Hungary;32nd Department of Pathology, Semmelweis University,
Budapest, Hungary;4PentaCore Lab Ltd, Budapest, Hungary.
Cold nodules are one of the most common findings on scintiscans and
ultrasound examinations of the thyroid gland. About 5-10% of these nodules
turn out to be histologically malignant. Our aim was to examine the
predictive value of somatogenetic alterations associated with thyroid cancer
in FNA samples of thyroid cold nodules being citologically benign at the
beginning of the study. These alterations included single nucleotide
mutations
(BRAF, HRAS, NRAS, KRAS) and genetic translocations
(RET/PTC1, RET/PTC3, PAX8ex7/PPARgamma, PAX8ex9/PPAR-
EP1386
gamma). The SNPs were tested by real-time PCR with fluorescence melting
curve analysis and the rearrangements were detected by Taqman probe-
Solitary metastasis of papillary thyroid cancer in the sellar region and
based quantitative real-time PCR. We have analyzed 779 consecutive FNA
cavernous sinus
samples and followed the patients up for 5 years. We identified 39 BRAF, 23
Lila Brakni, Lounes Haffaf, Yamina Aribi, F Hameg & Samia Ouldkablia
NRAS, 9 HRAS, 1 KRAS mutations and 1 RET/PTC3 rearrangement. No
Army Hospital, Algiers, Algeria.
PAX8/PPARgamma rearrangements were demonstrated in the nodules.
During the five-year follow-up, 57 cases (7.3%) were classified as malignant
by histology, from which we indentified genetic alterations in 27 (47.4%).
The commonest site of metastasis from papillary carcinoma is regional
The statistical performance of our genetic panel showed a specificity of
lymph nodes. Distant metastases are rare, most presenting synchronously.
93.6%, sensitivity of 47.4%, a negative predictive value of 95.8% and a
Brain metastases in papillary carcinoma are rare, reported with a frequency
positive predictive value of 37.0%. In summary, our test approach may be
of 0.1-5% and cavernous sinus metastasis is extremely rare.
used for the prediction of malignant transformation of thyroid cold nodules,
Case report
however, its sensitivity requires improvement.
A 62-year-old woman presented with a history of non-secretory pituitary
DOI: 10.1530/endoabs.49.EP1384
macroadenoma present with symptoms of hypopituitarism. MRI of the brain
revealed a 4.5!3.1!3 cm, extension into the cavernous sinuse. The tumorwas
not rescable, she Underwent a simple biopsy in view of the haemorrhagic nature
of the tumor. Histopathology revealed a tumor with diffuse papillary architecture.
On immunohistochemistry: positive for TTF1, PAX8, thyroglobulin, TPO;Ki67
(10-15%) and negative for GH, LH, FSH, ACTH, TSH. A diagnosis of metastatic
papillary carcinoma was made. Thyroid ultrasound revealed two hypoechoic
nodules. After thyroidectomy the histopathology was papillary micro- carcinoma
thyroid-follicular variant of 05 mm. She received radioiodine therapy.
Discussion
EP1385
The incidence of distant metastases from papillary carcinomas is reported to be 6-
Usefulness of preoperative ultrasonography and computed tomography
23%, the majority occurring within 5 years of the initial diagnosis. There have
for evaluation of recurrent laryngeal nerve invasion by Papillary
been case reports of papillary carcinoma with metastasis at unusual sites like the
Thyroid microcarcinoma
breast and cavernous sinus. All these cases were associated with a missed
Keiko Ohkuwa, Tadatoshi Osaku, Tetsuyo Maeda, Yuna Ogimi,
diagnosis of thyroid carcinoma, like our case, should be considered exceptional.
Chie Masaki, Junko Akaishi, Kiyomi Y Hames, Chisato Tomoda,
There have been five reports of papillary carcinoma with metastasis to the skull
Akifumi Suzuki, Kenichi Matsuzu, Takashi Uruno, Wataru Kitagawa,
base.
Mitsuji Nagahama, Kiminori Sugino & Koichi Ito
Conclusion
Ito Hospital, Tokyo, Japan.
There is no consensus for the treatment of papillary thyroid carcinoma with
cavernous sinus metastasis. Thus, that solitary distant metastasis from
Background
thyroidcarcinoma though rare, is a possibility, a difficult diagnosis to be made
Papillary thyroid microcarcinoma (PTMC) has low malignant potential and an
on radiology.
extremely good prognosis. However, surgical findings of asymptomatic PTC,
DOI: 10.1530/endoabs.49.EP1386
can occasionally reveal tumor invasion into the recurrent laryngeal nerve (RLN).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1387
thyroid cancer after three years of stable diasease showed a neuroendocrine
progression with multiple metastases. SSA treatment was started and we plan to
Calcitonin: clinical and laboratory evaluation in a tertiary hospital
perform peptid receptor radionuclide therapy (PRRT).
Catarina Silvestre, Maria João Bugalho, Joaquim Sampaio, Helena Proença
& Raquel Carvalho
DOI: 10.1530/endoabs.49.EP1388
Santa Maria Hospital, Lisbon, Portugal.
Background
Calcitonin is a hormone secreted by thyroid C cells, and is considered an excellent
marker for medullary thyroid carcinoma (MTC). However, the use of calcitonin to
screen patients with nodular thyroid disease (NTD) remains controversial.
Objective
Defining the frequency of hypercalcitoninemia among NTD patients followed at a
tertiary referral hospital.
EP1389
Methods
Cytohistologic correlation of thyroid nodules
Retrospective analysis of basal calcitonin measurements and corresponding
Ines Barka, Senda Ouerdani, Molka Chaieb, Asma Ben Abdelkrim,
patients’ records between January 2011-December 2015. The method used was
Amel Maaroufi, Maha Kacem & Koussay Ach
immunochemiluminescent assay. Hypercalcitoninemia was defined as O
Endocrinology Department, FARHAT Hached University Hospital, Sousse,
10 pg/ml.
Tunisia.
Results
In five years, there was a total of 6551 calcitonin measurements requested, by
different physicians from different services, to 5149 patients: median age 57
Background
years,
80.6% female. Calcitonin measurements were divided into 3 groups
The discovery of a thyroid nodule exposes the problem of the possibility of
according to their levels: GI %10 pg/ml; GII 10-100 pg/ml; GIII R100 pg/ml.
thyroid cancer. The difficulty of management of this situation is the fact that only
Excluding patients with no clinical information, there were
3097, with the
the histopathological examination can confirm or refute the malignancy. Fine-
following distribution: GI 2913, GII 158, GIII 26. Among these, calcitonin was
needle aspiration (FNA) is used as a diagnostic tool to assess thyroid nodules. The
requested in NTD context to 1504 patients: 69 patients had hypercalcitoninemia
purpose of our study is to correlate the clinical, ultasonographic, the FNA results
(GII and GIII). Of these, 21 underwent surgery (GI 12, GIII 9); a histological
and final pathology to determine the predictors of malignancy of thyroid nodules.
diagnosis of MTC was established in 12 (GII 3/25%, GIII 9/100%). Surgery was
Patients and Methods
decided based, solely, on calcitonin levels in 7 cases, since only 5 had a positive
We conducted a retrospective study on 33 patients with thyroid nodule. Data were
cytology.
obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic
Conclusions
findings.
NTD was the reason for calcitonin measurement in less than 50% of total
Results
measurements. Hypercalcitoninemia was found in
4.6% of NTD patients.
The average age of our patients was
41.7yearsG15.6
SD with a female
Calcitonin levels R100 were associated to a greater CMT risk, comparative to
predominance (100%). Ultrasound findings were as follows: singles nodules,
values between 10 and 100 and reinforcing results from other groups. A cost-
multinodular goiter (MNG), and multiple nodules in respectively 48.5, 39.4 and
effective approach includes avoid unnecessary requests, adequate interpretation
12,1% of cases. Thyroid function tests prior to surgery were normal in all patients.
of results as well as appropriate selection of patients to surgery.
Among the 33 patients, 7 (21.2%)have malignant tumors in histological findings:
Two patients had signs of locoregional compression. A case of fixed nodule was
DOI: 10.1530/endoabs.49.EP1387
noted and one patient had cervical lymphadenopathy. On ultrasonogrqphy: the
average size of the nodules was
34.0G14.5 mm, three nodules were
hypoechogenic, and 1 case of mixed vascularity was diagnosed. The FNA was
benign in 90.9% of cases (nZ30), and indeterminate in 9.1% (nZ3). Of the 30
patients with a benign FNA result, 7 were found to have carcinoma on final
pathology for 23.3% false negative rate and sensitivity of 76.7%. 1 patient were
found to have incidental microcarcinoma which was located in the palpated
lesion.
Conclusion
EP1388
FNA biopsy is essential in the assessment and management of thyroid nodules.
Neuroendocrine progression of medullary thyroid cancer - case report
However, we report a high rate of malignancy among FNA diagnosed as benign
Krisztian Sepp1, Zsuzsanna Besenyi2, Laszlo Tiszlavicz3 &
lesions. This high rate of malignancy is the basis for our recommendation for a
Zsuzsanna Valkusz1
surgical approach for benign lesions.
1First Department of Medicine, University of Szeged, Szeged, Hungary;
DOI: 10.1530/endoabs.49.EP1389
2Department of Nuclear Medicine, University of Szeged, Szeged, Hungary;
3Department of Pathology, University of Szeged, Szeged, Hungary.
Thyroid cancers represent approximately 1% of new cancer diagnoses. Thyroid
malignancies are divided into papillary carcinomas (80%), follicular carcinomas
(10%), medullary carcinomas (5-10%), anaplastic carcinomas (1-2%) other rare
tumours (primary thyroid lymphomas, primary thyroid sarcomas). The main
therapeutic options are surgery
(mainly total thyreoidectomy), radioiodine
treatment (depending on the type and stage of the tumour), levothyroxine therapy
(thyroidea stimulating hormon - TSH suppression dose), others (external beam
EP1390
irradiation, chemotherapy, thyrosine kinase receptor inhibitors). Thyroid
Importance of central compartment neck metastasis in the
aspiration cytology was performed due to a rapidly growing neck mass of a 41
differentiated thyroid microcarcinomas
years old male patient, revealed a suspicion of neuroendocrine tumor. After the
Cátia Cunha1, Vítor Guedes2, António Garrão2 & Olímpia Cid2
total removal of the thyroid gland and paratrecheal and upper mediastinal lymph
1Hospital Beatriz Ângelo, Loures, Portugal;2Hospital da Luz, Lisboa,
node dissection histology showed medullary thyroid cancer and metastases in the
Portugal.
lymph nodes. Somatostatin receptor scintigraphy (SRS) was negative. PET-CT
showed suspicion of mediastinal metastases, at this time external beam
radiotherapy was performed. During the follow up calcitonin and chromogranin
A levels decreased presenting a stable disease, imaging investigations showed
Elective central compartment neck dissection in the treatment of differentiated
small remnant of the tumour without any progression or metastases. After three
thyroid carcinomas (CDT) remains controversial. In a series of 1500 patients
years of the operation the patient had weight loss and diarrhea, CT scan showed
undergoing thyroid surgery, the authors evaluated the prognosis related to central
cervical and mediastinal lymph node enlargement, hepatic and pancreas
compartment neck metastasis in differentiated microcarcinomas.
metastases, bone scintigraphy showed multiple bone metastases. SRS was
DOI: 10.1530/endoabs.49.EP1390
positive in these areas, somatostatin analogue
(SSA) treatment was started.
Histological verification of the metastases are in progress. In our case a medullary
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1391
Results
169 patients were included. Mean age: 40.05G6.20 years; \: 76.3%; Papillary
The impact of age and gender on the presentation and prognosis of
subtype: 89.3%.The great majority were classified as Stage I-II (81.1%). At the
medullary thyroid cancer - an Israeli multicenter study
end of the follow-up, 72.2% had achieved a complete remission. 6 to 12 months
Orit Twito1, Simona Grozinsky-Glasberg2, Carlos Benbassat4,6,
after thyroid ablation, s-Tg was negative in 111 patients and WBS control showed
Sigal Llevy3, Gideon Bachar5,6, David J Gross2 & Dania Hirsch6,7
negative uptake in 98 of these patients. In 13 patients (13/111), uptake remained
1Institute of Endocrinology, Meir Medical Center, Kfar-Sava, Israel;
in the thyroid bed but no evidence of disease was found. In 4/111 subjects,
2Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service,
persistence of disease was detected by ultrasound scan, all of them with negative
Hadassah-Hebrew Universirt Medical Center, Jerusalem, Israel;3Academic
WBS. Of 58 patients with detectable s-Tg (O0.3 ng/ml), only 22 showed
College of Tel-Aviv Yaffo, Tel-Aviv, Israel;4Institute of Endocrinology,
pathological uptake in the thyroid bed (nZ16) or in the distance (nZ6). In 36
Assaf Harofe Medical Center, Zerifin, Israel;5Otorhinolaryngology, Rabin
patients with evidence of disease (62.1%) uptake was not observed. In 43 of these
Medical Center, Beilinson Hospital, Pethch-Tikva, Israel;6Sackler Faculty
58 patients disease-free status has not been reached. This facts reflect a low
of Medicine, Tel-Aviv University, Tel-Aviv, Israel;7Institute of Endo-
correlation between s-Tg level and results of the WBS
(I.KappaZ0.226;
crinology, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel.
PZ0.001). The diagnostic accuracy of WBS was founded to be low
((SensitivityZ0.36;
95% CI: 0.22-0.49) (SpecificityZ0.85;
95% CI: 0.79-
Background
0.91)).
Data regarding the effect of gender and age on medullary thyroid cancer (MTC)
Conclusions
presentation and prognosis is limited. Although older age and male sex were
WBS performed at 6-12 months after initial treatment is out of clinical utility,
found to correlate with poorer prognosis in some studies, this correlation may
especially in the presence of a s-Tg !0.3 ng/ml. WBS does not correlate with
reflect differences in MTC presentation between sex and age groups, or a mixture
results of s-Tg determination and its accuracy has turned out to be low.
of hereditary and sporadic MTC forms.
DOI: 10.1530/endoabs.49.EP1392
Objective
To evaluate the impact of age and sex on the presentation and outcomes of MTC.
Methods
Epidemiological and clinical data of MTC patients was extracted from a joint
registry of four medical centers in Israel.
Results
The study included 193 MTC patients (106 females, age 48.9G18.6, median 51),
who were followed for 10.1G9.4 years. Female gender was associated with
smaller tumor diameter (22.3 vs 28.7 mm, PZ0.032), lower rate of lymph nodes
involvement (42/70, 60% vs 49/64, 76.6%, PZ0.044) and lower rate of distant
metastases
(11/87,
12.6% vs
23/75,
30.7%, PZ0.007). Although females
achieved higher cure rates (47/97, 48.5% vs 20/72, 27.8%, PZ0.007), disease
related mortality and all cause mortality did not differ between the genders.
Patients aged !45 year at diagnosis had higher rates of hereditary familial forms
EP1393
of MTC (32/74, 43.2% vs 3/114, 2.6% .4%, P!0.0001). Analysis of the sporadic
Evolution in the management of thyroid cancer: an observational study
MTC cases (nZ137) revealed that younger age at presentation was associated
in two Belgian referral centres
with higher number of metastatic lymph nodes
(19.7G23.5 vs 10.2G9.3,
Bernard Peene1, Annick Van den Bruel2, Carolien Moyson1 &
PZ0.05) and more therapeutic interventions during the follow-up (62.9% vs
Brigitte Decallonne1
33.7%, PZ0.04). However, cure rate and disease related mortality were similar
1University Hospitals Leuven, Leuven, Belgium;2General Hospital Sint
between the age groups.
Jan, Brugge, Belgium.
Conclusions
In concert with previous literature, female MTC patients present with milder
disease and achieve higher cure rates than males. However, younger age in the
Background
sporadic MTC form is associated with more advanced disease at presentation.
Thyroid cancer incidence is increasing, especially the cancers %1 cm (T1a).
Neither age nor gender affected disease related mortality.
Previous evidence suggests underuse of FNA. Several international guidelines for
the management of thyroid cancer have been published. Especially the year 2006
DOI: 10.1530/endoabs.49.EP1391
was a hallmark, with the publication of both the ETA consensus and ATA
guidelines.
Aim
Compare thyroid cancer subtypes and management before and after 2006.
Methodology
Retrospective observational study of non-medullary thyroid cancer patients
diagnosed after total thyroidectomy in two Belgian referral centres (University
Hospital Leuven, General Hospital StJan Bruges), comparing pre/per/postopera-
tive parameters of patient cohort1 (diagnosis 2004-2005, nZ69) and cohort2
(diagnosis 2011, nZ60).
EP1392
Results
Is post-treatment whole body scan useful in differentiated thyroid
The histology and tumor dimensions were comparable, with papillary thyroid
cancer after thyroid ablation?
cancer (PTC) as main histologic subtype (86% of cohort1, 82% of cohort2) and
Inmaculada Prior-Sánchez1, María Rosa Alhambra Expósito1,
T1a as most frequent dimension subtype (respectively 30 and 38%). In cohort2 a
Ángel Rebollo Román1, Ana Barrera Martín1, Estefania Moreno Ortega2,
comparable low proportion first presented following incidental finding at imaging
Juan Antonio Vallejo Casas2 & María Ángeles Gálvez Moreno1
(21 vs 17% in cohort 1). Pre-surgical FNA was performed in 91% in cohort1 and
1Department of Endocrinology and Metabolism, Reina Sofia University
86% in cohort2. The indications for thyroidectomy were comparable, with
Hospital, Cordoba, Spain;2Department of Nuclear Medicine, Reina Sofia
Bethesda 5-6 as most frequent indication (44% in cohort1 and 53% in cohort2).
University Hospital, Cordoba, Spain.
The execution of a simultaneous lymph node dissection in the PTC subgroup was
not different, neither the frequency of postoperative hypoparathyroidism and
Background
recurrent nerve paresis after 1 year. However, radioiodine ablation was less
The short-term follow-up of patients with differentiated thyroid cancer (DTC)
frequently given in cohort2
(58
vs
76% in cohort1, PZ0.03) and neck
after the initial treatment is based on the measurement of stimulated thyroglobulin
ultrasonography at
1 year was performed in a higher proportion of OT1a
(s-Tg) and the use of diagnostic whole body scan (WBS).
patients (73 vs 49% in cohort1, PZ0.02).
Objective
Conclusion
To evaluate the clinical utility of WBS performed at
6-12 months after
In two Belgian referral centres the use of FNA is high and established, and the
thyroidectomy. Examine the correlation between s-Tg and results of WBS.
proportion of T1a cancers is stable and low compared to the national data. A clear
Methods
change in the postoperative management of thyroid cancer patients is observed
We retrospectively evaluated all patients who were diagnosed with DTC
towards more restrictive use of radioiodine ablation and increased use of neck
(nZ213) at a tertiary hospital center in Cordoba (Spain), between January 2000
ultrasound.
and December 2013. The patients who had positive anti-thyroglobulin antibodies
DOI: 10.1530/endoabs.49.EP1393
microcarcinomas (Tumors ! 1 cm) were excluded from the study. Patients were
classified according to the new ATA- guideline.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1394
Results
The ongoing test has been performed on 17 patients, aged (23-67), 11 M, 6 F.
Retrospective analysis of unusual thyroid tumours with clear cell
Mean calcitonin values were: basalZ19.98 pg/ml (normal range: 1-11.8 pg/ml);
features: morphology and differential diagnosis
at 2 minZ209.159 pg/ml; at 5 minZ143.619 pg/ml, at 10 minZ100.557 pg/ml;
Alexander Abrosimov1,2 & Alexei Sidorin3
10 subjects had a significant 2 min stimulated calcitonin (O100 pg/ml) and were
1Federal State Institution, Endocrinology Research Center, Moscow, Russia;
operated, 3 subjects had an intermediate response (53.31-81.7 pg/ml) and 4
2National University of Science and Technology, MISIS, Moscow, Russia;
patients had low stimulated values(!54 pg/ml) therefore they are to be followed
3Federal State Institution, Medical Radiology Research Center, Obninsk,
up. C cell hyperplasia (CCH) and MTC was confirmed histologically in 4 out of
Russia.
10 patients (2 CCH and 2 MTC); 2 subjects had benign nodular goiter and 2
papillary thyroid microcarcinomas. More results are expected.
Background
Conclusions
In accordance with the WHO Classification of tumours of endocrine organs
Stimulated calcitonin may be useful in the early diagnosis and follow-up of MTC
(Lyon, 2004) clear cell thyroid lesions have not been separated in one category as
and could reduce false negative rate of basal calcitonin measurement.
they are occurred quite rare, characterized by various cellular origin,
DOI: 10.1530/endoabs.49.EP1395
heterogeneous morphological type, and malignant potential. Difficulties of
morphological diagnosis of clear cell thyroid lesions are also obvious.
Aim
Retrospective morphological study of clear cell thyroid tumours has been
performed by pathologists of two research centres (MRRC and ERC) for the
period of 10 years (2007-2016) to analyse difficulties of diagnosis related with
different histotype, and tumour grade.
EP1396
Materials and Methods
The relationship between extrathyroidal extension and BRAFV600E
Histological sections of paraffin blocks from 14 cases of clear cell tumours in 5
mutation in papillary thyroid cancer
male and 9 female aged from 15 to 78 years have been stained with H&E, and
Mehmet Celik1, Buket Yilmaz Bulbul1, Semra Ayturk1, Nuray Can2,
immunohistochemistry (IHC) for Thyroglobulin (Tg), Thyroid Transcription
Ebru Tastekin2, Atakan Sezer3, Funda Ustun4 & Sibel Guldiken1
Factor
1
(TTF1), Calcitonin
(Cal), Chromogranin A
(Chr A), Parathyroid
1Rakya University, Medical Faculty, Department of Endocrinology and
Hormone (PTH), CD10, and Ki-67.
Metabolism, Edirne, Turkey;2Trakya University, Medical Faculty,
Results
Department of Pathology, Edirne, Turkey;3Trakya University, Medical
Retrospective review of H&E and IHC stained sections allows to make diagnosis
Faculty, Department of Surgery, Edirne, Turkey;4Trakya University,
of 3 benign follicular thyroid adenomas (FTA), 2 follicular thyroid carcinomas
Medical Faculty, Department of Nuclear Medicine, Edirne, Turkey.
(FTC), 3 papillary thyroid carcinomas (PTC), 1 medullary thyroid carcinoma
(MTC), 2 poorly differentiated thyroid carcinomas
(PDTC) with clear cell
features,
2 intrathyroid parathyroid carcinomas
(ITPTC), and
1 renal cell
Aim
metastasis into thyroid (RCC metastasis). Tumour cells of FTA (2 pure clear
BRAF is one of the serine threonin kinases that activates mitogen activated
cell and 1 signet ring cell), FTC, PTC, and PDTC are Tg-, and TTF1-positive, in
protein kinase (MAPK) signal pathway.The aim of this study is to evaluatethe
comparison with negative Cal-, Chr A-, PTH-, CD10-staining. Ki-67 is expressed
relationship between extrathyroidal extension (ETE) and BRAFV600E mutation
by nucleus of more than 30% PDTC tumour cells in comparison with low
in the subjects with papillary thyroid cancer.
expression rate (less than 1%) of highly differentiated tumours. Tumour cells of
Materials and methods
MTC are Tg-, PTH-, and CD10-negative, but positive for TTF1-, Cal-, and Chr A-
Clinical and laboratory data of 455 patients, who had been followed-up in our
staining. Cells of ITPTC are Tg-, TTF1-, Cal-, CD10-negative, but Chr A-, and
clinic between the years 2010 and 2015 for PTC, were evaluated. The relationship
PTH-positive. Cells of RCC metastasis are positive for CD10, but negative for
between extrathyroidal extension and BRAFV600E mutation was examined in
Tg-, TTF1-, Cal-, Chr A-, and PTH.
the subjects enrolled in the study.
Conclusions
Results
Clear cell thyroid tumours are rare and should be distinguished in accordance with
Among 455 patients, 382 (83.9%) were female and 73 (16.1%) were males. The
their different cellular origin and histotype, as well as various tumour grade and
mean age of the participants was 49G11.8 years. While 368 (80.9%) of the
prognosis.
patients had no extrathyroidal extension,
87
(19.1%) of the patients had
DOI: 10.1530/endoabs.49.EP1394
extrathyroidal extension. 362 (79.6%) of the patients were BRAFV600E mutation
(K) and 93 (20.4%) patients were BRAFV600E mutation (C). 320 patients were
negative for both BRAFV600E mutation and extrathyroidal extension. The
prevalence of PTC larger than 1 cm was significantly more common among
BRAFV600E mutation and ETE (C) cases (P:0.004). The prevalence of capsular,
lymphovascular and perineural invasion, lymph node metastasis and ultrasono-
graphically detected pathologic lymphadenopathy was significantly higher among
EP1395
BRAFV600E mutation (C) and ETE(C) subjects (P:0.004, P!0.05, P!0.05,
P:0.05, P:0.01).
Stimulated calcitonin levels as a predictor of medullary thyroid cancer
Conclusion
Cristina Alexandra Gheorghiu1, Cristina Corneci1, Simona Jercalau1,
In this study, BRAFV600E mutation and ETE positivity were found to be poor
Ruxandra Dobrescu1, Daniel Mihai1 & Corin Badiu1,2
prognostic parameters in the patients with PTC. However, the evaluation of long
1National Institute of Endocrinology, C.I. Parhon, Bucharest, Romania;
term follow-up data is required to more clearly understand prognostic effect and
2Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
especially to determine the effect of this situation on mortality.
DOI: 10.1530/endoabs.49.EP1396
Abstract
Medullary thyroid cancer (MTC) is a highly aggressive neuroendocrine tumour
originating in the thyroid parafollicular cells. Calcitonin measurement and RET
gene ascertainment have been used as markers for early diagnosis of MTC. Since
pentagastrin is not available, calcium stimulation test helps to preclude ‘gray
zone’ values of basal calcitonin, diagnose minimal residual disease and help the
early diagnosis of C cell hyperplasia.
Aim
To establish a gender specific threshold for positive calcium stimulation test as
EP1397
well as indication for thyroidectomy and therefore prevention of MTC through
Insulin resistance and BRAFV600E mutation in the patients with
early diagnosis.
differentiated thyroid carcinoma
Materials and methods
Mehmet Celik1, Buket Yilmaz Bulbul1, Semra Ayturk1, Ebru Tastekin2,
We conducted the calcium stimulation test on a series of patients with either
Nuray Can2, Atakan Sezer3 & Funda Ustun4
nodular goiter, single nodule, RET positive or history of MTC associated with
1Trakya University, Medical Faculty, Department of Endocrinology and
elevation of basal calcitonin values. Calcium gluconate 25 mg/kg adapted on the
Metabolism, Edirne, Turkey;2Trakya University, Medical Faculty,
ideal BMI was administered over 3 min under ECG monitoring. Blood was
Department of Pathology, Edirne, Turkey;3Trakya University, Medical
collected before, at
2;
5 and 10 min after calcium infusion. Calcitonin was
Faculty, Department of Surgery, Edirne, Turkey;4Trakya University,
measured using LIAISON XL assay.
Medical Faculty, Department of Nuclear Medicine, Edirne, Turkey.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Aim
1Trakya University, Medical Faculty, Department of Internal Medicine,
The incidence of nodular thyroid disease is high among patients with insulin
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
resistance. The aim of this study is to evaluate the relationship between
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
BRAFV600E mutation and insulin resistance in the patients with papillary
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
thyroid cancer.
University, Medical Faculty, Department of Surgery, Edirne, Turkey;
Materials and methods
5Trakya University, Medical Faculty, Department of Nuclear Medicine,
We examined clinical and laboratory data of 103 patients who had been followed
Edirne, Turkey.
up by our department between the years 2010 and 2015. The diagnosis of insulin
resistance (IR) was made when the homeostasis model assesment of insulin
Aim
resistance (HOMA-IR) index was higher than 2.5.
ATA guideline recommends complementary thyroidectomy after thyroid
Results
lobectomy in case of tumor diameterO1 cm, in the presence of metastatic
90
(87.4%) of 103 patients were female, while 13 (12.6%) of them were male.
tumor, invasion, history of radiation therapy, familial history of thyroid cancer,
HOMA-IR was R 2.5 in 58 (56.3%) patients and !2.5 in 45 (43.7%) patients. 19
multifocal or agressive variant tumor. In this study, we aimed to evaluate the
of the patients were BRAFV600E mutation (C), while BRAFV600E mutation
relationship between the necessity of complementary thyroidectomy and post-
was (K) in 84 cases. Among 58 patients with insulin resistance, 46 (79.3%)
surgery clinical, radiologic and histopathologic results in the patients who
patients were BRAFV600E mutation
(K) and
12
(19.7%) patientswere
underwent complementary thyroidectomy for papillary thyroid cancer (PTC).
BRAFV600E mutation (K). There was no statistically significant relationship
Method
between BRAFV600E mutation and HOMA-IR in terms of demographic data,
We retrospectively evaluated the data of
110 patients who had undergone
clinical and histopathologic results.
complementary thyroidectomy following lobectomy and been followed-up by our
Conclusion
department between January 2010 and January 2017. 67 of these patients had
In this study, no statistically significant relationship was detected between insulin
unifocal and 43 had multifocal PTC. The relationship between demographic data,
resistance and BRAFV600E mutation among the patients with PTC.
histopathologic results, BRAF mutation status and complementary thyroidectomy
DOI: 10.1530/endoabs.49.EP1397
was evaluated.
Results
Among 110 patients, 85 (77.2%) were female and 25 (22.8%) were male. The
mean age of the subjects was 47.8G12.3 years. Following complementary
surgery, 70 (63.6%) of the patients were found to have benign pathology and 40
(36.4%) were found to have PTC on controlateral lobe. Parameters such as
gender, age, hormonal status, presence of Hashimoto disease, tumoral variant,
lymphocytic thyroiditis, tumor localisation, tumoral focality, number of tumoral
foci, perineural invasion, capsular invasion, lymphovascular invasion, extra-
thyroidal extension, lymph node metastasis and BRAFV600E mutation status
EP1398
were found to be insignificant for complementray thyroidectomy.
Beware a rapidly enlarging Thyroid mass- a case of Thyroid
Conclusion
Lymphoma
We suggest that unifocality or multifocality of single lobe tumor is not
Suhel Ashraff, Ahmed Al Sharefi & Satyajit Nag
determinative for complementary surgery during initial operation. However,
James Cook University Hospital, Middlesbrough, UK.
long-term follow-up data is required to determine the effect complementary
thyroidectomy on prognosis and mortality.
DOI: 10.1530/endoabs.49.EP1399
Primary Thyroid Lymphoma is rare comprising less than 5% among all
thyroid malignancies. It is historically associated with Hashimotos
thyroiditis. It typically presents as a rapidly enlarging, painless goitre
resulting in compression symptoms. Thyroid ultrasound and FNA cytology,
using flow cytometry and immunohistochemistry, remain the primary
modalities to confirm the presence of lymphoma. Treatment depends on the
immunohistology. The prognosis is subtype depended and is generally good.
A 53 years old female was seen in the Endocrine clinic with a right sided
EP1400
neck lump. On examination a smooth enlarged right thyroid lobe was noted.
A case report: co-occurence of medullary thyroid carcinoma and
Her history suggested Hashimoto’s thyroiditis but she has an enlarged right
papillary thyroid carcinoma
thyroid lobe. Biochemically her TSH was
11.87
with a FT4
being
Beliz Camur1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
low/normal at 13. She had positive TPO antibodies. She was referred for
Ebru Tastekin3, Nuray Can3, Atakan Sezer4, Funda Ustun5 &
a Fine needle aspiration of the right lobe demonstrated lymphoid cells
Sibel Guldiken2
consistent with lymphocytic thyroiditis and was started on Levothyroxine
1Trakya University, Medical Faculty, Department of Internal Medicine,
50mcg as she was symptomatic and an interval scan was recommended in 3
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
months’ time. She was seen in a 4 months’ time with her scan results and her
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
right sided thyroid swelling appeared to have increased in size. A repeat
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
ultrasound scan confirmed an increase in size compared to previous scans
University, Medical Faculty, Department of Surgery, Edirne, Turkey;
with level 6 and 4 lymph nodes. A core biopsy showed features consistent
5Trakya University, Medical Faculty, Department of Nuclear Medicine,
with an Extranodal marginal zone lymphoma (MALT-type). A staging CT
Edirne, Turkey.
showed stage 2E with FDH avid right thyroid lobe and 4 cervical lymph
nodes of
10mm. A bone marrow aspiration showed no lymhomatous
infiltrate. She underwent a radical radiotherapy with 24 Gy in 12 fractions
Introduction
with good effect. A repeat PET CT scan showed no residual disease. This
Co-occurence of medullary thyroid carcinoma and papillary thyroid carcinoma in
case demonstrates that a rapidly enlarging thyroid lump should be
the same patient is unusual. We report a case with this rare event.
investigated urgently to facilitate early diagnosis of the underlying cause,
Case
Thyroid lymphoma being one of them.
A 39 year old woman was presented with cough and shortness of breath. She had
DOI: 10.1530/endoabs.49.EP1398
no prior history of radiation exposure, cigarette or alcohol consumption and no
family history of thyroid cancer. On physical examination, a 3x5 cm thyroid
nodule was palpated in the middle portion of thyroid gland, which could be
noticed after neck extention. Laboratory examination revealed calcitonin 348
pg/ml(n:0-10), CEA 12,39 mg/L (n: ! 3,8 mg/L), FT3: 3,6 pg/mL (n: 1,71-3,81),
FT4:
1,41
ng/dl
(n:0,7-1,48), TSH:0,53
mlU/ml
(n:0,35-4,94). Thyroid
ultrasonografy examination demonstrated a hypoechogen 3*3*5 cm sized nodule
EP1399
invading thyroid gland. I131
thyroid uptake scintigraphy was negative and
autoantibodies were also found to be negative. Cytologic examination of fine
Complementary thyroidectomy in papillary thyroid cancer
needle aspiration biopsy was suspicious for follicular neoplasia. Therefore, she
Yusuf Durmus1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
underwent total tyroidectomy. Pathologic examination of the specimen revealed
Ebru Tastekin3, Nuray Can3, Atakan Sezer4, Funda Ustun5 &
both medullary and papillary thyroid carcinoma. 3.5 cm sized classic variant
Sibel Guldiken2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
papillary tyroid carcinoma was reactive for thyroglobulin and tumor stage was
1Trakya University, Medical Faculty, Department of Internal Medicine,
reported as pT3pNxpMx; 5*3*3 cm sized medullary thyroid carcinoma was
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
reactive for calcitonin. Investigation for multıple endocrine neoplasia (MEN)
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
detected RET protooncogen mutation. She underwent 100 mCi radioactive I131
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
treatment. Since CEA and calcitonin levels were high during follow-up period,
University, Medical Faculty, Department of Surgery, Edirne, Turkey;
neck ultrasonography was performed, which revealed no pathologic lymphadeno-
5Trakya University, Medical Faculty, Department of Nuclear Medicine,
pathy. PET/CT examination detected metastasis in the upper lobe of the right
Edirne, Turkey.
lung, mediastinal lymph nodes and liver. The patient was given vandatanib
chemotherapy by medical oncology department. In conclusion, co-occurence of
medullary and papillary thyroid carcinoma in the same gland has rarely been
Ectopic thyroid tissue is the localization of thyroid tissue at any place other
reported. Occurence of medullary and papillary tyroid carcinoma are
than the normal localization of the thyroid during the migration of
independent; however, common points of pathogenic events can not be ruled
embryonic period. Concurrent normal thyroid tissue may accompany. It
out in their carcinogenesis.
usually is seen in women and in the midline. Very rarely thyroid carcinoma
DOI: 10.1530/endoabs.49.EP1400
can develop. Treatment is like normal thyroid carcinomas, suggesting
simultaneous thyroidectomy if accompanied by normal thyroid tissue. A
42-year-old female patient presented with complaints of swelling on the
right side of the neck for 3 months. There was no chronic disease or drug use
in her story. On physical examination, a painless, moving 30!30 mm mass
lesion was detected in the middle cervical region. Imaging revealed a mass
lesion in the lower right cervical region near the right lobe of the thyroid
EP1401
gland, 36!25!35 mm heterogeneous signal density same as the thyroid
Thyroid papillary carcinoma in the patients with resistance to
gland. Histopathological examination of the excised mass revealed TTF1
thyroid hormone
positive, galectin positive, CK19 positive, HBME1 positive and 36!30 mm
Mehmet Celik1, Buket Yilmaz Bulbul1, Sibel Guldiken1, Hakan Gurkan2,
encapsulated follicular variant papillary carcinoma considered as thyroid
Semra Ayturk1, Nuray Can3, Ebru Tastekin3, Atakan Sezer4 & Funda Ustun5
carcinoma and lymphoid tissue has not been observed. Thyroid function
1Trakya University, Medical Faculty, Department of Endocrinology and
tests and laboratory findings were normal. Thyroid ultrasonography revealed
Metabolism, Edirne, Turkey;2Trakya University, Medical Faculty,
bilateral hypoechoic and isoechoic nodules maximal 1 cm in diameter and
Department of Genetic, Edirne, Turkey;3Trakya University, Medical
malignant lymphadenopathy 2 cm in the left cervical area. As a result of
Faculty, Department of Pathology, Edirne, Turkey;4Trakya University,
total thyroidectomy C neck dissection, 8 and 9 mm diameter papillary
Medical Faculty, Department of Surgery, Edirne, Turkey;5Trakya
thyroid carcinoma encapsulated follicular variant was detected in the right
University, Medical Faculty, Department of Nuclear Medicine, Edirne,
lobe and thyroid carcinoma metastasis were observed in 3 of 10 lymph nodes
Turkey.
removed in the left cervical area. This was evaluated as high-risk thyroid
carcinoma and treated with radioactive iodine (RAI-131) at 150 mCi. At
post-RAI whole body scan screening, 2 local foci were observed in the
thyroid location and were followed up. The patient was followed for 6
Resistance to thyroid hormone (RTH) is a genetic disease characterized by a
months with asymptomatic levothione suppression therapy. We aimed to
reduced target tissue responsiveness to thyroid hormones and increased or
present a rare case of ectopic thyroid carcinoma.
normal TSH level despite elevated levels of thyroid hormones. This
DOI: 10.1530/endoabs.49.EP1402
condition is mainly caused by mutations of thyroid hormone receptor beta
(THRB) gene. The role of THRB mutation in carcinogenesis is still unclear.
In here, we report a case of papillary thyroid carcinoma (PTC) with RTH,
with a past medical history of subtotal thyroidectomy due to diffuse goiter. A
61-year-old woman was referred to our hospital with recurrence of goiter
and displayed elevated serum thyroid hormones and unsuppressed TSH
levels. Genetic analysis of THRB identified a missense mutation, (Exon 7,
rs3752874, c.735COT) leading to diagnosis of RTH. The neck ultrasono-
graphy showed an isoechoic 9!11!11 mm sized nodule, a cystic 13!
13!15 mm sized nodule with microcalcification in the right lobe, a 7!9!
9 mm sized nodule with thin hypoechoic ring around in the right isthmus,
a 9!12!14 mm sized, iso-hypoechoic,uniformly restricted nodule with
cystic component in the left isthmus and a
17!25!29 mm sized
EP1403
hypoechoic nodule in the left lobe. Ultrasound-guided fine-needle aspiration
Co-occurrence of papillary and follicular thyroid carcinoma in a
biopsy was performed for microcalcific nodule in the right lobe. Cytologic
patient
examination of fine needle aspiration biopsy specimen was suspicious for
Ahmet Yigitbasi1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
follicular neoplasm. Total thyroidectomy was performed. Pathologic
Nuray Can3, Ebru Tastekin3, Atakan Sezer4, Funda Ustun5 &
examination of thyroid tissue revealed capsulated oncocytic variant
Sibel Guldiken2
papillary thyroid cancer in 32 mm sized nodule in the left lobe and 7 and
1Trakya University, Medical Faculty, Department of Internal Medicine,
2 mm sized nodules in the right lobe. The patient was scheduled for
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
radioactive I-131 treatment. There is no consensus on the management of
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
thyroid carcinoma in patients with RTH. The main concerns are the
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
relationship between differentiated thyroid cancer and thyroid hormone
University, Medical Faculty, Department of Surgery, Edirne, Turkey;
resistance, whether it is a coincidence, how to suppress TSH levels, which
5Trakya University, Medical Faculty, Department of Nuclear Medicine,
treatment regimen should be chosen and which parameters should be
Edirne, Turkey.
considered in the follow-up of these patients. Further studies are required to
find scientific answers to these questions.
DOI: 10.1530/endoabs.49.EP1401
Occurance of papiller carcinoma with foliculer thyroid carcinoma is a rare
situation. We report a 49-year-old male with asymptomatic goiter. The first
biopsy from the right tyroid lobe from a 6!6!4 cm iso-hypoechogen
heterogeneous nodule showed bening, hurthe cell and thyrocyte rich
cytology. Two months later the patient went through right lobectomy which
patology defined as 4.3 cm minimal invasive follicular carcinoma. Two
months after right thyroidectomy, a second operation was performed on the
left thyroid to complete the process of total thyroidectomy. The speciment
EP1402
was sent to patology which bore the following result: Papillary
A rare case: papillary thyroid carcinoma in the ectopic thyroid
microcarcinoma with follicular variant. This was evaluated as high-risk
Yusuf Durmus1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
thyroid carcinoma and treated with radioactive iodine(RAI-131) at 100 mCi.
Ebru Tastekin3, Nuray Can3, Atakan Sezer4, Funda Ustun5 &
At post-RAI whole body scan screening, 2 local foci were observed in the
Sibel Guldiken2
thyroid location and were followed up. This work shows two different
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
carcinomas that belong to different lineages existing in two different lobes of
noninvasive techniques. Elastography is the imaging new technic,to evaluate the
the thyroid with no coheisive malignity triggering factors.
nodules. Aim of this study to evaluate the results of FNAB and elastography
performed in patients with thyroid nodules.
DOI: 10.1530/endoabs.49.EP1403
Methods
173 thyroid nodules were examined by Elastography and fine needle aspiration
biopsy. Strain elastography was performed with Siemens Acuson s1000 14L5
lineer transducer. Elastography findings were evaluated together with b-mode
ultrasonography. The susceptible nodules with an S/R ratio of over 2,6 were
accepted as malignant nodules.
Results
Results of 155 (89%) FNAB were benign, 18 (10.4%) were malignant. The
elastographic appearance was categorized at the time of the examination, 154
(89%) of them were categorised as benign and 19 (10.9%) of them were
EP1404
categorized as malignant. The sensitivity of Elastography for malignancy was
90.0%, specificity was 22%, PPV was 21%, NPV was 90% and accuracy was
A rare cause of respiratory failure: Anaplastic carcinoma
83.2%.
Ece Celik1, Mehmet Celik2, Buket Yilmaz Bulbul2, Semra Ayturk2,
Conclusion
Nuray Can3, Bilkay Serez4 & Sibel Guldiken2
Elastography seems to require more experimentation in this regard with hope
1Edirne Sultan 1. Murat State Hospital, Department of Chest Diseases,
being a technique. Our study strongly suggests, biopsy is still the most reliable
Edirne, Turkey;2Trakya University, Medical Faculty, Department of
method for the evaluation of nodules.
Endocrinology and Metabolism, Edirne, Turkey;3Trakya University,
Medical Faculty, Department of Pathology, Edirne, Turkey;4Trakya
DOI: 10.1530/endoabs.49.EP1405
University, Medical Faculty, Department of Chest Diseases, Edirne, Turkey.
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal
human malignancies. The median survival time following diagnosis is
typically six months or less. Rapidly growing tumors may cause respiratory
failure by compressing trachea. A
71-year-old woman presented with
1-month history of dyspnea, cyanosis and rapidly enlarging neck mass for
the past 2 weeks. She had been suffering from multinodular goiter disease.
Physical examination revealed a large, fixed and mildy tender thyroid mass
EP1406
and cyanotic extremities. Breath sounds were bilaterally decreased on
Association of TIMP-3 expression and BRAF V600E mutation status in
auscultation. Arterial blood gas analysis showed hypoxia. Chest X-ray
papillary thyroid cancer
imaging revealed bilateral multiple nodular opacities, which were found to
Maryam Zarkesh1, Mehdi Hedayati1, Azita Zadeh-Vakili1,
be bilateral metastatik nodular lesions involving all segments on thoracic
Afsoon Daneshafrooz1, S Adeleh Razavi1, S-Ahmad Fanaei2,
tomography. In addition, a 35!20 mm sized lingular metastatic lesion
Forough Foroughi3 & Fereidoun Azizi4
invading 5th rib was present in the left lung. Thyroid gland was slightly
1Cellular and Molecular Endocrine Research Center, Research Institute for
larger than normal with heterogeneous parenchyma and there were multiple,
Endocrine Sciences, Shahid Beheshti University of Medical Sciences,
heterogeneous and hypoechoic nodules, the biggest one was being 30!
Tehran, Iran;2Association Professor of General Surgery, Erfan Hospital,
32!30 mm in size in the right thyroid lobe. In addition, 2 cm sized multiple
Tehran, Iran;3Department of Pathology, Shahid Beheshti University of
necrotic lymph nodes were visible. Laryngoscopic examination demon-
Medical Sciences, Tehran, Iran;4Endocrine Research Center, Research
strated externally compressed trachea. Tru-cut biopsy of left thyroid lobe
Institute for Endocrine Sciences, Shahid Beheshti University of Medical
detected anaplastic carcinoma with rhabdoid giant cell formation. Despite
Science, Tehran, Iran.
oxygen supplementation, hypoxic state worsened and the patient was
referred to intensive care unit following emergent tracheostomy. In
conclusion, although it is rare, anaplastic carcinoma should be considered
Background
in the patients presenting with respiratory failure. Anaplastic thyroid
The aim of this study was to assess the association between tissue inhibitor of
carcinoma should should be considered in patients presenting with rapidly
metalloproteinase-3
(TIMP-3) gene expression and B-Raf Proto-Oncogene
growing neck mass and respiratory failure.
(BRAF) V600E mutation in marginal and tumoral tissues of papillary thyroid
carcinoma (PTC) patients.
DOI: 10.1530/endoabs.49.EP1404
Methods
Sixty fresh frozen tissues of PTC including 55.3% women were collected during
thyroidectomy surgery. All clinicopathologic features of subjects were collected
which confirmed by a pathologist. The exon 15 of BRAF gene was genotyped by
sequencing, TIMP-3 gene expression was assessed using SYBR-Green Real-
Time PCR, and the protein level of TIMP-3 was measured using ELISA.
Results
The mean age in men and women was 39.6G15.6 and 37.5G11.6 years,
respectively. BRAF mutant was found in 24 (31.6%) of PTC samples. The mean
of TIMP-3 mRNA level was higher in marginal tissue compare to tumoral ones
EP1405
(PO 0.05). However, the mean of protein level of TIMP-3 was significantly
higher in marginal tissue compare to tumoral (PZ0.001). Moreover, in subjects
Our experience of strain elastography in the evaluation of thyroid
with BRAF positive mutation, the mean of TIMP-3 gene expression was higher in
nodules
marginal compare to tumoral tissues (PZ0.066). On the other hand, in subjects
Semin Melahat Fenkçi1, Mehmet Co¸kun2, Senay Topsakal1 &
without BRAF mutation, the mean of TIMP-3 protein level was significantly
Guzin Fidan Yaylalı1
lower in tumoral tissues compare to marginal tissue (PZ0.003). However, this
1Pamukkale University Endocrinology Department, Denizli, Turkey;2Katip
difference was not significant in subjects with negative BRAF mutation
C¸ elebi University Ataturk Hospital Radiology Department, Izmir, Turkey.
(PZ0.084).
Conclusion
Introduction
This study showed that although the gene expression of TIMP-3 was marginally
Thyroid nodule is a common finding in neck ultrasonography performed in adult
different in two BRAF positive and negative mutation groups, it was significantly
age group. Appropriate management of patients with thyroid nodules accuretly is
different in protein levels.
very difficult process. Fine needle aspiration biopsy (FNAB), is the traditional
DOI: 10.1530/endoabs.49.EP1406
invasive method used to identify nodules. Investigations are continuing for
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1407
total thyroidectomy (TT). This study was aimed to describe clinical outcomes in a
retrospective large series of low and intermediate risk thyroid cancer patients
Histologically-proven Hashimoto’s thyroiditis significantly decreases
treated with LT or TT.
the risk of structural recurrence in patients with low risk
Methods
intra-thyroidal papillary thyroid cancer
We evaluated retrospectively 336 patients affected with differentiated thyroid
Vincenzo Marotta1,2, Concetta Sciammarella2, Maria Grazia Chiofalo3,
cancers (DTC); 292 of them were treated with TT and 44 with LT. The initial
Claudio Gambardella4, Claudio Bellevicine5, Marica Grasso6,
surgical treatment was not chosen based on the risk class. The median age was
Giovanni Conzo4, Gerardo Botti6, Simona Losito6,7, Giancarlo Troncone5,
48 yrs, 274 were females and 62 males. Remission or persistent/recurrent disease
Luciano Pezzullo3, Annamaria Colao1 & Antongiulio Faggiano3
was defined on the basis of biochemical and/or structural evidence of disease after
1Department of Clinical Medicine and Surgery, Federico II University,
a median follow-up period of 65 months.
Naples, Italy;2IOS & COLEMAN s.r.l., Naples, Italy;3Thyroid and
Results
Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei
Only 1/292 patients treated with TT needed additional therapy (surgery for
Tumori-IRCCS ‘Fondazione G. Pascale’, Naples, Italy;4Department of
malignant lymph node metastases), and none of them was submitted to
Anesthesiologic, Surgical and Emergency Sciences, Division of General and
radioiodine ablation. On the other hand, 15/44 patients treated with lobectomy
Oncologic Surgery, University of Campania Luigi Vanvitelli, Naples, Italy;
were submitted to following treatment (completion thyroidectomy alone in 3,
5Department of Public Health, University of Naples ‘Federico II’, Naples,
associated with lymphadenectomy and radioiodine treatment in 12 cases). As far
Italy;6San Giovanni di Dio e Ruggi D’Aragona, Universitary Hospital,
as the outcome concerns, remission was documented in 281/292 cases (96.2%)
Division of General Surgery, University of Salerno, Salerno, Italy;
and 30/44 cases (68.2%) in the TT and LT groups, respectively (P!0.0001).
7Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei
Conclusions
Tumori-IRCCS ‘Fondazione G. Pascale’, Naples, Italy.
Our data suggest that lobectomy should be performed only in patients with a very
low risk at diagnosis, in order to avoid the need for a second treatment. Moreover,
Introduction
since virtually all patients treated with TT were cured after surgery, our data
Due to the absence of randomized controlled trials, management of low risk
support the selective use of radioiodine ablation treatment.
papillary thyroid cancer (PTC), which represents the most commonly diagnosed
DOI: 10.1530/endoabs.49.EP1408
form of thyroid malignancy, remains controversial. Hashimoto’s thyroiditis (HT)
is significantly more frequent in patients with PTC, as compared with subjects
carrying benign lesions as well as different tumour histotypes. Despite still
controversial, HT is considered a protective factor in PTC being associated with
favourable tumour features and better outcome. Nevertheless, all studies dealing
with this issue included all PTC stages. We aimed to assess prognostic value of
histologically-proven HT in a large cohort of consecutive low-risk intra-thyroidal
PTC.
Patients and methods
Multicenter retrospective study including pT1/2 PTC without any evidence of
extra-thyroidal disease, who were subjected to surgery and follow-up within the
EP1409
involved centers. Pathological review of all specimens was performed.
Does the delayed risk stratification system help to evaluate the risk of
Co-existing HT was defined by the presence of diffuse/focal lymphoplasmacytic
unfavorable clinical outcome in pT1aN0/Nx stage patients with
infiltrate, oxyphilic cells, lymphoid follicles with germinal centers, and atrophic
differentiated thyroid cancer treated without radioactive iodine?
changes involving normal thyroid tissue, whereas isolated peri- and intra-tumoral
Danuta Gasior-Perczak1, Iwona Palyga1, Monika Szymonek1,
lymphocytic infiltration was not considered as HT. Study endpoint was recurrent
Agnieszka Walczyk1, Janusz Kopczynski1, Anna Sluszniak1,
structural disease.
Ryszard Mezyk1, Stanislaw Gozdz1,2 & Aldona Kowalska1,2
Results
1Holycross Cancer Centre, Kielce, Swietokrzyskie, Poland;
Two-hundred eighty-four patients
(156 without and 128 without HT) were
2Jan Kochanowski University, Kielce, Swietokrzyskie, Poland.
included. Mean follow-up was 75G61 months (6.3 years). Concomitant HT was
related to significantly lower rate of recurrent structural disease (PZ0.018, OR
0.33 95% CI 0.13-0.86). This finding was confirmed by survival analysis, where
Introduction
PTC with HT showed significantly higher recurrence-free time. After adjustment
In ATA recommendations (2016) a delayed risk stratification (DRS) system
for other variables affecting prognosis at univariate analysis (age at diagnosis,
proposed by D.P. Momesso et al. was accepted as a diagnostic tool for the risk
tumour size, multifocality, and post-surgery radiometabolic treatment), con-
stratification of unfavorable clinical outcome and for monitoring the clinical
comitant HT retained its protective effect (PZ0.036, OR 0.34 95% CI 0.12-0.93).
outcome in differentiated thyroid cancer
(DTC) patients treated without
Conclusions
radioactive iodine (RAI).
In our series of low risk intra-thyroidal PTC, concomitant HT independently
The aim of the study
predicted recurrent structural disease and may therefore represent a useful tool for
To evaluate the DRS system in patients with low clinical stage (pT1aN0/Nx).
the decision-making process of these patients.
Material
DOI: 10.1530/endoabs.49.EP1407
304 patients after total thyroidectomy (nZ202) or lobectomy (nZ102) without
adjuvant RAI therapy, with a follow-up period of at least 24 months, treated at a
single center were enrolled to the study. The median age was 50.5 years, 91.1%
were women, 100% at baseline had a low risk according to ATA, the median
follow-up was 4 years (2-24).
Methods
DRS of the treatment response was conducted, based on the medical records,
according to the criteria by Momesso et al. The course of the disease was
evaluated (recurrence, death) as well as the status on 31.12.2016, which is the end
of the follow-up
(remission, persistent disease). The relationship between
EP1408
unfavorable outcome and the DRS system was evaluated.
Evaluation of disease outcome in patients affected with differentiated
Results
thyroid carcinoma treated with total thyroidectomy or lobectomy
The response to initial therapy was excellent in
272
patients
(89.5%),
Carla Colombo1, Simone De Leo1, Michela Perrino1, Marta Di Stefano1,
intermediate in 31 patients (10.2%) and biochemically incomplete in 1 patient
Gianmaria Cantoni3, Leonardo Vicentini3 & Laura Fugazzola1,2
(0.3%)
(increased concentration of TgAb). There was a recurrence in 2 patients
1University of Milan, Milan, Italy;2Istituto Auxologico Italiano, Milan,
from the excellent response group at 6 and 7 years of follow-up (after lobectomy).
Italy;3Fondazione Policlinico Ca Granda, Milan, Italy.
No patients with intermediate and biochemically incomplete response were
diagnosed with the structural disease and none of the patients died during the
follow-up.
Abstract
Conclusions
An individualized risk-based approach to the treatment of thyroid cancer is being
The DRS system did not prove useful in predicting the risk of unfavorable clinical
extensively discussed in the recent literature, but controversies remain about the
outcome and cannot be used to personalize the monitoring method of the disease
ideal surgical approach. In particular, if some data showed that properly selected
in patients at pT1aN0/Nx, not treated with RAI.
thyroid cancer patients can be treated with lobectomy (LT) with excellent clinical
DOI: 10.1530/endoabs.49.EP1409
outcomes, other results demonstrated an increased incidence of persistent
recurrent disease in patients submitted to LT with respect to those treated with
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1410
Stage ICII:71.8 vs 49.8%, III:20.5 vs 27.6%, IV:7.7 vs 22.7%, PZ0.007) with
the difference remaining significant in both sporadic (PZ0.022) and familial
The impact of post-radioiodine therapy SPECT/CT on risk
MTC (PZ0.035). MTC-DTC group had marginally better disease prognosis
stratification in differentiated thyroid cancer; a bi-institutional study
compared to MTC alone (remission: 67.6 vs 48.7%, stable: 16.2 vs 25.2%,
Szabina Szujo1, Livia Sira2, Laszlo Bajnok1, Beata Bodis1, Ferenc Gyory5,
progression:
16.2
vs
26.1%, PZ0.05). The 10-year probability of lack of
Orsolya Nemes1, Karoly Rucz1, Peter Kenyeres1, Zsuzsanna Valkusz6,
progression of disease did not differ between the two groups. Size of DTC did not
Krisztian Sepp6, Erzsebet Schmidt3, Zsuzsanna Szabo3, Sarolta Szekeres3,
seem to affect the clinical course of MTC-DTC.
Katalin Zambo3, Sandor Barna4, Endre V Nagy2 & Emese Mezosi1
Conclusions
1Ist Department of Medicine, University of Pecs, Pecs, Hungary;
Simultaneous occurrence of MTC-DTC is occasionally diagnosed. Even though
2Department of Medicine, Faculty of Medicine, University of Debrecen,
stage at diagnosis is better in MTC-DTC patients, there is no difference in 10-year
Debrecen, Hungary;3Department of Nuclear Medicine, University of Pecs,
probability of lack of progression of disease. We report for the first time an
Pecs, Hungary;4Department of Nuclear Medicine, Faculty of Medicine,
increased incidence of DTC in RET exon 8 (G533C) carriers. Whether this
University of Debrecen, Debrecen, Hungary;5Department of Surgery,
mutation-quite common in Greek MTC patients-might participate in shared
Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
pathogenic mechanisms needs further investigation.
6Ist Department of Medicine, University of Szeged, Szeged, Hungary.
DOI: 10.1530/endoabs.49.EP1411
Objective
SPECT/CT has numerous advantages over planar and traditional SPECT images.
The aim of this study was to evaluate the role of post-radioiodine therapy
SPECT/CT of patients with differentiated thyroid cancer (DTC) in early risk
classification and in prediction of late prognosis.
Patients and Methods
EP1412
323 consecutive patients, 181 at the University of Pecs and 142 at the University
Concomitant thyroid inflammatory myofibroblastic and
of Debrecen, were investigated after their first radioiodine treatment (1100-3700
follicular tumors
MBq). Both SPECT/CT and planar camera images of the head, neck, chest and
Romena Laukiene, Audra Padlipskaite & Edvardas Zurauskas
abdomen regions were taken four days after radioiodine therapy. Patients were
Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
re-evaluated 9-12 months later as well as at the end of follow-up (median 37
months).
Results
Abstract
Post-radioiodine therapy SPECT/CT showed metastases in 22% of patients.
We present a rare clinical case. Inflammatory myofibroblastic tumors (IMT) are
Lymph node, lung and bone metastases were detected in 61, 13 and 5 patients,
extremely rare neoplasms of unknown etiology and most commonly found in
respectively, resulting in early reclassification of 115 cases (36%). No evidence of
lungs and gastrointestinal tract. A rare clinical case of the thyroid IMT occurred in
disease was found in 251 cases at 9-12 months after radioiodine treatment and 269
a 50-year-old lithuanian female patient with clinical manifestation of breath-
patients at the end of follow-up. To predict residual disease at the end of follow-
lessness, dry cough, hemoptysis, neck mass, arrhythmia and loss of conscious-
up, the sensitivities, specificities and diagnostic accuracies of the current risk
ness. Because of elevated D dimers values, pulmonary artery thromboembolism
classification systems and SPECT/CT were: ATA: 77%, 47% and 53%; ETA: 70,
was suspected and CT scan was performed. CT showed no pulmonary embolism,
62 and 64%; SPECT/CT: 61, 88 and 83%, respectively. There was no difference
but revealed a large tumor in the neck. After patient was investigated in
between cohorts of the two institutions when data were analyzed separately.
cardiology department to exclude sick sinus syndrome, fine needle aspiration
Conclusions
cytology of thyroid nodus was done with non-diagnostic results. Thyroid
Based on our bi-institutional experience, the accuracy of post-radioiodine
scintigraphy showed cold node suggesting maligancy. All symptoms and findings
SPECT/CT outweighs that of the currently used ATA and ETA risk classification
indicated the need of surgical treatment. The patient underwent total
systems in the prediction of long-term outcome of DTC.
thyroidectomy. Histopathology analysis revealed two separative tumors:
DOI: 10.1530/endoabs.49.EP1410
follicular carcinoma and thyroid inflammatory myofibroblastic tumor. Because
of folicular carcinoma the patient was treated with radioiodine. She was
comfortable after treatment with thyroid hormone replacement therapy. We
managed to find only 20 cases of this type of tumor located in thyroid reported in
the literature. And we did not find reports with two concomitant thyroid tumors
including IMT.
DOI: 10.1530/endoabs.49.EP1412
EP1411
Clinical features of medullary thyroid carcinoma (MTC) in
simultaneous occurrence with differentiated thyroid cancer (DTC)
George Simeakis, Katerina Saltiki, Elli Anagnostou, Michalis Apostolakis,
Vasiliki Vasileiou & Maria Alevizaki
Endocrine Unit, Department of Medical Therapeutics, Alexandra Hospital,
Athens University School of Medicine, Athens, Greece.
EP1413
Is thyroid imaging reporting and data system useful in prediction of
Objective
malignancy in thyroid nodules with persistent nondiagnostic cytology?
Simultaneous occurrence of MTC and DTC is frequently found. It is unclear
Husniye Baser1, Oya Topaloglu2, Sevgul Faki2, Afra Alkan3, Mustafa Omer
whether there is a common pathogenic mechanism. Aim of our study was to
Yazicioglu4, Hayriye Tatli Dogan5, Reyhan Ersoy2 & Bekir Cakir2
characterize clinical features of MTC when coexisting with DTC.
1Ataturk Education and Research Hospital, Department of Endocrinology
Methods
and Metabolism, Ankara, Turkey;2Yildirim Beyazit University Faculty of
Of 273 MTC patients followed-up in our department 39 (14.3%) had MTC
Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey;
simultaneously with DTC. They were divided in 4 subgroups according to size.
3Yildirim Beyazit University Faculty of Medicine, Department of
Biostatistics, Ankara, Turkey;4Yildirim Beyazit University Faculty of
Clinical histopathological data were recorded.
Medicine, Department of General Surgery, Ankara, Turkey;5Yildirim
Results
Beyazit University Faculty of Medicine, Department of Pathology,
The patients were followed for 1-35 yrs (median:5). Median age at diagnosis was
Ankara, Turkey.
45 yrs (4-81 yrs). Simultaneous occurrence of distinct MTC-DTC was observed
more frequently in patients diagnosed after 2001 compared to earlier (16.7 vs
6.3%, PZ0.036). Sex and history of familial disease did not differ. In familial
Introduction
forms of MTC, DTC occurrence was higher in carriers of RET exon 8 (G533C)
Although malignancy rate is low in thyroid nodules with nondiagnostic (ND)
mutation compared to other RET mutations (17.6 vs 1.8%, PZ0.004). Patients
cytology, it is reported as higher in persistent ND nodules. We aimed to determine
with concomitant MTC-DTC had less frequently lymph node infiltration from
the role of ultrasonography (US) features and Thyroid Imaging Reporting and
MTC compared to those with MTC alone (26.3 vs 47.8%, PZ0.015), marginally
Data System (TIRADS) in the prediction of malignancy in patients with persistent
smaller MTC size (median (IQR) 0.9 (1.5) vs 1.2 (1.4) cm, PZ0.058) and more
ND cytology.
often c-cell hyperplasia (58.6 vs 31.5%, PZ0.006). No differences were found
Methods
regarding capsular and soft tissue invasion, multifocality, distant metastases at
246 patients who underwent thyroidectomy with an indication of at least two ND
diagnosis. Stage at diagnosis differed between groups (MTC-DTC vs MTC alone:
cytologies were included in this study. Suspicious US features (solid component,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
hypoechogenicity, irregular margin, microcalcification, and taller-than-wide
EP1415
shape) and TIRADS categories (TIRADS category 3, 4a, 4b, 4c and 5) of each
Primary thyroid lymphoma: a differential diagnosis to be considered
nodule were obtained from medical records.
M Teresa Gallego, Lucia Vera, Cristina Del Peso, Amparo Meoro,
Results
Manuel Martin, Marife Candel, Emilio Terol & Francisco Pastor
Of the 246 patients, 218 (88.6%) had benign and 28 (11.4%) had malignant final
Hospital General Universitario Reina Sofia, Murcia, Spain.
histopathology. Of these 28 patients with malignant histopathology, 25 (89.3%)
were evaluated as papillary thyroid carcinoma, 1 (3.6%) as follicular thyroid
carcinoma,
1
(3.6%) as medullary thyroid carcinoma, and
1
(3.6%) as
Introduction
undifferentiated thyroid carcinoma. Frequencies of taller-than-wide shape,
Primary lymphoma of the thyroid, although rare, should be considered in the
solidity, hypoechogenicity, microcalcifications, and irregular margins were
differential diagnosis of patients with thyroid nodules or goiter, because its
similar in benign and malignant groups (PO0.05, all). TIRADS categories of
prognosis and treatment differ substantially from that of the other disorders.
246 nodules with ND cytology were as follows; 12 (4.9%) TIRADS 3, 53 (21.5%)
Thyroid lymphomas are nearly always of the non-Hodking type (70-80% B cell
TIRADS 4a, 104 (42.3%) TIRADS 4b and 77 (31.3%) TIRADS 4c. There was not
lineage). There is a 4:1 female predominance and the mean and median ages at
any nodule with TIRADS 5 category. Malignancy rates of categories 3, 4a, 4b,
diagnosis are between 65 and 75 years. Hashimoto’s thyroiditis is the only known
and 4c nodules were 0, 13.2,
9.6
and 14.3%, respectively. No significant
risk factor.
differences were found in TIRADS categories between benign and malignant
Case report
nodules (PO0.05, all).
A 70 years old woman with a rapidly enlarging goiter without local symptoms or
Conclusion
signs. The patient presented a history of hypothyroidism on treatment with
In the present study, malignancy rate was found as 11.4% in nodules with
thyroxine. Her tiroglobulin antibodies were positives but not TPO. An ultrasound
persistent ND cytology. There was not any suspicious US feature that was
scan of the thyroid showed a 7-cm mass in the left lobe and istm. The fine needle
predictive for malignancy in ND nodules. Thyroid nodules in TIRADS 4a, 4b and
biopsy was nondiagnostic but suggestive of Hashimoto’s thyroiditis. The
4c categories had higher malignancy rates than estimated risk of malignancy
excisional biopsy confirmed the diagnosis of a diffuse large B-cell lymphoma.
reported by the Bethesda system in ND cytology.
Imaging studies demonstrated cervical and mediastinal lymph nodes and bilateral
DOI: 10.1530/endoabs.49.EP1413
pulmonary metastases.
Discussion
Thyroid lymphoma represents no more than 2% of all malignant thyroid tumors.
The vast majority are of the non-Hodking type, the most frequent the B-cell
lineage. The typical presentation is a rapidly enlarging goiter with symptoms or
signs of tracheal, esophageal or neck vein compression. In 10-20% there is a
known goiter often with hypothyroidism. Up to
10% have systemic (‘B’)
symptoms of lymphoma
(fever, night sweats, weight loss). Diagnosis is
established by cytologic examination; when the fine needle biopsy is
nondiagnostic the excisional biopsy is required. The treatment includes Radiaton
and Chemotherapy. Definitive surgery is not usally performed. Our patient was
EP1414
treated with six cycles of CHOP followed by radiation.
Significant difference between the prevalence of C cell hyperplasia
Conclusions
(CCH) in benign thyroid nodules without histological thyroiditis (HT)
Thyroid lymphoma is a rare cancer but must be considered in the differential
and in papillary/follicular thyroid cancers (PTC/FTC) at histology
diagnosis of patients with thyroid nodules or goiter specially if a Hashimoto’s
Letizia Pieruzzi1, Eleonora Molinaro1, Laura Agate1, Valeria Bottici1,
thyroiditis is present. The risk of Thyroid lymphoma is at least 60 times higher
Liborio Torregrossa2, Clara Ugolini2, Fulvio Basolo2, Paolo Vitti1 &
than in patients without thyroiditis. The treatment is not the surgery like in the
Rossella Elisei1
others thyroid pathologies and the prognosis depends on the type and tumour
1Medical Area and Experimental Medicine Department, Endocrinology
extension.
section, University of Pisa, Pisa, Italy;2Department of Oncology Section of
DOI: 10.1530/endoabs.49.EP1415
Cytopathology, Pathology, University of Pisa, Pisa, Italy.
Background
CCH and serum hypercalcitoninemia (iperCT) can be found in benign thyroid
diseases such as thyroiditis and in some cases of papillary (PTC) or follicular
(FTC) thyroid microcarcinomas. The question of whether the association with
these latter is related to the malignancy of the nodule is still unclear.
Aim of the study
EP1416
To evaluate the difference in the CCH prevalence, at histology, in a series of
Relation between TSH levels and the aggressiveness of differentiated
benign (BTN) and malignant (PTC/FTC) thyroid nodules. The correlation with
thyroid carcinomas
the serum CT was also analysed.
Esra Aydinli2, Mustafa Kulaksizoglu1, Ahmet Kaya1 & Feridun Karakurt1
Materials and methods
1Necmettin Erbakan University, Meram Medical Faculty, Division of
We selected 315 consecutive cases surgically treated between 2012 and 2016 in
Endocrinology and Metabolism, Konya, Turkey;2Necmettin Erbakan
our Hospital: 137/315(43.5%) resulted to be BTN and 178/315(56.5%) to be
University, Meram Medical Faculty, Internal Medicine, Konya, Turkey.
PTC/FTC. In 27/315(8.5%) cases there was a serum iperCT (Immulite 2000,
Siemens). The definition of CCH was based on the presence of more than 50
C-cells at least in one microscope field, in a thyroid cross section.
Aim
Results
Differentiated thyroid carcinomas
(DTC) composes
95% of all thyroid
At a first analysis no differences were observed in the prevalence of CCH between
malignancies originating from thyroid follicular epithelial cells. DTC expresses
BTN and PTC/FTC. When we excluded from the analysis the cases with reported
TSH receptors so long time TSH stimulation may cause cancer occurrence or
HT, both benign and malignant, the prevalence of CCH was statistically
malignancy progression. So we aimed to assess the role of TSH levels in
significant more frequent and bilateral in PTC/FTC (32.6%) than in BTN (19.5%)
predicting thyroid cancer stage or aggressiveness.
(P!0.05). The cases with iperCT were exclusively in the PTC/FTC group and
Methods
among them those case with iperCT showed the highest prevalence of CCH
We retsopectively searched thyroid cancer patients fort he last 10 years in our
(P!0.001). In PTC/FTC with serum iperCT we observed that 11/21(52.4%) were
instution. Totally 329 patients record were eligible for the study. TSH levels and
follicular variant PTC(FVPTC) while this variant was present in only
disease stage, age and sex were evaluated.
30/84(35.7%) PTC/FTC without iperCT (P!0.05). The cases with iperCT
Results
were also more often multifocal (P!0.005).
322
(97.9%) were papillary thyroid carcinomas and 7 (2.1%) were follicular
Conclusions
carcinomas 261 79.3(%) were females, 68 (20.7%) were males. Median age was
CCH is more frequent in PTC/FTC than in BTN when the cases with HT were
45
(17-76) years old. Among the patients; 273 (83.0%) had stage 1 disease, 22
excluded; the serum iperCT was found exclusively in the PTC/FTC group and
(6.7%) had stage 2 disease, 11 had (3,3%) stage 3 disease and 23 (7.0%) had stage
these cases showed the highest prevalence of CCH; a higher prevalence of
4 disease. Median TSH level was 1.34 (0.01-9.97) mIU/ml. Serum TSH levels
FVPTC and multifocal cases were observed in the PTC/FTC group associated
were different when compared stage 1 and 4 patients (PZ0.004). But there was no
with CCH.
significant difference between other stages. Additionally, subjects with lymph
DOI: 10.1530/endoabs.49.EP1414
node at diagnosis had higher TSH levels according to patients who had not
(PZ0.0001).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Conclusion
Case report
Higher TSH levels were observed in patients with lymph node metastasis at the
A 46-yr-old man presented to the emergency department with a painful mass on
diagnosis and there was statistically higher TSH levels in stage
4 patients
the anterior side of his neck. Laboratory tests revealed leukocytosis, while thyroid
compared to stage 1 patients. But this relation was not seen in other stages.
functions tests, calcitonin, carcinoembryonic antigen and calcium levels were in
Further studies with larger number of patients could show the relation with TSH
the normal limits. Neck ultrasound revealed an enlarged thyroid gland with a
levels and thyroid cancer aggressiveness.
2.5 cm dominant nodule on the right thyroid lobe. Fine-needle aspiration cytology
DOI: 10.1530/endoabs.49.EP1416
showed ‘atypia of undetermined significance’ (AUS). The patient underwent total
thyroidectomy. Histological examination revealed a papillary carcinoma 1.4 cm
in diameter with central fibrosis, degenerative necrosis and the presence of foam
histiocytes. It also showed multiple solid cell nests, nodular hyperplasia and rare
lymphoid aggregates in the rest area of the thyroid.
Discussion
Rare cases of concurrent PTC up to 1 cm and SCNs have been described in the
literature. SCNs may harbour multipotent stem cells which after a combination of
EP1417
mutations affecting their differentiation and unlimited growth potential may
Ultrasonographic features of thyroid nodules with suspicious or
generate cancer stem cells predisposing to thyroid cancer. Immunohistochemical
malignant cytology
and molecular studies of neoplastic SCN lesions are needed to better understand
Vasileios Chambidis, Athanasios Siolos, Lazaros Lazarou,
the complexity of stem cells and their malignant counterparts, advancing our
Zoe Efstathiadou, Athanasios Panagiotou, Fotini Adamidou & Marina Kita
knowledge on thyroid pathophysiology, carcinogenesis, and treatment.
Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
DOI: 10.1530/endoabs.49.EP1418
Introduction
Thyroid sonography has become the first line diagnostic procedure for thyroid
nodules. The characterization of specific sonografic patterns associated with high
risk of malignancy has enabled physicians to determine which nodules are more
likely to be malignant and thus merit further evaluation.
Aim
EP1419
We investigated whether the ultrasonographic nodule characteristics proposed in
Statistical analyses on thyroid cancer in Romania
the literature were able to predict cytology findings after ultrasound-guided fine
Mariana Purice1, Andrei Liviu Goldstein1, Iulia Andreea Chiriac1,
needle aspiration biopsy (USg-FNAB), in our centre.
Monica Radulescu2, Sorin Rusu2, Alexandra-Cristina Mihai1,
Materials and methods
Andreea Giurgi5, Madalina Olteanu3, Adina Mariana Ghemigian1,4 &
A retrospective analysis of patients who had undergone USg-FNAB between Jan
Catalina Poiana1,4
2014 and Nov 2015 was performed. Nodules were classified according to the
1‘C.I.Parhon’ National Institute of Endocrinology, Bucharest, Romania;
following sonographic characteristics a) size, b) solid hypoechoic nodule, c)
2SOFTWIN S.A, Bucharest, Romania;3Universite Paris I Panthéon
presence of microcalcifications, d) irregular borders, e) vertical growth (‘taller-
Sorbonne, Paris, France;4‘Carol Davila’ University of Medicine and
than-wide’ orientation), and, f) increased vascularity. Cytology reports were
Pharmacy, Bucharest, Romania;5Faculty of Biology, University, Bucharest,
classified, according to the Royal College of Pathologists guidance, as non-
Romania.
diagnostic for cytological diagnosis (Thy 1), negative for malignancy (Thy2),
neoplasm possible (Thy3), suspicious for malignancy (Thy4) and malignant
(Thy5). Category Thy1 nodules were excluded from the analysis. The association
of suspicious ultrasound characteristics with the composite cytology outcome of
For over 50 years the casuistic of patients with thyroid cancer registered in
possible neoplasm, suspicious or malignant (Thy3, Thy4, Thy5) was investigated.
the Nuclear Medicine Department of the National Institute of Endocrinology
Results
in Bucharest, Romania, has over 12 000 cases. In the last 6 years, a total of
During the study period, 736 nodules in 571 patients were biopsied. The most
2580 new cases have been added. They are organized in a ‘classic file’
common ultrasonographic feature was low echogenicity
(175/736,
23.8%),
format. As a necessity and the first step in order to build a digital national
whereas the most rear was the vertical nodule growth
(‘taller-than-wide’
database, we developed the BIOMAT-ENDO software as a Windows Forms
appearance, (28/736, 3.8%)). In a logististic regression model, where patient
application that stores all the main data regarding the patient hospitalized in
age was entered along with the ultrasonographic features, all variables emerged as
the department, starting with the first hospitalization, continuing with all the
predictors of the composite category Thy3, Thy4, Thy5 cytology, except vertical
periods of radioiodine therapy and the follow up. The patient-monitoring
nodule growth and increased vascularity.
MODULE contains: clinical parameters, surgery details, in vivo and in vitro
Conclusion
investigations, therapy information. Correlations can be done between any
Sonographic nodule characteristics proved to be accurate predictors of cytology
input data. We present preliminary results on 2000 cases of patients with
in the present patient series. Thyroid ultrasonography is a useful tool in
thyroid cancer digitalized during one year in this database. We used the
determining which nodules should be biopsied.
Structured Query Language in order to verify the functionality of the system,
DOI: 10.1530/endoabs.49.EP1417
the correctness of the existing data and for some preliminary statistics.
Results shows the following distributions: onset disease age: ! 18 year:
3%; 19-45 year: 37%; 46-65 year:42%; O66 year:18%; genders: F:84%;
M:16% M, area distribution: urban:74%; rural:26%, personal history: multi
nodular & nodular goitre:
81%, Graves’s
1%, Hashimoto:
1%; no
history:16%, risk factors: endemic area:70%; non-endemic area:30%,
histopathology: papillary/follicular:30%; papillary: 28%; follicular: 17%;
micro-carcinoma: 20%; others: 5%. Preliminary results on a target group
EP1418
with the onset disease age
!18 years (nZ58) show the following
Development of papillary thyroid carcinoma in a patient with multiple
distribution on: TNM: T1:7%; T2:14%; T3:19%; T4:5%; unclassified: 9%
solid cell nests of the thyroid
and on disease stage: STD1:57%; STD2:4%; STD3:23%; STD4a:10% and
Theodoros Liarigkovinos1, Vasiliki Daraki1, Paraskevi Floroskoufi1,
STD 4b:6%.
Helen Moustou2, George Kalikakis1 & Stathis Papavasiliou1
DOI: 10.1530/endoabs.49.EP1419
1Department of Endocrinology, Diabetes and Metabolic Diseases,
University Hospital of Crete, Heraklion, Greece;2Laboratory of Pathology,
University of Crete, School of Medicine, Heraklion, Greece.
Introduction
EP1420
Solid cell nests (SCNs) of the thyroid are considered embryological remnants of
Prognostic value of preoperative serum calcitonin concentration on
the ultimobranchial bodies and the thyroid diverticulum. They are frequently (61-
primary surgery outcomes in medullary thyroid cancer
89%) detected in the thyroid gland, but their biological significance remains
Tomasz Gawlik, Aleksandra Kukulska, Zbigniew Wygoda,
disputable. According to the fetal cell thyroid carcinogenesis hypothesis SCNs
Jolanta Krajewska, Ewa Stobiecka, Agnieszka Czarniecka & Barbara Jarzab
may act as a source for specific thyroid cancer stem cells generating distinct
Maria Sklodowska-Curie Morial Institute and Centre of Oncology, Gliwice
thyroid cancer phenotypes. We report a case of a patient with concurrent SCNs
Branch, Gliwice, Poland.
and papillary thyroid carcinoma (PTC).
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1422
Calcitonin assessment in thyroid diseases is recommended when medullary
thyroid cancer (MTC) is suspected in fine needle biopsy, as well as in
Incidental thyroid uptake detected by68Ga-DOTANOC positron
‘suspicious for a follicular neoplasm’ class, especially oxyphilic type, in
Emission Tomography: is it clinical significant?
patients with germinal RET proto-oncogene mutation and in nondiagnostic
Tiago Nunes da Silva1, Joaquim Gomes Santos2, Ana Catarina Matos1, João
biopsy when no surgical treatment is planned. This assessment is also
Pedro Teixeira3, Carla Oliveira4, Joana Castanheira4, Susana Carmona2,5,
suggested before any planned thyroid surgery to exclude MTC. Beyond
Hugo Duarte3, Durval Costa4, Luis Oliveira5, Ana Isabel Santos2 &
diagnosis confirmation it is also suggested to take the concentration into
Jorge Portugal
account planning the extent of neck lymph node resection, although the
1Endocrinology Department Hospital Garcia de Orta, Almada, Portugal;
threshold values are not precisely established. The aim of this work was to
2Nuclear Medicine Department Hospital Garcia de Orta, Almada, Portugal;
assess the prognostic impact of preoperative serum calcitonin concentration
3Nuclear Medicine Department - IPO Porto, Porto, Portugal;4Nuclear
on primary surgery outcomes in medullary thyroid cancer. Among 1575
Medicine department Champalimaud Centre for the Unknown, Lisboa,
MTC patients followed-up in single clinical centre 248 patients were
Portugal;5Nuclear Medicine Unit - Oncological Centre Dr.a Natália
identified in whom serum calcitonin concentration before primary thyroid
Chaves/Joaquim Chaves Saúde, Carnaxide, Portugal.
surgery was available (63 men and 185 women). Its mean concentration was
3647.8G18862.7 pg/ml (median - 612 pg/ml, max. 286 643, min. 2 pg/ml).
Background
All patients underwent total thyroidectomy, and in 233 at least central and
The detection of thyroid incidental uptake of radiopharmaceuticals has been
unilateral neck lymph node resection. In postoperative assessment in 145
increasing. Those detected by
18F-fluorodeoxyglucose positron emission
patients serum calcitonin was undetectable and in 187 remained within
tomography (PET) have been associated with a significant risk of malignancy
normal ranges for healthy population (!10 pg/ml; in 11 of them in the
(8-64%). Gallium-68 (Ga-68) labelled peptides are now the standard imaging
follow-up calcitonin increased). In
217
patients after surgery no
modality for staging neuroendocrine tumours (NET). Its high sensitivity has
macroscopic cancer foci were visible in the imaging, and in further
increased the discovery of incidental findings. The aim of this study was to
follow-up in 11 metastases or recurrence were found. Maximal preoperative
evaluate the frequency and clinical significance of incidental thyroid uptake as
concentration in patients who had no nodal metastases and normal calcitonin
detected by68Ga- DOTANOC PET in patients without a history of thyroid cancer.
after surgery was 2513.8 pg/ml. Maximal preoperative concentration in
Methods
patients in whom postoperative calcitonin was normal and were free from
A retrospective analysis was conducted over
49
patients who underwent
relapse in further follow-up was 15302.0 pg/ml. The minimal preoperative
68Ga-DOTANOC PET as part of a work-up for non-thyroid cancer. The uptake
calcitonin in patients with histologiacally confirmed neck nodal metastases
in the thyroid gland (focal/physiologic) was evaluated and compared with the
was 23 pg/ml. Conclusions: High preoperative serum calcitonin concen-
uptake in the liver.
tration up to a value of almost 12 000 pg/ml does not exclude the possibility
Results
of radical surgical treatment in MTC patients. Neck nodal MTC metastases
24
(49%) of the 49 patients were female with a median age of 64 years (p25 53
can be found when serum calcitonin is as low as 23 pg/ml.
and p75 74). Thyroid nodules were known in 14 patients with a median size of
DOI: 10.1530/endoabs.49.EP1420
9.1G8.4 mm. The reasons for68Ga-DOTANOC PET staging were: intestinal
NET in 29 (59.2%), bronchial NET in 10 (20.4%), pancreatic NET in 5 (10.2%),
paraganglioma in 2 (4.1%), an ectopic ACTH in one (2%), ectopic GH in 1 (2%)
and meningioma in 1 (2%). Eight patients (16%) had68Ga-DOTANOC thyroid
uptake: one (2%) had anomalous focal uptake, and 7 (14%) had physiologic
uptake. The patient with focal uptake, had thyroid nodules on the corresponding
side, as detected by anatomic imaging with a final diagnosis of a benign nodule.
Of the seven patients with physiologic uptake, 3 (47%) had a corresponding
EP1421
nodule on ultrasonography and 1 (14%) had a papillary thyroid carcinoma. Ten
patients with known nodules did not have68Ga-DOTANOC uptake, including a
Standardized mortality of thyroid cancer in Korea between 1985 and
follicular tumour.
2015: analysis of Korean national data
Conclusions
Yun Mi Choi1, Won Gu Kim2, Hyemi Kwon2, Min Ji Jeon2, Minkyu Han2,
In contrast to the published research of68Ga-DOTANOC uptake in patients with
Tae Yong Kim2, Young Kee Shong2, Sang Mo Hong1, Eun-Gyoung Hong1
known thyroid cancer, in our short series, the incidental uptake in thyroid gland
& Won Bae Kim
does not seem to be related.
1Hallym University Dongtan Sacred Heart Hospital, Seoul, Republic of
Korea;2Asan Medical Center, University of Ulsan College of Medicine,
DOI: 10.1530/endoabs.49.EP1422
Seoul, Republic of Korea.
Background
The prevalence of thyroid cancer has increased very rapidly in Korea. However,
there is no data focusing on thyroid cancer mortality in Korea. In this study, we
aimed to evaluate standardized thyroid cancer mortality using national data from
Statistics Korea.
Methods
Population and mortality data from 1985 to 2015 were obtained from Statistics
Korea. Age-standardized mortality rates (ASMR) of thyroid cancer per 100 000
EP1423
were calculated according to the standard population of Korea, as well as World
An association between breast cancer and the development of
Health Organization
(WHO) standard population and International Cancer
thyroid cancer
Survival Standard (ICSS) population weights.
Lila Brakni
Results
Hospital of Army MS Nekkache, Algiers, Algeria.
The ASMRs of thyroid cancer was increased from 0.19 to 0.87 between 1985 and
2004. And the ASMRs were decreased from 2005 until 0.43 in 2015. The
estimated annual percent change
(APC) from 1985 to 2004 was 7.64 and
Introduction
corresponding value from 2004 to 2015 was K4.28. These changes in the ASMRs
Women with breast cancer (BC) have an increased risk of developing thyroid
were similar patterns in males (APC 8.23, 1985-2003 and APC K4.33, 2003-
cancer (TC), specifically papillary and follicular thyroid carcinomas at a median
2015) and females (APC 7.33, 1985-2004 and APC K4.63, 2004-2015). These
of 5 years. The aim of the present retrospective study is to describe the clinical
patterns of the change of ASMR were also observed in elderly subgroup (R55
characteristics of women who present this association.
years). When ASMRs were calculated based on the WHO standard population
Results
and ICSS population weights, those was similarly increased until 2004, and
A total of 260 patients with an authenticated TC who were the median age at
decreased from 2004.
diagnosis is 41 years old (36-65). All our patients live in areas of moderate iodine
Conclusion
deficiency. The frequency of the association of BC-TC Z6/260 (4.3%). The
Thyroid cancer mortality in Korea was increased until 2004 and started to
median duration between the two diagnoses Z24 months (12-84). The BC has
decrease after then. The increase in early diagnosis of thyroid cancer might be
always preceded theTC. The histopathological aspects are respectively for the
associated with decrease of thyroid cancer mortality in Korea.
BC: invasive ductal carcinoma (nZ4) invasive lobular carcinoma (nZ2) and TC:
DOI: 10.1530/endoabs.49.EP1421
pure vesicular (nZ2); Papillary (nZ4). All these women underwent chemother-
apy, hormone therapy and radiotherapy for BC and total thyroidectomy and an
irradiation (100 mCI 131) for TC.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Discussion
Materials and methods
The coexistence BC and TC is not fortuitous but the related pathophysiological
Five hundred and thirty four patients done total thyroidectomy by general surgery
mechanisms remain poorly elucidated Exposure to estrogens and to thyroid-
were evaluated retrospectively from July 2015 to July 2016. Preoperative thyroid
stimulating hormones may play a role in the development of breast cancer or
function tests, anti-thyroid antibodies, thyroid ultrasonography findings, fine
thyroid cancer. Radiation exposure is also a well-known risk factor for the
needle aspiration biopsies of nodules and pathology results of total thyroidectomy
development of TC, so a germline mutation could be responsible for the
were examined. According to pathology results, HT was detected in 139 patients.
connection between breast and thyroid cancers.
Patients with PTC and HT (group 1) and PTC without HT (group 2) were
Conclusion
compared in terms of demographic characteristics, tumor size, focus number of
The association of these two pathologies is not incidental and should lead
tumor, invasion, extrathyroidal spread and lymphatic metastasis presence.
otherwise to the systematic screening of the thyroid cancer in women with breast
Findings
cancer.
PTC was detected in 70 (%50.4) patients in group 1 and 156 (%39.5) patients in
DOI: 10.1530/endoabs.49.EP1423
group 2 (PZ0.026). There was no statistically significant difference between
them in point of gender, age, tumor size, microcarcinoma-macrocarcinoma
distribution, focus number of tumor, invasion, extrathyroidal spread and
lymphatic metastasis. The number of patients with PTC who had at least 1 kind
of high anti-thyroid antibody was greater in group 1 then group 2 (P!0.001).
Results
In our study,we determined more PTC among HT patients but we find no
difference according to age, gender, tumor size, invasion and metastasis. By the
way anti-thyroid antibody positiveness was higher in cancer patients of group 1.
Long term follow-up studies are necessary for detecting the effect of HT to PTC
prognosis.
EP1424
DOI: 10.1530/endoabs.49.EP1425
Lung metastases from differentiated thyroid carcinoma: long term
outcome and its prognostic factors related to progression free survival
Seo Young Sohn1, Hye In Kim2, Sun Wook Kim2 & Jae Hoon Chung2
1Division of Endocrinology, Department of Medicine Seonam University
College of Medicine, Myongji Hospital, Goyang, Republic of Korea;
2Department of Endocrinology and Metabolism Samsung Medical Center,
Seoul, Republic of Korea.
Background
Distant metastasis rarely occurs in differentiated thyroid carcinoma (DTC), but
represents most common cause of death in patients with DTC. Lung and bone are
EP1426
the most frequent sites of distant metastases. This study investigated long term
A new strategy to estimate levothyroxine requirement after total
outcomes of lung metastasis in DTC patients and its prognostic factors
thyroidectomy and radioiodine remnant ablation for ‘intermediate’
influencing disease progression and cancer specific survival (CSS).
and ‘high’ risk differentiated thyroid cancer
Methods
Rosa Maria Paragliola, Annapina De Rosa, Vincenzo Di Donna,
A total of 134 DTC patients presenting with lung metastasis from 1994 to 2012
Giampaolo Papi, Alfredo Pontecorvi & Salvatore Maria Corsello
were retrospectively analysed. Factors predictive of the outcome were determined
Endocrinology, Università Cattolica del Sacro Cuore, Rome, Italy.
by Cox-proportional model.
Results
With a median follow up of 81 months after surgery, the 5- and 1-year CSSs were
Introduction
80 and 66%, respectively. The predictors of disease progression were older age
The approach for initial thyroid hormone suppression in patients who undergo
(R45 years),131I non-avidity and co-existing bone metastases other than lung.
surgery for differentiated thyroid cancer (DTC), is based upon the risk of disease
Similarly, older age (R45 years),131I non-avidity, co-existing bone metastases
recurrence. In particular, recent American Thyroid Association guidelines
and follicular pathology was associated with CSS. Cox proportional hazard ratio
suggest to maintain TSH levels between
0.1
and
0.5 mU/l and less than
for progression-free survival and disease-free survival showed that older age was
0.1 mU/l for patients with ‘intermediate’ and ‘high’ risk respectively. The aim of
the only independent predictive factor for poor prognosis.
the study is to identify the major predictive factors of LT4 requirement to obtain
Conclusions
semisuppressed or suppressed TSH levels and to elaborate a new method that
Older age, additional bone metastases,131I non-avidity and follicular histology
could improve the accuracy of the LT4 therapeutic starting dose in intermediate
were found to be significantly associated with poor clinical outcome. Therefore,
and high risk DTC patients.
strict surveillance should be tried in these patients.
Methods
DOI: 10.1530/endoabs.49.EP1424
Two hundred and nineteen patients who underwent total thyroidectomy and
radio-remnant ablation for DTC have been retrospectively evaluated. One
hundred and forty nine were on TSH suppressive therapy (TSH!0.1 mU/l) and
70 on TSH semisuppressive therapy (TSH: 0.1-0.4 mU/l). The results obtained by
this retrospective analysis were used to formulate a nomogram for the calculation
of the LT4 dose.
Results
For both groups
(suppressive and semisuppressive LT4
therapy) the best
parameters to predict the optimal LT4 starting dose are body mass index (BMI)
and age. On the basis of the nomogram, the LT4 dose in mg/kg to obtain
suppressed and semisuppressed TSH levels ranged from 1.6 to 2.1 mg/kg per day
EP1425
and from 1.5 to 1.9 mg/kg per day respectively. The dose is higher in younger
Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer?
patients with lower BMI.
Zeynep Cetin1, Ozden Ozdemir Baser1, Dilek Berker1 & Serdar Guler2
Conclusion
1Numune Training and Research Hospital, Ankara, Turkey;2LIV Hospital,
In our study BMI and age represent important parameters to predict LT4 dose in
Ankara, Turkey.
intermediate and high risk DTC patients. LT4 requirement decrease with the
increase in age and BMI, probably due to the relative decrease of lean body mass.
Based on these data, a user-friendly nomogram, representing an efficient method
Aim
to calculate LT4 starting dose in patients who underwent thyroidectomy for
Hashimoto’s thyroiditis (HT) is the commonest autoimmune thyroid disease.
differentiated thyroid cancer, has been created.
Papillary thyroid cancer (PTC) is the most often thyroid cancer and its incidence
DOI: 10.1530/endoabs.49.EP1426
is increasing yearly. It is not clear that HT is a predisposing factor for PTC. We
studied PTC’s frequency among HT patients went to total thyroidectomy.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1427
Method
Data of patients diagnosed with DTC between 2007 and 2014 at our institution
Follicular thyroid carcinoma in a patient with graves’ disease
were analysed retrospectively. TNM, MACIS, EORTC, AMES, De Groot, ETA,
Nesrine Cheikhrouhou, Intidhar Elbez, Kaouthar Limam, Aida Mhiri,
LATS, and ATA staging systems were applied to patients according to their
Bechir Ltaeif & Mohamed Faouzi Benslimene
original description. In ATA risk classification system, we classified patients into
Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.
four categories considering inappropriate postoperative thyroglobulin levels.
Results
Introduction
There were 983 patients (218 male and 765 female) with a mean age of 49.4G
Follicular cancer has a low incidence in Graves’ disease when compared to
12.5 and a mean follow-up of 42.6G24.3 months. Distribution of patients
papillary thyroid cancer. Some studies have not reported any follicular cancer in
according to the staging systems were as follows; TNM: 81.1%, 4.7%, 12.7%,
patients with Graves’ disease. We describe a rare occurrence of follicular cancer
1%, 0.3%, 0.2% of patients in stage I, II, III, IVA, IVB, IVC respectively;
in a patient with Graves’ disease.
MACIS: 91%, 5.9%, 2.2%, 0.8% of patients in group 1-4 respectively; EORTC:
Observation
39.4%, 36.7%, 19.8%, 4%, 0.1% of patients in group 1-5 respectively; AMES:
A 37-year-old female patient presented to our institute with symptoms of
82.2% of patients in low risk and 17.8% in high-risk group; De Groot: 81.6%,
thyrotoxicosis. She had no family history of thyroid cancer or of radiation
4.7%, 13.3%, 0.4% of patients in stages 1-4 respectively; ETA: 35.5%, 25.9%,
exposure in the neck area. She presented with typical clinical and biochemical
12.4%, 26.1% of patients in very low, low, high and undetermined risk groups
features of Graves’ disease. Tc-99m scintigraphy of the thyroid showed diffusely
respectively; LATS: 35.5%, 26.7%, 17.7%, 20.1% of patients in very low, low,
increased uptake with hypo functioning (cold) nodule. She underwent uneventful
high and undetermined risk groups respectively. According to ATA, distribution
surgery after achieving an euthyroid state. A total thyroidectomy was performed
of patients in low, intermediate, high and undetermined risk groups were
with resection of an enlarged lymph node detected on intra-operatively. A
respectively 26.4, 8.7, 40.8 and 23.6% in category 1, 39.7, 12.9, 23.8 and 23.6% in
follicular thyroid carcinoma was diagnosed on the cold nodule with metastatic
category 2, 46.7, 15.2, 14.5 and 23.6% in category 3, and 3.9, 19.2, 3.3 and 23.6%
lymph node. Patient was given an ablative dose of I131. Post-therapeutic
in category 4.
scintigraphy revealed a significant residual thyroid tissue/residual tumor in the
Conclusion
neck. The TSH-stimulated serum Thyroglobulin level measured by radio-
Variable scoring systems with variable risk assessments were suggested for DTC
immunoassay was 13 ng/ml. Being sensitive to iodine, patient will continue to
in the literature. A standardized categorization is required to overcome confusion
receive I-131cures to complete remission.
and help clinicians during management of these patients.
Conclusion
DOI: 10.1530/endoabs.49.EP1429
Surgical treatment should be indicated if graves disease is associated to suspected
nodule.
DOI: 10.1530/endoabs.49.EP1427
EP1430
EP1428
A rare association of thyroid micro carcinoma and thyroid tuberculosis
Papillary thyroid carcinoma in children: report of 15 cases
Intidhar Elbez, Nesrine Cheikhrouhou, Kaouthar Limem, Ihsen Slim,
Intidhar Elbez, Nesrine Cheikhrouhou, Kaouthar Limam, Aida Mhiri,
Aida Mhiri, Béchir Ltaeif & Med Faouzi Ben Slimene
Ihsen Slim, Bechir Ltaeif & Med Faouzi Ben Slimene
Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.
Department of Nuclear Medicine, Salah Azaiez Institute, Tunis, Tunisia.
Introduction
Papillary thyroid carcinoma is rare in young patients and have a good prognosis,
Thyroid tuberculosis is a rare disease, its frequency is 0.15-0.2% of autopsic data.
although it is often diagnosed at the stage of lung metastases. Our multicenter
We report a case of micro papillary carcinoma of thyroid revealed by thyroid
study included
15
children aged between
5
and
18
years with female
tuberculosis.
predominance, followed for differentiated thyroid cancer with lung metastases.
Observation
All these patients underwent a whole body scan with I-131, serum thyroglobulin,
Mrs. K.J aged 54 years presented a multinodular goiter without ultrasound signs
chest radiography and/or cervico-thoracic CT. Scintigraphy had shown
of malignancy. The patient underwent total thyroidectomy. Histological
pulmonary miliary among all patients. Iodine treatment was successful in all
examination revealed a granulomatous and giganto cellular inflammation which
patients, which proves the high sensitivity of these metastases to iodine treatment.
is in favor of a tuberculosis. The left lobe of the thyroid contained a 4 mm
The differentiated thyroid cancer is characterized by local aggressiveness and a
papillary microcarcinoma. No metastatic adenopathy was found. The tumor was
high frequency of distant metastases. Prognosis does not seem to be influenced by
classified pT1aN0Mx. The patient was addressed to department of nuclear
histology alone, but by its association with other prognostic factors: age,
medicine for supplementation of radioactive iodine treatment. In addition, the
metastases and surgery.
patient had benefited of anti-tuberculosis treatment for 7 months.
Conclusion
DOI: 10.1530/endoabs.49.EP1428
Thyroid tuberculosis is a rare entity. In the absence of other tuberculous sites,
diagnosis is often difficult. It is based on bacteriological and
/ or thyroid
anatomopathological evidence. The association with a microcarcinoma is also
rare and has to be carefully investigated by the anatomopathologist
DOI: 10.1530/endoabs.49.EP1430
EP1429
Evaluation of differentiated thyroid cancer patients according to
different scoring systems: a single center experience
Bekir Cakir1, Cevdet Aydin1, Berna Evranos Ogmen2, Ali Abbas Tam1,
Sefika Burcak Polat1, Husniye Baser2, Neslihan Cuhaci1, Fatma
Dilek Kahramanca2, Nagihan Bestepe2, Cuneyt Bilginer1, Sevgul Faki1,
Mehmet Kilic4, Aydan Kilicarslan3 & Reyhan Ersoy1
EP1431
1Department of Endocrinology and Metabolism, Faculty of Medicine,
Ataturk Education and Research Hospital, Yildirim Beyazit University,
GA/GG Heterozygosity of ARG280HIS polymorphism in XRCC1
Ankara, Turkey;2Department of Endocrinology and Metabolism, Ataturk
GENE: Genetic susceptibility genotype in differentiated thyroid
Education and Research Hospital, Ankara, Turkey;3Department of
cancer?
Pathology, Faculty of Medicine, Ataturk Education and Research Hospital,
Nazli Gulsoy Kirnap1, Neslihan Bascil Tutuncu1, Yaprak Yalcin2,
Yildirim Beyazit University, Ankara, Turkey;4Department of Surgery,
Hasibe Verdi2, Asli Nar1 & Belgin Atac2
Faculty of Medicine, Ataturk Education and Research Hospital, Yildirim
1Department of Endocrinology and Metabolism, Ba¸kent University Faculty
Beyazit University, Ankara, Turkey.
of Medicine, Ankara, Turkey;2Medical Biology, Ba¸kent University
Faculty of Medicine, Ankara, Turkey.
Introduction
True risk evaluation is important in the management of thyroid cancer. We aimed
Background
to evaluate patients with differentiated thyroid cancer (DTC) according to the
Thyroid carcinomas are the most frequent endocrine malignancies of which more
different staging systems.
than nighty percent are differentiated thyroid carcinomas (DTC). It’s known that
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
genetic variation plays
75% role in the development of papillary thyroid
EP1433
carcinoma (PTC).
Material and methods
In a case control setting subjects between January 2005 and December 2015 were
Abstract withdrawn.
evaluated for inclusion in the study. We aimed to compare the genotype
frequency distributions of three common X-ray repair cross-complementing
group 1 (XRCC1) SNPs in those with differentiated thyroid carcinoma (n: 228)
and cancer-free patirents with benign nodular goiter (n:100) and the healthy
controls (n:98) with regard to some predefined risk factors like existence of
Hashimoto’s thyroiditis, smoking, obesity, family history of thyroid cancer, and
radiation exposure. In the present study we tried to assess the genotype frequency
distributions of three common XRCC1 SNPs. Genomic DNA was extracted from
peripheral lymphocytes using phenol-chloro form extraction. XRCC1
Arg194Trp, Arg280His and Arg399Gln polymorphisms were detected by
amplification with real-time PCR followed by melting-curve analysis with
fluorescence-labeled hybridisation probes in a LightCycler.
EP1434
Results
Mutation analysis of papillary thyroid cancers using a newly developed
Heterozygous GA/GG genotype frequency of the Arg280His polymorphism in
targeted multi-gene panel in Hungarian population
DTC cases was significantly higher than in those with benign nodular goiter and
Barbara Kocsis-Deák1, Kristóf Árvai1, Bernadett Balla1, Bálint Tóbiás1,
in those in the healthy control group (64.5 and 3%, respectively; P!0.001). The
Andrea Kovesdi1, János Kósa1, Balázs Járay2, Tamás Székely2,
frequency of homozygous AA genotype of Arg280His polymorphism was lowest
János Horányi3 & Péter Lakatos1
in the DTC group (35.5%). The difference was statistically significant (P!0.001).
1Department of Internal Medicine, Semmelweis University, Budapest,
Presence of family history of thyroid cancer was 7.9% in DTC group and 1% in
Hungary;2Department of Pathology, Semmelweis University, Budapest,
benign nodular group. The difference was statistically significant (PZ0.014).
Hungary;3Department of Surgery, Semmelweis University, Budapest,
Discussion
Hungary.
In conclusion, our study demonstrates that Arg280His GA/GG genotype of
XRCC1 gene polymorphism is more frequently encountered in DTC than in
cancer-free controls. GA genotype frequency is highest in those DTC cases with a
Thyroid cancer is the most common malignancy of endocrine organs and its
family history of thyroid cancer.
incidence is steadily growing worldwide. Approximately 80% of differentiated
thyroid tumors are papillary carcinomas. Next-generation sequencing (NGS)
DOI: 10.1530/endoabs.49.EP1431
allows for high-throughput sequencing analysis of large number of samples at a
time in a cost effective manner. We have developed a targeted sequencing parallel
testing panel for multiple mutations in genes involved in thyroid cancer
pathology. A custom-made AmpliSeq hot spot panel was designed to target 23
cancer genes (NRAS, MET, CTNNB1, PIK3CA, DICER1, VHL, BRAF, PTEN,
LPAR4, EIF1AX, HRAS, RET, GAS8-AS1, KRAS, TSHR, AKT1, GNAS,
TERT, TP53, AXIN1, APC, IDH1, SMAD4) which containes 357 known
mutational hot spot areas with COSMIC IDs. Semiconductor sequencing was
EP1432
performed to analyze DNA from 56 papillary thyroid carcinomas with matched
Expression analyses of HABP2 in neoplastic and normal thyroid tissues:
normal fresh frozen samples. The average coverage was 400X. BRAF, TSHR,
could this gene play a role in the pathogenesis of familial non medullary
APC, RET, LPAR4, TP53, AXIN1 and SMAD4 genes were the most mutated
thyroid cancer?
genes in our papillary thyroid cancer samples. Altogether, mutations, with at least
Marina Muzza1,2, Carla Colombo1,2, Maria Carla Proverbio1,2,
5% variant coverage and less than
1% minor allele frequency in general
Giulia Ercoli1,2, Michela Perrino1,2, Valentina Cirello1,
population, could be shown in all of the samples, while mutation could be seen in
Leonardo Vicentini1,2, Stefano Ferrero1,2 & Laura Fugazzola1,2
seven control samples. The distribution of genetic alterations was similar to the
1Division of Endocrine and Metabolic Diseases, Istituto Auxologico IRCCS,
published data. The sensitivity and the specificity of the method were 100% and
University of Milan, Milan, Italy;2Endocrine Unit, Division of Pathology,
90%, respectively with a positive predictive value of 87%. Our multi-gene panel
and Endocrine Surgery Unit, Fondazione IRCCS Ca’ Granda-Ospedale
testing approach allows parallel analysis for multiple mutations with high
Maggiore Policlinico, Milan, Italys.
accuracy and sensitivity, and short turnaround times.
DOI: 10.1530/endoabs.49.EP1434
Recently, the G534E variant of the HABP2 gene was reported as the underlying
genetic defect in large kindred with non-syndromic familial non medullary
thyroid cancer (FNMTC), but these data were not confirmed in additional cohorts.
Consistently, we found in our wide series of FNMTC that the HABP2G534E
variant is frequent, but does not segregate with the disease. Nevertheless, a
possible role for this gene in the pathogenesis of FNMTC cannot definitely ruled
out also because contrasting but interesting expression data are available in other
human tumors. To get more insights into the expression of this gene in thyroid
tumor and normal tissues, HABP2 expression levels were determined by non-
quantitative or quantitative Real-time PCR of RNA extracted from nine
neoplastic and matched normal thyroid tissues: seven sporadic papillary thyroid
EP1435
cancer (PTC) cases not carrying HABP2G534E, 1 FNMTC from a member
K1 cell line in vitro: the impact of diagnostic absorbed doses from131I
carrying HABP2G534E and 1 FNMTC from a member not carrying the variant.
Mariusz Stasiolek1, Zbigniew Adamczewski2, Boleslaw Karwowski3,
Immunohistochemistry for HABP2 was performed in 6 neoplastic and matched
Marek Dedecjus4 & Andrzej Lewinski2
normal thyroid tissues: 2 sporadic PTC cases, 2 FNMTC from members carrying
1Department of Neurology, Polish Mother’s Memorial Hospital - Research
the HABP2G534E variant and 2 FNMTC from members not carrying the variant.
Institute, Lodz, Poland;2Department of Endocrinology and Metabolic
HABP2 mRNA had a very variable expression in tissues from FNMTC, sporadic
Diseases, Medical University of Lodz, Lodz, Poland;3Food Science
PTCs or contralateral normal tissues. In almost all cases, the gene appeared down-
Department, Medical University of Lodz, Lodz, Poland;4Department of
or up-regulated in tumors with respect to the corresponding normal tissue. At
Oncological Endocrinology and Nuclear Medicine, Maria Skłodowska-
immunohistochemistry, HABP2 was expressed in both tumor and matched
Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
control tissues, without differences between sporadic and familial cases. In
conclusion, our data confirm the apparent lack of co-segregation of the
Background
HABP2G534E variant with FNMTC. Nevertheless, the dysregulation of
Diagnostic whole-body scan is a standard procedure in patients with thyroid
HABP2 expression found in either sporadic or familial PTCs or normal thyroid
cancer prior to the application of therapeutic dose of
131I. Unfortunately,
tissues, suggests potential post-transcriptional and post-translational alterations,
administration of radioisotope in diagnostic dose may decrease further radio-
and is consistent with similar findings in other malignancies, possibly indicating a
iodine uptake
- the phenomenon called
‘thyroid stunning’. We estimated
role of this gene also in thyroid cancer.
radiation absorbed dose-dependent changes in genetic material, in particular
DOI: 10.1530/endoabs.49.EP1432
in sodium iodide symporter (NIS) gene promoter, and NIS protein level in K1
cell line.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Materials and methods
Antibodies) were within normal ranges. Thus, we did not find any evidence of
We used the K1 cell line derived from the metastasis of human papillary thyroid
thyroid disease. Two years later, the woman made an appointment at our clinic
carcinoma exposed to131I in culture. The different131I activities applied were
complaining of exercise - associated dyspnea. Her thyroid-stimulating hormone
calculated to result in absorbed doses of 5, 10, and 20 Gy.
(9.96 mU/l; normal, 0.4-3.6 mU/l) and TPOAb (685 kU/l; normal, 0-78 kU/l)
Results
were increased. The ultrasonography showed marked bilateral low parenchymal
Radioiodine did not affect the expression of NIS gene at the mRNA level,
echogenicity, inhomogeneous thyroid. In the left thyroid lobe, there were diffuse
however, we observed significant changes of the NIS protein level in K1 cells.
microcalcifications without focal mass. Sonographically, the thyroid lesions were
The decrease of NIS protein level, observed in the cells subjected to the lowest
indicative of chronic lymphocytic thyroiditis. A subsequent fine needle aspiration
absorbed dose, was paralleled by significant increase in 8-oxo-dG concentrations
biopsy was performed. The cytologic examination assessed a suspicion of
(P!0.01) and followed by late activation of the DNA repair pathways.
malignancy with chronic lymphocytic thyroiditis. The patient underwent the total
Conclusions
thyroidectomy with lymph node dissection. Histopathologically, a chronic
Our findings show that the impact of radiation on living cells, in the range
lymphocytic thyroiditis and 0.7 cm size papillary microcarcinoma in the left
compared to doses absorbed during diagnostic procedures in patients, does not
lobe were detected. Numerous stromal psammoma bodies, lymphatic intralobular
show the linear dose-effect.
spread with lymph node metastasis were revealed. We have demonstrated a very
DOI: 10.1530/endoabs.49.EP1435
rare case of PTC with chronic lymphocytic thyroiditis ultrasonographically
presenting with diffuse microcalcification without thyroid nodes. In our case, an
atypical sonographic appearance of papillary microcarcinoma was associated
with lymphatic intralobular spread and numerous stromal psammoma bodies in
the thyroid. We conclude, in a case of ultrasonographically detected diffuse
microcalcification without focal lesions, a careful examination for thyroid
malignancy should be proposed.
EP1436
DOI: 10.1530/endoabs.49.EP1437
Massive thyroid gland metastasis from nonsmall cell lung cancer
Diana Simoniene1,2, Milda Daneliene1,2, Raimonda Klimaite1,2 &
Rasa Mikalauskaite2
1Hospital of Lithuanian University of Health Sciences, Kauno Klinikos,
Kaunas, Lithuania;2Lithuanian University of Health Sciences, Kaunas,
Lithuania.
EP1438
Columnar cell variant of papillary thyroid carcinoma
Despite that the thyroid gland is one of the most vascular organs of the body but
Marie Hlavá
ˇková
thyroid gland is an uncommon site for metastasis [1]. It represents less than 4% of
Institute of Endocrinology, Prague, Czech Republic.
thyroid malignancy in clinical and surgical studies [2, 3]. 58-year-old male, a
prior smoker, was diagnosed with nonsmall cell lung cancer T4N3M1 St IV,
histopathological findings - infiltrative adenocarcinoma, G1. About eight months
Columnar cell variant is rare variant of papillary thyroid carcinoma. It occurs in
he was treated with chemotherapy. At the beginning of the disease, the patient
both genders with the most common occurence in the middle age of life. It differs
was examined by the endocrinologist and diagnosed a nodule thyroid. A fine
from common PTC both in morphology and especially in biological behavior.
needle aspiration (FNA) revealed a cystic degeneration. It was intended to repeat
The cancer cells also commonly harbor BRAF mutation. We describe a case of
the FNA after three
- 6 months. After
2 months, a patient presented to
young women, who came for the examination of the thyroid gland before in vitro
Endocrinology department of Hospital of Lithuanian University of Health
fertilization. We found normal thyroid function tests, negative antibodies. A small
Sciences Kauno klinikos because of increasing volume of the neck, shortness of
cystic lesion in the middle line of her neck under hyoid bone was seen at
breath, changes in voice and swallowing disorder. Thyroid ultrasound
ultrasound. The small primary tumor in pyramid lobe of thyroid gland was found
examination showed an enlarged thyroid gland, its structure was hypoechogenous
and cystic lesion was identified as the metastatic lymphonode. We scrutinized the
and non-homogenous. Because of rapid tumor growth, we differentiated between
genetic background of this more aggresive PTC variant and BRAF mutation was
lymphoma, anaplastic and hypopharyngeal cancer, lastly metastatic lesion.
found. We mentioned the necessity of the differential diagnosis of cystic lesion of
Metastasis from primary lung cancer was confirmed by thyroid fine-needle
the neck. This case has happy end untill now thanks to early diagnosis.
aspiration, cervical lymph nodes and laryngeal biopsies. After
1
week
DOI: 10.1530/endoabs.49.EP1438
complications progressed. Thyroid was dramatically enlarged, acute respiratory
failure evolved and the patient was unsuccessfully treated at Intensive Care Unit.
In conclusion, a diagnosis of metastatic disease should be considered when new
thyroid lesion is identified in any patient with a known history of malignancy until
such a diagnosis can be ruled out. Because detection of metastasis to the thyroid
gland often indicates a poor prognosis, aggressive treatment in time may be
EP1439
sufficient.
A higher frequency of papillary thyroid carcinoma in
DOI: 10.1530/endoabs.49.EP1436
myotonic dystrophy
Adrien Ben Hamou1,2, Claire Marie Dhaenens1,4, Stephanie Espiard1,2,
Kanza Benomar1,2, Vincent Tiffreau1,5, Robert Caiazzo1,3,
Sebastien Aubert1,4 & Marie Christine Vantyghem1,2
1
Lille University Hospital, Lille, France;2Endocrinology, Diabetology and
Metabolism, Lille, France;3Endocrine Surgery Unit, Lille, France;4Institute
of Biochemestry and Molecular Biology - Biology and Pathology Center,
Lille, France;5Neuromuscular Reference Center, Lille, France.
EP1437
Papillary thyroid cancer and chronic lymphocytic thyroiditis present-
Background and purpose
ing with diffuse microcalcifications without focal mass on ultrasound
Type 1 myotonic dystrophy (MD), associates neuromuscular, cardiac, respiratory
Jelena Vainikonyte-Kristapone, Jurgita Makstiene, Raimondas Valickas,
and endocrine disorders. The aim of this study was to determine the prevalence of
Neli Jakuboniene, Dalia Kozloviene & Gintaras Kuprionis
thyroid disorders and of any causal factors.
The Hospital of Lithuanian University of Health Sciences Kauno klinikos,
Methods
Kaunas, Lithuania.
A retrospective single centre study was conducted, between 2000 and 2016, in
127 MD patients, diagnosed by familial genetic screening after informed consent.
The detection and characterization of PTC are based on the evaluation of specific
Clinical examination, TSH assay, 120-min glucose and insulin levels post-OGTT,
ultrasonographic features of thyroid nodes. However, there is limited data
number of CTG repeats and ultrasound thyroid exam were performed. Eleven
regarding diagnostics without typical malignant-appearing nodules. We report a
patients refused the assessment. The 116 remaining were divided into 2 groups
very rare case of PTC in underlying chronic lymphocytic thyroiditis
according to the presence of a goiter defined as an ultrasound volume ! (usNG)
ultrasonographically manifested with diffuse microcalcification without focal
or O (usG) 18 ml, whatever the presence of nodules.
mass. A 22-year-old woman visited our institution complaining of weight loss,
Results
general weakness, and headache. A physical examination revealed a painless, firm
The whole population (61.2% female) was aged 45.1G12.2 years; the BMI was
thyroid without a palpable mass. In an ultrasonography of the neck, the pathology
26.2G6.5 kg/m2; at least one palpable nodule or a goiter was present in 33.6%,
was not assessed. The thyroid hormones concentration, TPOAb (Thyroperoxidase
and hypothyroidism in 8.6%. The percentage of usG was 38.8%. Age (46.6G9.6
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
vs 44.1G13.6 years), BMI (28.1G7.1 vs 24.9G5.9 kg/m2), and frequency of
advanced disease to the palliative care stage. However, chronic and escalating
papillary thyroid carcinoma (PTC) (17.8% vs 1.4%) were significantly higher in
somatic symptoms during the treatment may promote the appearance of
usG than in usNG. UsG was associated with BMI increase (P 0.017, IC 95%
depressive reactions. It can be expected that a cognitive image of the disease,
(K5.609 to K0.556), and hyperinsulinism (trend: PZ0.069), but not with CTG
as a collection of subjective beliefs concerning patient’s own illness and
repeats. 11 (24.4%) of the 45 usG patients had a total thyroidectomy. Six micro
treatment, will be an important determinant of mental functioning. The aim of the
(whose one had a capsule rupture) and 3 macro-PTC (with a high-risk level for 2
study was to define a mutual dependence between the intensity of somatic
of them (pT2N1aM0, pT3N0M0) were diagnosed. 80% of these 9 PTC were
problems, self-image of the illness and depression in patients receiving an
associated with a palpable thyroid anomaly.
experimental treatment of TC.
Conclusion
Material and methods
A third of these 116 MD patients had a palpable thyroid anomaly and 7.7% a PTC
The study included 32 patients treated with MKI due to TC for at least one year.
vs respectively 10% and 0.1% of the general population. The risk of usG was
The study was cross-sectional and it based on different questionnaires: List of
more related to a high BMI than to CTG repeats. Clinicians should be aware of
Somatic Problems, Beck’s Depression Inventory and Short Questionnaire of
this high prevalence of PTC in MD.
Diseases Perception (B-IPQ).
DOI: 10.1530/endoabs.49.EP1439
Results
Nineteen patients showed severe somatic symptoms
(HSS; High Somatic
Symptoms), whereas 13 patiens demonstrated none or mild physical symptoms
(LSS; Low Somatic Symptoms). The depression intensity was higher in HSS
patients than in LSS group. In HSS group a mediating role of self-image
relationship to disease somatic symptoms and depression was noticed. The direct
EP1440
effect of somatic symptoms on depression severity was insignificant. While, the
belief about a negative impact of physical symptoms on the daily functioning was
Management of treatment-related toxicity caused by multi kinase
an important mediator of relations between somatic symptoms and depression in
inhibitors administered due to advanced thyroid carcinoma
the study group.
Jolanta Krajewska, Aleksandra Kukulska, Daria Handkiewicz-Junak,
Conclusions
Ewa Paliczka-Cieslik, Tomasz Olczyk, Tomasz Gawlik,
The inclusion of interaction aimed at changing the perception of a negative
Aleksandra Ledwon, Barbara Michalik & Barbara Jarzab
impact of the disease and its treatment on daily life in TC patients can reduce the
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
risk of deterioration in depressive symptoms. The role of a nurse in psychologist-
Gliwice, Poland.
physician-nurse team is crucial for better patients care and quality of life.
DOI: 10.1530/endoabs.49.EP1441
Multi kinase inhibitors (MKIs) constitute a new therapeutic option in advanced
RAI-refractory differentiated thyroid cancer
(DTC) and medullary thyroid
carcinoma (MTC). To date four different MKIs demonstrated a beneficial effect
on progression free survival in DTC (sorafenib, lenvatinib) and MTC (vandetanib
and cabozantinib). However, the treatment related toxicity, which potentially may
limit their clinical use and lead to a negative impact on the quality of life, have
been widely discussed recently.
Material and methods
The study group involved 81 patients with advanced thyroid cancer, who received
different MKIs:
24
patents
- lenvatinib,
20-vandetanib,
22-sorafenib,
4-cabozantinib,
4-motesanib and
3-axitinib. All side effects were classified
according to the Common Terminology Criteria for Adverse Events (CTCAE),
version
4.0. Median treatment duration was
21.3
months (range 0.7-100.0
EP1442
months).
Malignancy risk stratification in thyroid nodules according to the
Results
Bethesda system for reporting thyroid cytopathology
Among the most common adverse effects were hypertension (73%), skin reactions
Aldona Kowalska1,2, Agnieszka Suligowska1, Janusz Kopczynski1,
(70.3%), diarrhea (54.1%), weight loss (54.1%) and stomatitis (43.2%). The
Kornelia Niemyska1 & Stanislaw Gozdz1,2
majority of side effects fulfilled G1 (mild) and G2 (moderate) criteria except of
1Holycross Cancer Center, Kielce, Poland;2The Faculty of Health Sciences
hypertension mainly classified as G3 (the necessity of the administration of at least
of the Jan Kochanowski University, Kielce, Poland.
2 antihypertensive drugs). The management of treatment related side effects was
based mainly on cautious follow-up (wide panel of laboratory examinations,
regular ECG monitoring, echocardiography and other examinations, if necessary),
Introduction
non-pharmacological methods (sun blockers, moisture creams), concomitant
Fine needle aspiration biopsy (FNAB) plays a crucial role in the diagnosis of
pharmacotherapy (antihypertensive drugs, loperamide and other depending on
thyroid nodules. The choice of further therapeutic strategy depends largely on its
different side effects) and dose modifications: 52.7% of patients needed dose
result. Knowledge of the risk of malignancy in each diagnosis class in the
reduction. Multidisciplinary team involving oncologists, internists, dermatolo-
population is necessary. The aim of the research was to analyse the risk of
gists, cardiologists, nurses and psychologists was also an important part of our
malignancy in thyroid nodules in each diagnosis class according to Bethesda
successful patients care. Only 14.5% of patients required drug withdrawn due to its
system.
poor tolerability.
Materials and methods
Conclusion
Retrospective research included 1001 patients with thyroid nodules diagnosed
The proper management of MKI-related side effects is essential to keep patients
and treated surgically between
2002 and 2015 in one department. Women
on therapy as long as the treatment is beneficial without an unfavorable impact on
accounted for 86% of the research group. The median age was 52 years. The
their quality of life.
results of the guided FNAB performed before the introduction of the Bethesda
scale (621) were re-evaluated and qualified to the appropriate group according to
DOI: 10.1530/endoabs.49.EP1440
the new criteria.
Result
The preoperative FNAB results presented as follows: non-diagnostic material
(class I)
- 6
(0.6%); benign
(class II)
- 522
(52.1%); follicular lesion of
undetermined significance
(class III, FLUS)
- 62
(6.2%); suspicious for a
follicular neoplasm (class IV, SFN) - 138 (13.8%); suspicious for malignancy
EP1441
(class V) - 74 (7.4%), malignant (class VI) -199 (19.9%). The postoperative
Cooperation between an endocrine nurse, psychologist and physician
histology follow-up in the research group were spread as follows: benign - 708
and their mediating role in the care of depression in patients treated
(70.7%); malignant - 292 (29.3%). Malignancy risk for each class according to
with multi kinase inhibitors due thyroid cancer
Bethesda system amounted to respectively: I - 33%, II - 4.21%, III - 11.2%, IV -
Alina Rozanska, Anna Syska-Bielak, Justyna Kraus, Malgorzata Ocieczek,
13.04%, V - 59.46%, VI - 100%.
Ewa Wojtyna & Jolanta Krajewska
Conclusions
M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,
The present study shows that the risk of malignancy in class III and IV is low. The
Gliwice, Poland.
diagnosis of FLUS or SFN in the absence of clinical indications is not a basis for
surgical treatment.
The treatment with multi kinase inhibitors (MKI) under clinical trials due to
DOI: 10.1530/endoabs.49.EP1442
advanced thyroid cancer
(TC) may postpone moving on the patients with
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1443
present in
104 patients. Extrathroidal extension was present in 32 patients.
In logistic regression analysis, age
(!45 years old (P!0.001 OR:4.193)),
The sensitivity and positive predictive value (PPV) of 131I-post-therapy
lymphovascular invasion
(P!0.001 OR:7.762), capsule invasion (P!0.002
whole body scan is higher than serum Tg values in detecting metastases
OR:3.054), extrathyroidal extension (P!0.001 OR:6.450) and bilaterality (P !
in early stage of differentiated thyroid cancer patients
0.001 OR: 0.217) involvement were significantly associated with cervical lymph
Alfredo Campennì1, Salvatore Antonio Pignata1, Massimiliano Siracusa1,
node metastasis.
Teresa Manuela Vicchio2, Francesco Trimarchi3, Rosaria
Discussion
Maddalena Ruggeri2 & Sergio Baldari1
We found that the risk of cervical lymph node metastasis was high in the presence
1University of Messina, Department of Biomedical and Dental Sciences and
of extrathyroidal extension, multifocality and lymphovascular invasion. In
Morpho-functional Imaging, Nuclear Medicine Unit, Messina, Italy;
contrast to previous reports, the risk was found to be high for the age group
2University of Messina, Department of Clinical-Experimental Medicine and
lower than 45. Clinically, lymph node metastasis does not develop in all patients,
Pharmacology, Division of Endocrinology, Messina, Italy;3University of
knowing risk factors of cervical lymph node metastasis can determine the
Messina, Accademia Peloritana dei Pericolanti, Messina, Italy.
operation type, the treatment and the follow-up.
DOI: 10.1530/endoabs.49.EP1444
The work-up of Differentiated Thyroid Cancer (DTC) patients includes thyroid
surgery, thyroid remnant ablation (TRA) with 131-radioiodine and long life
follow-up. 131I-post therapy whole body scan (pT-WBS) and thyroglobulin (Tg)
are used in identifying metastatic patients. Some authors suggested to use post-
surgical Tg (ps-Tg) values in deciding for or against TRA. The aim of our study
was to verify the sensitivity and PPV of 131I-pT-WBS compared to serum Tg
levels in detecting metastases in early stage of DTC patients.
Material and method
We retrospectively reviewed the records of 570 patients affected by pT1-pT3
DTC (FZ450, MZ120, mean age 48.5G13.2; F/M ratioZ3.7:1) referred to our
Nuclear Medicine Unit in the last five years. None of our patients had: 1) loco-
regional or distant metastases at the time of recruitment; 2) age %16 years; 3)
EP1445
positive thyroglobulin-antibody (Tg-Ab); 4) pT4 stage, 5) poorly-differentiated
Theranostic management of medullary thyroid cancer (MTC) with
thyroid cancer. The majority of patients (98.2%) were affected by papillary
(111In/177Lu) CP04: how close are we to a clinical solution?
carcinoma. Before TRA, all patients underwent neck-ultrasonography, laboratory
Alicja Hubalewska-Dydejczyk1, Paola Erba2, Clemens Decristoforo3,
test and, if treated in hypothyroid state (321/570, 56%), radioiodine thyroid
Katja Zaletel4, Renata Mikolajczak5, Helmut Maecke6, Theodosia Maina-
uptake. Both ps-Tg and Tg values obtained at TRA were matched with 131I
Nock7, Mark Konijnenberg8, Petra Kolenc-Peitl4, Malgorzata Trofimiuk-
pT-WBS results.
Muldner1, Elwira Przybylik-Mazurek1, Irene Virgolini2, Dariusz Pawlak5,
Results
Marion de Jong8, Alide C Froberg8, Christine Rangger3, Georg Goebel3,
131I pT-WBS discovered metastases in 82 out of 570 (14.4%) patients. Seventy-
Lorenza Scarpa3, Konrad Skorkiewicz9, Luka Lezaic4, Pirotr Garnuszek5,
three out of these patients (90.2%) showed ps-Tg levels %1 ng/ml. At TRA, forty
Anna Sowa-Staszczak1, Berthold A Nock7, Damijan Bergant4,
of them (54%) maintained Tg levels %1 ng/ml. The majority of these patients
Sebastijan Rep4 & Boguslaw Glowa9
(38/40, 95%) showed lymph-node metastases at 131I-pT-WBS while three had
1Jagiellonian University Medical College, Krakow, Poland;2Azienda
lung metastases (one of them showed lymph-node metastasis). The metastases
Ospedaliero-Universitaria Pisana, Pisa, Italy;3Innsbruck Medical
were confirmed by targeted morphological studies.
University, Innsbruck, Austria;4University Medical Centre Ljubljana,
Conclusion
Ljubljana, Slovenia;5Radioisotope Centre Polatom, NCBJ, Otwock,
ps-Tg cannot be used to decide for or against TRA. In early stage of DTC, 131I-
Poland;6University Hospital Freiburg, Freiburg, Germany;7Molecular
pT-WBS is an accurate method in detecting metastases also in patients with
Radiopharmacy, INRASTES, NCSR Demokritos, Athens, Greece;
stimulate Tg values %1 ng/ml, showing sensitivity and PPV significantly higher
8Erasmus MC, Rotterdam, The Netherlands;9University Hospital, Krakow,
than Tg (100% vs 29.3% for both).
Poland.
DOI: 10.1530/endoabs.49.EP1443
Effective targeted therapy for advanced endocrine malignancies is a goal of
modern endocrinology. We herein present promising results of the first phase
of clinical part of European project (Gran-T-MTC) aimed to assess the safety of
gastrin analogue CP04
(DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2)
i.v. administration in dose (50 mg) useful for translation to 177In-CP04 for PRRT.
CP04 has been selected for MTC therapy based on a high CCK-2 receptor
expression in MTC and superior pharmacokinetics properties among gastrin
EP1444
analogues tested. Positive results of preclinical part of the study confirmed
Evaluation of clinicopathological factors in papillary thyroid cancer
possibility of 111In-CP04 applying in humans.
with cervical lymph node metastasis
Aim
Betul Aydin Buyruk1, Medine Nur Kebapci1, Goknur Yorulmaz1,
To assess111In-CP04 safety, biodistribution and dosimetry.
Aytug Buyruk2 & Mahmut Kebapci3
Material and methods
1Department of Endocrinology, Eskisehir Osmangazi University Medical
Four patients: three with progressive/metastatic MEN2A-related MTC (18F-FDG-
Faculty, Eskisehir, Turkey;2Department of Ear, Nose, Throat, Eskısehır
PET/MRI positivity), one with sporadic MTC (short calcitonin doubling time)
State Hospital, Eskisehir, Turkey;3Department of Radiological,Eskisehir
were enrolled. Basal calcitonin levels ranged between 279 and 824 pg/ml.
Osmangazi University Medical Faculty, Eskisehir, Turkey.
Study design
During the first clinical trial phase each patient received 111In-CP04 (200 MBq)
Introduction and purpose
in 2 different doses: a low (10 mg) and high (50 mg). Biodistribution and dosimetry
More than 90% of differentiated thyroid cancers are papillary thyroid cancer
data were assessed based on serial planar and SPECT/CT images over time.
(PTC). Lymph node metastasis is common in PTC and has been reported to have
Results
no effect on prognosis. The risk of cervical metastasis is high in the presence of
No side effects were observed during injection of either CP04 dose. In all patients
clinicopathologic factors including extrathyroidal extension, multifocality and
111In-CP04 uptake was confirmed in MTC lesions regardless of peptide dose (in
lymphovascular invasion. In this study, it was aimed to evaluate the
one patient uptake was low). The compound showed both a renal clearance and
clinicopathological features of lymph node metastasis development.
uptake in the stomach wall with subsequent intestinal clearance with for both
Materials and methods
peptide doses similar kinetics and little variation across patients. The Effective
Patients with papillary thyroid carcinoma diagnosed between 1995 and 2016 were
dose was 6 mSv/200 MBq, irrespective of the amount of peptide. The kidney
retrospectively reviewed. Patients who previously had another cancer story were
absorbed dose for the 50 mg therapeutic amount of CP04 if labeled with 177Lu
excluded from the study. The demographic characteristics and pathology findings
was estimated at 0.32Gy/GBq and the stomach absorbed dose at 0.13Gy/GBq.
(histopathology, tumor size, lymph node metastasis, lymphovascular invasion,
Conclusions
multifocality, capsule invasion, bilaterality) and antiTG, antiTPO values were
MTC metastases can be detected with 111In-CP04. Biodistribution and dosimetry
compared in patients with and without cervical lymph node metastasis.
data show CP04 promising radiopharmaceutical for MTC therapy if labeled with
Results
177Lu. The confirmatory second part of clinical phase of trial has just begun.
In 419 papillary thyroid cancer patients, 52 lymph node metastases were detected.
DOI: 10.1530/endoabs.49.EP1445
Lymphovascular invasion was present in 24 patients and capsule invasion was
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1446
without cervical adenopathies. The patient had a total thyroidectomy whose
anatomopathology returned without anomaly. The hormonal assessment showed
Medullary thyroid carcinoma - diagnosis and outcome of patients
an undetectable level of thyroglobulin (TG). (TSH: 30.24 Uu/ml, TG: 0.55 mg/l
treated in a tertiary center
and anti-TG antibody: 1.2 IU/ml). Levothyroxine was increased to 150 mg/day.
Joanna Prokop, Ana Palha, Teresa Sabino, Carolina Neves, Luísa Cortez,
Iratherapy is considered for our patient.
José Silva-Nunes, Cristina Santos, Lurdes Matos, Natércia Candeias,
Conclusion
António Afonso, Fernando Fonseca & Ana Agapito
The papillary cancer on TDC is an exceptional localization. It can develop at the
expense of residues of thyroid follicles within the cyst of the TDC, or may be
secondary to thyroid papillary carcinoma metastasis. Its management consists of
Medullary thyroid carcinoma (MTC) is a rare tumor of C cell origin, that may be
an excision of the cyst. Hormone replacement therapy is systematic. Total
sporadic or familial. Diagnosis is often delayed and its course variable.
thyroidectomy is indicated in cases of thyroid suspicious of malignancy, also if
Objectives
extra-cystic extension. Lymph node dissection is indicated in the presence of
Evaluation of clinical characteristics and outcome of patients diagnosed with
adenopathy. A complement by Iratherapy is not systematic, however in our
MTC.
patient it is indicated because the presence of a lymph node metastasis. The
Methods
monitoring will be on long term and generally the evolution is favorable.
Retrospective analysis of clinical records of patients with MTC between 2005 and
DOI: 10.1530/endoabs.49.EP1447
2016. We considered undetectable serum calcitonin as criteria of cure.
Results
Sixteen patients (12 women) were observed: mean age at presentation 63.8 years
(46-79), mean follow-up: 2.2 years. Thyroid nodules were present in all. Four
patients had compressive symptoms, three lymphadenopathy and one chronic
diarrhea. Eight patients were diagnosed on the basis of histological examination
without previous clinical suspicion of MTC. Genetic testing for RET proto-
oncogene mutations was performed in nine patients and in one germinative
mutation was detected (isolated familiar MTC). Eight patients with previous
suspicion of MTC underwent total thyroidectomy with central lymph node
dissection, and in five of these also lateral lymph node dissection. Among patients
diagnosed after surgery: two had undergone total thyroidectomy with central
lymph node dissection, in one of these combined with lateral node lymph
EP1448
dissection, three total thyroidectomy and three hemithyroidectomy. One
Impact of RAC1/1b signalling on Sodium Iodide symporter regulation
completed thyroidectomy and the other two maintain undetectable calcitonin
Márcia Faria1,2, Paulo Matos1,3, Maria João Bugalho4,5 & Ana Luísa Silva4,5
(follow-up: 0.5-1.3 years). After surgery seven patients were cured. One of them
1Faculty of Sciences, BioISI - Biosystems & Integrative Sciences Institute,
suffered recurrence with hepatic metastases 4 years later. Among patients with
University of Lisbon, Lisboa, Portugal;2Research Unit of Molecular
disease persistence there were six with progression in serum calcitonin, one with
Pathobiology, Portuguese Institute of Oncology of Lisbon - Francisco Gentil
radiologic evidence of metastases. This patient had cervical lymph node
E.P.E., Lisboa, Portugal;3Department of Human Genetics, National Health
metastases
(calcitonin doubling time-CDT:6
months)
7
years after MTC
Institute ‘Dr. Ricardo Jorge’, Lisboa, Portugal;4Department of Endo-
diagnosis and underwent reoperation without cure.
crinology, Diabetes and Metabolism, Centro Hospitalar Lisboa Norte E.P.E
Discussion
- Hospital de Santa Maria, Lisboa, Portugal; 5ISAMB, Genetics Laboratory,
In this cohort of patients MTC diagnosis was made often after surgery (50%),
Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
which raises the question of presurgical calcitonin testing. MTC may have
indolent or aggressive course as observed in this study, and turns difficult optimal
treatment and follow-up strategy in the individual patient.
The Sodium Iodide Symporter (NIS) is responsible for active transport of iodide
DOI: 10.1530/endoabs.49.EP1446
into thyroid cells. Its expression in thyroid tumors allows the use of radioactive
iodine (131I) as co-adjuvant therapeutic tool to eliminate remaining tumor cells
and metastases after total thyroidectomy. Nevertheless, certain subsets of patients
with advanced forms of thyroid cancer lose the ability to respond to radioiodine
therapy, which drastically reduces their survival rates. Recent studies have
implicated the Rac1/p38 pathway in the stimulation of NIS expression through a
mechanism that remains unclear. Additionally, the overexpression of RAC1b, a
hyperactive splicing variant of RAC1, was recently shown to be overexpressed in
a subset of papillary thyroid carcinomas carrying the activating mutation
BRAFV600E and to be associated with unfavorable outcome. BRAFV600E
mutation, in turn, has been associated with the downregulation of NIS. Here, we
further investigate the role of RAC1/RAC1b on NIS expression levels, and
developed new cellular models to functionally assess the impact of these GTPases
EP1447
on NIS-mediated iodide uptake. To evaluate whether RAC1b has a role in NIS
expression modulation, we determined NIS transcript levels in a cohort of 64
Papillary carcinoma of thyroglossal duct cyst with cervical lymph
follicular cell-derived thyroid tumors, comparing tumors presenting RAC1b
node metastasis
overexpression (nZ32) to those that did not (nZ32). RAC1b-overexpressing
Si Youcef Hafsa, Boussata Amani, Azzoug Said & Fedala Nora Someya
tumors were defined as those with expression levels above a defined threshold
CHU Mohamed Lamine Debaghine Bab El Oued, Algiers, Algeria.
(corresponding to the mean value plus two SDs of RAC1b expression level in a
normal thyroid group). RAC1b and NIS expression was assessed by quantitative
Introduction
RT-PCR. We found that samples negative for RAC1b expression presented
Neoplasias in the thyroglossal duct cyst (TDC) are rare, their prevalence varies
higher levels of NIS in comparison to RAC1b-overexpressing samples (4.402G
from 1 to 1.5%. The most common cancer is papillary cancer representing 85% of
1.271 vs 1.916G0.5423, respectively; PZ0.0384, two-tailed Student’s t-test).
cases. The diagnosis is often fortuitous following to the anatomopathological
Thus, our results show an inverse correlation between RAC1b and NIS expression
examination of the surgical specimen.
levels, suggesting that RAC1b might antagonize RAC1
effectiveness at
Patient and method
stimulating NIS expression. To further explore the impact of RAC1/1b signalling
Our patient has 33-years-old, with no previous medical history, which underwent
on NIS expression regulation, we established a halide-sensitive YFP-based
a resection of a TDC of 29 mm in diameter, diagnosed by an anterior cervical
reporter in a normal thyroid cell line system, allowing us to detect differences on
tumefaction. The anatomopathological examination of the cyst was in favor of
iodide influx upon TSH stimulation. Our preliminary results support the relevance
papillary carcinoma. The evolution is marked by the appearance of a left cervical
of further studying the impact of RAC1/1b on NIS regulation.
adenopathy. The patient has benefited by a biopsy excision, and histology was in
DOI: 10.1530/endoabs.49.EP1448
favor of a metastasis of a papillary carcinoma. Cervical ultrasound: normal,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1449
abnormalities were detected in the thyroid on ultrasound, the patient was referred
for total thyroidectomy. The histopathological specimen revealed the presence of
The usefulness of the study of sodium iodide symporter expression in
multifocal PTC within the thyroid, the largest being 1 mm, and one metastatic
thyroid primary tumors
lymph node. Due to the increased post-surgical thyroglobulin concentration and
Catarina Tavares1,3, Maria João Coelho1,4, Catarina Eloy1,2, Miguel Melo1,5,
the suspicion of metastasis to other cervical lymph nodes on ultrasound
Adriana Gaspar da Rocha1,7, Ana Pestana1,3, Rui Batista1, Luciana
examination, the patient required two subsequent lymphadenectomies followed
Bueno Ferreira1,3, Elisabete Rios1,3, Bruno Cavadas1,2, Luísa Pereira1,3,
by radioiodine therapy to achieve remission. No further recurrence of the disease
Samia Selmi-Ruby10, Manuel Sobrinho Simo˜ es1,3 & Paula Soares1,3
was observed in a 6-year follow-up period.
1Instituto de Investiga
¸
˜o e Inova
¸a˜o em Saúde (i3S), Universidade do
Conclusions
Porto, Porto, Portugal;2Institute of Molecular Pathology and Immunology
In such patients two scenarios should be considered: (i) PTC in BCC is a primary
of the University of Porto, Porto, Portugal;3Medical Faculty of the
lesion arising from ectopic thyroid tissue concomitant with multifocal PTC of the
University of Porto, Porto, Portugal;4Institute of Biomedical Sciences of
thyroid or (ii) neck cyst is a cystic degeneration of a metastatic lymph node, while
Abel Salazar, Porto, Portugal;5Department of Endocrinology, Diabetes and
primary site is located in the thyroid. Detection of PTC in BCC requires
Metabolism, University and Hospital Center of Coimbra, Coimbra,
verification of the thyroid for concomitant neoplastic lesions. Despite normal
Portugal;6Medical Faculty, University of Coimbra, Coimbra, Portugal;
thyroid on ultrasonography, histopathological examination may reveal the
7University and Hospital Center of Coimbra, Coimbra, Portugal;8Depart-
presence of multifocal occult PTC in the thyroid. Therefore, following
ment of Pathology and Oncology, Medical Faculty of the University of
the diagnosis of PTC in BCC, completion total thyroidectomy should be the
Porto, Porto, Portugal;9Department of Pathology, Hospital de S.Joa˜o, Porto,
recommended procedure.
Portugal;10Inserm UMR-S1052, CNRS UMR5286, Centre de Recherche en
Cancérologie de Lyon, Lyon, France.
DOI: 10.1530/endoabs.49.EP1450
Thyroid cancer therapy is based on surgery followed by radioiodine treatment of
tumor remnants and metastases. The incorporation of radioiodine by cancer cells
is mediated by sodium iodide symporter (NIS), normally present in thyroid
follicular cells’ membrane. We studied the expression of NIS in a series of 229
thyroid primary tumors using real time PCR and immunohistochemistry, and
searched for possible associations between NIS expression and clinicopatholo-
gical features, molecular data, response to therapy and prognosis. NIS mRNA
levels were significantly lower in carcinomas than in normal adjacent thyroid;
EP1451
carcinomas from males or with vascular invasion presented significantly less NIS
Comparative analysis of clinicopathological characteristics between
mRNA expression than carcinomas from women and non invasive carcinomas.
Korean and Italian thyroid cancer patients
BRAFV600E tumors and those presenting extrathyroidal extension had a
Jee Hyun An1, Sin Gon Kim1, Hoon Yub Kim2, Kwang Yoon Jung3,
tendency to display lower NIS mRNA expression than tumors BRAFWT and
Yang Seok Chae4, Gianlorenzo Dionigi5, Stefano Rausei5,
no extrathyroidal extention. Regarding immunohistochemistry, only 12/211 of
Maria Laura Tanda6, Eliana Piantanida6 & Stefano La Rosa7
the cases demonstrated NIS in the basolateral membrane of tumor cells; these
cases showed variable outcomes concerning therapy response and prognosis. All
1Division of Endocrinology, Department of Internal Medicine, KUMC
but one of the aforementioned cases were wild type for BRAF, NRAS and TERT
Thyroid Center, Korea University College of Medicine, Seoul, Republic of
promoter mutations. NIS immunohistochemical expression in primary tumors did
Korea;2Department of Surgery, KUMC Thyroid Center, Korea University
not predict tumor behavior or response to therapy. NIS mRNA expression was
College of Medicine, Seoul, Republic of Korea;3Department of
more informative of tumor aggressiveness than NIS protein expression. In order
Otolaryngology-Head and Neck Surgery, KUMC Thyroid Center, Korea
to validate our data we also searched possible associations between NIS mRNA
University College of Medicine, Seoul, Republic of Korea;4Department of
expression and clinicopathological and molecular features on
378 primary
Pathology, KUMC Thyroid Center, Korea University College of Medicine,
papillary thyroid carcinomas of the TCGA database. Further studies are needed to
Seoul, Republic of Korea;5Endocrine Unit, 1st Division of General Surgery,
confirm the association observed between the presence of the oncogenic
Department of Medicine and Surgery, Research Center for Endocrine
mutations (BRAF, NRAS and TERT promoter) and both lower mRNA expression
Surgery, University of Insubria, Varese, Italy;6Endocrine Unit, Department
and diminished membrane targeting of NIS protein.
of Medicine and Surgery, University of Insubria, Varese, Italy;7Institute of
Pathology, University Hospital of Lausanne (CHUV), Lausanne,
DOI: 10.1530/endoabs.49.EP1449
Switzerland.
Background
The incidence of thyroid cancer in South Korea has increased rapidly. Increase in
medical surveillance and access to health care services have enhanced the
detection of asymptomatic tumors. We investigated the differences of tumor
characteristics between South Korean patients and Northern Italian patients
subject to different healthcare systems.
EP1450
Methods
Concomitant occurrence of papillary thyroid cancer (PTC) in a
The demographic, histopathologic and management features of thyroid cancer
branchial cleft cyst (BCC) and an occult multifocal PTC in the
operated in two tertiary referral hospitals in Seoul, South Korea (nZ4,474) and
thyroid gland
Varese, Northern Italy (nZ2,897) from years 2000 to 2015 were analyzed.
Ewelina Szczepanek-Parulska1, Martyna Borowczyk1, Alina Kluk1,
Results
Grzegorz Dworacki2, Marcin Orłowski3, Katarzyna Ziemnicka1 &
The mean age of diagnosis was similar (49 years) among the Korean and Italian
Marek Ruchała1
patients. However, the proportion of female was higher among Korean patients
1Department of Endocrinology, Metabolism and Internal Medicine, Poznan
(81.3 vs 74.2%, P!0.001). The proportion of papillary subtype was higher (99.2
University of Medical Sciences, Poznan, Poland;2Department of Clinical
vs 92.6%, P!0.001) and the size of tumor was smaller (1.03G0.83 vs 1.79G
Immunology, Poznan University of Medical Sciences, Poznan, Poland;
1.01 cm, P!0.001) in the Korean subjects. Interestingly, the prevalence of
3Department of Pathology, Provincial Hospital in Poznan, Poznan, Poland.
multifocality (37.8 vs 8.2%), extrathyroidal extension (41.6 vs 13.1%) and lymph
node metastasis (34.8 vs 6.7%) was also higher in the Korean patients (P!0.001).
Introduction
Most of the Italian cases received total thyroidectomy (96.0%). In comparison, a
BCC is a congenital epithelial neck cyst, which occurs due to failure of the second
considerable number of the Koreans (21.9%) received hemithyroidectomy as
branchial cleft to obliterate during embryogenesis. Development of PTC inside
initial surgical treatment (P!0.001). The proportion of the patients who received
the cyst is extremely rare.
radioactive iodine therapy was significantly higher among the Korean patients
Case description
(53.3 vs 29.7%, P!0.001).
A 29-year-old female presented to the endocrinology clinic with a gradually
Conclusion
increasing painless mass in the right lateral region of the neck, identified on
We have identified distinct lineaments of thyroid gland cancer between the two
ultrasound examination as an anechoic cyst of size 2!2!5 cm with a smooth
different nationalities which could not be explained entirely by early detection
wall. Despite repeated biopsies and evacuation of the fluid, the cyst was a
from screening. Further prospective studies with controlled treatment strategies
recurrent problem. Hence, a decision for surgical removal was made. The
are needed to determine long-term prognosis.
histopathological examination revealed a cystic structure with lymphatic weaving
DOI: 10.1530/endoabs.49.EP1451
in the wall and PTC in both the lumen and lymphatic weaving. Despite no
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1452
body mass index (BMI) were measured prior the surgery. A fasting blood sample
obtained from all study participants prior the surgery to measure serum neopterin
Malignant struma ovarii and synchronous tumour of thyroid gland in
levels. Post-thyroidectomy, according to pathology results patients were divided
the same patient: a single pathway for two different tumours?
into two groups,as DTC and benign pathology.
Ricardo Capita˜o, Catarina Saraiva, Francisco Santos, Cátia Férrinho,
Results
Catarina Roque, Carlos Bello & Carlos Vasconcelos
Of thesepatients, 39 were diagnosed with DTC and 47 had benign pathology
Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal.
according to postoperative histologic evaluation. There were no significant
differences between the two groups in terms of age, weight, height and body mass
Background
index. Demographical data and laboratory results are given in the table. There was
Struma ovarii (SO) is the presence of thyroid tissue as a major cellular component
a positive correlation with neopterin levels and tumor size (rZ0.776, P!0.001).
in an ovarian tumour.
Discussion
Case report
Our study indicates that there is a strong association between plasma neopterin
A 35-year-old, Caucasian female, asymptomatic and with normal physical
levels and DTC. Thus, if it is supported with high volume larger studies, neopterin
examination was submitted to left oophorectomy due to an ovarian mass (8.2!
may be a useful marker forpredicting the DTC preoperatively.
7.0!6.0 cm) detected in routine pelvic examination. Her mother also had history
of oophorectomy for an ovarian tumour and partial thyroidectomy for benign
DOI: 10.1530/endoabs.49.EP1453
thyroid nodule. The histological examination of the mass showed a totally intra-
ovarian neoplasia predominantly composed of thyroid tissue (95%) with areas of
follicular variant of papillary thyroid carcinoma (FVTPC) which was compatible
with malignant SO. She was tested for thyroid function which was normal and
thyroid ultrasound revealed a slightly hypoechogenic nodule with 1.7 cm in the
right lobe. Fine needle cytology of this nodule was performed and was compatible
with FVTPC. She underwent total thyroidectomy and histology revealed a well
EP1454
differentiated thyroid tumour of uncertain malignant potential. No vascular or
Unexpectedly low thyroglobulin levels in differentiated thyroid
capsular invasions were recorded. She was treated with131I and suppressive doses
carcinoma - case report
of levothyroxine and remains asymptomatic, without signs of clinical or
Francisco Norton-Branda˜o1, Teresa Ferreira1, Manuel Rio Carvalho1,
biochemical recurrence of thyroid and ovarian tumours. The search for BRAF
Inês Patrocínio Carvalho1, Rita Sousa1, Pedro Ratão1, Lucília Salgado1,
mutations was negative.
Joana Simo˜es-Pereira2 & Valeriano Leite2
Discussion
1Nuclear Medicine Department, Portuguese Oncology Institute - Lisbon,
Three other cases of synchronous thyroid and ovarian thyroid tumours have been
Lisbon, Portugal;2Endocrinology Department, Portuguese Oncology
described so far to the best of our knowledge. In this case, since both tumours
Institute - Lisbon, Lisbon, Portugal.
were confined and no invasion was documented they were probably synchronous
tumours instead of metastasis. These two tumours are embryologically related so
we cannot exclude a common mechanism of genomic origin that possibly
Case report
explains the synchronous tumours and even the familiar history.
66 year old male with a neck growing mass performed an ultrasonography and
DOI: 10.1530/endoabs.49.EP1452
fine-needle aspiration biopsy which was suspicious for papillary carcinoma. The
patient was submitted to total thyroidectomy and central and left lateral
compartments lymph node dissection. The histological report showed a follicular
carcinoma of 9 cm, with multiple lymphovascular invasions and skeletal muscle
invasion. There was a focally positive surgical margin and resected lymph nodes
had no metastases. Thoracic CT showed multiple lung nodules; PET showed faint
uptake in a single nodule in the upper lobe of the right lung. Five months after
EP1453
surgery, 5,5 GBq (150 mCi) of iodine-131 (RAI) were administered. Forty-eight
hours after therapy whole-body scintigraphy (WBS) was performed: moderate
Does Preoperative Serum Neopterin Level Predict Differentiated
thyroid remnant and faint uptake in the lower third of the right thoracic area were
Thyroid Carcinoma?
visible. Non-stimulated serum thyroglobulin
(Tg) was undetectable and
Mazhar Muslum Tuna1, Narin Nasırog˘lu İmga2, Mehtap Navdar Ba¸aran2,
stimulated levels were
1.5 ng/ml; anti-thyroglobulin antibody
(ATg) was
Berçem Ayçi
¸ek Do
˘ an2, Canan Top
¸uog˘ lu3, Dilek Berker2 &
negative. Two years after RAI, Tg levels increased to 15.2 and to 43.1 ng/ml
Serdar Guler2
six months thereafter. ATg remained negative. Neck and thorax CT showed a new
1Umraniye Training and Research Hospital, Endocrinology and Metabolism
lesion in D3 and no progression of lung nodules. The patient referred light
Clinic, Istanbul, Turkey;2Ankara Numune Training and Research Hospital,
numbness in his left arm and hand. A second RAI was performed under thyroid
Endocrinology and Metabolism Clinic, Ankara, Turkey;3Ankara Numune
hormone withdrawal. Stimulated serum Tg was 229.0 ng/ml. PET-CT (Default 1)
Training and Research Hospital, Biochemistry Clinic, Ankara, Turkey.
was performed just before RAI administration: uptake in lytic lesions in D3 and
D4 was found (SUVmax Z11.3). Post-therapeutic WBS (Default 2) also showed
Introduction
intense uptake in the dorsal spine and faint uptake in pulmonary lesions.
The frequency of thyroid surgery for suspected malignancy but postoperative
Conclusion
resulted with benign pathology tends to increase in the worldwide. Therefore,
Serum thyroglobulin is usually useful to monitor disease progression. In patients
additional preoperative markers are needed to prevent excessive surgery.
with aggressive differentiated thyroid carcinoma, Tg alone may not reflect
Neopterin is a new molecule secreted by monocytes and macrophages and
indicates the activation of cellular immunity. Therefore it can be used as a marker
of immune activation. We aimed to evaluate the diagnostic value of serum
neopterin levels to determinedifferentiated thyroid cancers (DTC).
Material and method
This prospectivestudy included
86 patients
(67
female and
19 male) who
underwent thyroidectomy due to nodular goiter between March
2015 and
November 2015. Patients who had overt hyperthyroidism or hypothyroidism
Fig. 1 18F-FDG PET-CT.
andrenal or hepatic dysfunction were excluded from the study. Weight, height and
Table The comparison of demographical data and neopterin levels
between groups.
Group 1 (n:39) Group 2 (n:47)
P
Age (year)
47.2G12.8
48.4G12.9
0.719
Weight (kg)
79.3G15.5
76.6G15.5
0.455
BMI (kg/m2)
30G5.9
28.8G5.2
0.362
Preoperative TSH (mIU/lt)
1.57G1.47
1.21G1.27
0.127
Plasma neopterin (ng/ml)
50.8G48.2
22.1G20.7
0.009
Fig. 2 WBS.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
accurately disease progression, as in this patient with documented bone and
chest and abdominal lesions were described. Fine needle aspiration of the thyroid
pulmonary disease that is both differentiated and aggressive.
and the supraclavicular mass revealed anaplastic carcinoma, with no expression
of the thyroid transcription factor 1, mamoglobin 1 and positive expression for
DOI: 10.1530/endoabs.49.EP1454
CK7, CK19 and CK5. The tumour was considered unresectable and the patient
was started on chemotherapy with paclitaxel and carboplatin for 4 months. After
the first
2 rounds of chemotherapy she had an initial good response, with
shrinkage of the supraclavicular mass. The CT after the completion of
chemotherapy showed an increased volume of both the thyroid gland and the
supraclavicular mass, with thrombosis of the internal jugular vein and
supraclavicular bone erosion. She is under evaluation for external radiotheraphy.
The association between a toxic nodular goiter and anaplastic thyroid carcinoma
EP1455
after cervical radiotherapy, with no distant metastases has apparently not been
Papillary thyroid microcarcinoma: is it worth ablating the patients with
reported so far.
radioiodine?
DOI: 10.1530/endoabs.49.EP1456
Muammer Urhan, Eylem Cagiltay & Ferhat Deniz
Sultan Abdulhamid Training Hospital (Former Gata Haydarpasa Training
Hospital), Istanbul, Turkey.
Objective
Recently, radioablation has been offered for patients with thyroid microcarci-
noma, however some authors favor just follow-up as the prognosis of this disease
EP1457
is excellent. In this study, we compared the long-term follow-up results, for a
Evaluate the effectiveness of the Bethesda system for reporting thyroid
period of 16 years, in patients with thyroid microcarcinoma in a group of patients
cytopathology in the prediction of thyroid cancer (TBSRTC) on fine
with thyroidectomy only and in another both thyrodectomized and radioablated.
needle aspiration (FNA) in Moscow region, Russia
Methods
Timur Britvin, Olga Nechaeva, Alexey Krivosheev, Larisa Bavykina,
Two hundred sixty five patients with a proven diagnosis of thyroid cancer
Armine Kazaryan & Alexander Dreval
!10 mm among 1755 thyroid cancer cases were included in the study. Any
Moscow Regional Research Clinical Institute, Moscow, Russia.
patients with unfavorable characteristics such as capsular or perithyroidal
invasion, intrathyroidal spread, lymph node invasion or multicentirity were
excluded. In group IA, 18 patients (14 female, 4 male; mean age 74), patients
Aim
were hemi-thyroidectomized only and 64 patients (43 female, 21 male, mean age
To evaluate the effectiveness of the Bethesda system for reporting thyroid
66) in group IB had total or near-total thyroidectomy. In group II, 183 patients
cytopathology in the prediction of thyroid cancer on fine needle aspiration (FNA).
(123 female, 60 male; mean age; 61) underwent total or near total thyroidectomy
Materials and methods
and ingested I-131 (dose range; 30-85 mCi) while they were in ahypothyroid state
This is retrospective study of 70 detected thyroid cancer. Thyroid ultrasound and
(TSH O40 uIU/L). In the surveillance period, all patients were monitored with
FNA were performed on all patients. 66 of them with cancer suspicion were
periodical serum Tg/ATg measurement and ultrasound of the neck for a period of
communicated to the thyroid surgeon, 4 cases of papillary carcinoma were
two to 16 years.
accidentally diagnosed after hystological investigation. 65 patients underwent
Results
total thyroidectomy with or without lymph node dissection. One patient refused
In group IA and IB, lymph node metastasis was detected in 9 patients (11%) with
surgical treatment.
69 intraoperative samples were subjected to hystological
US-guided fine needle aspiration in the surveillance period. No patient asked for
examination.
additional treatment including surgical intervention and followed by L-T4
Results
suppression only. Serum Tg levels were less than 2 ng/dl (range; 0.2 to 3.9 ng/dl)
In the group with cancer suspicion category VI by TBSRTC was assigned in 51
in 56 patients an in the remaining 26, ranged from 2.0 to 9.8 ng/dl. Serum Tg
(77.3%) cases, category V in 13 (19.7%) cases, 1 case (1.5%) with category V and
levels decreased to lower values than 9.8 ng/dl after no more than one year. In
VI with multinodular goitre, and 1 case (1.5%) with category VI and IV with
group II, lymph node invasion were detected in 19 patients (10%) and 9 of them
multinodular goitre too. Hystological examination of 60 (91%) cases confirmed
had neck dissection for a complete cure. Initial serum Tg levels ranged from 2.1 to
thyroid cancer: papillary carcinoma in 56 (85%) cases; medullary carcinoma in 3
19.8 ng/dl in those patients. In 19 patients with lymph node invasion serum Tg
(4.5%) cases; mixed follicular and papillary carcinoma in 1 (1.5%) case. In 6 (9%)
levels ranged between 2.2-19.8 ng/dl.
cases the cancer wasn’t detected. 2 (3%) of these 6 cases were classified as
Conclusion
category VI and 4 cases (6%) as category V. Thyroid cancer was not detected in
In both groups, approximately 1/10 of patients presented with recurrent or
all the cases of categories II-III found after thyroidectomy for other reasons.
metastatic disease to regional lymph nodes. As the difference between
Conclusion
radioablated and not ablated groups is statistically not significant, we do not
Category VI corresponds with 97% of diagnosed thyroid cancer, and category V -
recommend completion thyroidectomy and radioablation for patients with thyroid
94%. Thyroid cancer was confirmed in only 4 of all cases with category IV. This
microcarcinoma (excluding any poor prognostic factor) and follow-up unless the
result indicates the need for additional diagnostic methods in the preoperative
disease becomes clinically apparent.
period for category IV - for which molecular genetic tests may have potential. To
DOI: 10.1530/endoabs.49.EP1455
determine the risk of malignancy of thyroid nodules with categories II-III requires
long-term monitoring.
DOI: 10.1530/endoabs.49.EP1457
EP1456
Anaplastic thyroid carcinoma and multinodular toxic goiter
Oana-Maria Capraru
EP1458
Saint Constantin Hospital, Brasov, Romania.
Outcomes and imaging results in patients with medullary
thyroid cancer
Thein Htay1, Mansour TA Sharabiani2, S Nimalasena2, Kate Newbold2 &
A 69 years old female with cervical radiotherapy 25 years ago for an unknown
Daniel Morganstein1,2
condition, known with multinodular goitre and hyperthyroidism for 6 years,
1Diabetes and Endocrinology Department, Chelsea and Westminister
presented with a 6 months history of enlarged right supraclavicular mass, local
Hospital NHS Trust, London, UK;2Thyroid Unit, Royal Marsden Hospital,
pain with difficulty in mobilization of the right arm and weight loss. She also
London, UK.
reported progressive bilateral exophtalmia especially on the right side, no
dysphagia, hoarseness or dyspnoea. Thyroid hormone levels were normal on
antithyroid drugs and the thyroid auto-antibodies and parathyroid levels were all
Medullary Thyroid Cancer (MTC) is sporadic in approximately 75% whilst 25%
normal. Neck CT showed an inhomogeneous large gland with several hypoechoic
of MTC occurs as hereditary forms due to RET mutations. Prognosis is relatively
nodules, compression of the trachea and oesophagus, severe compression of the
good with 10-year survival rates of 65%. However, many patients develop
right internal jugular vein with collateral blood flow and a right supraclavicular
recurrent disease and imaging is critical to localise the site of recurrence. Eighty-
adenopathy with no cleavage plan from the thyroid tissue. No significant head,
eight MTC patients, attending the Royal Marsden Hospital NHS Trust were
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
included in an analysis of overall survival. Median Follow-up duration was 7.5
Thyroid cancer is the most frequent endocrine cancer. Its incidence has been
years (IQR: 4.5-13.5). Twenty cases were hereditary and had a median survival
found to increase in recent years. Additionally, environmental factors, which may
12 year (7.7-22.5 95%CL). Sixty-eight patients with Sporadic MTC had a shorter
be implicated in the pathogenesis of thyroid disorders, such as iodine deficiency
survival outcome, median survival 5. 7 year (5.0-7.7 95%CL). Overall median
and salt iodine supplementation are changing and may have an impact on the
survival rate was
7.3
years
(5.3-9.3
95%CL). Hazard Ratio for Sporadic
epidemiology of thyroid cancer. The aim was to study the epidemiology of
Hereditary is 2.1 (1.2-3.5, PZ0.005). According to Kaplan-Meier estimate,
thyroid within a center of excellence in Athens in the modern world setting. A
65%(nZ13) of these Hereditary MTC survive 10 years. In contrast, 10 year
cohort of 63 patients, aged 46.3G1.77 (meanGS.E.M), range 16-81 years with
survival rate of sporadic cases was 28% (nZ19). We also evaluated the sensitivity
thyroid cancer was studied. The histology of the cancer was recorded. The
of different imaging modalities within three bands of calcitonin levels (0-100,
histological subtypes of papillary thyroid cancer were evaluated and recorded.
100-400, and O 400 ng/l). The findings demonstrated that USS neck had a
Within a cohort of 63 patients with thyroid cancer 60 were found to have papillary
superior sensitivity for localising diseases in those with calcitonin with less than
thyroid cancer, three were found to have follicular thyroid cancer, one was found
400: 0.25 (.0.073-.0.524 95%CL, calcitonin 0-100), 0.857 (0.421-0.996 95%CL
to have a mixed medullary follicular-derived thyroid cancer and one was found to
calcitonin 100-400,) and .0 556 (.0.308-785 95%CL calcitonin O 400). In
have a B cell lymphoma of the thyroid. Within the group of the patients with
contrast, in patients with calcitonin O 400, CT neck and body has a higher
papillary thyroid cancer, 39 (67.24%) were found to have papillary, 19 (32.8%)
sensitivity
0.667
(.0.49-0.814
95%CL) and .0745 (.0.604-0.857
95%CL)
were found to have the follicular variant of papillary thyroid cancer, 1 (1.72%)
respectively. Thus, USS neck should be considered as first line imaging modality
had encapsulated papillary thyroid carcinoma, and 1 (1.72%) was found to have
in follow-up in MTC in those with calcitonin ! 400 and CT should be considered
the tall cell variant of papillary thyroid carcinoma. It appears that in the modern
at higher calcitonin levels in order to identify site of disease relapse. In addition,
world setting within a center of excellence in Athens papillary thyroid cancer was
Hereditary MCT has better prognosis than sporadic cases.
the commonest type. Although papillary thyroid cancer and the follicular variant
DOI: 10.1530/endoabs.49.EP1458
of papillary thyroid cancer were the commonest forms of thyroid cancer recorded,
more aggressive types of thyroid cancer such as the tall cell variant were also
recorded.
DOI: 10.1530/endoabs.49.EP1460
EP1459
Lymph node metastasis of differentiated thyroid cancer: role of
thyroglobulin in the washout fluid of fine-needle aspiration biopsies
Bernardo Marques, Raquel Martins, Nuno Cunha, Joana Couto,
Jacinta Santos, Teresa Martins, Ana Paula Moniz, Olga Ilhéu, Joana Bastos,
Paulo Figueiredo, Frederico Valido & Fernando Rodrigues
EP1461
Instituto Português de Oncologia de Coimbra FG, EPE, Coimbra, Portugal.
Is thyroglobulin at ablation a good predictor of the thyroid remnant size
in differentiated thyroid cancer?
Introduction
Helder Martins1, Gracinda Costa1, Jorge Isidoro1, Paulo Gil1,
Thyroglobulin (Tg) measurement in needle washouts from fine-needle aspiration
Rodolfo Silva1,2 & João Pedroso de Lima1,2
biopsies
(FNA-Tg) increases the sensitivity of lymph node (LN) metastasis
1Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
diagnosis in differentiated thyroid cancer (DTC). However, the cutoff value for
2Instituto de Ciências Nucleares Aplicadas à Saúde, Coimbra, Portugal.
FNA-Tg has not been clearly established and there are large differences between
clinical studies, which hinders its interpretation. Our study aimed to investigate
the optimal cutoff value of FNA-Tg and evaluate its utility in the diagnosis of LN
Aim
metastasis of DTC.
Stimulated thyroglobulin (sTg), measured at radioiodine remnant-ablation (RRA)
Methods/design
in patients with differentiated thyroid cancer(DTC), is an important predictive
This was a retrospective study of 211 consecutive cases of FNA from 143 patients
factor of persistent disease. However, Tg produced by normal thyroid cells may
identified from our institutional database, who underwent FNA citology and Tg
also contribute to the sTg value.
measurement in needle washout for suspicious LN, between 2012 and 2016.
We aimed to study the relationship between sTg-level in RRA and the thyroid
Results
remnant size
(TRs), using post-therapy whole-body scan
(131I-ptWBS), at
From the total of 211 cases, 121 (57%) had personal history of DTC. FNA
different TSH stimulation method.
citology was benign in 114 (54%) and malignant in 64 (30%). The median FNA-
Materials and methods
Tg was 1168 ng/ml (interquartile range
27-11974) in malignant LNs, and
We review DTC cases referred for RRA, either prepared with recombinant-
0.1 ng/ml
(interquartile range
0-0.27) in benign LNs. LN ressection was
human TSH (rhTSH) or after 4-weeks levothyroxine withdrawal (hipo). Anti-
performed in 55 patients (38.4%), based on the combined results of FNA-Tg
thyroglobulin antibodies (TgAb) and sTg were measured. Patients with positive
and FNA citology. Histology reported LN metastasis of DTC in 45 of these (81%).
TgAb, 131I-uptake outside the thyroid bed and suspected to have persistent
Compared to FNA-Tg values above 0.2 ng/ml, FNA citology showed superior
disease on the first 6-12 months were excluded. Four hundred patients (331
specificity (95.4% vs 67.1%) but slightly inferior sensitivity (88.7% vs 91.5%).
women, 69 men;mean age sd:49.8 14.1 years-old) were selected. TRs was
FNA-Tg values above 10 ng/ml showed 80.3% sensitivity and 100% specificity.
assessed by 131I-ptWBS, using a fixed circular region-of-interest (ROI) placed in
Combining both diagnostic strategies
(FNA citology and FNA-Tg above
thyroid bed. The geometric mean (GM) of the total counts (cts) in the ROI was
0.2 ng/ml) showed superior diagnostic power than using either strategy alone
calculated, corrected for the thigh background and normalized for the treatment
(specificity 96.4% and sensitivity 91.5%). We evaluated the optimal cutoff values
activity (nGM). Based on nGM, remnants were classified into small(S)-nGM!Z
of FNA-Tg in determining malignant LNs from ROC analysis and the optimal
10cts/MBq; medium(M)-10cts/MBq!nGM!Z50cts/MBq and large
(L)-
cutoff value was 0.98 ng/ml (sensitivity, 85%; specificity, 95.4%).
nGMO50cts/MBq. Spearman’s rank correlation coefficient was used to test the
Conclusion
association between TRs and the sTg normalized for TSH(nTg). SPSS version-23
Our results show that combining FNA citology and Tg measurement is useful for
was used for statistical analyses.
the investigation of LN metastasis of DTC. A FNA-Tg cutoff value above 1 ng/ml
Results
should lead to its diagnosis.
A moderate positive correlation between nGM and nTg was found in rhTSH and
hipo patients (rsZ0.55, P!0.001 and rsZ0.59, P!0.03 respectively). For the all
DOI: 10.1530/endoabs.49.EP1459
population we found a strong positive correlation(rsZ0.61,P!0.002). A positive
moderate correlation was found in group-S and L (rsZ0.58, P!0.01; rsZ0.42,
P!0.034 respectively); a weak positive correlation in group-M
(rsZ0.08,
P!0.19).
Conclusion
EP1460
Radioiodine-scintigraphy and sTg are important tools to evaluate the functional
The epidemiology of thyroid cancer within a center of excellence in
status of both normal and neoplasic thyroid tissue. Our results suggest that TRs
Athens: Real life data
and sTg values are correlated, in the absence of clinical/imagiological disease,
Eleni Pantazi1, Alexios Travlos1, Evaggelia Vogiatzi1 &
regardless the method of TSH stimulation. We hypothesize that sTg values are a
Ifigenia Kostoglou-Athanassiou2
better predictor of TRs in patients with less TRs.
1Department of Endocrinology, Alexandra Hospital, Athens, Greece;
DOI: 10.1530/endoabs.49.EP1461
2Department of Endocrinology, Red Cross Hospital, Athens, Greece.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1462
(44.9% of N1b patients vs 46.3% of N1a patients; PZ0.812), tumour size (mean
size was 23.3 vs 23.2 mm; PZ0.958), persistence of disease (29.4% vs 21.1%;
Prevalence of thyroid cancer in malaga and province
PZ0.163), recurrence of disease (14.5% vs 9.1%; PZ0.182) and disease specific-
Carmen Hernández-García, Araceli Mun˜oz-Garach, Viyu Doulatram,
mortality (5% vs 1.5%; PZ0.1).
Lidia Pérez-Villa, J Mellado-Soria, L Robles-Cabeza, C González-Hermoso
Conclusion
& Francisco Tinahones-Madue
˜o
Our results suggest that there is no difference in patients’ outcome with LN
Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain.
metastasis in the central neck compared to LN metastasis in the lateral neck or
mediastinum, namely disease specific mortality, recurrence and persistence of
Introduction
disease. These data support the recently updated TNM classification in which
Thyroid cancer is the most common endocrine neoplasia, being its papirally
lymph node metastases location is not considered for staging purposes.
version the most frequent. (90% of all differentiated thyroid neoplasms). It is
DOI: 10.1530/endoabs.49.EP1463
usually multifocal and metastasizes normally to regional lymph nodes.
Objectives
To describe the prevalence of thyroid cancer and its histopathological variants in
the different regions of the province of Malaga.
Material and methods
We performed a retrospective descriptive study. We collected the thyroid cancer
EP1464
diagnoses in the databases of pathological Anatomy of the different hospital
Two cases with metastatic thyroid cancer
centers of the province between 2010 and 2015.
Murat Dagdeviren1, Mustafa Altay1, Ozge Safak2 & Tolga Akkan3
Results
1Endocrinology and Metabolism, Kecioren Education and Research
545 cases were collected, it is more frequent in women (79.63%) than in men
Hospital, Ankara, Turkey;2Sanatoryum Education and Research Hospital,
(20.37%); the average age at diagnosis was 50G15 years. Analyzing in different
Ankara, Turkey;3Internal Medicine, Kecioren Education and Research
areas: 30.1% East Málaga; 12.5% West Málaga, 30.1% Costa del Sol, 1.3%
Hospital, Ankara, Turkey.
Guadalhorce Valley,
1.5% Serranía de Ronda/ Sierra de las Nieves,
7.3%
Axarquía, 3.1% Antequera, 2.4%, 2.7% Melilla. The most frequent histological
Although the thyroid gland has an abundant blood supply, metastasis to the
variant was papillary (69.72%) and in the different areas: East Málaga: 76.22%
thyroid gland is a rare condition. Its incidence varies from 0.1% and 3% in clinical
papillary,
9.15% follicular,
6.71% micropapillary,
3.65% medullary, 1.83%
series. First case. A
56-year-old man presented to emergency service with
anaplastic,
1.22% Hurtle cel, 1.22% oncocytic. West Málaga; 63.25% were
neurological symptoms. CT of brain revealed multiple hyperdens lesions.
papillary,
11.76% were follicular, 13.23% were micropapillary, 4.41% were
Posteroanterior chest X-ray showed increased opacity in the left lung. Metastatic
medullary, 4.41% were oncocitic, 2.94% were Hurtle; Or anaplastic. Axarquia
lung cancer was considered as a preliminary diagnosis and PET/CT was
73.17% papillary, 4.88% follicular, 9.76% micropapillary, 9.76% medullary,
performed. PET/CT showed a mass lesion of 15.8!7.6!8.5 cm in the upper lobe
2.44% anaplasic. Gualdalhorce Valley 77.59% were papillary, 6.89% follicular,
of the left lung and multiple pathologic involvements with metastatic appearance
10.34% micropapillary, 1.72% medullary, 3.45% no data. Antequera, 64.71%
were present in many organs, especially in thyroid gland. A biopsy was performed
papillary; 17.65% follicular, 11.76% micropapillary, 5.88% medullary. Serranía
from the mass lesion and biopsy revealed squamous cell lung cancer. FNA was
Ronda/Sierra Nevis: 75% papillary, 12.5% follicular, 12.5% micropapillary. In
performed from a nodule located in the right thyroid lobe and cytopathological
Costa del Sol 59.76% papillary, 12.20% follicular, 8.54% micropapillary, 1.22%
analysis of aspiration material showed metastatic epithelial carcinoma. Second
medullary, 0.61% anaplastic, 4.27% Hurtle cel, 13.41% no data. Melilla: 80.02%
case. A 42-year-old man presented with fatigue, dyspnea and cough. Thorax CT
papillary,
6.66% follicular,
6.66% micropapillary, 6.66% anaplasic In other
revealed a nodular lesion of 27!17 mm in posterior segment of the right upper
provinces: 84.62% papillary, 7.14% follicular, 7.14% medullary. Tumor tissue
lobe. PET/CT showed increased FDG uptake in the lung, mediastinum and
was noticed to surpass the resection capsule in 19.08% (without data 11.93%).
abdominal multiple lymph node regions, thyroid gland and skeletal system.
In
33%, no ganglia were removed,
21.6% of affected nodes and distant
Biopsy was performed with fiberoptic bronchoscopy and the result was consistent
metastasesO1%.
with primary adenocarcinoma of the lung. FNA was performed from a nodule
Conclusions
located in the right thyroid lobe and from a suspicious right cervical lymph node
The prevalence of thyroids cancer in our population was similar to those
in level III. Cytopathological analysis of both aspiration materials revealed
described in Spain. In the analysis of different types, papilar was the most
metastasis of malign epithelial carcinoma. It was thought that medical palliative
frequent, followed by follicular and micropapillaries. The overall prognosis is
approach would be more appropriate treatment option for two cases when
good.
presence of multiple synchronous metastases, absence of local symptoms,
DOI: 10.1530/endoabs.49.EP1462
characterization of primary diseases, general condition and life expectancies of
the patients considered. Discussion. It should be known that the treatment
approach in patients with metastatic thyroid cancer affects survival and treatment
should be individualized.
DOI: 10.1530/endoabs.49.EP1464
EP1463
Lymph node metastases location (central vs lateral neck) in
well-differentiated thyroid carcinoma: Is it important?
Bernardo Marques, Raquel Martins, Joana Couto, Jacinta Santos,
Teresa Martins & Fernando Rodrigues
EP1465
Instituto Português de Oncologia de Coimbra FG, EPE, Coimbra, Portugal.
Isolated bone metastases: a rare form of presentation of papillary
thyroid carcinoma
Introduction
Mariana Peyroteo, Cátia Ribeiro, Pedro C Martins, Ana Ferreira,
Regional lymph node
(LN) metastases have prognostic significance in
Laurinda Giesteira, Rui Barbosa, Machado Carvalho, António Ramalho,
differentiated thyroid cancer (DTC). Several studies demonstrated that lateral
Augusto Moreira & Abreu de Sousa
neck LN metastasis, classified as N1b, have a greater impact on overall survival
IPO Porto, Porto, Portugal.
than central LN metastasis. Our study aimed to assess the risk of N1a vs N1b
involvement on outcome in patients with differentiated thyroid cancer (DTC),
Background
according to the 7th edition of the TNM staging system.
Papillary thyroid cancer (PTC) is the most frequent type of well-differentiated
Methods/design
thyroid cancer
(WDTC) and frequently poses a management dilemma. Its
This was a retrospective study of 276 patients identified from our institutional
indolent behavior associated with high long term survival support the trend
database, who underwent surgery for DTC between 2000 and 2013. All patients
towards a more conservative management approach. The authors present a case of
had: lymph node metastasis, apparent complete tumour resection, without distant
isolated bone metastases as the form of presentation of papillary thyroid
metastasis at diagnosis and nonaggressive histologic variant. The association
carcinoma. A 61-year-old man was admitted with complaints of lower back pain
between variables was assessed using chi-square and Student’s t-tests.
for the previous
3 months. A lumbosacral spine CT and sacral MRI were
Results
performed, showing a 9!9!7,5 cm mass centered on the sacrum infiltrating the
All patients were followed for a minimum of 3 years postoperatively (146.3G
sacral canal, with soft tissue density associated with extensive lytic lesions of the
87.1 months). Most patients had papillary thyroid cancer (99%). One hundred and
sacral vertebra, suggestive of chordoma. The patient was submitted to a
twenty seven patients (46%) were classified as N1b and mean age was similar in
sacrectomy with reconstruction. The histology of the removed specimen revealed
both groups (46.6 years in N1b patients vs 47.5 in N1a; PZ0.560). There was no
involvement of the sacrum by thyroid cancer, namely papillary type (follicular
significant association between N1b classification and extra-thyroid extension
variant), with positivity for thyroglobulin and TTF-1
on the
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
immunohistochemistry study. The thyroid ultrasound showed multiple nodes
Introduction
bilaterally and the FDG-PET scan showed increased uptake in the left thyroid
Follicular Thyroid Carcinomas (FTCs) and Follicular Variant Papillary Thyroid
lobe and in the area of the sacral surgery, without other areas of high uptake. The
Carcinomas
(FVPTCs) may present absence of suspicious ultrasonography
patient was submitted to a total thyroidectomy, with the histologic study of the
features more frequently than classic papillary carcinomas. Thus, some cases may
thyroid revealing a multifocal papillary thyroid cancer (follicular and oxyphilic
be identified with the pattern of ‘low suspicion’ rather than intermediate or high
variants). Ablative treatment with radioactive iodine was administered after the
suspicion defined in the American Thyroid Association (ATA) guidelines of
surgery.
2015. These guidelines establish a size cutoff of 1.5 cm to recommend fine-needle
Conclusion
aspiration in nodules belonging to this category of low suspicion, justified because
Distant metastatic disease at presentation is rare in WDTC, with these patients
the probability of distant metastasis in FTCs !2 cm is rare. The aim of this study
having less favorable outcomes. For this reason, many risk stratification
is to analyze the perithyroidal extension and the presence of variables associated
algorithms include metastatic disease as a high risk factor. This clinical case
with greater aggressiveness in cases of FTC and FVPTC as a function of the initial
reports a rare form of presentation, showing us that, although most PTC are
size.
indolent, there are still factors about this type of tumor we need to study in order
Description of methods
to be able to single out these specific cases for more aggressive treatment.
A retrospective study of 76 patients with diagnosis of FTC or FVPTC was
DOI: 10.1530/endoabs.49.EP1465
conducted. The presence of the followings clinical and histological parameters
were evaluated: initial perithyroidal extension; aggressive histologic variants
(extensive capsular invasion, oncocytic features, undifferentiated foci); presence
of vascular invasion, presence of lymph node metastases and distant metastases at
diagnosis and during follow-up. The differences between the 2 groups were
analysed according to nodular size: !1.5 cm (group A) and R 1.5 cm (group B).
EP1466
Results
Association between preoperative serum MMP-9 and histopathological
76 cases with a mean age of 53G16 years, 75% women. Group A: 40 cases, size
features of thyroid tumors
0.72G0.34 cm, 8% FTC and 92% FVPTC. Group B: 36 cases, size 2.76G
Ruxandra Dobrescu1, Catalina Picu1, Sorina Schipor1, Adriana Padure1,
1.04 cm, 33% FTC and 67% FVPTC. Extrathyroidal extension 5% vs 19.4%
Liliana Parvu1, Dana Manda1, Dumitru Ioachim1, Corin Badiu1,2 &
(p0,052); aggressive histologic variants 0% vs 22.2% (P0.002); vascular invasion
Andra Caragheorgheopol1
0% vs 19.4% (P0.003), lymph node metastases 10% vs 13.9% (P0.6); distant
1‘CI Parhon’ National Institute of Endocrinology, Bucharest, Romania;
metastasis 0% vs 2.3% (P0.28).
2‘Carol Davila’ University of Medicine and Pharmacy, Bucharest, Romania.
Conclusion
The presence of aggressive histologic variants and vascular invasion was
Introduction
significantly greater in the carcinomas R1.5 cm. None of the carcinomas
Matrix metalloproteinase-9 (MMP-9) is a zinc dependent proteolytic enzyme
!1.5 cm presented aggressive histological, vascular invasion or distant
used by cells for degradation of the extracellular matrix during invasion and
metastases at diagnosis or during follow-up. Our data agree with the
recommendation established by the ATA to choose a size cutoff of 1.5 cm for
migration. There are only a few reports regarding the role played by MMP-9 in
low suspicion pattern nodules.
papillary thyroid carcinoma (PTC).
Aim
DOI: 10.1530/endoabs.49.EP1467
To evaluate the association between MMP-9 secretion, reflected by preoperative
serum levels and the histopathological features of thyroid tumors.
Materials and methods
We assessed serum MMP-9 in 329 subjects: 309 patients with thyroid tumors and
20 healthy controls (C). Patients were divided into 2 groups, following the
EP1468
pathology report: benign disease group (BD) (nZ176, aged 50.5G12.88 years)
Ten years of TSH suppression therapy in differentiated thyroid cancer
and PTC group
(nZ133, aged
48.6G14.92
years). In the PTC group
analysed by HR-pQCT
histopathological features of thyroid tumors were analyzed according to
Natacha Germain, Katia Nadin, Bruno Estour & Bogdan Galusca
pathological stage, histological subtype, multifocality and invasion. The histology
Endocrinology Department, University Hospital of Saint Etienne,
showed classic PTC (cPTC) in 49 patients, follicular variant (fvPTC) in 52 and
Saint Etienne, France.
aggressive forms (AGR) in 32 patients. Sera were collected before patients
underwent surgery. MMP-9 was measured by Quantikine Elisa kit (R&D System).
The study was approved by Ethics Committee of the Institute.
Introduction
Results
TSH suppression therapy by thyroid hormones
(TST) in patients with
We found a significant difference in serum MMP-9 levels between controls and
differentiated thyroid cancer (DTC) could be associated with adverse effects on
thyroid tumors (BDCPTC) (meanGS.E.M.: 561.45G49.37 ng/ml vs 787.47G
bone metabolism in post-menopausal women. Recent recommendations suggest
31.24 ng/ml, P!0.0001). According to the pathology tumor stage (T1-T4), we
therefore to minimize time passed under TSH suppression therapy. However data
found higher MMP-9 levels in T3
(869G79.48 ng/ml) compared to more
in literature are controversial and few shows results on microarchitecture. This
incipient stages (T1 vs T3 P!0.01, T2 vs T3 P!0.03 respectively). fvPTC
study evaluated bone microarchitecture using High-resolution peripheral
showed lower MMP-9 levels vs cPTC or AGR (596.38G34.76 ng/ml vs 760.35G
quantitative computed tomography
(HR-pQCT, XtremeCT; Scanco Medical
70.54 ng/ml or vs 835.75G109.9 ng/ml, respectively, P!0,05). There was no
AG, Switzerland), in post-menopausal women under TST for more than ten years.
significance between cPTC and AGR. There was no difference in MMP-9 in terms
Patients and methods
of multifocality, but patients with invasive tumors had significantly higher serum
We conducted a descriptive, case-control, cross-sectional study, in
22
MMP-9 than non-invasive ones (838.14G80.3 ng/ml vs 618.68G30.9 ng/ml,
menopausal women under TST for more than 10 years (patients), compared
P!0.02).
with 32 menopausal women without any bone disease (controls). We measured
Conclusions
Bone Mineral Density (BMD) by Dual-energy X-ray absorptiometry (DXA),
Preoperative serum MMP-9 might differentiate patients at risk for invasive and
Bone Microarchitecture by HR-pQCT, bone markers (serum osteocalcin and
more aggressive tumor behavior, with implications in post-surgical radioiodine
cross laps).
treatment and follow-up.
Results
DOI: 10.1530/endoabs.49.EP1466
BMI were similar in both groups. PTH was higher in patients (37.2G2.2 ng/l)
compared with controls
(29.4G2.4 ng/l), PZ0.03. TSH was at
0.10G
0.03 mUI/L, with duration of TST of 17.9G1.2 years. No differences were
observed between the two groups for bone markers. Hip and lumbar spine BMD
were not impaired in patients group. However radial cortical bone density value
(Dcomp) was lower in patients (Dcomp at the radius: 816.7G24.5 g/cm3 vs
EP1467
863.3G11.3 g/cm3 in controls, PZ0.04).
Follicular thyroid carcinoma and follicular variant papillary thyroid
Conclusions
carcinoma: Clinical and histological features depending on the
This preliminary study shows an adverse effect of TST on radial Dcomp, while
initial size
BMD is not affected. The trabecular micro architecture is preserved. These
Fernando García Pérez1, Guillermo Martínez de Pinillos Gordillo1, Mariana
preliminary results need to be confirmed and impact of bone breaks need to be
Tomé Fernández-Ladreda2, Eyvee Arturo Cuéllar Lloclla1, José Álvaro
studied.
Romero Porcel1, Carmen Carretero Marín1 & María Victoria Cózar León1
DOI: 10.1530/endoabs.49.EP1468
1Hospital Universitario de Valme, Sevilla, Spain;2Hospital Punta de
Europa, Gibraltar, Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1469
1Ippokrateion General Hospital of Thessaloniki, Thessaloniki, Greece;
Metastatic papillary thyroid carcinoma with intraglandular
2Microdiagnostics Ltd, Thessaloniki, Greece;3St Luke’s Hospital,
dissemination in remission of Graves’ disease
Thessaloniki, Greece.
Dubravka Brdar, Davor Eterović, Gordana
ˇ ošo, Tina Majstorovi
´ &
Ante Punda
Background
University Hospital Center Split and Split University School of Medicine,
Lymph node metastasis from papillary thyroid cancer without detectable primary
Split, Croatia.
within the thyroid gland is extremely rare. We describe a case of a young woman
with a cervical metastasis, without detectable orthotopic or ectopic thyroid focus.
A 26-year-old woman was referred to our outpatient clinic, presenting with
Case report
A 30-year old woman with a history of adenocarcinoma of the ascending colon six
growing left sided neck mass. She was in remission of Graves’ disease for the last
years previously, presented at the 15th week of a normal second pregnancy, for
two years.Ultrasound examination revealed isoechogenic nodule with micro-
management of subclinical Hashimoto’s thyroiditis. She had received thyroxine
calcifications in the upper third of the left thyroid lobe measuring 9!6!6 mm
replacement during her first pregnancy 2 years earlier. She had a family history of
and conglomerate of lymph nodes on the left side of the neck, the largest node
colon cancer in her maternal grandmother and her mother’s two cousins. On
measuring 37!21!13 mm. Behind the lower pole of the left thyroid lobe we
examination she had a palpable node at the right lateral compartment and her
found lymph node. Fine needle aspiration of the isoechogenic nodule in the left
thyroid was not palpable. Ultrasound examination of the neck showed a small,
thyroid lobe, conglomerate of lymph nodes on the left side of the neck and lymph
mildly hypoechoic, heterogeneous gland and a well-defined, hypoechoic mass
node behind the lower pole of the left thyroid lobe revealed papillary carcinoma.
30!15!13 mm, lateral to the right carotid artery at level IV. The mass was
Total thyroidectomy with left modified radical neck dissection was performed.
finally excised one year postpartum and was found to be a lymph node occupied
Histopathological examination confirmed papillary thyroid carcinoma with
extensively by follicular variant of papillary thyroid cancer. She subsequently
intraglandular dissemination and metastases to 18 out of 26 lymph nodes. Patient
underwent total thyroidectomy with central and right lateral node dissection
recived ablative-therapeutic dose of 3.83 GBq of I-131. Now, 6 years later, the
without complications. Thorough histologic examination of the thyroid failed to
patient is disease free.
reveal cancer, central compartment nodules were negative (0/17) and one more
DOI: 10.1530/endoabs.49.EP1469
node harbored microscopic metastasis (1/18) on the right side. The contralateral
nodes dissected were negative (0/9). MRI of the oropharynx, mediastinum,
abdomen and pelvis and non-contrast CT of the lungs (scheduled for follow up of
the bowel carcinoma) were normal. The patient has been referred for radioactive
iodine treatment.
Conclusions
Papillary thyroid cancer presenting as a cervical mass in the absence of a thyroid
EP1470
primary, needs to be differentiated from ectopic thyroid cancer in the neck or
Thyroid nodule size and the risk of malignancy
elsewhere. A picocarcinoma or one that has spontaneously regressed cannot be
Entela Puca1, Ema Lumi4, Blertina Olldashi2, Sonila Bitri1, Dorina Ylli3,
excluded.
Agron Ylli3 & Edmond Puca3
DOI: 10.1530/endoabs.49.EP1471
1American Hospital 2, Tirana, Albania;2Neo-Style Clinic, Tirana, Albania;
3UHC Mother Teresa, Tirana, Albania;4Regional Hospital Teni Konomi,
Korce, Albania.
Introduction
Thyroid nodule size is routinely assessed and has been a cause for concern, if it is
a carcinoma or not.
EP1472
Aim
Birt-Hogg-Dubé and papillary thyroid carcinoma: a case report
Our aim was to evaluate the relationship between thyroid nodule size and cancer
Ines Barka1, Katherina Krompa1, Camille Baudry1, Frédéric Caux2 &
risk. It was a retrospective analysis of 386 patients with thyroid nodules who
Hélène Bihan1
referred to surgery in our hospital from January 2011 to March 2016. Patient’s
1Endocrinology, Diabetology and Metabolic Disease, Hôpital Avicenne -
demographic data, nodules size, and final pathology were recorded. All data were
Hôpitaux Universitaires Paris, Seine-Saint-Denis, France;2Dermatology,
analyses using SPSS18.
Hôpital Avicenne - Hôpitaux Universitaires Paris, Seine-Saint-Denis,
Results
France.
From the total of 386 patients, female were 86% and male 14%, with mean age of
46.75
years old G14.24 DS were included for this study. Based on final
pathology
179 patients
(46.5%) had malignant nodules. The mean size of
Background
malignant and benign nodules were
3.07G1.52
cm and 3.6G1.59 cm
Birt-Hogg-Dubé (BHD) syndrome has been reported to be associated with
respectively (P!0.003). For the purposes of this investigation, thyroid nodules
neoplastic conditions. Its association with thyroid carcinoma has been reported
!1 cm in diameter provided baseline cancer risk for comparison (5.6% risk of
but remains controversial. Here we report the case of a BHD patient with a thyroid
cancer). The overall prevalence of cancer in nodules 1.0-1.9 cm was 20.1%; 2-
papillary carcinoma.
2.9 cm was 30.8%; in nodules 3.0-3.9 cm, 23.4%; and in nodules R4.0 cm,
Case report
20.1%. The primary influence of this association was the low malignancy rate in
A 47-year-old man presented with asymptomatic facial papules, which had been
nodules under 1.0 cm. When comparing nodules 1.0-1.9 cm, 2.0-2.9 cm, 3.0-
gradually increasing in number for 6 years. A biopsy was taken from a papule on
3.9 cm, no difference in malignancy rate was demonstrated (PZ0.5). For nodules
the nose and histology examination showed epithelial proliferation. Mutation in
O4 cm the differences was statistically significant (OD: 3.17; CI95%: 1.01-
exon 4 of FLCN was identified which confirmed the diagnosis of BHDS. A
10.02; P!0.04).
systematic ultrasound examination of his neck showed a 2 cm solid isoechoic
Conclusion
nodule of the right thyroid lobe. The left thyroid lobe and the isthmus appeared to
These data provide strong evidence that thyroid nodule size O4 cm is associated
be normal. Serum levels of free thyroxine, and thyrotrophin were within normal
with an increased risk (three fold) of well-differentiated thyroid cancer and can be
ranges. Fine needle aspiration of the nodule revealed papillary clusters that had
applied in medical decision for thyroid surgery.
atypical nuclei and intranuclear inclusions and that appeared to be a papillary
carcinoma. Our patient underwent a total thyroidectomy with neck exploration.
DOI: 10.1530/endoabs.49.EP1470
The pathologic examination confirmed the diagnosis of papillary carcinoma
classified T1NXMX. The patient was put on L-thyroxine and a radioiodine
therapy will be considered.
Discussion
Birt-Hogg-Dubé syndrome consists of multiple fibrofolliculomas traditionally
associated with trichodiscomas and acrochordons. Medullary carcinoma of the
thyroid was the most reported type of cancers. Eventhough, other types of
EP1471
carcinoma as papillary carcinoma et carcinoma were not the common form of
Lateral cervical lymph node metastasis from papillary thyroid cancer of
BHD syndrome could also occur. Our report is of high scientific interest because
undetected primary: a case report
it will increase awareness of BHD in the medical community, as this syndrome is
Athanasios Panagiotou1, Fotini Adamidou1, Panagiotis Anagnostis1,
too often overlooked even when obvious clinical manifestations are present. So
Mattheos Bobos2, Dimitris Hatzibougias2, Keraso Tzelepi3 & Marina Kita1
the neck ultrasound is recommended for BHD patients and family members.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Among others BHD patients followed in our hospital, we will look for the
under control of endocrinologist and oncologist. In May 2014 patient was again
frequency and results of ultrasounds.
hospitalized and next lymphadenectomy was done. At that moment histopathol-
DOI: 10.1530/endoabs.49.EP1472
ogy of the lymph nodes indicated CASTLE (HMWCKC, p63C, CD5C, bcl2C,
CEAC, synaptophysinC, CalcK, THYK, TTF1K). Therefore, the thyroid
specimens were reevaluated again, and the presence of CASTLE in the gland was
also confirmed. In subsequent follow-ups there were no signs and symptoms of
the disease recurrence. Thyroid CASTLE might be easy overlooked because of its
rarity and similarity to some thyroid cancers like squamous cell carcinoma or
anaplastic carcinoma. Complete thyroid resection and lymphadenectomy are
important to improve the long-term survival and the locoregional recurrence rate,
EP1473
although CASTLE course is usually clinically indolent. The short review of the
Diagnosis of papillary thyroid carcinoma: Is it time to reconsider?
already published data regarding CASTLE was done.
Panagiotis Panousis, Stella Vasileiadou, Michael Katsamakas,
DOI: 10.1530/endoabs.49.EP1474
Maria Boudina, Anastasia Nikolaidou, Alexandra Chrysoulidou,
Kalliopi Pazaitou-Panayiotou & George Zafeiriou
Theagenio Cancer Hospital, Thessaloniki, Greece.
Aim
The aim of this retrospective study was to evaluate the diagnostic significance of
presurgical thyroid ultrasound in comparison with FNAC of thyroid nodules and
EP1475
their contribution in detecting thyroid cancer.
Minimally and widely invasive follicular thyroid carcinomas: are there
Patients and methods
significant differences in clinical behaviour and prognosis?
We retrospectively studied the files of 118 thyroid cancer patients, 18 men
Diana Martins1, Cristina Ribeiro1, Miguel Melo1, Joana Saraiva1,
(15.2%) and 100 women (84.8%), who underwent thyroidectomy from January
Maria Joa˜o Martins2, Carla Baptista1, Diana Oliveira1, Mara Ventura1,
2013 until December 2016, in the Department of Surgical Oncology of Theagenio
Adriana Lages1, Nelson Cunha1, Diana Catarino1, Lúcia Fadiga1,
Cancer Hospital, Thessaloniki, Greece. All patients were diagnosed and followed
Gracinda Costa3 & Francisco Carrilho1
up by the Section of Endocrinology and were operated upon by the same surgical
1Endocrinology, Diabetes and Metabolism Department of Coimbra Hospital
team. The mean patient age was 55 years (G12.26). We evaluated the suspicious
and University Centre, Coimbra, Portugal;2Anatomic Pathology Depart-
ultrasound findings according to the ATA Guidelines of 2015 (hypogenicity,
ment of Coimbra Hospital and Universitary Centre, Coimbra, Portugal;
microcalcifications, taller than wide shape, irregular margins, extrathyroidal
3Nuclear Medicine Department of Endocrinology, Diabetes and Metabolism
extension) and the results of FNAC (in accordance to Bethesda Score), in
Department of Coimbra Hospital and Universitary Centre, Coimbra,
association with the pathology report. All ultrasounds were scored based on the
Portugal.
suspicious characteristics.
Results
Mean tumor size was 7.1 mm (G8.73 mm), multifocallity was found in 69
Introduction
patients (58.5%). The Bethesda score was positive for malignancy in 45% of the
The existence of clear differences between the biological course and clinical
cases. On the other hand, the suspicious ultrasound findings were in accordance
behaviour of minimally invasive (MI) and widely invasive (WI) follicular thyroid
with the pathology report in 78.8% of the cases. Almost all patients with Bethesda
carcinomas (FTC) is still debatable. The present study was conducted to outline
II or III presented at least one or more suspicious ultrasound characteristics and
the clinical differences between MI and WI-FTC and evaluate outcomes in both
those with Bethesda VI at least three or more suspicious for cancer
tumors.
ultrasonographic findings. Based on our statistical analysis, ultrasound as a
Methods
diagnostic tool is more significant (P!0.05) and has a more positive predictive
We conducted a retrospective cohort study involving 80 cases of FTC. The
value in detecting thyroid cancer compared to FNAC.
comparison between MI-FTC and WI-FTC included an evaluation of clinic-
Conclusions
pathologic characteristics, including tumor staging, and outcome assessment.
Ultrasound characteristics and clinical suspicion are considered more valuable
Results
in the diagnosis of papillary thyroid carcinoma, especially for small lesions
The cohort included 65 patients with MI-FTC and 15 patients with WI-FTC.
(!10 mm) and multinodular goiter. Therefore, an ultrasound scoring system
Patients whose age at diagnosis was R45 years more frequently had WI-FTC
should be adopted by the clinicians coping with thyroid cancer.
(27.3% Vs 4.0%, PZ0.023). Mean tumor size was significantly greater in
WI-FTC patients than in the MI-FTC (43.07 vs 30.94 mm, PZ0.007). At
DOI: 10.1530/endoabs.49.EP1473
univariate analysis, vascular invasion, infiltrative margins and invasion of thyroid
capsule were significantly related to the presence of WI-FTC
(P!0.001,
P!0.001 and PZ0.010, respectively). A higher cancer stage (III-IV) was also
associated with the occurrence of WI-FTC (50% vs 8.6%, P!0.001). After a
mean follow-up of 52.6 and 76.4 months in MI and WI-FTC, respectively, one
patient of the first group and two patients of the second died of FTC. Patients with
MI and WI tumors respectively presented a disease-free survival of 100% and
EP1474
84% at 10 years.
Patient with thyroid carcinoma showing thymus-like
Conclusions
differentiation: a case study
The study reported a good outcome in both MI and WI patients, probably related
Małgorzata Kałuz˙na1, Adam Janicki1, Jacek Sygut2, Andrzej Marszałek2,
to an aggressive therapeutic strategy and strict follow-up. Our data confirm
Katarzyna Ziemnicka1 & Marek Ruchała1
previous studies which showed that WI-FTC are typically larger tumors with
1Department of Endocrinology, Metabolism and Internal Medicine,
higher stage, more frequent vascular invasion and invasion of the thyroid capsule.
University of Medical Sciences, Poznan, Poland;2Greater Poland Cancer
Accordingly, we believe that the tumor grade of invasiveness must be taken into
Centre, Poznan, Poland.
account on the staging process of disease.
DOI: 10.1530/endoabs.49.EP1475
Thyroid carcinoma showing thymus-like differentiation
(CASTLE) is an
extremely rare thyroid neoplasm. This type of tumour may arise from branchial
pouch remnants or ectopic thymus and is considered as independent
clinicopathological entity of thyroid neoplasms. There have been only about
100 cases described in the literature, so far. Here, we have retrospectively
analyzed the data from histopathology and clinics of a 70 year old female patient
with thyroid CASTLE who underwent total thyroidectomy in 2009 due to thyroid
nodule in the right lobe (25!25!30 mm) and suspicion of papillary thyroid
carcinoma in the fine needle aspiration biopsy. At that time histopathological
EP1476
examination suggested presence of metastasis to the thyroid likely from the ovary
or thymus however, the detailed clinical and imaging study did not confirm that
Cystic masses of neck: a case report
these organs could be the source of this lesion. In February
2011 patient
M Teresa Gallego, Lucia Vera, Amparo Meoro, Cristina Del Peso &
underwent neck lymphadenectomy that revealed metastases to the lymph nodes
Manuel Martin
with unknown origin but thyroid carcinoma was ruled out. Patient was all time
Hospital General Universitario Reina Sofia, Murcia, Spain.
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Introduction
EP1478
Cystic masses of neck consist of a variety of pathologic entities. The age of
Cystic nodule and carcinoma of thyroid gland, diagnosis and treatment
presentation and clinical examination narrow down the differential diagnosis. In
of cistic nodule
adults are considered to be malignancies until proven otherwise (thyroid lesions,
Snezana Mihajlovska & Marija Mihajlovska
salivary gland neoplasms, metastatic squamous cell carcinoma and lymphatic
1Department of Nuclear Medicine, Clinical Center ‘D-r Trifun Panovski’,
malformations such as the cystic lymphangioma. Ultrasound (US) is often used
Bitola, Macedonia;2Department of Endocrinology, General Hospital
for initial evaluation. Computed tomography (CT) and MRI provides additional
‘8-mi Septemvri’, Skopje, Macedonia.
information. FNAC has a supplementary role for confirmation of diagnosis but its
accuracy may depend on the experience of the cytopathologist.
Case report
The cystic nodule is by its origin a real or pseudo cyst. According to the date of
A 41 years old woman presented with a left-side neck mass that had slowly
literature the papillary thyroid carcinoma is being detected in the cystic nodule in
enlarged over the past
6
months with a serious burner. MRI showed a
up to 27% of the cases. Ultrasound is the best diagnostic method of the cystic
72*57*47 mm septate mass, with solid and cystic components with contralateral
nodule and fine needle aspiration under ultrasound examination is a diagnostic
airway displacement and posterior displacement of the carotid. Thyroid US had
method for cytological diagnosis.
revealed a normal gland. FNAC was nondiagnostic but the inicial diagnosis was a
Results
cystic lymphangioma and the patient was treated with Picibanil (OK-432) without
Seventy patients with detected cystic nodule underwent fine needle aspiration and
any result. Six months later she underwent surgical excision. The histopathology
the aspirational content was cytopathologically examined. In 31/70/ (44.3%) of
report came out as Cystic metastatic lymph node from Papillary carcinoma of the
patients there was a complete discharge of the cyst. In 4/70/ (5.7%) there was
thyroid. US demonstrated a poorly defined nodule with micro-calcification in the
partial discharge but without recidivans and in 35/70/ (50%) of patients there were
left lobe of the thyroid. One week later she underwent a total thyroidectomy and
recidivates of cystic contents. According to the fine needle pathohystological
bilateral cervical lymphadenectomy. The final diagnosis was a 12 mm Papillary
findings in nine patients was detected a malignancy (eight patients had papillary
Carcinoma with bilateral metastatic lymph nodes.
and one follicular carcinoma).
Discussion
Conclusion
Metastatic nodes from head-and-neck malignancy, especially papillary carcinoma
Cystic nodule in thyroid gland is diagnosed by using ultrasound. Fine needle
of the thyroid, are the most common types of nodal metastases presenting as
aspiration is used for discharging of the cyst. Cysts which recidivate after few
cystic masses in the neck. Eighty percent of the cystic masses in patients over 40
needle aspiration should be operated surgically, and the patient with proved
years of age are due to necrotic lymph nodes. On US presence of punctate
carcinoma are cured according to the protocol for the treatment of thyroid
calcification within the solid component of the cystic node warrants careful search
malignant disease.
for primary papillary carcinoma in the thyroid gland. In our patient the diagnosis
DOI: 10.1530/endoabs.49.EP1478
unfortunately was a challenge.
Conclusions
Cystic lesions of the neck are commonly encountered on imaging studies. Clinical
presentation along with imaging features as assessed by Doppler US or CT help in
accurate diagnosis. These imaging modalities also aid in optimal pre-operative
EP1479
planning. Imaging is essential for accurate diagnosis and pretreatment planning.
Incidence of thyroid cancer in the gray bethesda categories
DOI: 10.1530/endoabs.49.EP1476
Berta Barbosa, Moreira da Costa, Vitor Valente, Fatima Borges &
André Carvalho
Centro Hospitalar Porto, Porto, Portugal.
Objective
The recommendations for action in a Bethesda category III are to repeat the
cytology or to perform molecular tests, and if these are inconclusive, surveillance
EP1477
or surgical indication may be maintained, depending on the risk factors,
Staging of thyroid cancer at the time of its diagnosis in a single
ultrasound characteristics of the nodule and patient preference. In case of category
clinical centre
IV of Bethesda, the recommendation is the surgery. The objective of this study
Agata Bałdys-Waligorska1, Maciej Kolodziej1, Monika Buziak-Bereza1,
was to evaluate the impact of age, gender and nodule size on the incidence of
Michal Koziara1 & Andrzej Sokolowski2
malignant lesions in patients with thyroid nodules with Bethesda III and IV
1Jagiellonian University College of Medicine, Krakow, Poland;
classification.
2University of Economics, Krakow, Poland.
Material and methods
Retrospective observational study of patients undergoing Total Thyroidectomy
between July 2014 and June 2016. Totalizations were excluded. Descriptive
Medical documentation of 976 patients treated and followed-up over the years
analysis and statistical treatment with SPSS 20.
2001-2006 at our 131- radioiodine treatment centre was analysed with respect to
Results
their thyroid cancer staging. The mean age at their time of diagnosis was 59G
Four hundred ninety two patients were submitted to Total Thyroidectomy after
15.1 years. From histopathology, papillary, follicular or poorly differentiated
their presentation at the Multidisciplinary Thyroid Group consultation. The mean
cancer was diagnosed in 87.6, 11.7, and 0.7% of these patients, respectively. The
age of the patients was 54.6 years, being 82.7% female. Bethesda III was
mean ages of patients with papillary, follicular or poorly differentiated cancer
indicated in 52 patients, and Bethesda IV in 125 patients. In category III, in seven
were
58.4G15.0,
62.9G15.7
and
70.6G14.6
years, respectively, the age
patients (13.5%) the histology revealed to be a malignant lesion, 71.4% female,
differences between these patient groups being statistically significant
mainly in the 5th decade of life; the majority of patients were T1b. In category IV,
(PZ0.0014). On their admission, patients were TNM- staged. Patients with
in 20 patients (16%) the histology revealed a malignant lesion, 65% female,
microcarcinoma pT1a formed the largest group - 38.9%, followed by T1b-
mainly in the 6th decade of life; the majority of patients were T1b.
32.3%, T2K 10.0%, T3K12.3%, T4K3.0%, and Tx - 3.5%. In the last case the
Conclusions
tumour diameter was not established by the surgeon or pathologist. Most patients
In our series, 13.5 and 16% of patients with a category III and IV Bethesda
were staged at N0 - 88.9%, followed by N1aK 9.7%, and N1aCb - 1.4%. At the
surgical indications were found to be malignant lesions, respectively, according to
time of diagnosis, distant metastases to lungs or bones was staged as M1in only
the literature (5-15% for Bethesda III, 15-30% for Bethesda IV). It was not
0.6% of patients. On chi-square analysis of percentage distribution of tumour size
possible to find a statistically significant difference between the variables tumor
(T) in papillary cancer patients, pT1a was most frequent (42.8%), while T2
size, age group of patients and gender.
dominated in the follicular cancer group (32.3%). This difference was statistically
DOI: 10.1530/endoabs.49.EP1479
significant
(PZ0.0000). No differences were found with respect to N or M
classes. In the follow-up of this patient group, 77 patients were re-operated due to
lymph node or lung metastases, and 23 patients were operated three times.
Multiple I-131 treatment (2-6 times) was applied in this last group. Three patients
died due to thyroid cancer progression.
Conclusion
EP1480
On their diagnosis, patients with papillary cancer and follicular cancer
Sentinel lymph node biopsy in medullary thyroid microcarcinoma after
significantly differed with respect to age and stage of disease.
methylene blue dye mapping - a pilot study
DOI: 10.1530/endoabs.49.EP1477
Radan Dzodic1,2, Nada Santrac1, Marko Buta1,2, Merima Goran1,
Igor Djurisic1 & Ivan Markovic1,2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
1
Surgical Oncology Clinic, Institute for Oncology and Radiology of Serbia,
Table 1
Belgrade, Serbia;2Medical Faculty, University of Belgrade, Belgrade,
Serbia.
LN Number
P
N0
Nx
N1a
N1b
P
PD
7
(1-22)
0.01
0%
50%
75%
80%
0.002
Introduction
Remission
1
(0-2)
100%
50%
25%
20%
The aim was to analyse usefulness of sentinel lymph node (LN) biopsy of jugulo-
carotid regions after methylene blue dye mapping for selection of clinically N0
patients with medullary thyroid microcarcinomas
(MTMC) and lateral LN
reached remission was 0%(0/5) with extracapsular involvement vs 50%(5/10)
metastases for one-time modified radical neck dissection (MRND).
Materials and methods
without extracapsular involvement
(P
0.053). Among
15
patients with
From 2007 to 2016th, 15 patients were operated in our institution due to MTMCs
N1category, only three were cured (all had! 5 LN and a size LN! 2 cm).
with serum calcitonin levels lower than 1000 pg/ml, tumors under or 10 mm in
Conclusion
size and clinically negative regional LNs. Total thyroidectomy with central neck
In our case series we observed that N category and number of LN is associated
dissection was done in all patients. Sentinel LN mapping was performed by
with PD in the long term. Furthermore, there was a linear trend between the size
injecting 0.2-0.5 ml of 1%-methylene blue dye in the thyroid lobes. Blue stained
of the greatest LN and the extracapsular imvolvement with the PD. This
sentinel LNs were removed from II/III levels and examined by frozen section. In
reinforces the importance of a correct characterization of LN involvement.
case sentinel LNs were benign, additional non-colored LNs were removed for
standard pathological analysis. If sentinel LNs were positive on frozen section,
DOI: 10.1530/endoabs.49.EP1481
one-time MRND was performed.
Results
One patient had hereditary form of medullary thyroid carcinoma, with bilateral
subcentimeter tumors, while others had sporadic, unilateral MTMC. Sporadic
MTMCs showed neither central nor lateral LN metastases on bilateral sentinel LN
biopsy, with no indication for MRND. Hereditary MTMC had central LN
metastases, with positive sentinel LNs on both sides, thus one-time bilateral
EP1482
MRND was performed. This patient had metastases in other dissected LNs, as
A case of bilateralmetastaticrenal tumorof thyroid carcinoma
well, and serum calcitonin level of
221 pg/ml. Frozen section and definite
Lila Brakni
pathological analysis were 100% match.
Endocrinology, Algiers, Algeria.
Conclusion
Sentinel LN biopsy after methylene blue dye mapping can be precisely used for
intraoperative assessment of lateral neck LNs. It optimizes surgery of MTMCs,
Introduction
selecting clinically N0 patients with metastases on frozen section for one-time
Distant metastasis caused by thyroid carcinoma is common and usually found in
MRND. This pilot study is the first reported experience with sentinel LN biopsy of
lung or bone. Clinically detectebale, welldifferenciated metastatic thyroid
jugulo-carotid regions in medullary thyroid carcinomas using methylene blue
carcinoma to the kidney is rare. Only 16 cases have been reported in the
dye, focusing on the subgroup of microcarcinomas.
littérature. We describe a case of metastatic vesicular thyroid carcinoma to the
DOI: 10.1530/endoabs.49.EP1480
bilateral kidneys in a 61 years women, with bone, pulmonary lever and lynph
nodes metastasis.
Case report
A 61 old women with a past history of thyroid tumor that had been surgically
treated
19 years earlier She underwent a total thyroidectomy, radiotherapy,
s ablation treatment with iodine
131
and thyroxin suppression therapy
(200 mg/day) and has been diagnosed as vesicular thyroid cancer developped a
left renal metastasis with chest pain. The lesion was detected with iodine 131
scintigraphy which measured in the CT Scan 68/60/13 mm. Biological tests
EP1481
showed: The thyroglobulin 3000 ng/ml (0.8-55) - TSHZ0.02 mUI/ml. Sub-
Lymph node categorization as a prognostic factor in a historical series
sequent surgery and histopathology analysis of the renal lesion confirmed the
of medullary thyroid cancer cases within a regional hospital
diagnosis of vesicular thyroid metastatic carcinoma. Four years later a second
Nerea Aguirre Moreno, Elena Fernandez Gonzalez, Sandra Campos Mena,
metastasis of the right kidney appeared with pulmonary, bone, leaver and lymph
Monica Marazuela Azpiroz & Marcos Lahera Vargas
nods metastasis. She underwent surgery where metastatic carcinoma was
La Princesa Hospital, Madrid, Spain.
confirmed (3 cm of diameter).
Discussion - Conclusion
Only few cases of metastatic spread to the kidneys are described in the literature.
Introduction
16 cases have been reported. They are mostly unique and rarely bilateral. The
Medullary thyroid cancer (MTC) TNM classification categorizes lymph nodes
common use of the ultrasound and the CT Scan in assessment of monitoring of a
(LN) according to their location, but does not consider number and size of LN.
cancer, patient allowed bringing to light more frequently this kind of lesion. The
Objective
concomitant existence of metastasis in the other sites is variously appreciated in
To analyze the relationship between number and size of LN in MCT persistent
the literature. They varies from 50 to 100% observed cases and pejorative from
disease (PD).
the point of view of the prognosis. The most frequent locations are pulmonary,
Material and methods
mediastinal and bone. The patient has benefited a dialysis treatment and deceased
Retrospective study of patients with MTC followed up in a regional hospital from
a year later.
1985 to 2015. The main variables (expressed as qualitative in frequency and
quantitative as meanGS.D. or median (min-max)): size of largest LN, number of
DOI: 10.1530/endoabs.49.EP1482
node, extracapsular involvement and number of LN surgical procedures
undertaken. Univariate analysis was used to assess the relationship between LN
number and TMN stage with PD or remission. A P-value less than !0.05 was
considered significant.
Results
Thirty-five patients were included (age at diagnosis 51G18 years; 57% women).
Time to follow up:8.6G7.2 years. Presentation: 24% cervical mass, 38% through
EP1483
family screening, 8% as incidentalomas. Before surgery, calcitonin levels were
Is prophylactic central cervical dissection in papillary carcinoma of the
391 pg/ml (2-46022) and carcinoembryonic antigen levels were
11.8 ng/ml
thyroid justified?
(0-2009). TNM stage: I:47%; II:6%; III:12%; IV:35%. N0:37%; NX:20%,
Berta Barbosa, Moreira da Costa, Vitor Valente, Fátima Borges &
N1:43%(N1a:33%; N1b:67%). Size of greatest LN:2.5G1.6 cm (! 1 cm: 23%;
André Carvalho
1-3 cm: 46%; O3 cm: 31%). Number of node: 1(0-22) (! 5 LN:64%; 5-9
Centro Hospitalar do Porto, Porto, Portugal.
LN:14%;R10 LN:22%). Extracapsular involvement:
29%. Number of LN
surgery: 1G0.67 (0-4). At the last visit, 47% had PD.
Univariate analysis:
Objective
We found clinical differences, although they were not significant, in LN size (PD
Thyroid cancer is the most common of the endocrine tumors, with papillary being
31G15 mm vs remission 10G14 mm (P 0.058)). The percentage of patients who
the most frequent. There is no consensus about prophylactic central cervical
dissection in patients with papillary carcinoma of the thyroid. The aim of this
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
study is to analyze surgical complications and the rate of recurrence of papillary
carcinoma was diagnosed histologically following reassuring cytology and
carcinoma in patients undergoing total thyroidectomy and prophylactic central
radiological examination. This is a case of 28-year-old female who presented with
cervical dissection, and patients submitted to total thyroidectomy alone.
neck swelling. ThyUSS showed an enlarged left thyroid with cystic and solid
Material and methods
components; FNA was Thy2. Surveillance ThyUSS showed additional right-sided
Prospective study of consecutive patients submitted to total thyroidectomy and
nodules without pathological features; FNA was Thy1. The patient opted for
prophylactic central cervical dissection between January 1993 and December
thyroidectomy; histology showed two small foci of papillary carcinoma. 53-year-
1999, and consecutive patients submitted to total thyroidectomy alone, in the
old female referred with a right dominant nodule following ThyUSS; FNA was
same period of 7 years, for papillary carcinoma of the thyroid. The groups were
Thy2. Subsequent ThyUSS showed a mildly hypoechoic, vascularised nodule
compared in relation to surgical complications and the rate of disease recurrence.
with peripheric halo; FNA was Thy1. The patient opted for right thyroid
Totalizations of thyroidectomy were excluded. Statistical analysis with SPSS 20
lobectomy; histology showed benign follicular nodules with the dominant nodule
Results
containing an incidental papillary microcarcinoma. 60-year-old female had an
Fifty-nine patients underwent total thyroidectomy and prophylactic central
incidental finding of a left thyroid nodule on CT neck on a background of
cervical dissection (mean age 46.3 years, 86.4% female), 43 patients underwent
autoimmune hypothyroidism and a family history of thyroid cancer. ThyUSS
total thyroidectomy alone
(mean age 46.2 years, 95.3% female). Recurrent
showed a left-dominant nodule with increased peripheral vascularity and smaller
laryngeal nerve injury occurred in 10 patients after CCD and in two patients after
right-sided nodules; FNA was Thy2. The patient opted for a left thyroid
TT. Hypoparathyroidism occurred in 24 patients (20.8% definitive) after CCD
lobectomy; histology showed papillary thyroid carcinoma and subsequent right
and in seven patients (14.3% definitive) after TT. Disease-free survival rates were
thyroidectomy histology also showed papillary micro-carcinoma. 41-year-old
of 84.3% of patients 10 years after CCD, and 88.6% after TT alone.
female presented with T3-thyrotoxicosis with positive thyroglobulin antibodies
Conclusions
and swelling corresponding to the thyroid. ThyUSS showed a right-sided, solid
In our series, it was not possible to establish a statistically significant difference
homogenous nodule and two small left-sided nodules. Repeated ThyUSS over
between groups regarding recurrence of the disease, but a statistically significant
nine months were stable; FNA was Thy2 and Thy1c. Technetium scan showed a
difference regarding surgical complications. According to our results, we consider
right-sided toxic nodule and co-existent cold nodule. Following right hemi-
prophylactic central cervical dissection in papillary carcinomas thyroid not
thyroidectomy histology showed benign follicular adenoma and an incidental
justified.
papillary microadenoma.
DOI: 10.1530/endoabs.49.EP1483
Conclusion
These cases demonstrate that whilst the U- and Thy-Classifications are reassuring
they do not exclude malignancy. This uncertainty should be highlighted to
patients when discussing management of thyroid nodules.
DOI: 10.1530/endoabs.49.EP1485
EP1484
Thyroid cancer frequency over three decades
Cecilia Sanchez-Ragnarsson, Silvia Gonzalez & Edelmiro Menendez-Torre
HUCA, Oviedo, Spain.
Aim
EP1486
To investigate the frequency of thyroid carcinoma and its subtypes in one region
Timing to repeat thyroid fine-needle aspiration after a follicular lesion
over three decades.
of undetermined significance result - does it matter?
Material and methods
Francisco Sousa Santos1, Cátia Ferrinho1, Ricardo Capitão1,
Data retrospectively collected from a tissue bank where all hospitals in a region
João Sequeira Duarte1, Martinha Chora˜o2, Clotilde Limbert1 &
with a little above 1 million inhabitants should send samples from all operated
Carlos Vasconcelos1
tumors, from 1981 to 2010.
1Centro Hospitalar Lisboa Ocidental - Servic¸o de Endocrinologia, Lisbon,
Results
Portugal;2Centro Hospitalar Lisboa Ocidental - Serviço de Anatomia
From 1981 to 1990 there where 156 thyroid cancers; 206 from 1991 through 2000
Patológica, Lisbon, Portugal.
and 362 from 2001 through 2010, with a 132% rise from the first decade to the last
one. Papillary cancer accounted for just 42% in the first decade, rising to 65% in
the 2000s. There was also an absolute 50% rise in follicular cancer incidence,
Introduction
although the relative percentage fell from 40% in the first decade to 26% in the
Regarding thyroid nodules, in case of follicular lesion of undetermined
last one. Medullary cancer incidence rised by 150%, but relative percentage
significance
(FLUS), performing repeat fine-needle aspiration
(FNA) is a
remained stable between 3 and 4%. Frequency of other rare types of thyroid
common follow-up strategy. It has been suggested that a waiting period of at
neoplasms such as anaplastic, lymphoma or squamous carcinoma remained
least 3 months between FNAs would increase the diagnostic yield. Our study aims
stable.
to clarify the optimal time for repeat FNA in case of an initial FLUS result.
Conclusions
Methods
Thyroid carcinoma incidence is rising, mainly due to a rise in papillary
We identified retrospectively all thyroid FNA FLUS results that occurred in our
carcinoma, as previously reported, but we also observed an increased incidence in
institution in 2016 and analysed only the patients who were submitted to repeat
follicular cancer.
FNA. We recorded cytologic diagnosis, time between FNA and histologic results
in case of surgery.
DOI: 10.1530/endoabs.49.EP1484
Results
A total of 79 patients were included, with ages between 34 and 86 years. Mean
nodule diameter was 26.7G11.7 mm. After the second FNA, 8 (10.18%) patients
also underwent a third one. A total of 6 (7.6%) had surgery performed at some
time during follow-up - 2 cases with malignant histology results. The result of the
second FNA was non-diagnostic in 27.8% of cases and remained FLUS in 26.6%.
Mean time interval between the first and second FNA was 3.8G1.4 months. We
EP1485
did not find a statistically significant difference in diagnostic yields (PZ0.267) or
Thyroid nodules: a huge dilemma!
diagnostic non-FLUS results (PZ0.523) between second FNA’s performed 3
Bonnie Grant1, Bethan Goulden1, Raj Tanday1, Edel Casey1,
months or earlier (36 patients) compared to those preformed later (43 patients).
Antony Pittathankal2, Akin Ojo2, Imran Syed3 & Khash Nikookam1
Timing (as well as sex, age and nodule diameter) remained not correlated with
1Diabetes and Endocrinology Department, Barking Havering and Redbridge
diagnostic yield or diagnostic non-FLUS results after regression analysis using
University Trust, Greater London, UK;2Surgery Department, Barking
time between FNAs as a continuous variable.
Havering and Redbridge University Trust, Greater London, UK;3Radiology
Conclusion
Department, Barking Havering and Redbridge University Trust, Greater
Although our study had limited numbers, its results suggest that in case of a first
London, UK.
FLUS FNA result, and if the decision to repeat is considered by the clinician, the
timing of the second FNA does not seem to affect its diagnostic yield or the
likelihood of another FLUS result.
Current UK guidelines for thyroid nodules advise a thyroid ultrasound (ThyUSS)
with U-Classification with or without Fine Needle Aspiration (FNA) with Thy-
DOI: 10.1530/endoabs.49.EP1486
Classification to determine malignancy risk. We report four cases where thyroid
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP1487
small cell lung cancer and thyroid cancer respectively. Advanced non-small cell
lung carcinomas (NSCLC) or medullary and differentiated thyroid carcinomas
Development of hypoparathyroidism due to targeted therapies
(MTC and DTC) may present with bone metastatis in the presence of bone pain,
Asena Gokcay Canpolat1, Berna Imge Aydogan2, Sule Canlar1,
elevated serum calcium or elevated alkaline phosphatase levels. We, hereby
Sevim Gullu1 & Murat Faik Erdogan1
represent two patients who had diagnosis of NSCLC and MTC with bone
1Department of Endocrinology and Metabolism, Ankara University Faculty
metastatis, both treated with EGFR inhibitors and presented surprisingly with
of Medicine, Ankara, Turkey;2Batman State Hospital, Batman, Turkey.
hypocalcemia in our outpatient clinic as a result of hypoparathyroidism. Sudden
declines in calcium levels after initiating EGFR inhibitors contrary to the
Due to inhibition affect on proliferation, motility, resistance to apoptosis and
evidence of bone metastasis in these cases preoccupied that these agents may
growth of metastasis, the epidermal growth factor receptor (EGFR) inhibitor
prevent parathyroid cell growth and decreased PTH levels lead to hypocalcemia.
erlotinib and vascular endothelial growth factor receptor (VEGF) and EGFR
DOI: 10.1530/endoabs.49.EP1487
inhibitor vandetanib are viable treatment options for treatment of advanced non-
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Author Index
Aancute, A EP213, EP260
Ackermann, D EP820
Aguiar-Oliveira, MH
Akman, S EP673
& GP34
& OC13.5
EP949 & GP178
Akram, M EP205, EP761,
Aancutei, A EP809
Acosta-Calero, C EP105,
Aguilar, C EP3
EP1092 & EP1225
Abacar, KY EP266
EP170, EP193, EP390,
Aguilar-Diosdado, M EP714,
Aksyonova, E EP670
& EP440
EP530, EP621
EP715 & EP1278
Akturk, M EP1144
Abbas, A EP280 & EP334
& EP757
Aguirre, N EP180
Akyıldız, AB EP266
Abboud, D EP928
Acu, B EP427
Ahbab, S EP86
Akyurek, F EP1167
Abd elbaky, RS EP425
Ada¸, M EP113
Ahern, T EP1169
Al Kadi, H EP292
Abdalaziz, A EP395
Adam, M EP692
Ahlem, B EP762
Al-Attas, O GP77
Abdallah, NB EP87,
Adamczewski, Z EP1325
Ahmadpour, F GP164
& EP263
EP147, EP482, EP832
& EP1435
Ahmed, A EP552
Al-Daghri, N GP46, GP77
EP1232 & EP1233
Adamidou, F GP40, EP68,
Ahmed, AG EP1363
& EP263
Abdallah, RB EP167
EP771, EP827, EP828,
Ahmed, KS EP70 & EP339
Al-Saleh, Y GP46 & EP263
& GP113
EP1303, EP1307,
Ahmed, M EP1150,
Al-Sharefi, A EP89
Abdelkrim, S EP633
EP1417 & EP1471
EP1153 & EP487
& EP1230
Abdelsalam, MM EP1363
Adamska, A EP1104
Ahmed, S GP180
Al-Trawneh, O EP489
& EP497
& EP466
Ahmeti, A EP585
Alaguney, ES EP427
Abderrahmane, SA
Adaramoye, O EP1095
Ahmetov, I GP170
Alaguney, S EP69, EP90
EP219, EP450
Adaway, J EP1169
Ahn, C EP738 & EP1100
& EP264
& EP633
Adebayo, O EP1095
Ahn, CW EP452, EP531,
Alam, M EP534
Abdulkhaliq, A EP652
Adesanoye, O EP1095
GP54 & GP87
Alaminos, MEL EP920
Abduvakhabova, M
Adhikari, P EP692
Ahn, HJ GP162
Alapi, T EP742
EP686, EP1106,
Adomnicai, V EP1209
Ahn, SV EP236
Alarcón, E EP302
EP1186 & EP1187
& EP792
Ai Thu, B GP142
Alba, A EP99
Abe, S EP1029
Adorini, L EP377
Aichler, M OC1.1
Albani, A EP1056
Abell, S EP1115
Adrian, M EP148
Aida, BS EP762
Albert, C EP641
Aberer, F EP609
Af¸ar, ZT EP538
Aires, I EP599
Albert, L EP165 & GP238
Abernethie, A EP802
Afanasyev, D GP86
Aithal, G OC3.5
Albiger, N EP1042
Abeygunasekara, S EP575
Afentoulidi, A EP1202
Ajabnoor, G EP652
Albu, A EP943, EP1137,
Abid, D GP28
& EP859
& EP657
EP1138 & EP1147
Abid, M GP113, EP66,
Afonso, A EP32, EP1323
Ajdzˇanović, V EP359
Albu, AI EP307 & EP947
EP77, EP135, EP167,
& EP1446
Ajdinovic, B EP787
Albu, D EP1138 & EP1147
EP189, EP335, EP667,
Afonso, C EP887
Ajdzanovic, V GP62,
Albuquerque, JL EP841,
EP770, EP1128,
Afshan, K EP1092,
GP202 & EP779
EP899 & EP975
EP1349 & EP1361
EP1225, EP205
Ajmi, S EP355
Alcaide-Torres, J GP71
Abizanda, EP EP862
& EP761
Akın, O EP673
Alcantara-Aragon, V
& GP240
Afzal, N EP761
Akaishi, J EP1385
EP681
Abolaji, A EP1095
Agapito, A EP10, EP133,
Akalin, A EP12, EP244
Aldea, R EP1364
Aboshady, MM EP513
EP181, EP251, EP253,
& EP1033
AlDwairi, A GP88
Abouleka, Y EP1310
EP599, EP1000,
Akarsu, E EP1003
Alefishat, E EP360
Abraitiene, A EP990
EP1006, EP1049,
Akbar, S EP1262
Alegria, S EP996
Abreu, A EP984 & EP1005
EP1062
Akbiyik, F GP212
Alejandro, R OC6.2
Abreu, S GP98
& EP1446
Akcan, E EP1033
Aleknaite, A EP990
Abrosimov, A EP1394
Agate, L EP1414
Akdader-Oudahmane, S
Aleksic, M EP693
Abs, R EP884
Agersø, H GP152
EP1234 & EP6
Alemany, PA GP179
Abuin, J EP755
Aggarwal, R EP661
Akdeniz, CS EP296
Alevizaki, M EP1411
& EP808
Aghajanova, Y EP893
Akdeniz, YS EP1099
& GP230
Abushady, MM EP497
Aghajanova, YM EP422
Akdere, G EP418
Alevras, TM EP76
Abusoglu, S EP1167
Aglony, M OC5.1
Akgul, G EP344
Alexander, B EP1248
& EP419
Agoulnik, A EP754
Akin, S EP1097 & EP1368
Alexandra Ambarus
Ach, K EP441 & EP1389
Agoulnik, I EP754
Akkan, T EP1060,
Popovici, I EP813
Acierno, J GP153
& OC7.5
EP1343, EP1464
Alexandra Gheorghiu, C
Acik, ME EP296
Agrawal, S EP701
& EP186
EP1395
Acikgoz, SB EP1066
Agreda, J EP1030
Akkaya, L EP675
Alexandra Smarandoiu, G
Acikgoz, A EP378
Aguiar, A GP133
Akladious, C EP583
EP137
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Alexandraki, K EP176
Alors-Perez, E GP128
An, JY GP42, EP248,
Anjum, B EP741
& EP1253
Alpagat, G EP937
EP727, EP738 & EP1100
Anna, D EP989
Alexiu, F EP1221
Alpergin, ESS GP172
Ana, A EP1133
Ansaloni, A EP1166
& EP1353
Alqudah, M GP88
Anagnostis, P GP40,
& EP1383
Alfaqih, MA GP63
Alramadan, M EP443,
EP68, EP214, EP827,
Ansari Nawal, E EP309,
Alhambra-Expósito, M-R
EP524 & EP593
EP828, EP1084
EP311 & EP711
EP819 & EP907
Alshboul, O GP88
& EP1471
Ansari, NE EP1334
Alhambra-Expósito, MR
Altay, M EP186, EP1060,
Anagnostou, E GP45,
& EP476
EP500, EP941
EP1343, EP1347
GP230 & EP1411
Anselmo, J EP255
& EP1159
& EP1464
Anandappa, S EP134
& EP596
Ali Tam, A EP1250,
Altieri, B GP22 & EP161
Anastasia, L EP1047
Antal, I EP508
EP1258, EP1376
Altimari, A EP1381
Anastasiou, E GP230
Antic, IB EP177, EP75
& EP1377
Altinboga, A EP1326
Anaya-Torres, FJ EP437
& EP80
Ali, J EP762
Altinboga, AA EP1377
Anchutin, P EP539
Antic, J EP80
Ali, MS GP84
Altinok, A GP96
Andalib, A EP661
Antic, S EP64
Ali, N GP30, EP254,
Altinova, AE EP1144
Andereggen, L EP986
Anton, G EP1176
EP525 & EP1306
Altintas, YE EP834
Anders, H-J EP1027
& EP1180
Ali, S EP1318 & S11.2
Altun, I EP1194
Anders, S S2.2
Antonik, M EP1433
Alibrandi, A GP175,
Altuntas, Y EP109
Andersen, M OC8.3,
Antonini, S EP7
GP208, EP1056
Altunrende, B EP296
GP59, EP63 & GP181
Antonio Vallejo Casas, J
& EP1118
Altunta¸, S EP836
Anderson, C GP58
EP1392
Aliev, P GP92
Álvarez-Escolá, C EP886
Andersson, E GP9
Antun˜ ano, ML EP869
Alieva, D EP1106
Alves, I EP791
Andersson, I-L EP557
Antunes, P GP23, EP82
Alikasifoglu, M GP212
Alves, M EP106, EP706
Anderwald, C-H EP638
& EP772
Alimova, K EP965
& EP707
Andia, V EP1030
Antunes, S EP44
Alisik, M EP429
Alves, MG EP1179
Andjelkovic, M EP484
Antwi, K GP185
Alissa, E EP292
Alviggi, C EP1107
Andoskin, P GP92
Anyfantakis, A EP625
Aljohani, N GP46
Alzoubi, A EP424
Andrés, AL-d EP431
Anyfantakis, D EP625
& EP263
Amado, A GP228, GP229,
Andrés, AV EP1072
Aouiche, S EP629
Alkan, A EP1326
EP350, EP496,
Andrè, V GP130
Apaydın, M EP999
& EP1413
EP1049 & EP1279
Andrada, P EP227
Apaydin, M EP964
Alkebro, C GP117
Amani, B EP1447
Andrade, M OC4.3
& EP1368
Allakhverdieva, Y EP695
Amani, MEA EP1267
& EP807
Apicella, M EP238
Allenbach, G EP1373
& EP1268
Andrade, S EP816
Apostolakis, M GP230
Allende, F OC5.1
Amano, A EP273
Andrade, V EP235
& EP1411
Allinson, K GP27
Amar, L OC7.2, GP2
Andreassen, M GP150
Apostu, L EP1360
Allo, G GP73
& GP15
Andreea Oprea, A EP813
Appenzeller, S GP119
Allouh, M GP88
Amaral de Carvalho, G
Andrei, F EP148
Araújo, A EP1340
Allwood, W OC3.3
EP1244
& EP1371
& EP300
Almacioglu, S EP601
Amaral, A EP255
Andres, R EP986
Araújo, AN EP1255
Almaev, D EP1069
Amaral, C EP30, EP496,
Andrew, R EP802
Araújo, J EP573 & EP548
Almaraz, JH EP91
EP921 & EP1049
Andrey, S EP1248
Aragón-Alonso, A EP708
Almaraz, MC EP868
Amarawardena, WKMG
Androulakis, I OC4.5
& EP717
Almeida, C EP578
EP879
Andrusiewicz, M EP1252
Aragués, JM EP1204
& EP626
Amarilla, V EP1029
& EP1275
Arakelyan, L EP893
Almeida, CFT GP224
Ambroziak, U GP122
Andrysiak-Mamos, E EP230
Aranburu, M EP869
Almeida, JMG EP406
& EP48
Ang, T-L OC11.4
Aranda, G GP24
& EP407
Amel, M EP646 & EP1229
Angela Condorelli, R
Aranda, J EP1218
Almeida, M GP6
Amengual, A EP184
OC13.4
Aranda-Regules, S EP443,
Almeida, R EP350, EP460,
& EP185
Angelo Giagulli, V GP214
EP524 & EP593
EP462, EP496,
Amin, A OC3.5
Angelopoulos, N OC4.5
Arapova, S EP917
EP1049, EP1071
Ammar, M EP66, EP77,
Angelousi, A EP67
Araujo, A EP1012
& EP1080
EP135, EP167, EP770,
& GP236
Araz, M EP1003
Almeida-Coelho, J GP217
EP1128 & EP1349
Angrisani, E EP1064
Arbizu, J GP198
Alokail, M GP77 & EP263
Amer, HM EP425
Anile, C EP997
Arca, M EP397 & EP713
Alonso-Gordoa, T EP784
Amzar, D GP53, EP153,
Anisie, E GP34
Arcano, K EP891
Alors-Pérez, E EP178
EP306 & EP1068
Anisimowicz, S OC7.1
Archambeaud-
& EP472
An, JH EP1451
& GP118
Mouveroux, F GP120
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Ardeleanu, I EP1345
Arteaga, M EP1130
Aulinas, A EP944
Babajko, S GP142
Arefjeva, A GP92
Arteiro, C EP613
Auriemma, RS EP34
Babazono, T EP1014
Arefyeva, I EP1057
Artham, S EP1306
& GP184
Babenko, A GP92
Aretini, P EP348
Artola, YM EP1237
Austgulen, S EP794
Babic, KK EP1161
Argente, J EP435 & EP655
Arutyunova, M EP521
Austin, E EP1259
Baccini, M EP669 & EP671
Arhire, A EP262
Árvai, K EP1434
Avci, CB EP1379
Bacelar, C EP496 & EP887
Arhire, AI EP148
Arvaniti, A GP125
Avdikos, G EP423
Bachar, G EP1374
Ariander, A EP680
Arvat, E GP231
Avilés, AM EP432, EP433
& EP1391
Aribi, Y EP1386
Asanin, M GP197
& EP705
Bacigaluppi, S EP1251
Arici, B EP942
Asghari, G OC5.2, EP662
Awan, Z EP652
Baciu, I EP980 & EP1007
Arif Jadoon, N EP316
& EP642
Ayçiçek, B EP538 & EP1122
Backeljauw, P GS1.4
Arifjanov, I EP15
Ashawesh, K EP453,
Ayala-Cuellar, AP GP144
& GP66
Arikan, IH EP851
EP534, EP597
Aycicek, B EP56
Baculescu, N GP137
Arizanovic, Z EP127
& EP1004
Aydin, C GP233, EP1002,
Bacun, T EP23
& EP42
Ashraff, S EP89, EP1230
EP1250, EP1258,
Badak, B EP69, EP264
Arkan, T EP1066
& EP1398
EP1264, EP1320,
& EP90
Arlt, W OC1.3, OC3.3,
Asik, M EP1099
EP1326, EP1376,
Badak, I EP1316
OC3.5, GP69, GP122,
Asimakopoulou, A
EP1377 & EP1429
Badalyan, M EP304
GP180, EP798,
EP1098
Aydin, F EP884
Badenhoop, K EP5 & GP83
EP1051, EP1150
Askaoui, S EP640
Aydin, H EP440
Badiu, C GP21, EP108,
& EP1153
& EP888
Aydin, K EP289
EP830, EP1046,
Armasu, I EP188, EP792,
Askitis, D EP1378
Aydin, M EP1347
EP1094, EP1176,
EP809, EP1209
Aslan, MS EP1368
Aydinli, E EP1416
EP1180, EP1216,
& EP1360
Asoglu, V EP201, EP271
Aydogan, BI EP1487
EP1220, EP1395
Armbrecht, G EP353
& EP848
Aydogdu, A EP1165
& EP1466
Armignacco, R GP8
Assadi-Porter, F GP172
Aye, M EP83
Bae Kim, W OC14.5
Armstrong, M OC3.5
Assem, M EP1240
Aykut, E EP249
Bae, KH GP56, EP383,
Armstrong, P EP259
Assié, G OC7.2, GP28
Aylwin, S EP985
& EP506
Arnás-León, C EP530
& GP160
Ayoub, MA EP1123
Bae, S-J EP514
Arnés, JAG EP868
Assmann, T GP79, GP94
Aytekin, C EP362
Baek, K-H EP554 & EP690
Arnas-Leon, C EP105,
& EP411
Ayturk, S EP118, EP121,
Baena-Nieto, G EP1174,
EP170, EP193, EP390,
Assmann, TS OC2.1, GP93
EP201, EP271, EP848,
EP1200 & EP1203
EP621 & EP757
& EP457
EP981 EP1198,
Baena-Nieto, M EP535
Arnau-Vives, MJ EP944
Assonitis, N EP67
EP1396, EP1397,
& EP1287
Arnoriaga, M EP1030
Assumpta, C EP641
EP1399, EP1400,
Baena-Nieto, MG EP858
Aronov, D EP598
Assyov, Y EP699
EP1401, EP1402,
& EP915
Aronov, DM EP598
Astaf ’eva, L EP220
EP1403 & EP1404
Baetu, M GP21
Arosa, V EP1332
& EP895
Ayuk, J GP180 & EP1051
Baffoni, C EP268
Arosio, M GP43, EP20,
Astafieva, L EP799
Azad, K EP428
Bagci, B EP675
EP924 & EP1043
Atac, B EP1431
Azal, O EP362 & EP1165
Bagci, G EP675
Arpaci, DK EP282
Ataoglu, E EP86
Azcona-Monreal, I EP619
Bagdonaite, K EP637
Arqués, PB EP183
Atasoy, A EP86
Azevedo, A EP1058
Bagg, W EP1314
Arranz, MTH GP240
Atencia, J EP1030
Azevedo, I EP100
Bagir, GS EP963 & EP969
& EP862
Ates, I EP1061 & EP1347
Azevedo, T EP106
Bahçeci, M EP937
Arranz, S EP1218
Athanaselis, S GP80
Aziz, N EP115
Bahadir, B EP282
Arrieta, AY EP1023
Athanasiou, V EP859
Azizi, F EP1406
Bahia, H EP379
Arrizabalaga, C EP128,
& EP1202
Azizyan, V GP157
& EP488
EP1040 & EP1217
Athanassiou, L EP275
Azkutia, A EP184 & EP185
Bahijri, S EP652 & EP657
Arrizabalaga, JJ EP1332
& EP366
Aznar, PT EP920
Bahlous, A EP482
Arroyo, SQ EP107
Athanassiou, P EP136,
Azoicai, D EP439, EP811
Bahougne, T EP1352
Arsene, AL EP376
EP222, EP275, EP366,
& EP1231
Bahri, M EP743
& EP1137
EP368 & EP1300
Azpiroz, MM EP574,
Baik, SH GP91 & EP1116
Arsenescu-Georgescu, C
Atkinson, M EP926
EP1072 & EP1481
Bailleux, D EP179
EP1345
Atkinson, MJ OC8.1
Azzoug, S EP743
Baitman, T EP1316
Arslan, M EP1097
Atmaca, M EP834
Bajkin, I EP116, EP245,
& EP673
Aubert, S EP1439
EP709, EP1024
Bałdys-Waligorska, A
Arslan, MS EP327
Audi, L EP1090
& EP1089
EP1477
Artas, H EP249
Auernhammer, C EP154
Ba¸aran, MN EP1453
Bajnok, L EP1410
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Bajraktari, G EP585
Baranowski, E OC1.3
Barros, E OC5.1
Bayrasheva, V GP92
Bak, AM EP654
Barbakadze, G EP315
Barros, L EP45
Bazán, AA EP125
Bakar, F EP344
& EP658
Barroso, F EP923
Bazyka, D GP86
Baker, E EP386
Barbano, B EP537
Barrros, R EP30
Bchir, N EP482
Baker, K EP1145
Barbaro, G EP702
Barsiene, L EP164
Bdeoui, N OC11.2
Baki, S EP476
Barber, T EP668
& EP839
Beauchet, A GP189
Bakiner, O EP963 & EP969
Barbier, N EP1015
Bartalena, L EP688,
Beaufaron, J GP148
Baksanskaite, J EP173
Barbieri, AM EP1043
EP691 & S12.2
Beck, J EP986
Bakstyte, V EP173
Barbosa, AP EP1083,
Bartfai, G EP731
Beck, K EP802 & EP822
Bala, C EP560
EP232, EP234
Bartholdi, D GP153
Beck, P EP609
Balaceanu, R EP813
& EP243
Bartonkova, I EP805
Beck-Peccoz, P EP912
& EP961
Barbosa, B EP1029,
Bartoshevich, O EP749
Beckers, A EP928 & OC8.1
Balas, M GP53, EP153,
EP1479 & EP1483
Basaran, Y EP1165
Bęczyk, M EP1433
EP306 & EP1068
Barbosa, D EP1037,
Baser, H EP1264, EP1326,
Bednárová, A EP1173
Balasko, A EP71 & EP81
EP1083, EP1085,
EP1377, EP1413
Bednarczuk, T EP48
Balcere, I EP931
EP243, EP310, EP320,
& EP1429
& MTE7
Baldaia, H EP53
EP95, GP237 & GP239
Baser, OO EP1035,
Bednarek-Tupikowska, G
Baldane, S GP96, EP256,
Barbosa, R EP1465
EP1317, EP1329,
GP165
EP419, EP421,
Barbot, M EP1042
EP1425 & EP287
Beer, S EP597
EP1101, EP1167
Barbu, C EP1048,
Bashir, M EP160
Begolli, L EP585
& EP1214
EP1371, EP215,
Basile, V EP26 & GP123
Beguin, Y EP883
Baldari, S EP1443
EP262 & EP943
Basinski, P EP1282
Behan, L-A EP1150,
Baldeiras, I EP704
Barbu, CG EP1137, EP148
Baskal, N EP967
EP1153, EP487,
Baldeweg, SE EP1075
& EP947
Basker, K GP125
EP572 & EP70
Baldweg, S EP985
Barcala, J EP1278
Baslund, B EP40
Bejinariu, E EP272
Baleanu, F EP225
Barcin, C EP362
Basmaz, SE EP109
Bekaert, M EP1191
Balin, M EP249
Barenholz-Goultschin, O
& EP836
Bel Pen˜ a, N EP401
Balkan, MB EP265
EP624 & OC4.1
Basolo, F EP1414
Belaid, R EP1232,
Balla, A EP804
Bárez-López, S GP217
Bassetti, M GP27
EP1233, EP147
Balla, B GP37, EP1384
Bargi-Souza, P EP716
Bassi, I OC8.2
& EP87
& EP1434
& GP224
Basta-Kaim, A GP158
Belaya, J EP1069
Ballano, DA EP920
Bargiota, A EP483,
Bastos, J EP1459
Belaya, Z EP1028,
Ballarino, C EP385
EP559, EP618, EP861
Bastos, M EP887
EP1034, EP220,
Bally, M EP942
& EP864
Bastyr, MP EP733
EP345, EP346
Balsa, A EP428
Bari, FD EP1118
Batagelj, E EP385
& EP881
Balsa, AM EP106
Barka, I EP1389, EP1472
Batchelor, JM EP1192
Belceanu, A EP792
Baltzinger, P EP1352
& EP441
Bates, A EP1259
Belceanu, AD EP1073,
Bampilis, A EP1008
Barkan, A EP1039
Bathelt, C OC9.2
EP1076 & EP1360
& EP38
Barmpa, E EP559
Bathon, K GP1, GP28 & GP5
Belgundi, P EP1140
Banakh, I EP426
Barna, S EP1410
Batista, L GP213
Belis, C EP1202
Bancos, I GP122 & GP3
Barnaeva, E EP754
Batista, R EP1449
& EP859
Bandurska-Stankiewicz, E
Barnes, E OC3.5
& OC14.3
Bellarbi, D EP1315
EP17
Barnett, J EP1433
Batman, A EP109
Bellastella, G EP1121
Banerjee, R EP254,
Baron, F EP883
& EP836
& EP1293
EP272, EP525
Barrasso, M EP1121
Battaglia, C EP370
Belle, EV OC5.3
& EP732
Barreiros, E EP1049,
Baudin, E EP179, GP123
Bellevicine, C EP1407
Banfi, G EP653 & EP777
EP896, EP897, EP898
& OC7.2
Bellis, AD EP1121
Banik, S EP343
& EP974
Baudrand, R OC5.1
Bello, C EP1088, EP1177,
Banisauskaite, I EP173
Barreiros, L EP1049,
Baudry, C EP1472
EP1207, EP1311,
Bankovic, J EP166
EP896, EP897, EP898
Bauer, A GP79
EP1452 & EP414
Baptista, C EP175, EP392
& EP974
Bauer, AC GP93
Bello, CT EP258 & EP951
& EP1475
Barrera Martín, A EP1392
Bautista, C EP302
Bellusci, L GP223
Baptista, L EP723
Barrera-Martín, A EP159,
& EP341
Belo, C EP57
Bar, J EP1185 & EP405
EP776, EP819, EP907
Bavykina, L EP1457
Belo, F EP1009
Barabash, N EP983
& EP941
Bayburdyan, G EP893
Belo, G EP1330
Baranda, C EP952
Barreto, F EP235
Bayburdyan, GM EP422
Belo, S EP1079, EP194,
Baranowska, B EP908
Barrios, V EP435 & EP655
Bayraktarli, RY EP113
EP477, EP493, EP564,
Baranowska-Bik, A EP908
Barroca, H GP227
Bayraktaroglu, T EP282
EP576 & EP719
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Belousov, I EP1164
Berthon, A OC1.2
Bilen, A EP261
Bodart, G EP883
Belousova, L EP978
Bertolucci, C EP789
Bilen, H EP261
Bodis, B EP1410
Belska, L EP622
Besenyi, Z EP1388
Bilezikian, JP GP47
Bodnar, P EP1146, EP622
Belyavskaya, E EP13
Beshyah, S EP28
Bilgen, OF EP752
& GP60
& GP68
Bestepe, N EP1152,
Bilgen, S EP752
Body, J EP225
Ben Abdelkrim, A EP1389
EP1377, EP1429,
Bilgic, B OC12.1
Boemi, I OC7.4
Ben Hamou, A EP1439
EP331, EP843
Bilginer, C EP1429
Bogalho, P EP10, EP181,
Ben Slimene, F EP1290
& EP856
& EP843
EP253 & EP599
Benítez, IC EP769
Betivoiu, M EP943
Bilginer, MC EP1264
Bogavac, T EP1114,
Benbassat, C EP1374,
Betivoiu, MA EP947
& EP1376
EP166, EP177, EP191,
EP1391 & EP199
Betsi, G EP1008 & EP38
Bilha, SC GP34
EP75, EP80 & GP139
Benbassat, CA EP1313
Bettaieb, J EP207
Bilic-Curcic, I EP23
Bogazzi, F EP970
Bendacha, Y OC11.2
Bettany, E EP103
Bilir, B EP446 & EP842
Bogdanet, D EP70
Benecke, A GP15 & GP2
Bettencourt-Silva, R
Biller, B EP1010 & GP192
Bogdanova, S GP170
Benedict, C S28.1
EP477, EP564, EP576,
Biller, BMK EP1015 & GP187
Bogner, E-M OC8.1
Benedini, S OC6.2
EP630, EP719, EP773
Billig, H EP1096
Boguszewski, C EP1013,
Benli, AR EP1228
& EP872
Bilora, F EP1042
EP1029, EP235
Bennet, A GP7
Bettikher, O EP485
Bilovol, O EP489 & OC2.2
& GP187
Benomar, K EP1439
Betz, M OC9.2
Bima, C EP991 & EP997
Boj-Carceller, D EP619
& OC5.3
Beun, J N2.3
Bin-Nabhan, AS EP513
Bokal, EV EP1105
Bensing, S GP9
Beuschlein, F EP20, EP52,
Binart, N S3.1
Bolanowski, M EP1135,
Benslimene, MF EP1427
GP1, GP122, GP123,
Biondo, C EP1029
GP165, GP72 & S8.3
Bento, J EP100
GP160, GP5, OC7.2
Birgisson, G EP19 & EP21
Bollerslev, J GP155, GP181
Benvenga, S EP1118
& S30.3
Biscarini, F EP1342
& OC8.3
& EP1171
Bevan, C OC3.2
Bisogno, F EP1064
Bolotko, Y GP78
Berdal, A GP142
Bevan, JS GP191
Bitri, S EP1470
Bolt, JW EP155
Berea, HO EP365
Béu, G EP490 & EP492
Bjorkman-Burtscher, I
Bondarenko, I EP659
Beregova, T GP60
Bex, M GP187
EP1070 & GP182
& EP685
Berends, MA EP155
Beyan, E EP1060 & EP186
Bjarne Christiansen, O
Bone, HG GP47
Beretta, E GP130
Bhagwat, N EP844
OC13.2
Bonea, M EP215
Berg, Gvd EP1045
Bhardwaj, C EP1277
Bjekic-Macut, J EP1114,
Bongiovanni, M EP1373
Bergamim, A EP794
& EP526
GP139 & GP140
Boniakos, A OC4.5
Bergant, D EP1445
Bhudia, J EP525
Blánquez Martínez, D
Bonne, G OC5.3
Berger, M GP90
Biagetti, B EP944
EP581
Bonner, C EP103 & EP58
Berges-Raso, I GP238
Bialas, P EP1252
Black, D D3.2
Bonneville, JF S8.2
Berinder, K GP9
Bianchi, A EP991, EP997
Black, K EP592
Bonomi, M OC8.2 & OC9.5
Berker, D EP1035,
& OC12.5
Blanchard, A GP19
Bonora, E S29.3
EP1317, EP1329,
Bianco, A S6.1
Blanco-Acevedo, C EP929
Bontea, VF EP399
EP1425, EP1453,
Bianconi, E EP688
Blaschke, M EP353
Borai, A EP652 & EP657
EP287, EP538, EP56,
& EP691
Blasio, C GP184
Boran, G EP1150,
EP589, EP810
Bicer, B EP131
Blazekovic, A EP595
EP1153, EP487,
& EP977
Bicer, C EP1347 & EP429
Bleicher, L OC4.3
EP572 & EP70
Berlik, H EP362
Bicho, M EP1083, EP232,
Bliddal, S OC13.2
Borba, V EP235 & EP79
Bernaczyk, P OC7.1
EP234, EP243, EP562,
Bloom, S GP131
Bordogna, P GP43
Bernal, MDF EP708
EP632 & OC5.4
Bloomer, L EP534
Borges, F EP1049,
& EP717
Biczysko, M EP1275
Boama, V EP597
EP1279, EP1479,
Bernarde, K EP142
Bidlingmaier, M EP639
Bobillo, J EP1331
EP1483, EP496,
Bernardes, I EP1077
& GP196
Boboridis, K EP827
EP921, GP228
& EP1078
Biebermann, H OC2.3
& EP828
& GP229
Bernardi, S GP204
Biehl, M OC1.3 & OC3.5
Bobos, M EP1471
Borges, T EP818, EP887,
Berruti, A GP231
Bielecka, A EP826
Bobronnikova, L EP489
EP899, EP923
Bertagna, F OC10.3
Bielik, J EP1344 & EP734
& OC2.2
& EP975
Bertagna, X EP1015
Bielohuby, M GP105
Bobrov, A EP1069
Bornikowska, K EP469
Bertelli, E EP922
Bihan, H EP1472
Boccard, J EP782
Bornstein, S S20.2
Berthaut, I GP148
Bik, W EP908
Bocheva, Y EP1271
Borovecki, F EP595
Bertherat, J EP20, GP12,
Bilbao, I EP869
Bochud, M EP820
Borowczyk, M EP1433
GP120, GP13, GP160,
Bilem, O EP1099
& OC13.5
& EP1450
GP28, GP5 & OC7.2
Bilem, Y EP1099
Bock, O EP353
Borozan, S EP857
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Borresen, SW EP40
Brøndstad, I EP59
Brouze, M OC7.1
Burlacu, MC EP1342
Borretta, G EP268
Bruning, J GP105
Brovkina, O EP220
Burlacu, NP EP1137
Borsari, S EP278 & EP348
Brabant, G EP800
Brucker-Davis, F GP120
Burman, P GP9 & OC12.2
Borson-Chazot, F EP966,
& GP183
Bruckert, E GP189
Burnadze, K EP315
GP177 & S14.2
Bracaccia, ME EP991
Brue, T GP192
& EP658
Boscaro, M EP1042,
Bradnová, O EP1143
Brunner, B GP105
Burnier, M EP820 & OC13.5
GP123 & GP3
Bragança, G EP887
Bruno, C EP1260
Bursuc, A EP1073,
Boskovic, O EP1283
Braham, A EP355
Brutskaya-
EP1076, EP1209,
& EP857
Brailly-Tabard, S GP148
Stempkovskaya, E
EP1360 & EP188
Bossowski, A EP1046
& GP19
EP269, EP286, EP312,
Buruiana, A EP117
& EP1226
Braithwaite, V S5.2
EP480 & EP737
Burulday, V EP529
Bost, F EP745
Brakni, L EP1386,
Bryngelsson, I-L GP9
Burumkulova, F EP50
Botelho de Sousa, A EP133
EP1423, EP1482,
Brzozowska, M EP577
Busquets, J EP150
Botella, S EP227
EP219, EP450
Buades-Rotger, M EP800
Buta, M EP1480 & GP225
Botezatu, A EP1176,
& EP633
Bubnoa, M EP598
Butaru, M EP1068
EP1180 & EP1216
Bram, Z GP12
Bubnova, MG EP598
Butz, H GP3
Botfield, H EP798
Brancatella, A EP238
Buchfelder, M GP192
Buyruk, A EP1444
Bothou, C OC4.5
& EP274
& S13.3
Buyruk, BA EP110,
Botling, J GP194
Branco, CC EP567
Bucur, M EP1048
EP1444 & EP69
Botoula, E EP1047
Branco, SC EP519
Budek, A EP283
Buyukkaragoz, B EP815
Botti, G EP1407
Brandi, M-L S22.1
Budianu, O EP1371
Buzas, EI GP3
Bottici, V EP1414
Brandi, ML GP33
Budziszewska, B GP154
Buzduga, C EP961 & GP34
Bouc¸as, AP EP457 & GP94
Branisteanu, D EP213,
Budzynska-Nosal, R
Buziak-Bereza, M EP1477
Bouc, YL GP19
EP260, EP838, EP961
EP1372
& EP283
Boucelma, F EP633
& GP34
Buey, GG EP227 & GP198
Byrne, J GP180
Bouchard, P GP148
Branisteanu, DD EP252
Bugalho, MJ EP1037,
Byrne, MM EP1318
& MTE10
Brasoveanu, D EP1221
EP1083, EP1085,
Boudiba, A EP629
Brassil, C EP720
EP119, EP1204,
Cabac, M EP1076
Boudina, M EP1473
Bravenboer, B GP41
EP1255, EP1269,
Cabanelas, C EP723
Boudouvi, E EP885
Bray, BFG EP862 & GP240
EP1340, EP1387,
Cacic, M EP43
Bouillon, R S27.3
Braycotton, L EP409
EP1448, EP157,
C´aćić,M EP172
Bouizammarne, I EP847
Brdar, D EP1469
EP174, EP243, EP300,
C´aćić P EP463 & EP549
Bouligand, J GP45 & GP7
Breault, D OC1.2
EP320, EP896, EP897,
C´aćićM EP463 & EP549
Boulkroun, S GP15 & GP2
Breen, N EP295
EP898, EP95, EP974,
Cáceres, LD EP574
Boulmarka, I EP450
Brehar, A EP206
GP226, GP237
Cadirci, K EP478, EP566,
Boulo, T EP1123
Brenda, VB EP74
& GP239
EP710 & EP873
Bouloux, P EP985
Bresciani, G EP196
Bukowski, S GP41
Caeiro, C EP773
Bourcigaux, N GP148
& EP197
Bula, G EP349
Caetano, J EP1227
Bourdeau, I GP123
Brezean, I EP16
Bulbul, BY EP118,
Cagiltay, E EP1455
Bourko, I EP1308
Brianso-Llort, L EP753
EP1198, EP121,
Cagir, BB EP1060
Bourko, O EP1308
Briet, C GP143
EP1399, EP1400,
Cagir, Y EP1060
Boury, S EP1369
Brigante, G EP1383
EP1401, EP1402,
Cagliani, R GP77
Boutzios, G EP1253,
& GP245
EP1403, EP201,
Caiazzo, R EP1439
EP176 & GP80
Briganti, S OC6.2
EP271, EP848
Cailleux, A GP177
Bouvier, C EP192 & EP746
Bright, GM GP65 & GP66
& EP981
Caimari, F EP1075
Bouzid, A EP246 & EP381
Briner, M EP1087
Bulusu, R GP27
Caixàs, A EP165 & GP238
Bouznad, N EP1350
Brismar, K EP557
Bulbul, BY EP1404
Cakal, E EP1060, EP1097,
Boyle, J EP747
Brito, M EP451
Bumbu, A EP1310
EP1368, EP327
Boysan, SN EP296
Britvin, T EP126, EP1457
Bunte, K OC1.3
& EP999
Bozek, T EP1161 & EP595
& EP50
Buranasupkajorn, P
Cakir, B EP1002, EP1152,
Bozhinovska, N EP285
Brom, Rvd EP1045
EP1288
EP1258, EP1264,
Bozic Antic, I EP191
Bromin´ ska, B EP1433
Burbridge, W EP409
EP1320, EP1326,
Bozic-Antic, I EP1114,
Brondani, L GP94
Burcak Polat, S EP1152
EP1377, EP1413,
EP166, GP139
Brondani, LA EP457,
& GP49
EP1429, EP237,
& GP140
GP90 & OC2.5
Burcea, I EP1007
EP331, EP843, EP856,
Bozkirli, E EP963 & EP969
Bronstein, M EP1039
Burekovic, A EP976
GP233 & GP49
Bozkurt, N EP384
Broutin, S EP179
Burggraf, M EP747
C¸ akir, A EP101
Bozkus, Y EP39
Brouwers, AH EP155
Burgos-Ramos, E EP655
Cakir, E EP86
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Cakir, SD EP109 & EP836
EP1401, EP1402,
Caragheorgheopol, A
Carvalho, A EP1279,
Caklili, OT EP447
EP1403, EP1404,
EP1007, EP1018,
EP1479, EP1483,
Cakmak, GK EP282
EP271 & EP981
EP1063, EP1216,
EP496 & GP228
Calıskan, M EP327
Canale, D EP274
EP1220, EP137,
Carvalho, B EP1077
Calan˜ as-Continente, A
Canani, L EP411
EP1466, EP206,
Carvalho, D EP1058,
EP776
Canani, LH GP93, GP94
EP240, EP817
EP1077, EP1078,
Calabrò, V GP204
& OC2.1
& EP911
EP1079, EP1081,
Calabretto, M GP168
Canaz, F EP69 & EP90
Caragheorghopol, A EP16
EP1181, EP1206,
Calafell, MA EP1023
Candan, F EP675
Carceller, DB EP920
EP1289, EP1357,
Calanchini, M EP1145
Candeias, N EP1446
Cardinale, S EP60
EP140, EP169, EP194,
& GP138
Candel, M EP1415
Cardoso, C EP632
EP195, EP305, EP477,
Calatayud, M EP1044
Cander, S EP1017, EP102,
Cardoso, H EP818, EP921
EP493, EP53, EP54,
Caldara, R OC6.2
EP131, EP132,
& EP923
EP564, EP576, EP613,
Calderón-Vicente, D
EP1335, EP332,
Cardoso, I EP841, EP899
EP630, EP719, EP773,
EP443, EP524
EP333, EP336, EP601,
& EP975
EP870, EP871, EP872,
& EP593
EP608, EP679, EP72
Cardoso, L EP392
GP199 & GP217
Calebiro, D GP1, GP28,
& EP852
Cardoso, MH EP146
Carvalho, I EP486
GP5 & OC4.4
Candido, DFF EP389
& EP496
Carvalho, IP EP1454
Calejo, L EP1155
Canelles, S EP435
Cardoso, R EP1227
Carvalho, L GP18
Calejo, M EP567
& EP655
& GP109
Carvalho, M EP1465
Calero, CA EP107
Canlar, S¸ EP277
Cardoso, S EP807 & EP84
Carvalho, MR EP1340,
Calhau, C EP403
Canlar, S EP1059, EP1487
Cardoso, SC OC4.3
EP1454, EP157,
Calhaz-Jorge, C GP133
& EP967
Cardoso, T EP841
EP300, EP896, EP897,
Calle-Pascual, A EP900
Cannarella, R EP1163
Cardot-Bauters, C GP120
EP898 & EP974
Calle-Pascual, AL GP179
& OC13.4
Caric, B EP168
Carvalho, R EP119,
Calleja, A EP227
Cannavò, S GP175
& EP767
EP1387, EP921
Calles, L EP1040 & EP112
Cannavo, S EP1056
Cariou, B S16.1
& GP226
Calles, LA EP1217
& EP26
Carlessi, R GP94
Casa, SD EP161
Callewaert, B EP812
Cano, A EP165 & GP238
Carlioglu, A EP1108,
Casadio, E EP669 & EP671
Calmarza-Calmarza, P
Canpolat, A EP967
EP1113, EP429,
Casals, G GP24
EP619
Canpolat, AG EP1059,
EP529 & EP873
Casamitjana, L EP165
Calogero, AE EP1163,
EP1199 & EP277
Carlos, C EP1133
& EP641
EP35 & GP127
Canpolat, IP EP296
Carmina, E D4.2
Casanova, ME EP1005
Caltık Yılmaz, A EP815
Cansu, GB EP1375
Carmona, S EP1298
Casar-Borota, O GP155
Camacho-Hubner, C
& EP244
& EP1422
& GP194
EP748, EP884, GP192
Cantante, H EP1323
Carnaghi, C OC7.4
Casares, MLdlT EP581
& OC8.4
& EP32
Carnaille, B EP1369
Casarini, L EP1107,
Camargo, A EP472
Cantinho, G EP1269
Carnovali, M EP653
EP1112, EP1123,
Camargo, JL OC2.5
Cantini, G GP8
Caro, AC EP544
EP1131 & GP245
Camilo Fernandes, A
Cantoni, G EP1408
Caron, P GP191 & GP7
Casciano, O EP1121
EP791
Cantrell, D EP1313
Carra, S EP1222
& EP1293
Camozzi, V GP33
Canu, L EP92, EP93, GP25
Carracedo, A EP725
Casey, E EP103, EP1213,
Campana, C OC14.1
& GP8
Carrano, M EP1064
EP1354, EP1485,
Campennı`, A EP1443
Cap, J EP1197 & EP837
Carrasco, A EP636
EP308, EP58 & GP115
Campigotto, F GP187
Capatina, C EP911
& GP132
Casey, R GP27
Campino, C OC5.1
Capel, I EP165 & GP238
Carrasco, R EP1331
Casini, G EP1247
Campos, A EP460, EP462
Capita˜ o, R EP1088,
Carrasco-Valiente, J EP790
Cassar, S EP747
& EP904
EP1177, EP1207,
Carrilho, F EP1009,
Cassatella, D GP153
Campos, S EP180
EP1311, EP1330,
EP1195, EP1475,
Cassiolato, JLB EP380
& OC10.2
EP1452, EP1486,
EP175, EP203, EP392,
Castan˜ o, J-P EP182
Campos, VC EP949
EP414 & GP222
EP394, EP44, EP444,
& EP819
& GP178
Cappabianca, P EP927
EP445, EP45, EP61,
Castan˜ o, JP EP178,
Camur, B EP1400
Cappellani, D EP274
EP922, GP35 & OC14.3
EP472, EP698, EP790,
Camussi, G OC11.1
& EP970
Carroll, P EP985
EP929, GP128 & S3.3
Can, B EP1317
Capraro, J EP18
Carsote, M EP117
Castan˜ o, O EP1005
Can, N EP1198, EP121,
Capraru, O EP1456
& EP846
& EP984
EP1396, EP1397,
Car, N EP585
Carujo, A EP1289
Castan˜ o-Fuentes, JP
EP1399, EP1400,
Cara, J EP884 & OC8.4
Carvajal, C OC5.1
EP941
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Castan˜ o-León, AM
Ceccato, F EP1042
Chambidis, V EP1303,
Chianetta, R GP108
EP1044
Celebi Tayfur, A EP815
EP1307 & EP1417
Chiara Zatelli, M EP196,
Castanheira, J EP1422
C¸ elik, A EP440
Chambidou, E EP1303
EP197 & EP789
Castedo, J EP1181
Celik, C EP1101
Chambo, JL GP6
Chiellini, G GP172
Castedo, JL EP1077,
Celik, E EP118, EP1404
Chamera, K GP158
& GP223
EP1078, EP630 & EP870
& EP848
Champion, B EP1265
Chihaoui, M EP1193,
Castela, A EP490 & EP492
Celik, H EP1327
Chander Wasoori, S
EP1201, EP1208,
Castellano, E EP268
Celik, M EP118, EP1198,
EP1277
EP1212, EP1322,
& GP33
EP121, EP1396,
Chang, Cy GP63
EP1324, EP1328,
Castellino, G GP108
EP1397, EP1399,
Chang, HB EP700
EP207, EP340
Castelo-Branco, M EP704
EP1400, EP1401,
Chanson, P GP189
& EP570
Castro Oliveira, S EP1289,
EP1402, EP1403,
& GP19
Chikalova, I GP86
EP194 & EP195
EP1404, EP201,
Chantzichristos, D EP55
Chikhrouhou, N EP441
Castro, AMG EP406
EP271, EP848
& GP9
Child, T EP1145
& EP407
& EP981
Chapurlat, R S22.3
Chiloiro, S EP991, EP997
Castro, C EP1058 & EP146
Celiker, D EP1343
Charazac, A EP745
& OC12.5
Castro, JJ EP139
Celikmen, M EP1281
Charfi, N EP1128,
China, D EP1079
Castro, JJd EP1359
Cellai, I EP377
EP1349, EP167,
Chini, M EP239
Castro, M EP7
& GP147
EP189, EP335 & EP77
Chiodini, I EP1043, EP20
Castro, MA EP948
Cenci, V EP60
Charles-Obi, D EP525
& GP33
Castro, R EP1177, EP329,
Cenik, F EP1327
Charlton, C EP728
Chiofalo, MG EP1407
GP228 & GP229
Can˜ izo-Gómez, FJd EP431
Charlton, RW GP65
Chiotinis, N EP1098
Castro-Correia, C EP403
Centanni, M EP825
& GP66
Chira, RI EP114
& GP227
& GP221
Charneco, MQ EP581
Chiriac, A EP1231
Castro-Feijóo, L EP725
Centeno, RG EP1030
Chatterjee, K GP27
& EP811
Catak, M EP1317,
Cepero, D GP111
Chatzi, A EP588
Chiriac, AE EP1231,
EP1329, EP287
Cerina, V EP43
Chatzipanagiotou, S
EP439 & EP811
& EP589
Cerovic, S EP787
EP417, EP442
Chiriac, IA EP1221
Catalano, R EP20
Cerqueira, L EP1000
& EP509
& EP1419
Catapono, A S16.3
& EP1062
Chatzistergiou, V EP1084
Chisalita, SI OC6.4
Catarino, A GP242
Cerqueira, ML GP224
Chavda, S GP180
Chiti, A GP231
Catarino, AL EP174
Certo, R GP208
Chaves, C EP596 & OC5.4
Chlebus, M EP577
Catarino, D EP1195,
Cerveira, F EP1330
Chaves, YD EP365
Cho, D-H EP438 & EP514
EP1475, EP444
Cesario, F EP268
Chee, D EP494
Cho, HA EP590
& EP445
César, R EP255 & EP596
Chefu, S GP92
Cho, NH GP56
Catheline, JM OC11.2
Cetani, F EP278, EP288,
Cheikh, C EP616
Cho, Y-W EP516
Cátia, R EP1133
EP348 & GP33
Cheikhrouhou, N EP1290,
Chochishvili, N EP650
Catalán IP GP48
Cetin, K EP289
EP1427, EP1428
Choi, E EP236
Caune, O EP931
Cetin, Z EP1317, EP1329
& EP1430
Choi, HS GP207
Caux, F EP1472
& EP1425
Chekanova, A EP50
Choi, J EP1256 & EP960
Cavaco, B GP126 & GP23
Cetinkaya, G EP968
Chen, G GP171
Choi, K-C EP1109,
Cavadas, B EP1449
C¸ etinkaya, S EP1241
Chen, K EP1263
EP1189, EP151,
Cavalcante, I GP6
Chabbert, M GP143
Chen, M-J OC14.2 & OC4.2
EP739 & GP144
Cavallo, LM EP927
Chabre, O GP12, GP120
Chen, P-L EP1319
Choi, KM GP91
Cavicchi, O EP1381
& OC7.2
Chen, Y-T EP1319
Choi, YK EP383, EP506
Cavun, S GP112 & GP161
Chae, YS EP1451
& EP551
& GP56
Cayón-Blanco, M EP1174,
Chafer-Vilaplana, J EP900
Chenegreha, M EP450
Choi, YM EP1421
EP1200, EP1203,
Chagunava, K EP647
Cheng, S-P OC14.2
& EP517
EP290, EP372, EP374,
Chaieb, M EP1389
Chentli, F EP1267
Chong, LT OC6.4
EP610, EP611, EP612,
& EP441
& EP1268
Chora˜ o, M EP1486
EP858 & EP915
Chaker, F EP1193,
Cherebillo, V EP978
Chortis, V GP122 & S30.2
Cay-Melero, S EP619
EP1201, EP1208,
Chernenkov, Y EP1224
Chou, C GP129
Cayon-Blanco, M EP1287
EP1322, EP1324,
Chertko, E EP286
Choulia, M EP1296
& EP535
EP1328, EP207,
Chevalier, N EP745
Chow, B EP916
Cazares, J OC6.5
EP340 & EP570
Chew, SL EP985
Chow, BKC EP894
Ceausu, RA EP935
Chalasani, S EP592
Cheyne, E EP85
Chowen, JA EP655
Ceccarini, G EP238
Challa, A EP299
Chi, H-C GP64
Chrapek, M EP1382
& EP397
Challis, B GP27
Chi, Y-T EP1319
Christ, E EP986 & GP185
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Christ-Crain, M EP687,
Claessens, F S11.3
EP1073, EP1076,
Costache Outas, M EP817
EP889, EP918, EP942,
Clara, JG OC5.4
EP1209 & EP1345
Costantini, D EP702
OC11.3 & OC9.2
Clark, J EP124
Conzo, G EP1407
Coudenys, E GP41
Christensen, LL GP59
Clarke, BL EP291 & GP47
Corapcioglu, D EP1059,
Coutant, R GP143
Christin-Maitre, S GP148
Clarke, I GP135
EP1273, EP277,
Couto, J EP1459
Christou, M EP1172
Clarke, S GP131
EP967 & EP988
& EP1463
Christou, P EP1172
Claro, I EP174
Corbett, R EP386
Covelli, D EP1342
Chronopoulou, G EP1098
Clavel, S EP745
Corbetta, S GP130 & GP33
Coves, M8J OC12.3
Chrousos, G GP46
Clemente, H EP392
Corbin, CJ EP1190
Covic, A GP34
Chrusciel, M GP118
C¸ akir, a EP101
Corcetto, F GP147
Cowley, M EP373
& OC7.1
Clerici, M GP77
Corcoy, R EP586
Cox, R EP730
Chrysoulaki, M GP32
Clu-Fernández, C GP71
Cordan, I EP545
Cozzolino, A EP1050
Chrysoulidou, A EP1473
Coín-Araguez, L GP71
Cordeiro, J EP1143
& EP1056
Chudecka, A GP190
Co¸kun, M EP1405
Cordeiro, MC EP1298,
Cranston, T OC10.5
Chudek, J EP726
Cobbold, J EP682 & GP138
EP226 & EP996
Crespo, I GP36
Chula, D EP235
Cobzac, G EP328
Cordeu, MPdC EP1023
Crespo-Hernández, I
Chung, CH EP236
Codella, R OC6.2
Cordido, F EP891
EP900
Chung, DJ EP554
Cody, D EP696
Cordova, RSM EP581
Crisan, D EP114
Chung, JH EP1424
Coelho, MJ EP1449
Coremans, P EP393
Crisosto, N EP1120
& OC9.4
Coelho, P GP200
Corlan, AS EP935
Crisostomo, T EP216
Chuvashova, M EP1266
Coelho, R EP613
Cormack, AM GS2.2
Crispim, D EP411, EP457,
Cianferotti, L GP33
Coelho, TH GP227
Corneci, C EP1220
EP648, GP79, GP90,
Cianflone, K EP701
Coeli-Lacchini, F EP7
& EP1395
GP93, GP94 & OC2.1
Cianga, P GP34
Cohen, R EP616 & OC11.2
Cornejo-Pareja, I EP614
Crista, C EP945
Ciccantelli, B EP713
Colao, A EP1056, EP1407,
Cornejo-Pareja, IM GP71
Cristani, M GP208
Cicciarella, F GP123
EP34, EP786, EP839,
Cornianu, M EP153
Cristea, C EP961
Cid, M GP242
GP184 & OC9.5
& EP306
Cristina Staicu, D EP1157
Cid, O EP1390
Coles, T EP1263
Corno, C GP147
Crock, P GP176
Cifci, A EP1280, EP529,
Colet, AM EP76
Corona, M GP238
Crowley, R EP259
EP604 & EP683
Colita, A EP763
Corone, C GP148
& EP430
Cima, L EP148, EP262
Colkesen, F GP96
Correia, CC EP512
Crujeiras, AB NSA6
& EP855
Collombat, P S20.3
Correia, F EP313
Crumpei, F EP188
Cima, LN EP763
Collongues, N EP1352
Corsello, SM EP1341
& EP792
Cimino, L EP35
Colombo, C EP1408
& EP1426
Crumpei, I EP1073,
Cimpean, A EP935
& EP1432
Cortes, SN EP76
EP1076, EP1209,
C¸ inar, B EP101
Colpo, A EP927
Cortez, L EP1006,
EP1360, EP792
Cinel, M EP967 & EP988
Colucci, G EP1342
EP1049, EP1062
& EP809
Ciobanu, D EP188
Combarnous, Y EP1123
& EP1446
Cruz, I EP794
Cipri, C GP33
Comeglio, P EP377
Cosar, R EP1280
Cruzado-Begines, C EP535
Cipriani, S EP370
& GP147
Cosma, DT EP398, EP399
Cuéllar, EA EP298
Circo, E EP1301, EP1302
Comenda, E EP1323
& EP400
& EP623
& EP1304
& EP32
Cosma, DT EP114, EP158
Cuatrecasas, G OC12.3
Circo, R EP1301
Comite, P OC14.1
& EP328
Cucinotta, D EP1118
& EP1304
Comninos, A GP131
Costa, A EP1279
Cucu, A-P EP1132
Cirello, V EP1432
Conaglen, H EP1312
Costa, C EP100, EP1012,
Cudal, I EP216
Ciresi, A EP1056
Conaglen, J EP1312
EP1021, EP1255,
Cudlip, S GP180
Ciric, J EP111 & EP1261
Conceiça˜ o, F EP794
GP213 & GP222
Cuellar, L EP603
Ciric, V EP64
Conceiça˜ o, I EP1204
Costa, D EP1422
Cuesta-Hernández, M
Cirkovic, V EP1184
Conde, JB EP725
Costa, G EP1461, EP1475,
EP900
Cirla, A EP206
Condorelli, RA EP1163,
EP198, EP203
Cuhaci, FN EP1326
Ciubotaru, V EP1063
EP35 & GP127
& OC14.3
& EP1377
& EP1073
Conley, A EP1190
Costa, HS EP562
Cuhaci, N EP1429
Ciudin, A EP944
Connell, JM GP58
Costa, J EP1323 & EP32
Cuixart, G EP586
Ciurea, A EP158 & EP328
Conry, B EP134
Costa, MM EP1077,
Cullen, D EP295
Civita, P EP348
Constantinescu, A EP1073
EP1078, EP1181,
Cuneyt Bilginer, M
Cláudia , A EP253
& EP1076
EP630, EP719, EP870,
EP1258
Claahsen-van der Grinten,
Constantinescu, D GP34
EP871, GP18 & GP227
Cunha, AL EP100
H GP10
Constantinescu, G
Costa, UMM GP178
Cunha, C EP1390 & GP199
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Cunha, F EP305
da Costa, M EP1479
Das, S EP520, EP552
de Miguel-Yanes, JM
Cunha, N EP1009,
& EP1483
& EP555
EP431
EP1195, EP1459,
da Rocha, AG EP1449
Dash, K EP552
de Oliveira, SNP EP389
EP1475, EP203,
da Silva, AP OC5.4
Dato, CD EP537 & OC9.5
de Pinillos Gordillo, GM
EP392, EP394, EP44,
da Silva, TN EP226
Dauksa, A EP1346
EP769
EP444, EP445, EP45,
& EP486
& GP244
de Pinillos, GM EP298
EP61 & GP35
Dabrowska, A EP547
Dauksiene, D EP1346
& EP623
Cunha, V EP807 & OC4.3
Dae Moon, S EP690
& GP244
de Quirós, JMG EP298,
Cunningham, K EP720
Dagdelen Duran, İ EP810
Daumerie, C EP1342
EP623 & EP769
Cuocolo, A GP231
Dagdeviren, M EP1060,
Davey, L EP295
De Quiros, JMG EP270
Curic, N EP1024
EP1343, EP1464
David, J GP203
de Rijke, YB GP116
& EP709
& EP186
& GP206
De Rosa, A EP1341
Curkovic, S EP64
Dahl, SR EP59
Davidenko, I EP415
& EP1426
Currò, M GP175
Dahlgren, C GP117
& EP73
de Sanctis, L GP43
Curria, M EP211
Dahlqvist, P GP9
Davies, E GP58
De Schepper, J EP812
Cusini, C EP688
Dal, J GP181
Dbouk, R OC11.2
De Seze, J EP1352
& EP691
Dalama, B EP944
de Agredos, ÁG-MV EP11
de Sousa, A EP1465
Cvetkovic, S EP470
Dalar, L EP296
& EP955
& EP98
Cvijovic, G EP694
Dallenga, AHG GP116
de Almeida, MM GP226
de Sousa, JA EP82
Człapka-Matyasik, M
Dalmatova, A EP978
de Alonso, IA EP632
de Souza, B EP411
EP1074
Dalvi, F EP130
de Angelis, C EP786
de Souza, BM EP457
Czajka-Oraniec, I GP173
Dalvi, M EP130
de Angulo Martín, DR
de Souza, PB GP128
Czarniecka, A EP1420
Dalwadi, P EP844
EP708
de Valk, H EP635
Czarnywojtek, A EP1275
Daly, A EP928
de Carvalho, AC GP229
De Vathaire, F GP148
& GP220
Daly, AF OC8.1
de Castro, DO EP714
De Vincentis, S GP146
Czech, M EP577
Damas-Fuentes, M EP614
de Castro, RV EP1204
De Waure, C EP1341
Czekanska, P EP1148
Damasceno, M EP54
& EP1269
De
˘irmenciog˘lu, S EP971
& EP371
Damjanovic, S EP166,
de Ciriza, MP EP869
De, P EP409, EP501,
Czepczyn´ ski, R EP1433
EP177, EP191, EP75,
de Courten, B EP1115,
EP558 & EP584
Czepielewski, M EP919
EP80, GP197
GP135 & GP141
Deak, K EP731
Czyzyk, A EP1348
& S25.1
De Feo, ML GP33
Debono, M EP879
Danciu, M EP792
De Francia, S EP26
Decallonne, B EP1393
Daneliene, M EP1436
De Geyter, C GP153
& OC14.4
D’Allagnol, A OC2.5
Daneshafrooz, A EP1406,
De Giorgi, F EP702
Decaroli, MC EP1166
D’Aluisio, D GP16
EP642 & EP662
de Heide, L EP402
& GP146
D’Amelio, P S7.1
Dang, M GP195
de Jong, M EP1445
Deciu, D EP1067
D’Angelo, A GP33
Dani, C GP7
de Krijger, RR EP155
Decmann, A GP3
D’Antongiovanni, V EP92,
Daniela Belceanu, A
& OC7.2
Deconde Le Butor, C
EP93 & GP25
EP188
de la Higuera, M GP198
EP745
D’Sa, S EP1075
Danieluk, M EP1433
de la Mata, M EP698
Decourtye, L OC5.5
d’Uscio, CH EP820
Daniil, G GP15
de la Morena, LH EP125
Decristoforo, C EP1445
Díaz, JA EP184 & EP185
Danila, R EP252
& EP886
Dedecjus, M EP1435
Díaz, PRC EP125
Dantas, IA EP389
de la Rúa Franch, ER
Dedov, I EP1036, EP220,
Díaz-Guerra, GM EP8
Dantas, R EP106
EP569
EP568, EP881, EP913
Díaz-Perdigones, C EP614
Danyarova, L EP436
De La Torre, FJM EP401
& EP914
& GP71
Danyte, E EP1321, EP434
de la Vega, IR GP179
Deeks, J GP122
Díaz-Yelamos, A EP715
& EP543
De la Vieja Escolar, A
Defreyne, J EP1032
Díez, A EP863
Daphne, FA EP1032
GP235
degli Uberti, E EP789
Díez, JJ EP784, EP891
Daraki, V EP1418 & GP32
De Leo, S EP1408
Dehara, Y EP840
EP94 & GP241
Daramilas, C EP588
de Lima, JP EP1461
Dekkers, O GS2.1
Dundar, M EP1129
Darashkevich, I EP540
de Linares, LUL EP603
Dekkers, OM GP17
da Conceiça˜o Pereira, M
& EP541
De Linares, UL EP3, EP9
& OC12.2
EP816
Daroszewski, J EP775
& EP952
del Mar Moreno, M EP790
da Costa, AM GP228
& GP72
De Marinis, L EP991,
del Olmo, MI EP99
& GP229
Darstein, C GP177
EP997 & OC12.5
del Olmo, RC EP99
da Costa, JM EP706
Darwis, I EP363
De Martino, MC EP34
Del Peso Gilsanz, C EP432
& EP707
das Oliveiras, P EP794
De Miguel Novoa, P GP179
& EP705
Das, J EP1296
de Miguel-Díez, J EP431
Del Peso, C EP1415
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Del Prato, S D6.1
Di Sante, S OC9.5
do Vale, S EP281, EP898,
Dragomir, L EP979
del Río-Moreno, M EP178,
Di Stefano, M EP1408
EP96 & GP213
Drakopoulou, A EP217
EP698 & EP790
Diaconescu, MR EP764
Dog˘an, BA EP1453
Drakopoulou, M EP62
Del Val-Zaballos, F EP456
Diaconescu, S EP764
Doblas, IM EP998
Draman, MS EP1342
& EP955
Diamanti-Kandarakis, E
Dobrescu, R EP1395
Dravec, D EP1265
Delemer, B GP7
EP1098 & EHM1
& EP1466
Drelon, C OC1.2
Delerue-Matos, C EP403
Diamonde, A OC11.5
Dobrinja, C GP204
Dreval’, A EP936
Delgado, CG EP1023
Diana Ilie, M EP1220
Dobrota, VD EP1161
Dreval, A EP1141,
Delgado, L EP1289
Dias, C GP199
Doga, M OC10.3
EP1457, EP50, EP905
& GP199
Dias, D EP1142, EP297,
Dogan, F EP182, EP332
& GP193
Delgado-Lista, J EP472
EP783, EP788
& EP933
Drews, M EP388
Delia Santana-Suarez, A
& EP816
Doganay, M EP968
Drosdzol-Cop, A EP1119
EP193
Dias, S EP100
Dogansen, SC EP1038
Dušková, M EP1143,
Delia, CE EP1364
Diazzi, C GP146
& OC12.1
EP1170 & EP14
Delibasi, T EP1039
Dick, B EP820 & OC13.5
Dokmetas, HS EP834
Duarte, G EP411
Dellal, FD EP1377
Dieter, C EP411 & GP79
Doknic, M EP1046,
& GP79
& GP233
Diez, JJ EP88
EP892, EP953, EP954,
Duarte, H EP1422
Demaj, E EP634 & EP765
Diez-Perez, A GP84
EP956 & GP188
Duarte, I EP51
Demidowich, A EP13
Dik, W S12.1
Domínguez, ÓM EP886
Duarte, JS EP1486, EP414
Demir, O EP277
Dima, L EP774
Domínguez, M EP756
& EP951
Demir, O EP1165, EP962
DiMarchi, R OC2.3
Dombrovska, N GP86
Duarte, N EP243
& EP967
Dimitrijevic-Sreckovic, V
Domingues, A EP313
Duarte, R EP562
Demirba¸, T EP1122
EP367, EP677
Domingues, V EP403
Duarte, V EP139
Demircan, S EP249
& EP678
Donadille, B GP148
Dublang, M EP112,
Demirci, I EP1165
Dina, R EP123
& GP19
EP1217 & EP128
Dempster, N EP682
Dinc, M EP1165
Donath, MY EP687
Duceac, A EP1063
& EP730
Dinccag, N EP821
& OC11.3
Dudich, O EP1308
Demura, M OC3.1
Dinis, A GP109
Donato, I EP288
Dudina, M EP1248
den Bruel Annick, V
Dinis, I EP1227 & GP109
Donato, S EP1142,
Dudler, V OC13.5
OC14.4
Dinu Draganescu, D
EP1219, EP258,
Dudzinska, M EP144
Dendale, R GP189
EP1176
EP772, EP783, EP788,
Dugonjic, S EP787
Deng, Y EP1
Dinu-Pirvu, CE EP376
EP816 & GP23
Dukhan, K EP1004,
Denham, DS GP47
Dionigi, G EP1451, EP688
Dong, X EP551
EP453 & EP597
Deniz, F EP1455
& EP691
Donini, L EP713 & GP168
Duma, D EP547
Derya Bulus, A EP815
Diosdado, MA EP544
Donini, LM EP702
Dumanovic, MS EP470
Descombes, X EP745
Dirikoc, A EP1320
Donnay, S EP1332
Dumeige, L OC5.5
Desmet, C EP883
& EP1377
Donsa, K EP609
Dumitrache, C EP319
Detka, J GP154
Dirikoc, M EP1320
Dores, J EP460, EP462
Dumitrascu, A EP1007,
Dettoraki, A EP885
Ditsiou, A EP785
& EP921
EP137, EP352, EP911
Deutschbein, T EP932
Diz, Y GP52
Dorfman, L GP79
& EP980
& GP160
Diz-Chaves, Y GP156
Doroszewska, K EP1111
Dumitrascu, I EP1364
Devia, DG GP187
& GP75
& EP141
Dumitrescu, A EP1352
Devosa, I EP731
Dizdarevic-Bostandzic, A
Doroszko, M GP118
Dumitrescu, C EP206
DeVries, H MTE6
EP976
& OC7.1
& EP352
Dexneit, T GP121
Djamila, M EP279
Dotan, I EP661
Dumitrescu, I-B EP376
Dey, A EP1117
Djelic, M EP470
Dottore, GR EP1247
Dumitru, N EP117
Deyneli, O EP47 & EP851
Djerrou, Z EP743
Dottorini, M GP231
Dunauskas, V GP31
Dhaenens, CM EP1439
Djordjevic, M EP528
Doulatram, V EP1462,
Dunn, W OC3.3
Dharan, SS EP115
Djukic, A EP484
EP755, EP756
Duntas, L OC4.5
Dhayat, NA EP820
Djurdjevic, SP EP956
& EP808
Duparc, C GP12
Dhillo, W GP131 & S28.3
& GP153
Doulgeraki, A GP99
Dupuis, N EP928
Di Bari, F EP1171
Djurisic, I EP1480
Dounousi, E EP299
Dura˜ es, C EP1357
Di Dalmazi, G GP1 & GP5
& GP225
Dousset, B OC7.2
Dura˜ es, J EP394
Di Donna, V EP1341
Djurovic, MN EP956
Doyle, C GP131
Dural, AC EP1235
& EP1426
& GP188
Dozio, E EP688 & EP691
Duran, ID EP977
Di Franco, A GP8
Dmitriev, Y GP92
Draganescu, DD EP1180
Duran, P EP1130
Di Gennaro, G EP34
Do Cao, C EP1369
Dragoi, CM EP1137
Duranteau, L GP19
Di Martino, M EP713
do Han, K EP554
& EP376
Durmaz, S EP873
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Durmaz, SA EP1280,
El Ansari, N EP1065
Elouarradi, N EP1065
EP758, EP759, EP778,
EP529, EP604, EP683
& EP1350
Eloy, C EP1449
EP852 & GP102
& EP684
El Azeem, NEDA EP416
Elston, M EP1312
Ersoy, O EP1264, EP856
Durmic, T EP470
El Houda, KN EP149
Elyousfi, A EP534
& GP49
Durmus, I EP427
El Kareem, HA EP416
Emini, M EP585
Ersoy, R EP1002, EP1152,
Durmus, Y EP121,
El Mghari, G EP1065
Emous, M EP402
EP1250, EP1258,
EP1399, EP1402
El Zein, R GP2
Emral, R EP1273, EP277,
EP1264, EP1320,
& EP848
Elías, E EP869
EP967 & EP988
EP1326, EP1376,
Duro, D EP704
El-Khouly, G EP513
Emre, AU EP282
EP1377, EP1413,
Dursunoglu, D EP1101
El-Koussy, M EP986
Encica˘, S EP328
EP1429, EP237,
Dusan, V EP1089
Elaffandi, A EP160
Endelman, M EP1237
EP331, EP843, EP856,
Dusceac, R EP1018
Elamid, M EP7
Enderle, G EP1020
GP233
Dusek, T EP71 & EP81
Elamin, Y EP430
Eneva, N EP1141
& GP49
Duvvuru, S EP555
Elansari, N EP847
Engeli, R EP781
Ersoz Gulcelik, N EP1175
Dvorak, Z EP805
Elasaify, W EP1230
Engels, M GP10
Ertan, Y EP1194
Dworacki, G EP1433
Elbuken, G EP446
Engstrom, BE GP9
Erten, S EP843
& EP1450
& EP842
Eraydin, A EP1003
Ertorer, ME EP963
Dwyer, A GP153 & N1.2
Elbasan, O EP608
Erba, P EP1445
& EP969
Dydyshka, Y EP737
Elbere, I OC6.3
Ercan, O EP101
Ertugrul, DT EP1343
Dyrmishi, B EP2 & EP1370
Elbez, I EP1290, EP1427,
Ercoli, G EP1432
Erturk, E EP1017, EP132,
Dzantieva, E EP1164
EP1428 & EP1430
Ercolino, T EP92, EP93
EP332, EP336, EP608,
& EP695
Elbuken, G EP265
& GP8
EP72 & EP852
Dzeranova, L EP1034,
Eldin, AMB EP1299
Erdélyi, L EP804
Escalada, J S9.3
EP1036, EP913,
Elena, G EP989
Erdem, B EP815 & GP74
Escher, G OC13.5
EP914 & GP157
Elena, M EP591
Erdemir, RU EP282
Escobar-Morreale, H
Dzherieva, I EP539
Elena, S EP591
Erden, E EP967
MTE12
& EP760
Elena-Iuliana, P-G EP587
Erdogan, M EP1379
Escola, CÁ EP125
Dzib, FG GP15
Elewa, A EP1299
Erdogan, MF EP1199,
Escolano, E OC10.2
Dzivite-Krisane, I EP1046
Elewa, AA EP513
EP1487, EP277
Escola, CÁ EP125
Dzodic, R EP1480 & GP225
Elezovic Kovacevic, V
& EP967
Espín, MlBG EP705
EP191
Erek, M EP533 & GP102
Espín, NVG-T EP432
Eastell, R MTE5
Elezovic, V EP1114,
Erel, O EP1347
& EP433
Ebbehoj, AL OC1.4
EP166, EP177, EP75
Erel, O EP1108 & EP1320
Espada, M EP1332
Ebrahimi, F EP687
& GP139
Eremkina, A EP257,
Espallardo, MÁC EP708
& OC11.3
Elezovic, VK EP80
EP318 & EP347
& EP717
Echiburu, B EP1120
Elfaleh, E EP482
Erfurth, E-M EP1070
Esperto, H EP392
Eckstein, A EP1342
Elfekih, H EP1349,
& GP182
Espiard, S EP1439, GP120
Economou, E GP32
EP1361, EP189,
Erfurth, EM GP9
& GP28
Ediboglu, E EP277
EP335, EP66
Ergang, P EP1082
Espiart, S OC5.3
Efaishat, R EP360
& EP770
Ergur, AT EP1223
Espiga, J EP128
Efe, B EP264, EP418,
Elhadd, T EP160, EP453
& EP724
Espinosa-Nava, MA EP437
EP427 & EP90
& EP597
Eriksen, EF S1.3
Esposito, I EP692
Efremidou, EI EP1378
Elhem, BJ EP762 & EP780
Erkutlu, I EP1003
Esposito, K EP1121
Efstathiadou, Z EP1303,
Elias, N EP211
Erlic, Z EP104
& EP1293
EP1307, EP1417
Eliasson, B EP55
Ermetici, F OC6.2
Esteves, C EP1181,
& EP223
Elisabet, G EP641
Eroglu, M EP1099
EP1289, EP1357,
Egan˜ a, N EP869
Elisei, R EP1414, EP288
Erol, RS EP109
EP576, EP613, EP773,
Ehret, G EP820 & OC13.5
& GP231
?& EP836
EP870, EP871
Eisa, M EP83
Elleuch, M EP1128,
Ersoz Gulçelik, N EP810
& GP199
Eisenhofer, G EP92, EP93
EP135, EP1361,
Ersoy, A EP533, EP751,
Esteves, CM EP887
& GP25
EP167, EP66, EP77,
EP752, EP758, EP759,
Estevez, LT EP365
Ekberg, NR EP557
EP770 & GP113
EP778 & GP102
Estorninho, J EP133
Eker, EP673
Elleuch, N EP355
Ersoy, C EP1017, EP102,
Estour, B EP1126, EP1468
Ekiz-Bilir, B EP446
Elli, FM GP43
EP131, EP132,
& OC11.5
& EP842
Elmghari, G EP1337,
EP1335, EP332,
Eterović, D EP1469
Ekman, B EP1070, EP22,
EP711 & EP847
EP333, EP336, EP533,
Etxeberría, E EP1217
GP11, GP182, GP20
Elo, L EP692
EP601, EP608, EP679,
Etxeberria, E EP1040
& GP9
Eloranta, E GP50
EP72, EP751, EP752,
& EP112
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Eugenio Calogero, A
Fanni, E EP370
Fernández, F EP99
Ferreira, L EP350 & EP57
OC13.4
Farahan, AH GP164
Fernández, HG EP294
Ferreira, LB EP1449
Eugenio, B EP641
Farahani, P EP579, EP583
Fernández, I EP298
Ferreira, M EP1362,
Eun Song, D OC14.5
& GP110
& EP623
EP267, EP57 & GP98
Evans, JMM EP481
Faraldi, M EP777
Fernández, J EP1044
Ferreira, MA EP1269
Evason, J GP195
Fardella, CE OC5.1
Fernández, LP GP235
Ferreira, PA GP234
Evliyaoglu, O EP101
Fareleira, A GP234
Fernández, M EP863
Ferreira, T EP1454
Evora, F EP578 & EP626
Farha, RA EP360
Fernández-Amigo, PM
Ferrer, FM EP365
Evran, M EP1241
Farhat, K EP883
EP224
Ferrer, M EP754
Evranos Ogmen, B EP1152
Faria, C EP1037, EP1083,
Fernández-Cancio, M
Ferrero, S EP1432
& GP49
EP1085, EP1133,
EP1090
Ferrigno, R EP34
Evranos, B EP331
EP1340, EP243,
Fernández-Ladreda, MT
Ferrinho, C EP1088,
Evren, B EP330, EP620
EP320, EP95, GP237
EP1331, EP1467,
EP1177, EP1207,
& EP703
& GP239
EP563 & EP769
EP1311 & EP1486
Expósito, A EP128
Faria, M EP1448
Fernández-Marmiesse, A
Ferrinhos, C EP414
Expósito, MRA EP474,
Faria, T GP200
EP725
& EP951
EP602 & EP882
Farkash, R OC4.1
Fernandes, A EP706,
Feuchtinger, A EP52
Faro, ACN EP949
EP707 & GP200
& GP22
Férrinho, C EP1452
& GP178
Fernandes, AC EP140
Feuvret, L GP189
Furstenberger, C EP781
Farooqi, S S4.2
& EP54
Fezoulidis, I EP559
Fabbri, A EP1145
Fassnacht, M EP161,
Fernandes, C EP1362
Fian˜ o, RS EP725
& GP138
EP932, GP1, GP119,
Fernandes, G EP773
Fica, S EP1371, EP143,
Fabre, JM OC11.2
GP121, GP122,
Fernandes, I EP174
EP763, EP817, EP855,
Fabregat, J EP150
GP123, GP22, GP5,
Fernandes, L GP222
EP943 & EP947
Fabris, B GP204
OC1.1 & OC7.2
Fernandes, V EP57
Figueiredo, P EP1459
Fadiga, L EP1195,
Fattorini, G GP149
Fernandes-Rosa, F GP15
Figurová, J EP1127
EP1475, EP444
Fauconnier, A EP1126
Fernandes-Rosa, FL GP2
Filetti, S GP231
& EP445
Faucz, FR GP236
Fernandez, B EP3
Filho, JCC GP163
Fafa, N EP718
Favaro, E OC11.1
Fernandez, E EP180
Filice, A GP231
Fagg, C EP807
Fawzi, M EP1240
Fernandez, EG EP459
Filipa Martins, A GP213
Faggiano, A EP1407,
Fayzullaev, R EP15
Fernandez, LP EP920
Filipe, E EP519
GP33 & OC9.5
Fazal-Sanderson, V GP114
Fernandez, M GP111
Filipović, B EP212
Fahad Arshad, M EP190
Fazel, J GP160
Fernandez-Ladreda, MT
& EP359
& EP316
Fazzini, A EP1166
EP270
Filipović-Grcˇić, M EP172,
Fahmy, E EP412
Fechner, PY GP65
Fernandez-Real, JM GP24
EP463 & EP549
Faillot, S GP28
Fedala, NS EP1315
Ferone, D GP177
Filipovic, B GP202
Fajardo-Araujo, ME EP437
Fedala, S EP718
Ferrín, G EP698
Filipovic-Grcic, M EP43
Faki, S EP1002, EP1152,
Fedorenko, E EP749
Ferraù, F GP160 & GP175
Filippi, S EP377 & GP147
EP1250, EP1258,
Feelders, R EP182, EP933
Ferrante, E EP1043
Filisan, C EP1137
EP1264, EP1413,
& GP187
Ferrari, F EP397
Finan, B OC2.3
EP1429, EP237
Feelders, RA GP116
Ferrau, F EP1056
Finucane, FM EP720
& EP843
Feki, H EP77
Ferreira, A EP1465
Fiore, D EP537
Fakra, E OC11.5
Feldt-Rasmussen, U EP40,
& EP599
Fiore, E EP238
Falalyeyeva, T GP60
EP63, GP150, GP181
Ferreira, AG EP1298,
Fiorelli, M EP1054
Falca˜ o-Pires, I GP217
& OC13.2
EP226, EP486
Fiorentino, M EP1381
Falch, CM OC8.3
Felicia, B EP939
& EP996
Firat, SN EP384
Falcon-Perez, J NSA2
Felipe, GDJ GP2
Ferreira, AS EP660
Fish, D EP134
Falkowski, B EP388
Feller, K EP1090 & GP153
Ferreira, B EP30
Fjalldal, S EP1070
Falletta, S EP196 & EP197
Felsenberg, D EP353
Ferreira, D GP205
& GP182
Falzacappa, CV EP825
Felsinger, J EP426
Ferreira, E EP267
Fluck, C EP1090 & GP153
& GP221
Fenichel, P EP745 & S21.1
Ferreira, F EP1055,
Flamant, F NSA4
Fambrini, M EP370
Fenkçi, SM EP1405,
EP1204, EP329,
Flegg, P EP83
Fanaei, S-A EP1406
EP656, EP971
EP791, EP887, EP897
Fleseriu, M GP187
Fandin˜ o, J GP156, GP52
& EP972
& EP898
Fletcher, C EP682
& GP75
Feola, T EP1050 & EP537
Ferreira, J EP1083
Flitsch, J EP932 & GP176
Fanelli, F EP1166, EP669
Feraru, L EP813 & EP961
Ferreira, JA EP923
Florea, S EP143, EP215
& EP671
Ferjan, S GP136
Ferreira, JL EP129
& EP855
Fani, M GP185
Ferla, ML EP348
& EP337
Florentino, CA EP74
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Flores, PM EP1072
Frara, S GP231 & OC10.3
Gunes, SO EP1223
Garay, IB EP1023
Florian, S EP979
Frattini, F EP688 & EP691
& EP724
Garbis, S GP46
Floroskoufi, P EP1418
Freel, EM GP58
Gunes-Ciftci, H EP842
García, C EP869
& GP32
Freitas, C EP1279, EP496,
Guvenç, G EP964
García, CH EP627
Fokina, N EP142
GP228 & GP229
Gabalec, F EP1197 & EP837
García, CR EP406
Foldesi, I EP731
Freitas, J EP232, EP234,
Gabery, S EP1070
& EP407
Folin, C GP9
EP818 & EP923
& GP182
García, DS EP1237
Follin, C EP1070, GP182
Freitas, M GP163
Gacic, J EP367
García, F EP298 & EP623
& MTNE2
Freitas, P EP1081, EP140,
Gadaleta, R OC3.2
García, IR EP756
Fonseca, AC EP1204
EP169, EP194, EP195,
Gadawska-Juszczyk, K
García, JE EP948
Fonseca, F EP1000,
EP493, EP53, EP54,
EP1274
García, M EP9
EP1006, EP1049,
EP576, EP630
Gadelha, M S8.1
García, MIDO EP183
EP1062, EP1446,
& EP719
Gadelha, MR GP160
García, ML EP1237
EP181 & EP251
Frey, J EP986
Gadelha, P EP841, EP899
& EP1251
Fonseca, L EP567, EP824
Friis-Hansen, L EP40
& EP975
García, MTG EP432,
& EP921
Froberg, AC EP1445
Gagliano, T EP196,
EP433 & EP705
Fonseca, M EP887
Frolova, A EP1266
EP197, EP785
García, NP EP948
Fonseca, R EP414
& EP1316
& EP789
García, PdD EP920
Font, A EP1330
Fuentes, MD EP406,
Gahete, MD EP178,
García-Almeida, JM EP224
Font, MN EP294
EP407 & EP627
EP472, EP698, EP790
García-Fernandez, E
Font, P EP486
Fuentes-Fayos, AC EP929
& GP128
EP944
Fontoura, M EP1058,
Fugazzola, L EP1408
Gaillard, D GP45
García-García-Doncel, L
EP403, EP512, EP887
& EP1432
Gajate, P EP784
EP858 & EP915
& GP227
Fujikawa, N EP1242
Gajdosiik, M EP638
García-Giralt, N GP36
Forleo, R EP60
Fujimoto, S EP643
Gajkowski, P EP48
García-Jurado, P-B EP819
Formenti, AM GP231,
Fukagawa, M EP4
Gala-Błędzin´ ska, A
& EP907
OC10.3, OC12.5
Fumarola, A OC9.5
EP1338
García-Notario, P EP443,
& S22.2
Fuqua, JS GP65
Galanis, P EP1084
EP524 & EP593
Fornai, F GP223
Fureraj, T EP1370, EP2,
Galdiero, G EP786
García-Ruiz, R EP11,
Fornari, G EP1112
EP495 & EP765
Galdiero, M GP184
EP456 & EP955
Forni, D GP77
Furtado, I EP350 & EP824
Galesanu, C EP957
García-Sancho, P EP88,
Forno, I GP130
Fustinoni, S EP1043
& EP961
EP891 & EP94
Foroughi, F EP1406
Futeran, C EP228
Galfi, M EP742
García-Talavera Espín, NV
Forsgren, M GP117
Fysekidis, M OC11.2
Galie, N EP16
EP705
Foster, P GP125
Gallagher, F GP27
Goreía-Talavera Espin, MB
Foti, M EP692
Gallardo, GL EP1218
EP705
Fotinou, A EP62 & EP885
Gálvez-Moreno, M-Á
Gallego, MT EP1476
Garcia, C EP952
Foukaki, M EP625
EP159, EP500, EP941
Gallo, D EP688 & EP691
Garcia, E GP73
Fourtanier, G OC11.2
& EP1159
Gallwitz, B S9.2
Garcia, MM EP920
Fruhbeck, G S24.2
Gálvez-Moreno, MA
Galofré, JC EP227, EP733,
Garcia-Eguren, G GP24
Frade, J EP44
EP178 & EP929
GP198 & GP235
Garcia-Garcia-Doncel, L
Frago, LM EP435
Gérard, S OC11.2
Galoiu, S EP1007 & EP980
EP1174, EP1200,
& EP655
Gómez, JF EP365
Galusca, B EP1126,
EP1203, EP1287
Fragoso, MC GP6 & GP160
Gómez, JTC EP125
EP1468 & OC11.5
& EP535
Fraile, ES EP76
Gómez, MF EP708
Galva˜ o, S EP152
Garcia-Ramirez, J-R
Fraile, MR EP227
& EP717
Galvez-Moreno, MÁ
EP666
Francaite-Daugeliene, M
Gómez, NS GP179
EP819, EP907
Garcia-Segura, LM GP156
EP448 & EP449
Gómez, RC EP183
& EP1159
Gargallo, J EP227
Franceschi, S EP348
Gómez-Alfonso, FJ EP11,
Gama, P GP224
& GP198
Franceschini, SS EP1247
EP456 & EP955
Gambardella, C EP1407
Gargantini, E OC11.1
Franco, C EP100
Gómez-Gómez, E EP790
Gambaro, G EP1260
Garnelo-Caban˜ as, S EP666
Francou, B GP45
Gómez-García, I EP11
Gamian, A GP72
Garnuszek, P EP1445
Francque, S OC3.5
& EP955
Gan, KJ EP259
Garoufalia, Z EP1253
Franek, E EP577
Gorar, S EP1053
Gangemi, S GP208
Garra˜o, A EP1390
Frankel, M EP228
Gulçelik, NE EP977
Gangitano, E EP702
& GP242
Franklin, R EP682
Gulcelik, NE EP854
Gannon, A-L GP4
Garrahy, A EP1318
Franks, S EP1110
Guler, S EP1453, EP538,
Gar, C EP639 & GP196
& EP768
Franzén, S EP55
EP810 & EP977
Garach, AM EP627
Garrido, S EP57
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Garrote, S EP603
Germak, J EP291
Gielerak, G OC12.4
Gluvić, Z EP1245 & EP356
Garzón, RD GP240
Gesmundo, I GP151
Giessen, H EP18
Gluvic, Z EP484
Gasinska, T EP1348
& OC11.1
Giesteira, L EP1465
Gnanalingham, K EP1022
Gasior-Perczak, D EP1274,
Gethings, L OC3.2
Giger, O GP27
Gnessi, L EP702, EP713
EP1382 & EP1409
Ghagre, R EP844
Giglio, RV GP108
& GP168
Gasiorek, M EP1282
Ghanem, A EP649
Gil, EP632
Gon˜ i, F EP1040 & EP112
& EP1372
Ghanmi, S EP1238
Gil, A OC5.4
Go, R-E EP739
Gaspar da Rocha, A
Gharbi, R EP570
Gil, P EP1461
Godbole, A OC4.4
OC14.3
Ghasemi, A EP615
Gil, SM EP385
Godinho, C EP1330,
Gasparini, DI EP669
Gheibi, S EP615
Gilioli, L EP1131
EP750, EP795, EP796
& EP671
Gheludcova, O EP1057
Gilis-Januszewska, A
& EP829
Gastaldello, A EP802
Ghemigian, A EP117
EP1026
Godsland, I EP1084
Gaston-Massuet, C OC8.5
& EP1364
Gilleron, J EP745
Goebel, G EP1445
Gata, L GP109
Ghemigian, AM EP1221
Gillies, R EP682
Goena, MM EP869
Gateva, A EP699
& EP1419
Gilligan, L EP798, GP125
Goffin, V S23.1
Gathercole, L EP730
Ghemigian, MV EP1221
& OC3.5
Gogitidze, T EP983
& GP69
Gheorghe, I EP1138
Gilsanz, CDP EP433
Goitia, MS EP1332
Gattlen, C EP1087
& EP1147
Giménez-Palop, O EP165
Gokalp, D EP937
Gatu, A EP213 & EP260
Gheorghiu, CA EP108
Gimenez-Roqueplo, A-P
Gokcay Canpolat, A
Gatu, C EP252
Gheorghiu, ML EP1364
S17.2
EP1273 & EP1487
Gautier, J-F GP19
& GP137
Gioia, I GP214, GP215
Gokce, M EP282
Gautier, JF MTE13
Gherasim, I EP143
& GP216
Gokkaya, N EP261
Gavira, IM EP544
Gherlan, I EP1221, EP206
Giordano, C EP1056
Golchert, J OC3.4
Gavriilidou, S EP1202
& EP352
Giordano, T S17.1
Golda, A EP826
& EP859
Ghervan, C EP846
Giorgio, MRD GP16
Goldstein, A EP1353
Gavris, C EP774
& EP979
Giovinazzo, S GP208
Goldstein, AL EP1221
Gawlik, A GP67
Ghigo, E GP151 & GP192
Girdziute, M EP156
& EP1419
Gawlik, T EP1420
Ghizlane, E EP845
Giritharan, S EP1022
Goldstein, D EP1221
& EP1440
Ghizlane, EM EP1350,
Gissler, M EP1285
Golic, I EP693
Gawrychowski, J EP349
EP379, EP387
Gittoes, N EP1051
Golu, I EP1068, EP153,
Gay, S OC14.1
& EP488
& GP180
EP306 & GP53
Gaysina, L EP617
Ghorbel, D EP1128,
Giubbini, R GP231
Gomes, A EP1133, EP119,
Gazizova, G EP617
EP1349, EP1361,
& OC10.3
EP897 & EP898
Gedik, V EP967
EP167, EP189, EP66
Giudici, F GP204
Gomes, AC EP157, EP896
Geelhoed-Duijvestijn, N
& EP667
Giuffrida, G GP208
& EP974
EP635
Ghosh, M EP1296
Giugliano, D EP1121
Gomes, ARC EP1083
Geenen, V EP883
Ghyselinck, NB GP2
& EP1293
& EP243
Gehrig, A GP119
Giagulli, VA GP215
Giulea, C EP1371
Gomes, B EP899
Gelmini, S GP8
& GP216
Giulietti, K EP745
Gomes, L EP1009,
Gen, R EP835
Giamas, G EP785
Giulio, MD EP278
EP1049, EP1195,
Gener, I EP1094
Giampietro, A EP991,
Giurgi, A EP1419
EP444, EP445 & EP45
Genest, J EP661
EP997 & OC12.5
Giusti, M OC14.1
Gomes, M EP468
Gennaro, GD EP786
Giandalia, A EP1118
Giustina, A EP1020,
Gomes, R EP548
Genser, B GP107
Gianfrilli, D EP1054,
GP231, OC10.3
& EP573
Gentilin, E EP196
EP537 & GP149
& OC12.5
Gomes, V EP1055,
& EP197
Giannetta, E EP1050,
Giveon, S EP735
EP1083, EP1204,
Georgescu, C EP1364
EP537 & OC9.5
Gluer, C-C EP353
EP1269, EP243,
Georgescu, CE EP114,
Giannetta, V GP149
Glatz, P EP734
EP329, EP791, EP897
EP158, EP328 & EP846
& OC9.5
Glazunova, A EP521
& EP898
Georgescu, O EP855
Gianotti, L EP268 & GP33
Gleeson, H EP1052
Gomez Balaguer, M
Georgiou, E EP864
Giardino, E EP20 & EP924
Gligic-Kuzmanovic, A
EP1178
Georgiou, T EP1303,
Giatra, C EP1047
EP694
Gomez, R EP1046
EP1307, EP68, EP771,
Giatromanolaki, A
Glinianowicz, MO EP726
Gomez-Hoyos, E EP900
EP827 & EP828
EP1378
Glintborg, D GP59
Gomez-Sanchez, C EP37
Georgiu, C EP158
Gibney, J EP1150,
Glombik, K GP154
Gomez-Sanchez, CE EP52
Gerasimov, A GP78
EP1153, EP487,
& GP158
& GP2
Germain, N EP1126,
EP572, EP70 & EP798
Gloor, B GP185
Gomez-Sanchez, E EP37
EP1468 & OC11.5
Gibson-Helm, M EP747
Glowa, B EP1445
Gonçalves, A EP586
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Gonçalves, F EP548
Gountios, I EP861
EP985, GP114, GP138
Guldiken, S EP118,
& EP573
& EP864
& GP180
EP1198, EP121,
Gonçalves, H EP567
Gourdin, L GP143
Grothey, A EP785
EP1396, EP1399,
Gonçalves, HS EP468
Gourgiotis, D GP99
Group AMTCO, EP719
EP1400, EP1401,
Gonçalves, J EP567
Gouveia, P EP1279,
Groussin, L OC7.2
EP1402, EP1403,
Gonçalves, JA EP30
GP228, GP229
Grove, J OC3.5
EP1404, EP201,
Gonca Tamer, H EP447
& GP98
Grozinsky-Glasberg, S
EP271, EP848
Gondal, A GP125
Goyogana, A EP3, EP9
EP1391
& EP981
Gonen, MS EP296
& EP952
Gruppioni, E EP1381
Guler, S EP1317, EP1425
Gontijo, MdCD EP1011
Gozdz, S EP1382, EP1409
Grussendorf, M OC10.1
& EP56
González, A EP1218
& EP1442
Grycova, A EP803
Gulfam, T EP1358
González, CL EP862
Gozel, N EP249
& EP805
Gullu, S EP1059, EP1487,
& GP240
Graça, L EP54
Grytaas, MA EP33
EP277 & EP967
González, D EP302
Graça, S EP1291
Grzymislawski, M EP721
Gumeniuk, O EP1224
González, DM EP886
& EP1292
Gu Kim, W OC14.5
Gumuscu, HH EP467
González, EF EP1072
Grama, MA EP319
Gualtieri, A OC8.5
Gumuskaya Ocal, B GP49
& EP574
Granata, R GP151
Guan, M EP801
Gunasekara, R EP103
González, J EP863
& OC11.1
Guaraldi, G EP1166
Gundogan, R EP1223
González, L GP52
Granberg, D GP194
& GP146
Gunduz, C EP1379
González-Hermoso, C
Granda, MJD EP569
Guarnieri, V GP130
Gunes, Y EP362
EP1462
Grande, D GP214, GP215
Guarnotta, V EP1056
Gungor, K EP447
González-Lázaro, P EP11,
& GP216
Guastamacchia, E GP214,
Gungunes, A EP1280,
EP456 & EP955
Grande, E EP784
GP215 & GP216
EP529, EP604, EP683
González-Matías, L GP156
Granieri, L GP184
Guasti, D GP25
& EP684
& GP75
Grant, B EP1213, EP1354,
Gubaidullina, S GP170
Gunnarsdottir, H EP19
González-Pereira, C EP456
EP1485 & EP308
Guclu, M GP112
& EP21
González-Rubio, S EP698
Granzotto, PCD EP1244
Gudermann, T MTBS1
Gunness, A EP1150,
Gonzalez, C EP681
Grasso, LFS GP184
Gudmundsson, J EP19
EP1153 & EP487
Gonzalez, D EP341
Grasso, M EP1407
& EP21
Guntaite, V GP31
Gonzalez, EF EP1481
Gratiana, G EP199
Guedes, V EP1390
Guo, Y EP1
Gonzalez, JV OC5.1
Gravholt, CH GS1.1
Guelho, D EP1362
Gupta, A EP701
Gonzalez, S EP1484
Graziadio, C EP1054
& EP267
Gupta, P EP1039
Gonzalez-Molero, I EP755,
Grazie, GL EP537
Guerra, AL EP1030
Gupta, SK EP520
EP756, EP808
Grebennikova, T EP220
Guerra, E EP807
Guran, T OC1.3
& EP868
Greco, E OC9.5
Guerra-Navarro, L EP443,
Gurkan, H EP1401
Gonzalez-Rodriguez, E
Green, C GP69
EP524 & EP593
Gurlek, A GP212
EP170
Green, P GP124 & OC7.3
Guerreiro, S S28.2
Gurnell, M EP877 & GP27
Gonzalo, M EP808
Greenman, Y D1.1
Guerrero, F EP88
Gursel, BE EP752
Goodwin, L EP83
Gregová, J EP1086
Guessous, I EP820
Gursel, E EP752
Goran, M EP1480
Grieve, J GP195
& OC13.5
Gusova, Z EP695
& GP225
Griffin, H EP720
Gueye, M EP745
Gutiérrez, CA EP574
Gordillo, GMdP EP1331,
Grigore, A EP1371
Gugenheim, J OC11.2
Gutiérrez, MC EP8
EP1467, EP270
Grigore, C EP376
Guglielmi, G EP288
Gutiérrez, MT EP1217
& EP563
Grigorescu, F GP137
Guha, N OC3.5
Gutierrez-Aguirre, K-I
Gordon, DM EP876
Grigorie, D EP16
Guimara˜es, J EP106
EP666
Gorostidi, F EP1373
& EP240
& EP57
Guy, T EP1032
Gorska, M EP1104, EP31
Grigoriev, A EP220, EP917
Guimara˜es, JA GP90
Guzel, H EP362
& EP466
& GP157
Guimara˜es, JT GP205
Gyory, F EP1410
Gorukmez, O EP322
Grigorovici, A EP252
Guiochon-Mantel, A GP7
Gorvin, CM OC10.5
Grineva, E EP200, EP978,
Gul, AE EP289
Hána, V jr EP208
Goschnik, M EP1188
GP78 & GP92
Gul, OO EP1017, EP102,
Hána, V EP1046 & EP208
Gothilf, Y OC8.2
Grira, W EP207
EP1335, EP332,
Hanninen, A GP167
Gotovac, K EP595
Groeneweg, S S26.3
EP333, EP336, EP679
Haring, H-U P4
Gougoura, S EP618
Groma, V GP209
& EP852
Hofner, K GP22
Goulart-Silva, F GP224
Groop, L GP76
Gul, Z GP112 & GP161
Holl, B EP609
Goulden, B EP1485
Gross, DJ EP1374
Gulcelik, MA EP344
Horsch, D GP177
Goulis, D EP1084
& EP1391
Gulcelik, NE EP344
Hoybye, C EP912 & GP9
& EP214
Grossman, A EP1145,
& EP384
Haak, H GP123
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Hacker, N EP1188
Hanson, P EP668
Hernández, MC GP179
Hong, E-G EP1421
Hacques, E EP966
Hanzu, FA GP24
Hernández, TM EP569
& EP517
Haddad, M EP629
Haouchine, Z EP1182
Hernández-Barrera, V
Hong, S EP517
Hadj-Bekkouche, F
Hara, L EP16
EP431
Hong, SM EP1421
EP1234 & EP6
Harbeck, B EP800
Hernández-García, C
Hoon Chung, J GP219
Hadjkacem, F EP1349,
Harlamov, A EP415
EP1462, EP614
Hoorens, A EP1191
EP1361, EP66, EP667
Harris, NI EP1263
& GP71
Hopurcuog˘lu, D EP101
& EP770
Hartikainen, A-L EP1285
Hernando, ME EP681
Horányi, J EP1384
Hadoke, PWF EP802
Hasanbegovic, M EP1283
Hernik, A EP388
& EP1434
Hadoux, J EP179
Hasenmajer, V GP16
Herraiz, L EP184 & EP185
Horchani, I EP482
Haenelt, M EP639
Hashimoto, A EP1242
Herrera, EP EP107
Hormaechea-Agulla, D
& GP196
Hassan-Smith, Z OC3.5
Herrera-Martínez, A-D
EP790
Haffaf, E EP219
Hassiba, K EP138
EP159, EP776
Hornby, C EP798
Haffaf, L EP1386
Hatem, G EP616
& EP907
Hortopan, D EP1063
Hafiane, A EP661
Hatipogulu, B EP1015
Herrera-Martínez, AD
& EP16
Hafsa, SY EP1447
Hatri, S EP219
EP178 & EP182
Horváth, P GP37
Hagel, C EP932
Hatton, S EP430
Herrmann, E EP5
Horzelski, W GP183
Hahner, S EP52 & GP123
Hatzibougias, D EP1471
Herscovitch, P OC7.3
Hosoi, M EP27
Haj Kacem, F EP135
Hatzitolios, AI EP588
Herterich, S EP161
Hospers, G EP1045
Hajdukovic, Z EP787
Hauschild, M GP153
& EP932
Hotaran, G EP945
Hajjar, Y EP657
Hawari, R EP1192
Hescot, S EP179
Houang, M GP120
Hakaste, L GP76
Hawkins, A EP58 & GP115
Heshe, S EP70
Houari, S GP142
Hakkarainen, J EP364
Hayashi, S EP1029
Hespanhol, V EP773
Houchard, A GP191
& OC13.3
Haydar, S GP137
Hetland, ML EP40
Houlihan, D EP259
Halawa, MR EP1363
Haydardedeoglu, FE
Heuer, H S26.1
Houtman, R EP802
& EP513
EP963 & EP969
Hey-Hadavi, J EP1010,
Hoxha, V EP495 & EP765
Halder, L EP668
Haymana, C EP1165
EP1046, EP748,
Hoyos, EG GP179
Haldimann, M OC13.5
& EP362
EP884 & GP192
Hristozov, K EP1271
Halhalli, GSK EP1066
Hayon, M GP111
Heye, T GP185
Hrncic, D EP1184
Haliti, E EP585
Hazlehurst, J EP728,
Hiam, D EP1115
Hryniewicka, J EP1104
Halperin, I GP153 & GP24
EP730 & GP70
Hibbert, E EP1265
Hsiang, J OC11.4
Ham, HJ EP506
Healy, ML EP339
& EP592
Hsu, Y-C OC14.2
Hamad, F EP631 & EP649
Heaney, A GS2.5
Hidalgo, MD EP1331
Htay, T EP1458
Hamamatsu, K EP273
Heath, K EP904
Hilding, A EP557
Htet, TD EP426 & EP747
Hameg, F EP1386
Heaton, D EP386
Hill, JW EP1125
Hu, M EP1096
Hames, KY EP1385
Hebenstreit, D OC3.3
Hill, M EP1170
Hu, X EP754
Hammami, A EP355
Heck, A GP181
& EP208
Huang, C GP153
& EP762
Hedayati, M EP1406,
Hilsted, L EP40
Huang, H GP171
Hammond, G EP753
EP642, EP662 & OC5.2
Hiltermann, J EP1045
Huang, Z EP754
Hammouda, HB EP1236
Heikela, H EP692
Hirsch, D EP1374
Hubalewska-Dydejczyk, A
& EP1238
Helkkula, T GP76
& EP1391
EP1026, EP1297,
Hamouli-Said, Z EP1234
Hellstrom, A EP949
Hlavácˇková, M EP1438
EP1445, EP283,
& EP6
Helvaci, N GP212
Ho, B EP754
EP284, MTE8 & OC9.3
Han, J-H EP690
Hendawy, LM EP425
Hodes, A EP13
Huerta, ÁS EP183
Han, K EP690
& EP497
Hodson, L EP682, EP728,
Huerta, YZ EP862
Han, M EP1421
Hendra, H EP575
GP69 & GP70
& GP240
Handkiewicz-Junak, D
Henrik Nielsen, C OC13.2
Hodzic, M EP325
Huertas, RL EP882
EP1440
Henrion, D GP143
Hofland, H S30.1
Hughes, B OC3.5
Hanen, J EP762
Henrique, R EP146
Hofland, L EP182 & EP933
Hughes, BA OC1.3
Hankus, M GP67
Henry, B GP135
Hofland, LJ EP196
Hughes, D EP1192 & EP97
Hanley, B EP259
Hepsen, S EP1097
& EP197
Hughet, I EP1072
Hanna, P GP45
Herberg, F GP28
Hogan, A EP696
Huguet, I EP180 & OC10.2
Hannan, F S1.2
Hermann, P GP59
Hogea, MD EP774
Huh, JH EP236
Hannan, FM OC10.5
Hermann, W GP123
Holien, J EP1190
Huhtaniemi, I GP118
Hannon, Am EP1041
Hermosilla, AMG EP569
Hollenberg, A S6.3
& OC7.1
Hans, D EP243
Hermus, AR GP160
Holst, J S9.1
Hui, Z GP166
Hansen, A EP40
Hernández, IC GP179
Homorodean, C EP399
Hulsbergen-van de Kaa, C
Hanson, J EP928
Hernández, J EP984
Homuth, G OC3.4
GP10
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Humphriss, E GP65
Iglesias, P EP784, EP88,
Isabel Oliveira, A EP194,
Jain, A EP1052
& GP66
EP891, EP94 & GP241
EP195 & GP217
Jako, M EP731
Hunter, M GP131
Iglesias, SG EP8
Isailovic, T EP1114,
Jakob, F MTE9
Hunter, S EP1041
Igna, CP EP1364
EP166, EP177, EP191,
Jakobi, M OC7.1
Hunyady, L EP804
Ihtiyar, E EP110
EP75, EP80 & GP139
Jakuboniene, N EP1437
Huo, Y GP129
Ikonomi, M EP1370
Isenović, ER EP1245
& EP479
Hurej, S EP1382
Il’in, A EP1036
& EP356
James, A EP1306
Hurme, S GP50
Ilhéu, O EP1459
Ishimwe, J EP37
Jan vanderLely, A EP1010
Husebye, E EP49
Ilhan, TT EP1101
Isidori, AM EP1050,
Jana, J EP553
Husebye, ES EP33
Ilias, I EP793
EP1054, EP537,
Jandíková, H EP14
& EP59
Ilic, D EP1114, EP166,
GP149, GP16 & OC9.5
Janezˇ, A EP1105
Husi, G EP495
EP177, EP191, EP75,
Isidoro, J EP1461
Janeski, H EP367, EP677
Huson, L GP131
EP80, GP139 & GP140
Isik, S EP56
& EP678
Huten, N OC11.2
Ilic, I EP64
Islam, N EP1016
Janeski, N EP367
Hutter, N OC9.2
Ilie, MD EP830
Ismail, M EP205
Janez, A GP136
Huzmeli, C EP675
Illes, P EP803
Ismailov, S EP1186,
Jang, HW OC9.4
Hwang, K-A EP739
Ilovayskaya, I EP1141,
EP1187 & EP686
Jang, J-Y EP438
& GP144
EP905 & GP193
Isomaa, B GP76
Janicki, A EP1433
Hyuk Kim, T GP219
Ilsley, D EP409
Istók, R EP1384
& EP1474
Ilyin, A EP521, EP568
Ito, K EP1385
Janković, S EP359
Iacovazzo, D EP991
& EP881
Ito, S GP14
Jankovic, A EP693
Iacoviello, M GP214,
Imen, A EP780
Itoh, Y EP273
Jankovic, D GP197
GP215 & GP216
Imga, NN EP1035
Ittmann, M OC7.5
Jannini, EA EP370
Iacuaniello, D EP1056,
İmga, NN EP1453
Iushko, K EP458
Janssen, J GP174
EP34 & EP927
Imhof, R EP782
Ivan, M EP240
Janssen, JAMJL GP116
Iancu, EM EP307
Imre, E EP47
Ivanova, A GP92
Jansson, M GP182
Iancu, S EP560
In Kim, H GP219
Ivashenko, O GP157
Jarek-Martynowa, IR EP561
Ianevskaia, L EP200
Inácio, A EP267
Ivovic, M EP127 & EP42
Jarić, I EP212 & EP359
Ibán˜ez-Costa, A EP698
Inácio, I EP106
Iwakura, Y GP14
Jaric, I EP779
& EP929
Ing, S EP291
Iwasa, T EP1156
Jarvis, S OC3.2
Iban˜ez-Costa, A EP941
Iniesta, J EP681
Iyidir, OT EP39
Jarzab, B EP1420, EP1440
Ino, R EP840
Izumi, Y EP1270
& EP349
Ibadula, S EP1301,
Inostroza-Nieves, Y OC6.5
Izuzquiza, A EP1040
Javier Martinez-Martin, F
EP1302 & EP1304
Ibarra-Reynoso, L-d-R
Ioachim, D EP1216,
EP193
EP666
EP1221 & EP1466
Járay, B EP1384 & EP1434
Jayanthy, R EP1140
Ibarra-Reynoso, LdR
Ioana, AA EP587
Jannari, M OC4.2
& EP475
EP437
Ioana, IA EP720
Jarvelin, M-R EP1110
Jayasena, C GP131
Ibragimova, N EP736
Ioannidis, D EP1139
Jørgensen, JOL GP17,
Jayaweera, J EP124
Ibraheem, N EP97
Ioannidis, J EP744
GP181, EP63, GP190
Jazbec, A EP508
Ibrahim, A EP1240
Ion, O EP1371
& EP654
Jaziri, H EP355
& EP649
Iordachescu, C EP1063
Jørgensen, N GP150
Jeandidier, N EP1352
Ibrahim, NA EP1299
& EP16
Jabrocka-Hybel, A OC9.3
Jeanneret, F EP782
Ibrahim, RH EP497
Iorgi, ND EP922
Jacewicz, M EP1104
Jedeon, K GP142
Ibrahim, WA EP425
Iozzo, P MTBS2
Jach, R EP141
Jedrzejuk, D EP1135
Ichihara, A EP1014
Ipekci, S EP1214, EP256,
Jackuliak, P GP38
Jemuovic, Z EP956, GP188
Icin, T EP1024, EP1089,
EP419 & EP421
Jacob, J EP1249 & EP1296
& GP197
EP116, EP245
Ipekci, SH EP1101,
Jacob, S EP597
Jendrzejewski, J EP396
& EP709
EP1167 & GP96
Jacyna, A EP577
Jenkinson, C EP798
Iconaru, L EP225
Ippolito, S EP688
Jae Chung, Y GP219
Jenny-Burri, J OC13.5
Ida Maiorino, M EP1293
%& EP691
Jaeschke, H OC4.2
Jensen, B EP40
Ientile, R GP175
Iqbal, Z EP1092, EP1225,
Jaffe, A EP735
Jensterle Sever, M GP39
Ifteni, PI EP774
EP205 & EP761
Jaganmohan, B EP552
Jensterle, M EP1105
Igarashi, Y GP14
Irahara, M EP1156
& EP553
& GP136
Igaz, P GP3
Iregui, IO EP1023
Jagucianskaite, G EP171
Jeon, MJ EP1366, EP1367
Iglesias, MMG EP1023
Irfan, M EP1262
& GP211
& EP1421
Iglesias, N EP1040
Irigoyen, L EP1332
Jahan, S EP1092, EP1225,
Jeon, S-Y EP1189 & EP151
& EP112
Irwin, S EP501, EP558
EP205 & EP761
Jeon, Y EP231, EP233
Iglesias, NC EP1217
& EP584
Jahromi, MS EP1125
& EP697
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Jeong, JS EP554
Joshi, S EP555
Kalthoum, M EP1128,
Karamagiolis, S EP559
Jeong, YA EP987
Joshi, SR EP553
EP189, EP77 & EP770
Karanikas, MA EP1378
Jercalau, S EP108,
Jouinot, A OC7.2
Kaltsas, G EP1253, EP176
Karapanagioti, A EP67
EP1395 & GP21
Jozkow, P EP1160
& EP67
Karapanou, O EP1047
Jeremic, D EP694
Jublanc, C GP189
Kaltzidou, V EP217
Karathanassi, I EP483
Jeremic, R EP470
Jueppner, H GP45
Kamada, T EP643
Karavanaki, K GP99
Jervis, N EP192 & EP746
Jung, GS EP506 & GP56
Kamalov, T EP736
Karavitaki, N EP1051,
Jesús, C EP641
Jung, KY EP1451
Kamaruddin, S EP25
GP114, GP180 & S13.1
Jessen, N EP654
Jung, SJ EP590
Kamenicky, P GP19
Karayel, T EP679
Jesus Obregon, M GP217
Junquera, F EP165
Kamenov, Z EP699
Karbownik-Lewinska, M
Jesus, C EP1323 & EP32
Jurecka-Lubieniecka, B
& GP82
EP1325
Jesus, DFM EP74
EP349
Kamilla, I EP1124
Karefylakis, C EP680
Jeunemaitre, X GP15
Jurek, A OC12.4
Kaminskyi, O GP86
Kareva, M EP1025
Jeung, E-B EP1100, EP248,
Juskiene, R EP171
Kamp, K S14.3
& EP345
EP727, EP738 & GP42
Juszczak, M EP682
Kamyshna, V EP454
Karim, R EP190 & EP316
Jevtic´, JT EP1245 & EP356
Juul, A GP150
& EP455
Karimova, M EP314
Jguirim, A EP833
Juul, R GP152
Kamyshny, A EP454
& EP324
Jhamb, R EP408
& EP455
Karlovich, N EP242
Ji Jeon, M OC14.5
Kósa, J EP1434 & GP37
Kanamoto, N EP27
& EP527
Jiang, M EP1
Kohrle, J OC3.4
Kandaraki, E EP1098
Karmali, R EP225
Jiménez, CM EP882
Komoglu, S EP565
Kang, H-C EP987
Karonova, T EP200
Jiménez, IA EP294
Kovesdi, A EP1434
Kang, HY EP727
Karsenty, G S7.2
Jiménez, MJJ EP581
Kugler, A EP91
Kang, R EP494
Kartal, I EP1243 & EP447
Jiménez, T EP1284
Kuhnen, P S24.1
Kang, S EP316
Karwowski, B EP1435
& GP210
Kusters, B GP160
Kang, SA GP42
Kasamaki, Y EP1270
Jiménez-García, R EP431
Kałuz˙na, M EP1074,
Kania, L EP577
Kasifoglu, N EP1294
Jiménez-Vacas, JM EP790
EP1433 & EP1474
Kanouta, F EP217
& EP467
Jiménez-Varas, I EP185
Kabacam, S GP212
Kaoustou, S EP239
Kasparova, P EP837
Jimenez, F OC8.5
Kablia Samia, O EP138
Kaplieva, M EP556
Kassi, E EP67 & GP236
Jimenez-Varas, I EP184
Kacem, FH EP1128,
Kapliyeva, M EP515
Kassi, G EP1008, EP1098
Jmaa, A EP355
EP167 & GP113
Kappeler, L OC5.5
& EP38
Joa˜o Bugalho, M EP1049,
Kapsalaki, E EP861
Kassir, N GP110
Kacem, M EP1389
EP1055, EP329
Kapusta, P OC9.3
Kastanakis, S EP625
& EP441
& EP791
Kara, M EP620
Kastelan, D EP71, EP81
Kadioglu, P GP187
Joa˜o Oliveira, M EP1155
Kadrina, N EP1036
Karabid, NM EP926
& GP122
& EP818
Kafetzi, M EP62 & EP885
Karabulut, E GP212
Kastelan, M EP71
Joao Martins, M OC14.3
Kaftanovskaya, E EP754
Karaburgu, S EP1129
Katalinic, D EP209
Joaquim, S EP1133
Kahraman, S EP1144
Karaca, A EP1175,
& GP232
Jodkowska, A EP187
Kahramanca, FD EP1429
EP317, EP344, EP384
Katamadze, N EP504,
& EP78
Kaikkonen, K EP1110
& EP854
EP650 & EP797
Johannsson, G EP55
Kaindl, G EP1087
Karaca, Z EP1129
Kats-Urgurlu, G EP155
& GP9
Kaiser, U EP1342
& EP968
Katsamakas, M EP1473
Johansson, A GP182
Kajdaniuk, D EP349
Karachaliou, F EP62
Katsavouni, C EP366
Jokela, H EP364 & OC13.3
Kajor, M EP1382
& EP885
Kaufman, J-M EP1191
Jona, E EP1115, GP135
Kakarigi, L EP71
Karachentsev, I EP982
Kaufmann, ML EP1087
& GP141
Kalaitzidis, R EP299
& EP983
Kaur, G EP558
Jonas, N EP13
Kalaitzidou, S EP217
Karaduman, T EP815
Kaur, H EP1249
Jonas, W OC3.4
Kalan Sarı, I EP1053
& GP74
Kawaguchi, S EP1242
Jones, G GP104
Kalantaryan, LG EP422
Karagoz, H EP644 & GP95
Kawamura, H EP1270
Jonsdottir, G EP19
Kalere, I GP209
Karahan, I EP604
Kawashima, A EP273
Jonsson, P EP1010, EP884
Kalhan, A EP303 & GP114
& EP683
Kaya, A EP1305, EP1416
& GP192
Kalikakis, G EP1418
Karakaya, P EP1235,
& EP545
Jordan-Perez, B EP666
Kalinin, A EP1025
EP644 & GP95
Kayas, D EP86
Jordana, L EP247
Kalinin, P EP799 & EP895
Karakaya, S EP1343
Kayatas, M EP675
Jorgensen, J MTE2
Kalisz, M EP908
Karakose, M EP1097,
Kazakou, P EP202
José Requena-Tapia, M
Kalnina, I OC6.3
EP1368, EP327
Kazaryan, A EP1457
EP790
Kalogeris, N EP239
& EP999
Kazmi, SAR EP761
Joshi, A EP844
Kalter-Leibovici, O EP735
Karakurt, F EP1416
Kearney, T EP1022
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Kearns, S EP430
Khan, I EP85
Kim, JH EP452, EP531,
Klimaite, R EP1321,
Kebapci, M EP1444
Khan, R EP498
GP162, GP54 & GP87
EP1436 & EP164
& EP69
Khasanova, K EP464,
Kim, K-S EP516
Kljajic Babic, K EP1151
Kebapci, MN EP110
EP465, EP617
Kim, M EP1366 & EP1367
Klocek, M EP357
& EP1444
& GP170
Kim, MJ GP56
Kloos, C EP528
Kebapci, N EP69
Khasawneh, A EP424
Kim, MK EP554
Klose, M EP40 & GP181
Kebapcilar, A EP1167
Khatib, M EP867
Kim, NH GP91
Klovins, J EP931 & OC6.3
Kebapcilar, AG EP1101
Khattak, A EP1339
Kim, S-M EP516, EP950 &
Kluczynski, L EP1026
Kebapcilar, L EP1101,
Khessairi, N EP1193,
EP1189
Kluk, A EP1450
EP1167, EP1214,
EP1208 & EP1212
Kim, SG EP1451 & GP91
Klusonova, P EP730
EP256, EP419, EP421
Khiari, K EP1232,
Kim, SK EP438
Kluth, O OC2.3
& GP96
EP1233, EP147,
Kim, SR EP590
Klyushina, A GP78
Kebebew, E GP124,
EP482, EP832
Kim, SW EP1424 & OC9.4
Knape, M GP28
GP186, OC7.3 & S19.2
& EP87
Kim, SY GP162
Knappe, U GP176
Kedad, L EP718
Khodgaeva, F EP1106
Kim, TH OC9.4
Knezevic, N EP71
Kee Shong, Y OC14.5
Khoo, B EP985
Kim, TY EP1366, EP1367
Knigge, U D2.1
Keerthi, AvB EP555
Khoo, J EP24 & OC11.4
& EP1421
Knip, M S29.1
Keevil, B EP1169
Khovidhunkit, W EP1288
Kim, WB EP1366, EP1367
Knispelis, R EP839
Kefeli, M GP243
Khripun, I EP1164
& EP1421
Knobloch, L EP932
Kehinde, A EP1095
& EP695
Kim, WG EP1366, EP1367
Kołodziej-Kłe˛k, A EP1338
Keil, M GP68
Khroyan, A EP304
& EP1421
Kołodziejczak, R EP1205
Keinanen-Kiukaanniemi, S
Khusniyarova, K EP1141
Kim, Y EP1256, EP452,
& EP1336
EP1110
Khyzhnyak, O EP982
EP531, GP54 & GP87
Kobyliak, N EP1146,
Keithellakpam, K EP408
& EP983
Kim, YB GP145
EP622, GP60 & OC2.4
Kek, PC EP29 & EP46
Kialka, M EP1111,
Kim, YM EP700
Koca, C EP1108
Kekstas, G GP31
EP1148, EP141,
Kim, YN OC9.4
Koca, N EP759
Kelepouris, N EP748
EP357, EP371
Kineman, RD EP698
Koca, TG EP759
Kelestimur, F EP1129,
& EP890
Kinikoglu, O EP834
Koch, M EP5
EP968 & S18.2
Kiamanesh, R D2.2
Kinlen, D EP696
Kochanowski, J EP908
Kelly, N EP1309
Kiec-Klimczak, M EP284
Kiokas, S EP423
Kocjan, T EP36, GP39
Kemali, Z EP219
Kilbane, M EP259
Kirac, CO EP1101,
& OC10.4
Kempegowda, P EP1052
Kilic, AU EP968
EP1214, EP256
Kocsis-Deák, B EP1434
& OC3.3
Kilic, I EP237
& GP96
Koetsveld, Pv EP182
Kendereski, A EP127
Kilic, M EP1377, EP1429,
Kirchner, J N2.2
Kogan, M EP1164
& EP42
EP237 & GP233
Kirchner, T EP52
Koh, SB EP236
Kendir, IC EP421
Kilicarslan, A EP1429
Kiremitci, S EP967
Kohler, F EP1369
Kenyeres, P EP1410
& GP233
Kiric, MM EP491
Kok, I EP332
Kermaj, M EP495, EP634
Kilicli, F EP834
Kirnap, NG EP1431
Kokareva, L EP736
& EP765
Kilit, TP EP1380
& EP39
Kokkinos, M EP67
Kero, J OC4.2
Kilkelly, K EP720
Kirschner, G GP37
Koksharova, E EP561
Kerstens, MN EP155
Killinger, Z GP38
Kiseleva, T GP170
Kolátorová, L EP14
& N1.3
Kim, A EP1141
Kiselova, I GP86
Kolag˘ası, O EP1053
Keskin, C¸ EP277
Kim, B EP233 & EP697
Kistorp, C EP63 & GP181
Kolackov, K GP165
Keskin, C EP1059, EP967
Kim, C-W EP1109
Kita, M EP1303, EP1307,
Kolenc-Peitl, P EP1445
& EP988
Kim, CH EP590
EP1417, EP1471,
Kolesnicova, G EP917
Keun, H NSA1
Kim, D-M EP438, EP605
EP223, EP68, EP771,
Kolici, E EP2
Keutgen, XM GP124
& EP729
EP828 & GP40
Koller, T EP1173
& OC7.3
Kim, DS EP1116 & EP925
Kitagawa, W EP1385
Kollerova, J EP1046
Khabeishvili, N EP658
Kim, G-S EP151
Kitajima, N EP4
Kollipara, P EP1354
Khachatryan, M EP304
Kim, H EP506, GP219
Kitsos, A EP299
Kolodkina, A EP1025
Khacimova, L EP200
& OC9.4
Kiyici, S EP322, GP112
Kolodziej, M EP1477
Khajavi, N EP806 & OC2.3
Kim, HI EP1424 & OC9.4
& GP161
Kolomiets, N EP749
Khalaj, A EP662 & OC5.2
Kim, HJ EP729
Kleber, ME GP107
Kolosszar, S EP731
Khalfallah, Y EP1126
Kim, HK EP987
Klein, J-P EP1126
Kolouri, O EP877
Khalid, M EP631 & EP649
Kim, HS GP145 & GP91
Kleinau, G OC2.3
Kolsi, B GP113
Khalimova, Z EP314,
Kim, HY EP1451
Kleine, MT EP385
Kolukula, VK EP552,
EP324 & EP901
Kim, I EP233 & EP697
Klephortova, I EP521
EP553 & EP555
Khan, A EP291
Kim, J-H EP729 & GP169
Klett, D EP1123
Komarowska, H EP388
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Komerdus, I EP1069
Kotaja, N OC13.3
GP22, GP119, GP121,
EP1366, EP1367 &
& EP50
Kotis, M EP217
& EP161
EP1421
Kometani, M OC3.1
Koukkou, E EP793
Krompa, K EP1472
Kyle, C EP1314
Kondracka, A EP48
Koukoulioti, E GP80
Krssak, M EP638
Kyoung Kim, M EP690
Kondratiuk, K EP1146,
& EP176
Krstevska, M EP499
Kyriacou, A EP481
EP622 & OC2.4
Koukoulis, G EP483
Krude, H MTE4 & OC2.3
Kyriienko, D OC2.4
Kondratiuk, V EP1146
Koukoulis, GN EP559
Kruljac, I EP43, EP172,
Kyrimis, T EP217
& EP622
& EP618
EP463 & EP549
Kondrotiene, A EP434,
Kouraklis, G EP1253
Krupinova, J EP257,
La Sala, D EP1064
EP839
Koussay, A EP646, EP780
EP318, EP323 & EP347
La Vignera, S OC13.4
& GP244
& EP1229
Krylov, V EP651
& EP35
Konijnenberg, M EP1445
Koutsilieris, M EP275
Krzesinski, P OC12.4
Lacˇković, M EP1245
Konishi, S OC3.1
Kovács, L GP44
Ksela, U EP204
Labashova, V EP480
Konrade, I EP931, GP209
Koval, S EP458
Ksiaa, M EP355 & EP762
Lacka, K EP721
& OC6.3
Kovaleva, E EP257
Kuzˇma, M GP38 & EP1173
& EP1348
Konstantinova, E EP663
Kovo, M EP1185
Kucharczyk, M GP154
Lacquement, E EP616
Konstantopoulos, K
Kowal-Bielecka, O EP466
Kudo, M GP14
Lacramioara Serban, I
EP417, EP442
Kowalczyk, M EP1348
Kudou, K GP134
EP809
& EP509
Kowalik, A EP1382
Kukulska, A EP1420
Lacroix, A P3 & EP1039
Kopchick, J S3.2
Kowalska, A EP1274,
& EP1440
Lacroix, D OC5.3
Kopczynski, J EP1382,
EP1297, EP1382,
Kulaksizoglu, M EP545,
Lacy, C EP558
EP1409 & EP1442
EP1409 & EP1442
EP1305 & EP1416
Laczmanski, L EP1135
Kopilova, O GP86
Kowalska, I EP466
Kulcsár, I GP44
Lafoyianni, S EP1139
Kor, A GP96
& EP1104
Kulczynski, L EP283
Lages, A GP35, EP44,
Korac, A EP693
Kozan, P EP592
Kuliczkowska-Plaksej, J
EP45, EP61 EP203,
Korac, A EP693
Koziara, M EP1477
EP1135
EP392, EP394, EP444,
Korac, B EP693
Koziolek, M EP229
Kumar Ch, S EP552
EP445, EP1009,
Korbonits, M GP160,
Kozloviene, D EP1437
Kumar, A GP195
EP1049, EP1195 &
GP195 & EP954
Kramer, U EP800
Kumar, H GP167
EP1475
Koreiviene, R EP164
Krajewska, J EP1420,
Kumar, J EP134
Laguna, MdCS EP581
Koren, R EP1313
EP1440 & EP1441
Kumar, M EP1210
Lahesmaa-Korpinen, A-M
Koren, S EP199 & EP1313
Krajnc, M EP204
Kumbasar, A EP1327
EP1285
Korevaar, T S5.1
Kraljevic, I EP71
Kummer, E EP199
lahner, H GP177
Korkmaz, HA EP410
& EP81
Kumru, H OC12.3
Lai, A EP688 & EP691
& EP413
Krasilnikova, V EP1308
Kundzina, L EP342
Lai, J EP321
Korolenko, H EP1308
Krasner, A GP47
Kunori, T EP1242
Lainetti, KR EP380
Korpershoek, E OC7.2
Krass, M EP607
Kunzke, T OC1.1 & EP52
Lainez, M EP1001
& EP155
Kratschmar, D EP781,
Kuppusamy, M EP37
Laiz, B EP99
Korzynska, W EP78
EP782 & EP822
Kuprionis, G EP1437
Lakatos, G GP37
Kósa, JP EP1384
Kraus, J EP1441
Kurek, A GP154 & GP158
Lakatos, P GP37, EP1384
Kosák, M EP14 & EP208
Krawczuk-Rybak, M
Kurowska, M EP831
& EP1434
Koschka, K EP1188
EP1226
& EP850
Lakis, Me GP124
Koseoglu, D EP287
Krawczyk, M EP775
Kursat, FM EP1235
Lal, V EP1239
& EP1329
Krcma, M EP293
Kurt, CC EP1379
Lalli, E EP91 & GP2
Kosilek, RP EP1027
Krebs, M EP638
Kurt, K EP1101
Laloglu, E EP1108
Kossiva, L GP99
Kreivaitiene, E EP543
Kuru, B GP243
Lalonde, MN EP1373
Kostareva, A GP78
Krentowska, A EP466
Kust, D EP172
Lam, A EP426
Kostic, S EP64
& EP1104
Kusumoto, T GP134
Lam, L EP1314
Kostin, G EP269 & EP286
Kriksciuniene, R EP543
Kut, A EP39
Lamaziere, A GP19
Kostitska, I EP628
& EP1102
Kutbay, NO EP1194 & EP1379
Lambert, E GP135
Kostoglou-Athanassiou, I
Krivonosov, N EP760
Kutin, M EP799 & EP895
& GP141
EP136, EP221, EP222,
Krivosheev, A EP126
Kuzior, A EP105, EP107,
Lambert, G GP135, GP141
EP275, EP276, EP366,
& EP1457
EP170, EP193, EP390,
& EP1115
EP368, EP1300 &
Krivosheeva, Y GP193
EP530, EP621 & EP757
Lambert, P EP295
EP1460
& EP905
Kuzmenko, N EP695
Lambrescu, IM EP763
Kostopoulos, M EP366
Krogh-Rasmussen, A
Kwapich, M OC5.3
Lambrinoudaki, I EP1084
Kostova, M EP1271
OC13.2
Kwon, H-S OC14.5,
& EP214
Kostovska, KB EP499
Kroiss, M OC1.1, OC7.2,
EP554, EP690,
Lameirao, C EP468
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Lamia, K EP279
León, MVC EP563, EP769,
EP713, EP1050 &
Limem, K EP1290
Lamy, C EP179
EP1331 & EP1467
EP1054
& EP1430
Landin, A OC3.4
Lean, M S24.3
Lenzi, P GP223
Lin, H EP1
Lanne, T OC6.4
Lebkowska, A EP466
Leo, M OC4.4
Lin, K-H GP64
Lang, F OC11.5
& EP1104
Leo, MD EP927
Lin, W GP171
Lang, K GP122
Leboulleux, S D5.2
Leon, MVC EP270
Lin, Y EP1
Langdahl, B D3.1
Leca, B EP855
Leopizzi, T GP214, GP215
Linardi, A EP793
Langova, D EP1272
Leca, BM EP143
& GP216
Linares, JLC EP406
Lania, A OC7.4
Lechner, A GP196
Lerchbaum, E S27.2
& EP407
Lania, AG EP924
& EP639
Lessi, F EP348
Lindgren, M GP117
lanschakov, K EP323
Lecumberri, B EP904
Leszczynska, E EP1226
Linglart, A S1.1 & GP45
Lanz, C EP609
Leczycka, M EP396
Leteurtre, E EP1369
Links, TP OC9.1 & EP155
Lapauw, B EP1019
Leczycka, ME EP766
Letra, L EP704
Lio, S EP1215
& EP1191
Ledwon, A EP1440
Leushev, B EP749
Lioni, A EP239
Lapshina, A EP917
Lee, C EP231
Leustean, L EP188
Lipinska, D EP466
Lara, A EP641
Lee, EJ EP960
& EP961
Lippert, J GP119
& EP1278
Lee, H-M GP47 & EP1109
Leví, AR EP1072
Lira, A EP1356
Lardiés-Sánchez, B EP461
Lee, HJ EP700
Levina, K EP142
LIRA, D EP490 & EP492
Laroche, S GP189
Lee, Hm EP729
Levine, F OC6.1
Litwiniuk, A EP908
Larrán, L EP1278
Lee, J-H OC14.2, GP91
Levine, MA GP47
Litwinowicz, M EP721
Larrauri, MZ EP125
& EP248
Levterov, G EP600
Liu, C-L OC14.2
Larsen, TH EP33
Lee, JH EP727 & EP1100
Levterova, B EP600
Liu, Q EP801
Larumbe, T EP3, EP9
Lee, K EP231
Levy, S EP1374
Livadas, S OC4.5 & EP588
& EP952
& EP959
Lewandowski, K GP183
Livingstone, DEW EP802
Laschet, C EP928
Lee, KY EP590
Lewicki, M EP144, EP338
Liyanarachchi, KD EP879
Lason, W GP154
Lee, M EP605
& EP865
Lizama, J OC5.1
Lassoued, N EP833,
Lee, MY EP236
Lewinski, A GP183,
Lizarraga, A EP1040
EP1236 & EP1238
Lee, S-H GP145, EP531
EP1325
& EP1217
Laszlo, A EP742
& EP690
& EP1435
Lizis, P EP1297
Lattarulo, MS GP214
Lee, SB GP54, GP87 &
Lezaic, L EP1445
Lizis-Kolus, K EP1297
& GP216
EP452
Lhadj, C OC5.5
& EP1382
Latt, J GP182
Lee, W GP129
Li, G EP551
Ljubic, S EP508
& EP1070
Leenhardt, L GP148
Li, L GP171
Ljubojevic, N EP806
Lau, E EP195
Lefebvre, H GP12 & GP120
Li, Q OC1.5
Llahana, S N2.4
Lau, N EP321
Lefter, A EP1067
Liang, J GP171
Llamazares-Iglesias, O
Laukiene, R EP1412
Leighton, E GP104
Liang, R GP119
EP866
Laura Tanda, M EP691
Leijon, H EP163
Liarigkovinos, T GP32
Llavero, M GP198
Laura, I EP939
Leita˜ o, C EP919
& EP1418
& EP227
Laura, MM EP74
Leita˜ o, F EP44
Libé, R OC7.2
Llevy, S EP1391
Lauretta, R GP149
Leita˜ o, P EP872
Libè, R GP123
Lloclla, EAC EP270,
Lauretti, L EP997
Leitao, C EP648
Libeert, D EP812
EP563 & EP1467
Laursen, T EP40
Leite, V MTE14, OC14.3,
Licchelli, B GP214, GP215
Lobo, C OC14.3
Lautier, C GP137
GP23, GP126, EP258,
& GP216
Lobo, J EP82
Lavenberg, J GP192
EP297, EP1219 &
Lichiardopol, C EP1364
Lobstein, T S4.3
Lavy, R EP199
EP1454
Lichtenegger, K EP609
Locatelli, M EP924
Law, N-M OC11.4
Leite-Moreira, A GP217
Lidiya, B EP989
Locht, H EP40
Lazúrová, I EP1127
Leiva, Ad EP681
Lienhardt, A GP120
Locsei, Z GP44
Lazúrová, Z EP1127
Leka-Emiris, S EP62
Lietzow, J OC3.4
Lodish, M GP68 & EP13
Lazanas, M EP239
Lemme, R EP152
Lila, B EP120 & EP138
Loeliger, R OC9.2
Lazaris, E EP423
Lemos, E EP51
Lim, HJ EP700
Lof, C OC4.2
Lazarou, L EP1417
Lemos, N GP79
Lim, J EP1314
Lofrano-Porto, A OC4.3,
Lazo-de-la-Vega-Monroy,
Lemos, R EP704
Lim, JS EP236
GP26, EP84 & EP807
M-L EP666
Lenarcik-Kabzda, A
Lim, SL EP115
Loh, LM EP29 & EP46
Lazo-de-la-Vega-Monroy,
EP1135
Lima, C OC4.3
Lohse, K EP806
ML EP437
Lenart-Lipinska, M EP144
Lima, LM GP234
Loiodice, S GP142
Lazovic, R EP1283
& EP338
Limam, K EP1427 & EP1428
Loktionova, A EP1141
Lea˜ o, M EP305 & EP807
Lenzi, A OC9.5, GP16,
Limbert, C GP222,
Lombès, M OC5.5
León, CA EP107
GP149, GP168, EP537,
EP1207 & EP1486
Lombardi, G EP777
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Lombes, M GP7
Ludecke, DK GP176
Maaroufi, A EP441
Maisnam, I EP343
Lomtatidze, G EP647
Ludgate, M EP1342
& EP1389
Maitre, SC GP19
Londero, T EP919
Ludwig, P EP52
Macário, F EP175
Majeed, M EP572
Longhurst, A EP280
Ludwig-Gałęzowska, A
Macário, MC EP394
Majewska, R EP890
Lopes, A EP567
OC9.3
Macazaga, VP EP294
Majewska, U EP1274
López, AA EP948
Luger, A EP638 & EP1010
Macedo, D EP297
Majic Milotic, D EP1151
Lopes, AM EP824
Luisi, F GP168
Macena, LB GP178
Majos, A GP173
López, AV EP878
Luiz, HV EP1298
MacFarlane, H EP1306
Majstorović, T EP1469
López, IF EP563
Lumi, E EP2, EP546,
Machado, C EP51, EP145,
Mak, G EP1339
López, J EP973
EP1370
EP1155, EP1211,
Mak, OK EP894
López-Fernández, J EP906,
& EP1470
EP1351 & EP1356
Makarchuk, N EP420
EP909 & EP910
Lungu, I EP114 & EP158
Machenahalli, P GP29
Makay, O EP1194
Lopes, JM EP174
Lunn, M EP1075
& GP30
Makhlina, A EP556
Lopes, L EP139, EP887 &
Luo, C-W EP1103
Machlowska, J OC9.3
Makhlina, E EP515
EP1359
Lupian˜ez, A EP681
Maciejewski, A EP721
Makhonin, A EP1286
López-Iglesias, M EP11
Luque, PS EP708 & EP717
& EP1348
Makitie, O OC10.5
& EP955
Luque, R-M EP819
Maciejewski, M EP1372
Maksoud, H EP766
Lopes, N EP468
Luque, RM GP128, EP178,
Maciel, A OC4.3
Makstiene, J EP1437
Lopes-Ventura, S GP126
EP472, EP698, EP790
Mackay, D GP45
Malagnino, V EP782
Lopez, FJV EP544
& EP929
MacKenzie, SM GP58
Malaktari- Skarantavou, S
Lopez, IF EP270
Luque-Fernández, I EP866
Macut, D GP139, GP140,
EP1202
Lopez, M GP111 & EJE1
Luque-Huertas, RM EP941
EP75, EP80, EP166,
Malaktari-Skarantavou, S
Lopez, MJ EP1001
Luster, M D5.1
EP177, EP191, EP484,
EP859
Lopez, MLA EP1023
Lutjohann, D EP359
EP1114 & EP1184
Malchiodi, E EP1043
Lopez, N EP944
Lutsenko, A EP1028
Madeo, B GP33 & GP51 &
Maldonado, G EP1332
López-Miranda, J EP472
Luzi, L OC6.2 & EP653
EP1383
Malecka-Tendera, E GP67
López-Presa, D EP1021
Lwow, F EP1135
Mader, JK EP609
& EP726
López-Tinoco, C EP1278
& EP1160
Maduen˜ o, FJT EP627
Malek, I EP120
López-Valasco, R EP858
Lyga, S OC4.4
Maduen˜ o, FT EP998
Males, D GP73 & EP1044
López-Velasco, R EP915
Lyhne, J GP17
Madureira, D EP1330
Maletkovic, J EP361
& EP1203
Lyra, R EP841, EP899
Maecke, H EP1445
Malhotra, N EP1249
Lopez-Tinoco, C EP544
& EP975
Maeda, T EP1385
Malicka, J EP831 & EP850
Lopez-Velasco, R EP535,
Lyratzopoulos, N EP1378
Maffei, M EP397
Malicka, K GP183
EP1174, EP1200
Lysianyi, M EP622
Maffezzoni, F OC10.3
Malik, R EP453
& EP1287
Lyssenko, V S29.2
Maffi, P OC6.2
Maliqueo, M EP1120
Lorena, DF EP74
Lyssikatos, C GP68,
Mafra, M EP1000
Mallo, F GP52, GP75
Lorena, SG EP74
GP236 & EP13
Magalha˜ es, D EP140,
& GP156
Losada, E GP84
Lyubov, M EP989
EP477, EP564, EP630,
Malm, J EP1246
Losito, S EP1407
EP719, EP871 & EP872
Malouf, J GP36
Lotfi, C GP6
Magas, S EP1161
Mamdouh, M EP1154
Lotfi, L EP149
Márquez, PO GP240
Maggi, M GP147, EP370
Mamedova, E EP345
Louiset, E GP12
& EP862
& EP377
& EP346
Lourenc¸o, A GP217
Márquez-Pardo, R EP858,
Maggioni, A EP922
Mami, FB EP502
Louro, P EP394
EP915 & EP1203
Magno, S EP397
Mammadova, A EP378
Louvigné, M GP143
Makela, S GP167
Magro, G EP268
Manani, C EP827
Løva˚s, K EP33, EP49 & EP59
Maki-Jouppila, J EP692
Maha, K EP646 & EP1229
& EP828
Ltaeif, B EP1290, EP1427,
Mannisto, T EP1285
Mahdi, A EP741
Mancha-Doblas, I GP71
EP1428 & EP1430
Marz, W GP107
Maher, E GP27
& EP614
Łuczyn˜ ska-Kotodziejczak, A
Méndez-Bailón, M EP431
Maher, M EP1299
Manchenko, O EP521
EP1336
Møller, N EP654
Maher, MM EP497
Mancini, A EP1260
Luís Medina, J EP1289
Muller, B EP18
Mahlina, E EP523
Mancini, C EP713
Luís, R GP226
Muller, N EP528
Mahmoodi, B OC5.2
Manda, D EP1063,
Lu, B EP934
Muller, T OC2.3
& EP642
EP1094, EP1176,
Lubrano, C GP168,
Muller, U EP528
Mahomed, F EP28
EP1180, EP1216
EP702, EP713
Muller-Reible, C GP119
Maia, JC GP234 & EP140
& EP1466
& EP1054
Munzker, J EP1188
Maillo-Nieto, A EP180
Mandache, E EP16
Luconi, M OC7.2, GP3 &
Mašlanková, J EP1127
Maina-Nock, T EP1445
Mangafas, N EP239
GP8
Ma, D EP1
Maiorino, MI EP1121
Mangelsdorf, D P2
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Maniatis, A GP66
Marconcini, G EP970
Marquez-Pardo, R EP535,
Martins, AC EP10, EP181
Manita, I EP486
Marcondes, J GP178
EP1174, EP1200
& EP599
Manjer, J EP1246
Marczewski, K EP826,
& EP1287
Martins, AF EP41, EP96,
Mannelli, M OC7.2, GP3,
EP1282 & EP1372
Marre, M EP1310
EP281, EP853, EP897,
GP8, GP25, GP123,
Marek, B EP349
Marshania, Z EP797
EP898, EP1012,
EP92 & EP93
Marelli, F OC8.2 & EP1222
Marszałek, A EP1474
EP1021 & EP1269
Mannfolk, P GP182
Marengo, AP EP88 & EP94
Martín, AA EP574
Martins, C EP923
& EP1070
Margarida Póvoa, A
Martín, AG GP89
Martins, D GP35, EP44,
Mannina, C GP108
EP1155
Martín, DRdA EP717
EP45, EP61, EP175,
Mannstadt, M GP47
Maria Aragués, J EP791
Martín, E EP180
EP203, EP392, EP394,
& EP291
& EP1055
Martín, FJM EP107
EP444, EP445,
Mannucci, E EP370
Maria Mongioı`, L OC13.4
Martín, LS GP241
EP1009, EP1195,
Manojlović-Stojanoski, M
Maria, RG EP74
& EP150
EP1475,
EP212
Mariani, L EP986
Martín, RDlV EP544
Martins, H EP1461
Manojlovic-Gacic, E EP954
Mariani, S GP168, EP702
Martín-Iglesias, D EP443,
Martins, JM EP281, EP41,
Manojlovic-Stojanoski, M
& EP713
EP524 & EP593
EP853 & EP96
GP62
Maric, A EP491
Martín-Portugués, AB
Martins, LS EP460
Manolachie, A EP188
Marie Kolte, A OC13.2
EP183
& EP462
& EP1360
Marijnissen-van Zanten, M
Martínez, A EP973
Martins, MJ EP1475
Manolopoulos, K OC3.3
GP10
Martínez, AH EP708
Martins, PC EP1465, EP82
Manosso, K EP1013
Marinò, M EP1247
& EP717
& EP98
Manskaya, K EP983
Marin, CC EP270
Martínez, C EP681
Martins, R EP1459
Manso, F EP706
Marin, M EP693
Martins, AD EP1179
& EP1463
& EP707
Marin, MG EP755
Martínez, CM GP238
Martins, S EP567
Mansoor, Q EP205
Marina, L EP42 & EP127
Martínez, MJ EP681
& GP205
Mansoor, R EP1262
Marinis, LD S13.2
Martínez-Aguayo, A
Martins, T EP1049,
Mantachik, M EP737
Marino, L GP153
OC5.1
EP1459 & EP1463
Mantel, A GP45
Marino, M GP245
Martínez-Chacón, G GP167
Martins-Costa, S EP457
Mantovani, A EP743
& EP1131
Marta, H EP641
Martynov, S EP521
Mantovani, G OC9.5,
Mariot, J EP1123
Marti, J EP247
Martynska, L EP908
GP43, EP924 &
Mariotti, M EP653
Marti-Ayerdi, J EP247
Martynyuk, L EP420
EP1043
Marjot, T GP70
Martin, L EP1190
Marugan, J EP754
Mantovani, G EP20
Markelic, M EP693
Martin, M EP1415
Marx, SJ OC7.3
Mantripp, D EP728
Marker, A GP27
& EP1476
Masaki, C EP1385
Manuel Cameselle-Teijeiro,
Markey, K EP798
Martin, P-Y OC13.5 & EP820
Masana, L MTE16
J OC14.3
Markosyan, RL EP422
Martin, S EP143, EP943,
Mascaren˜ o, I EP906,
Marc¸alo, J , EP157, EP300,
Markovic, I GP225
EP1263 & EP1371
EP909 & EP910
EP1255 & EP1340
& EP1480
Martin, SC EP947
Mascarenhas, M EP234,
Marín, CC EP563, EP1331
Markozannes, G EP1172
Martin-Grace, J EP430
EP897 & EP898
& EP1467
Marmarinos, A GP99
Martin-Perez, M EP193
Mascarenhas, MR EP1083
Marín, T EP603
Maroldi, R OC10.3
Martinelli, C EP7
& EP243
Marakoglu, K GP96
Marote, S EP133
Martinelli, S GP25, EP92
Mascarenhas, R EP232
Maranghi, M EP397
Marotta, V EP1407
& EP93
Maseroli, E EP370
Maraver, S GP111
Marouani, N OC11.5
Martinerie, L OC5.5
Masetti, G EP1342
& EP868
Marova, E EP917
Martinez, A OC1.2
Mashahit, M EP412
Marawan, D EP1299
Marques, A EP1206
Martinez, G GP73
Masiello, E EP688
Marazuela, M OC10.2
Marques, AP EP129
& EP459
& EP691
& EP180
& EP174
Martinez-Laguna, D GP84
Maslova, N EP760
Marc, J OC10.4 & GP39
Marques, B EP1459
Martinez-Martin, FJ
Mason, I GP4
Marcelino, M EP139
& EP1463
EP105, EP170, EP390,
Masood, Q EP606
& EP1359
Marques, C EP1049
EP530, EP621
Masovic, S EP693
Marcheggiani, F EP1260
Marques, H GP242
& EP757
Mastorakos, G EP1172,
Marcinkowska, E EP721
Marques, O EP706,
Martinez-Triguero, ML
EP588 & S25.2
Marcocci, C GP33, EP238,
EP707, EP1049,
EP99
Matías, LG EP365
EP274, EP278, EP288,
EP1071 & EP1080
Martino, G EP1260
Mat, A EP696
EP348, EP970 &
Marques, P GP195
Martino, MCD EP786
Matafome, P EP704
EP1247
Marques, PV EP468
Martins, A GP242, EP57,
Matchekhina, L S5.3
Marcon, L EP20
Marques, R GP222
EP599 & EP1058
Matei, L EP838
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Matens, H EP883
McCormack, A OC12.2
Mercadante, R EP1043
EP897, EP898
Mateo-Gavira, I EP714
McDermott, M EP291
Mercedes, R EP641
& EP974
& EP715
McDonnell, DP GP63
Mercier, L EP179
Miguel, Pd EP184
Mateos, CG-F EP290,
Mcgrath, R EP720
Mergen, H EP815 & GP74
& EP185
EP372, EP374, EP610,
Mchirgui, N EP1232,
Mergler, S EP806 & OC2.3
Miguel-Novoa, Pd EP900
EP611 & EP612
EP1233, EP147
Meric, C EP1165
Mihai, A-C EP1419
Materazzi, G EP278
& EP832
Meriem, B EP120 & EP138
Mihai, D EP1395
Mathieu, M OC1.2
McInnes, KJ EP802
Merino, JF EP99
Mihajlovska, M EP1355
Matias, A GP126
Mckone, E EP430
Merino-Torres, JF EP681
& EP1478
Matias, JS GP133
McLean, M GP27
Merkle, E GP185
Mihajlovska, S EP1355
Matias, R GP222
McNeil, C GP69
Mermejo, L EP7
& EP1478
Matos de Figueiredo, C
McQuaid, S EP1318
Mert, EO EP856
Mihu, D EP1364
EP818
Meatchi, T GP15
Mert, M EP1235, EP644
Mijares, AH EP1178
Matos, A EP632 & OC5.4
Med, MS EP149
& GP95
Mikšík, I EP1082
Matos, AC EP1422, EP226
Medeiros, S GP110
Meryam, E EP387
Mikadze, K EP658
& EP486
Medic-Stojanoska, M
& EP845
Mikalauskaite, R EP1436
Matos, L EP1446 & EP887
EP1089, EP116
Mesa, C EP1244
& EP479
Matos, LG EP519
& EP709
Mesa, EM EP862
Mikelaityte, G EP1321
Matos, MJ EP100 & EP82
Medina, D EP1278
& GP240
Mikhaleva, O EP568
Matos, P EP1448
Medina, JL GP199
Mesa, J EP944
Mikhaylova, D GP157
Matrone, A EP288
Medina-Rivero, D EP714
Mesenka, D EP1020
Mikhno, H EP351
Matsiushava, J EP286
& EP715
Meskine, D EP246, EP65
Mikina, E EP1274
Matsuzaka, T GP166
Mednieks, J EP142
& EP718
& EP1382
McEwan, B IPSEN1
Medras, M EP1160
Mesquita, A EP82
Mikolajczak, R EP1445
Matsuzaki, T EP1156
Megerle, F GP123
Messina, E EP1056
Mikulecka, A EP1082
Matsuzu, K EP1385
Mehmood, A EP692
Mestre, JL GP12
Milankov, A EP1024
Matta-Coelho, C EP1071,
Meienberg, F EP889
Methlie, P EP49
Miler, M EP359, EP779,
EP1080 & EP1091
Meijer, OC EP802
Meyer, A EP822
GP202 & GP62
Mattheisson, K EP426
Meireles, C GP26
Meyer, G EP5
Miletic, M EP111
Mattsson, A OC8.4
Mel’nichenko, G EP881
Meyer, J EP13
Milewicz, A EP1135
Matucha, P EP1143
Melchars, D EP802
Mezghani, I EP1324
Milewicz, T EP1111,
Matulevicius, V EP173
Mellado-Soria, J EP1462
Mezosi, E EP1410
EP1148, EP141,
Matusik, P EP726
Mellidez, J EP174
Mezoued, M EP65
EP357, EP371
Matuszewski, W EP17
Melmed, S S23.2
Mezyk, R EP1274
& EP890
Matyjaszek-Matuszek, B
Melnic, E EP935
& EP1409
Milheiro, A EP519
EP547 & EP865
Melnichenko, G EP220
Mezzullo, M EP1166,
Milic, N EP709
Maurer, J EP154
Melo, D EP53
EP669 & EP671
Milicevic, I EP177
Mauricio, D D6.2 & GP84
Melo, EG EP862 & GP240
Mghari Ghizlane, E EP309
Milin-Lazovic, J EP42
Maushart, C OC9.2
Melo, GB EP949
Mghari, GE EP1334
Milionis, C EP793
Mavragani, C EP275
Melo, M EP1449, EP1475,
& EP476
Miljic, D EP779, EP892,
Mavroeidi, V EP176
EP45, EP899, GP35,
Mhidhi, S EP502
EP953, EP954, EP956,
& EP67
OC14.3 & S19.3
Mhiri, A EP1290, EP1427,
GP188, GP197, GP202
Mayila, Y EP1156
Melo, P EP337
EP1428 & EP1430
& GP62
Mayoni, S EP1237
Melus, V EP1344
Min˜ ambres, I EP586
Miller, BS GP65 & GP66
Mazarico, I EP165
Memo, M OC10.3
Micali, G EP1163
Millo, C OC7.3
& GP238
Menéndez, E EP1332
Michalakos, S EP62
Mills, E EP1196, EP123,
Mazeh, H EP1374
Mena, SC EP1481
Michalik, B EP1440
GP29 & GP30
Mazerkina, N EP1025
Mendes de Almeida, M
& EP349
Milošević, V EP212
& EP1057
GP213
Michelli, A GP204
& EP359
Mazic, S EP470
Mendes, P EP1291
Micheu, A EP1134
Milos, I EP1068
Mazilu, A EP1254
& EP1292
Micic, D EP42, EP470
Milosevic, V EP779,
Mazur, G EP187 & EP78
Mendonça, E GP242
& EP694
GP202 & GP62
Mazzanti, C EP348
Menendez-Torre, E
Mickuviene, N EP1346
Milotic, DM EP1161
mazzeu, J OC4.3
EP1484
Middleditch, M EP1314
Mimita, W EP1232,
Mazziotti, G GP231,
Menor-Almagro, R EP374
Mieszkowska, A EP547
EP1233, EP147
MTE11, OC10.3
Meola, A EP288
Miftaraj, M EP55
& EP87
& OC12.5
Meoro, A EP1415
Miguéns, J EP1021,
Mimouni, S EP994
McAdams, B EP958
& EP1476
EP1049, EP896,
Minallah, S EP205
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Mineesk, D EP381
Mohamed, K EP160
Moolla, A EP730, GP138
Moskvicheva, T EP556
Mingrone, G S15.1
Mohamed, MS EP497
& OC3.5
Mosorin, M-E GP55
Minisola, S GP33
Mohamed, RB EP502
Moore, K EP1150, EP1153
Mostafa, BM EP1363
Minnetti, M GP16
Mohammed, A EP25
& EP487
Motomura, k GP166
Mintziori, G EP214, EP68
Mohammed, FR EP720
Moore, WV GP65
Mourad, B EP1154
& EP771
Mohammed, K EP190
Mora, M GP24 & GP57
Mouslech, Z EP588
Miranda, A EP1227
& EP395
Mora, PL EP406 & EP407
Moustou, H EP1418
Miranda, E EP341
Mohaupt, M OC13.5
Mora-Navas, L GP71
Moutschen, M EP883
Mirante, A EP1227,
Mohd Ali, N EP874
Moradgholi, S GP164
Moya, VA EP1178
EP887 & GP109
Mohd, A EP408
Morais, O EP84
Moyson, C EP1393
Mirica, A EP122
Mohideen, P GP131
Moran, L EP1115 & EP747
Mrabet, H EP1349,
Mirica, R EP122
Mohort, T EP523
Moran, M EP211
EP135, EP189
Mirmiran, P EP642,
Moilanen, L GP50
Morar, A EP846
& EP335
EP662 & OC5.2
Mokhort, A EP527
Moreira, Â GP18
Mrabet, HE EP1361
Mirnaya, S EP257, EP318
Mokhort, E EP749
Moreira, A EP1465, EP7
Mrabet, S EP355 & EP762
& EP347
Mokhort, T EP511, EP515,
& EP82
Mrad, M EP482
Mirošević, G EP172,
EP527, EP536, EP540,
Moreira, AM EP919
Mrdovic, I EP367
EP463 & EP549
EP663, EP664
Moreira, BM EP1179
Mrozinska, S EP1111,
Miron, A EP1371
& EP749
Moreira, C EP235
EP1148, EP141
Mirosevic, G EP43
Mokrysheva, N EP257,
Moreira, H EP203
& EP371
Mishevska, SJ EP875
EP318, EP323, EP345,
Moreira, S EP392
Msika, S OC11.2
Mishra, B EP408
EP346 & EP347
Morelli, A EP377
Mun˜oz de Nova, JL EP180
Missiroli, S EP789
Moleiro, F EP1323 & EP32
Morelli, S GP16
& OC10.2
Mitchell, C EP802
Molero, IG EP998
Morelli, V EP1043 & EP20
Mun˜oz, A EP9
Mitchell, R GP10, GP180
Molina-Vega, M EP614
Moreno Ortega, E EP1392
Mun˜oz, JMGdQ EP563
& GP4
& GP71
Moreno, Ó EP904
Mun˜oz, MR EP705
Mithieux, G S15.2
Molinaro, E EP1414
Moreno, B EP973
Mun˜oz-Garach, A
Mitrović, B EP356
& EP238
Moreno, C EP112 & EP1040
EP1462, EP224,
Mitrovic, M EP1089
Molitch, ME EP1015
Moreno, IH EP574
EP614 & GP71
Mittica, M OC14.1
Molka, C EP1229
Moreno, LM EP948
Mun˜oz-Jiménez, C EP1159
Mizamtzidi, M EP1139
& EP646
Moreno, MÁG EP474,
& EP941
Mladenović, V EP1245
Mollejo, M EP973
EP602, EP882
Mun˜oz-Jimenez, C EP500
Mladenovic, V EP484
Molnar, D EP491
& EP1932
Mun˜oz-Rivas, N EP431
Mnif, F EP1349, EP1361,
Molnar, Z EP742
Moreno, MÁG EP1932
Muco, E EP765
EP189, EP335, EP66,
Monaghan, P EP1169
Moreno, NA EP1072,
Mudenha, ET EP1192
EP77 & GP113
Monari, F EP1381
EP1481 & EP574
Mudiganti, NSV EP475
Mnif, M EP1128, EP1361,
Mondal, D EP1020
Moreno, PM EP474,
Muela, IS EP76
EP167, EP189, EP335,
Monereo, S EP1030
EP602 & EP882
Mueller, B EP687 & EP942
EP66, EP77 & EP770
Mongioı`, LM EP1163
Moreno, RMG EP574
Muhammad, A GP174
Moc¸o, R EP337
& EP35
Moreno-Moreno, P
Mujica-Mota, M GP100
Moata, H EP476
Moniz, AP EP1459
EP1159, EP159,
Mukherjee, AK EP343
Moazam, SG EP553
Moniz, C EP596
EP500, EP776, EP819,
Mukhopadhyay, S EP409
& EP555
Moniz, L GP222
EP907 & EP941
Mukhtar, R EP1230
Mocan, M EP398
Monoranu, CM EP932
Moresi, V EP825 & GP221
Mulatero, P EP37
& EP400
Monreal, IA EP920
Moretti, C OC9.5
Munichoodappa, K EP409
Mochort, T EP541
Montalto, G GP108
Morgado, P EP872
Munier, M GP143
Moehlecke, M EP648
Monteiro, J EP1362
Morgan, H EP303
Munkhzaya, M EP1156
Mofokeng, TRP EP28
& EP243
Morgan, RA EP802
Munteanu, V EP252
Moga, MA EP774
Monteiro, K OC2.5
Morganstein, D EP1458
Munter, G EP228 & OC4.1
Mogos, S EP213, EP252,
Monteiro, M GP18
Morgia, G GP127
Munukka, E GP167
EP260, EP838
Monteiro, MP EP1179
Morillas, V EP755
Murabe, H EP273
& EP961
& EP146
Morin-Papunen, L EP1110
Muratani, M GP166
Mogos, V EP1076,
Monteiro, N EP1323
& GP55
Muravyova, I GP86
EP1209, EP213,
& EP32
Mormando, M OC12.5
Mures, P EP3
EP252, EP260
Monteiro, S EP1211,
Morotti, A GP130
Murillo, FH EP1178
& EP961
EP1351, EP1356,
Morsi, H EP83
Muros, MM EP569
Mohamed Abdelsalam, M
EP145 & EP51
Mosbah, R EP743
Muros, T GP111
EP1154
Moola, A GP70
Moschouris, P EP67
Murphy, C EP720
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Murray, R EP912
Natalya, G EP989
Neves, C EP1006, EP1081,
EP1485, EP308, EP58
Murray, RD EP22, GP11
Natchev Natchev, E
EP1289, EP1357,
& GP115
& GP20
EP1046
EP140, EP1446,
Nikookam, Y EP103
Musat, M EP1063
Nathalie, E OC14.4
EP169, EP181, EP194,
Nikopoulou, S EP793
Mussap, M OC14.1
Nathanson, L OC7.5
EP195, EP493, EP53,
Niles, N EP321
Musson, P N3.1
Naumenko, E EP511
EP54, EP576, EP613
Nilubol, N GP124, GP186
Mustafa, A GP88
Naumova, L EP358,
& GP199
& OC7.3
Mutlu, HH EP447
EP507 & EP510
Neves, F EP807
Nimalasena, S EP1458
Mutluay, R EP1375
Naumova, M EP358,
& GP26
Nishi, M GP6
Muzza, M EP1432
EP507 & EP510
Neves, J EP567
Nishiyama, A OC6.5
Myhr, C EP754
Navalón, CI EP432, EP433
Neves, JS EP1081, EP140,
Nisic, T EP111 & EP1261
Mykhailiv, L EP420
& EP705
EP169, EP493, EP53,
Nistal, M EP904
Mykhalchyshyn, G OC2.4
Navaratnam, J EP134
EP54, EP576, EP719
Nivelo-Rivadaneira, M
Mykytyk, M EP982
Navasardyan, LV EP422
& GP199
EP390
& EP983
Navmenova, Y EP515,
Newbold, K EP1458
Nivelo-Rivadeneira, M
Myrzabaeva, A EP532
EP523 & EP556
Newell-Price, JDC EP879
EP105, EP107, EP170,
Mysliwiec, J EP31
Navrozidou, P EP483
Newsome, P OC3.5
EP193, EP530, EP621
Myszka, R EP592
& EP559
Nezi, M EP239
& EP757
Myszka-Podgórska, K
Nawal, E EP845
Nezos, A EP275
Nizam, N OC12.1
EP17
Nawal, EA EP1337,
Nezu, M GP14
Nobre, E EP1037, EP1085,
EP379, EP387, EP488,
Ng, D GP65
EP1269, EP1340,
Nadal, E GP241
EP640 & EP888
Nicolae, AC EP1137
EP320, EP897, EP898,
Nadin, K EP1468
Nazarovs, J EP931
& EP376
EP95, GP237 & GP239
Nadira, F EP279
Nazir, S EP761
Nicolaescu, I EP1138,
Nock, BA EP1445
Naem, E EP160
Nechaeva, O EP1457
EP1147 & EP307
Nockel, P GP124 & OC7.3
Nag, S EP1358, EP1398
Nechayeva, V EP539
Nicolas, G GP185
Noczynska, A EP775
& EP89
Necib, B EP149
Nicolay, SS GP196
Nodari, M GP231
Nagahama, M EP1385
Nedelcu, I EP1216
Nicoli, A EP1123
Nogués, X GP84
Nagaiceva, J EP142
Nedeljkovic-Beleslin, B
Niconova, L EP541
Nogueira, C EP1081
Nagatsuji, M EP27
EP111 & EP1261
Niculescu, A-M EP1216
& EP630
Nagtegaal, AP GP116
Nedergaard, J P5
Niculescu, D EP980
Noh, JH GP91
Nagy, EV EP1410
Nefedova, L EP1141
Niculescu, DA EP1018
Nolasco, F EP599
Nagy, Z GP3
Neggers, S EP1010
Niederlander, N GP153
Nolting, S EP154
Naik, M EP1277 & EP526
& GP174
Niedziela, M GP220
Noordzij, W EP155
Nakagawa, Y GP166
Neggers, SJCMM GP116
Nielsen, EH GP181
Norberto, S EP403
Naliato, E EP152
Negri, M EP34, EP786,
Nielsen, TL GP59
Nordstrom, C-H EP1070
Nam Kim, Y GP219
EP927 & GP184
Niemyska, K EP1442
& GP182
Nam, JS EP452, EP531,
Negru, M EP1345
Nieto, ÁM EP1072
Normann, KR OC8.3
GP54 & GP87
Nehlich, M OC5.5
Nieto-Gonzalez, A EP224
Noroozzadeh, M EP1183
Nam, JY EP960
Nejatian, N GP83
Nigro, N EP918 & EP942
Norris, J GP203, GP206
Nampoothiri, L EP1117
Nelimarkka, L GP50
Nikanava, L EP540
& GP63
Nana, M EP303
Nelson, L EP1263
Nikankina, L EP685
Norton-Branda˜ o, F
Napoli, F EP922
Nemes, O EP1410
& EP881
EP1454
Naqvi, A EP1196, EP123
Nemeth, A GP153
Nikitin, A EP220
Noruegas, MJ EP1227
& GP29
Németh, R GP44
Nikitina, I EP1146
Nota, N EP1032
Nar, A EP1431 & EP39
Nemoto, N EP1242
Nikolac, N EP209
Nour, E EP762
Narayanan, N EP555
Nermoen, I EP59
& GP232
Nourbakhsh, M GP164
Nardi, M EP1247
Neselioglu, S EP1347
Nikolaeva, N EP594
Novak, S EP491
Narimova, G EP15
Nesi, G GP223 & GP8
Nikolaidou, A EP1473
Novakovic Paro, J EP1024
Naseem, AA EP1092,
Nesic, J EP484
Nikolaou, N EP730
Novakovic-Paro, J EP116
EP1225, EP205
Nesovic, N EP677
& GP69
& EP709
& EP761
Nesovska, R EP285
Nikolic, D GP108
Novalbos-Ruiz, JP EP714
Naser, RA EP424
Nestorović, N EP212
Nikolic-Djurovic, M
& EP715
Nash, Z GP131
Nestorovic, N GP62
EP953, EP954
Nowak, K EP469
Nasiri-Ansari, N GP236
Neto, LL EP896 & EP974
& GP197
Ntali, G EP202 & GP180
Nasiroglu Imga, N EP56
Neumann, S NSA5.2
Nikolopoulos, G EP67
Ntova, V EP1008 & EP38
& EP589
Neuroendócrinos, GET
Nikookam, K EP103,
Nun˜ez, MS EP1072
Nasr, MS EP425
EP174
EP1213, EP1354,
& EP574
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Nunes, A EP389
Okamoto, K EP273
Ollila, M-M EP1110
Oruk, GG EP964
Nunes, J EP1133 & GP133
Okazaki, K EP273
Olmedilla, YL EP1030
Osório, AS EP1037,
Nunes, JS EP181
Oki, M EP4
Olmedo, C EP3, EP9
EP1083, EP1085,
Nunes, M-L GP120
Øksnes, M EP49
& EP952
EP1269, EP243,
Nunes, MT EP716, GP163
Oktas, B EP604
Olmezoglu, A EP964
EP320, EP897, EP898,
& GP224
Okurog˘lu, N EP266
Olofsson, C EP557
EP95, GP237
Nunes, T EP255
& EP440
Olsson, DS GP9
& GP239
Nur Firat, S EP317
Okuroglu, N EP565
Olsson, H GP177
Osaku, T EP1385
Nuria, AG EP74
Okuturlar, Y EP1235
Olsson, T GP9
Osowicz-Korolonek, L
Nurrulina, G EP464
& EP644
Olteanu, M EP1419
EP229
& EP465
Olaizola, I EP869
Olveira, G EP755, EP756,
Ostanek, B GP39 & OC10.4
Nuutila, P GP50
Olarescu, NC OC8.3
EP808 & EP868
Osuga, Y GP134
Nuzzo, F GP245
Olczyk, T EP1440
Omata, K GP14
Ostgren, CJ OC6.4
Nvokov, I EP735
Oleaga, A EP112
Omelchenko, E EP580
Otasevic, V EP693
Nye, E EP426
Oleg, K EP73
Omer Yazicioglu, M
Otero, J GP241
Nystrom, F OC6.4
Olga, G-P EP641
EP1413
Othonos, N GP70
Olivar, M EP973
Omer, T EP877
Ouali, S EP1322
O’Donovan, C EP505
Olivar-Azuara, M EP866
Omma, T EP1175, EP384
Ouannes, S EP1236,
O’Donovan, O EP505
Oliveira, A EP451, EP477,
& EP854
EP1238 & EP833
O’Hara, L GP159 & GP4
EP564 & GP200
Omri, M EP502
Oudjit, B EP219, EP450
O’Hare, JA EP1339
Oliveira, AI EP1079, EP53
Onbasi, K EP1294,
& EP633
O’Reilly, MM EP1150,
& EP54
EP1380 & EP467
Ouerdani, S EP1389
EP1153, EP798,
Oliveira, B EP313
Oncul, S EP821
Oueslati, H EP1322
GP180 & OC3.3
Oliveira, C EP1422
Ono, Y GP14
Oueslati, I EP1193,
O’Shea, D EP696
Oliveira, CRP EP949
Onofriichuk, I EP358,
EP1201, EP1208,
O’Shea, P EP720
& GP178
EP507 & EP510
EP1232, EP1233,
O’Sullivan, N EP259
Oliveira, D EP1009,
Oprea, L EP1063
EP1328, EP147,
Obel, E EP865
EP1195, EP1475,
Oprea, T-E EP215
EP207, EP340, EP482,
Obermayer-Pietsch, B
EP203, EP392, EP394,
Oprisor, I EP846
EP570, EP832
EP1188 & GP107
EP44, EP444, EP445,
Orłowski, M EP1450
& EP87
Obiols, G EP944
EP45, EP57, EP61,
Or, K EP1313 & EP199
Oukit, L EP1334 & EP476
EP922 & GP35
Orbetzova, M EP600
Ould-Kablia, S EP1182
Obolonczyk, L EP396
Oliveira, E EP382
Orchard, E EP1145
Ouldkablia, S EP1386
Obradović, M EP1245
Ocieczek, M EP1441
Oliveira, FT EP949
Ordo
˜ez-Can˜ izares, MC
& EP450
Odermatt, A EP730,
& GP178
EP224
Ounaslehto, A GP50
EP781, EP782, EP802
Oliveira, J EP1058, EP512,
Orehek, N GP39 & OC10.4
Overgaard, R GP152
& EP822
EP548, EP573
Orhan, B EP249
Øystese, KAB OC8.3
Oei, E EP744
& EP773
Oriola, J EP868
Oz, A EP842
Oei, L EP744
Oliveira, JM EP1351
Orlando, P EP1260
Oz Gul, O EP131, EP132,
Ogando, H GP52 & GP75
Oliveira, L EP1422
Orlov, A EP1286
EP601, EP608, EP72
Ogilvie, A GP195
Oliveira, MJ EP1211,
Orlova, E EP345
& EP751
Ogimi, Y EP1385
EP1351, EP1356,
Orlova, M EP1266
Ozawa, Y EP1270
Ogle, G EP428
EP145, EP51 & EP923
& EP1316
Ozbek, M EP1097,
Ogmen, B EP1377
Oliveira, P EP1009, EP203
Oros, S EP1094, EP1176
EP1368, EP327
& GP233
& EP44
& EP1180
& EP999
Ogmen, BE EP1429
Oliveira, PF EP1179
Orosia, M EP1332
Ozcan, M EP815 & GP74
Ognjanovic, S EP1114,
Oliveira, S EP613
Orsini, N EP557
Ozcelik, O EP1368
EP166, EP177, EP191,
Oliveira, SC EP1081,
Ortega, JV EP76
Ozdemir, A EP266, EP440
EP75, EP80 & GP139
EP169, EP493, EP53,
Ortega, N EP1130
& EP565
Oguz, S GP212
EP54, EP576, EP719
Ortega-Salas, R EP178
Ozdemir, B EP1235
Oh, H-S EP1366, EP1367
& GP199
Ortiz, A EP88 & EP94
& GP95
& OC14.5
Oliveira-Filho, AF EP389
Ortiz, AM EP769
Ozdemir, D EP1258,
Oh, S EP950
Oliveira-Neto, LA EP949
Ortiz, D OC5.1
EP1264, EP1377,
Ohkuwa, K EP1385
Oliveira-Santos, AA EP949
Ortiz, R OC6.5
EP331, EP843, EP856
Ohlsson, C OC3.4
& GP178
Ortolá, A EP184 & EP185
& GP233
Oliviero, S NSA3
Ortola-Buigues, A EP900
Ozdemir, K EP683
Ohno, H GP166
Olldashi, B EP1470
Oruc, A EP751
Ozderya, A EP289
Ohrman, T EP766
Ojo, A EP1485 & EP308
Olldashi, T EP2 & EP1370
Oruc, C EP821
Ozgen, G EP1194
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Ozgurtas, T EP362
Palazzo, F EP123
Papi, G EP1341 & EP1426
Patino, H GP187
Ozisik, H EP1194
Palermo, A GP33
Papierska, L EP469
Patocs, A GP3
Ozkan, C¸ EP1144
Palha, A EP1049, EP1062
Papoutsis, I GP80
Patrício, M EP704, EP887
Ozkan-Gurdal, S EP265
& EP1446
Pappa, D EP861 & EP864
& GP109
Ozkaya, M EP1003
Palha, AM EP1006
Pappalardo, MA EP1118
Patrascioiu, I OC12.3
Ozkul, Y EP1129
Paliczka-Cieslik, E EP1440
Paragliola, RM EP1341
Patt, M EP782
Ozmen, S GP161
Pallone, S EP1013
& EP1426
Patti, AM GP108
Ozturk, B GP96
Palma, I EP350, EP824
Pardi, E EP278 & EP348
Patyra, K OC4.2
Ozturk, FY EP109
& EP921
Pardo, JA EP948
Paul, BN EP701
& EP836
Palmieri, S EP1043
Paredes, I EP1044
Paula Moreira, A EP198
Ozturk, L GP49
& GP33
Paredes, S EP706 & EP707
Paula, G EP723
Ozturk, O EP362
Palomares-Ortega, R
Parente, R EP7
Paulino, J EP599
Ozugur, S EP289
EP500
Park, BY EP506
Pauliukiene, B EP1276
Palomera, E GP57
Park, JH EP925
Pauliukiene, R EP164
Pávai, D EP1086
Paluzzi, A GP180
Park, JS EP452, EP531,
Paun, D EP1176, EP1180
Pa˚lsson, A EP1070
Palyga, I EP1274, EP1382
GP54 & GP87
& EP240
Péchère-Bertschi, A
& EP1409
Park, K EP452, EP531,
Paun, DL EP122
OC13.5
Pamedytyte, D GP244
EP592, EP960, GP54
Paun, S EP122
Pérez, FG EP1467, EP563
Pampaloni, F EP370
& GP87
Pavai, D GP38
& EP769
Pan, k GP192
Park, KG EP383, EP506
Pavel, M GP177
Pérez, M EP938
Panagiotou, A EP1303,
& GP56
Pavlova, M EP1057
Pérez, MDA GP89
EP1307, EP1417,
Park, KH EP700 & GP169
Pavlovic, D GP197
Pérez, MSG EP294
EP1471, EP223, EP68
Park, S EP1366, EP1367,
Pawlak, D EP1445
Pérez-Fernández, L EP461
& GP40
EP605 & OC14.5
Payer, J EP1173 & GP38
& EP619
Panarotto, MB GP231
Park, SH EP960
Payumo, E EP216
Pérez-Luis, J EP906,
Panay, N GP131
Park, SI EP700
Pazaitou-Panayiotou, K
EP909 & EP910
Pancic, JM EP168
Park, SW EP516
EP1473
Pérez-Rodríguez, J EP443,
& EP767
Park, SY EP1100, EP248,
Pazanin, L EP43
EP524 & EP593
Pande, DG EP1277
EP738, GP42 & OC9.4
Pazderska, A EP1150,
Pérez-Villa, L EP1462
& EP526
Park, Y-M EP690
EP1153 & EP487
Pacak, K EP92, EP93,
Pandurevic, S EP42
Parker, M EP1190
Pchelin, I EP518 & GP92
GP25 & OC7.3
Pane, A GP24
Paro, JN EP245
Pen˜ a, A EP938
Paccapelo, A EP1381
Panebianco, MV EP1251
Partha, P EP25
Pen˜ a, IF EP563
Paccaud, F EP820 & OC13.5
Panocchia, N EP1260
Parv, F GP53
Pen˜ a, JIF EP270 & EP769
Pace, L GP231
Panousis, P EP1473
Parveen, N EP205
Peacey, S EP1259
Pach, D EP1026 & OC9.3
Pantazi, E EP1300,
Parvu, L EP1466
Peacock, M GP47
Pacha, J EP1082
EP1460, EP221,
Pascal-Vigneron, V EP966
Pechére-Bertschi, A EP820
Pacheco, LV EP432,
EP222 & EP276
Pascanu, I EP1364 & EP16
Pechuan, J GP111
EP433 & EP705
Panteleeva, E EP905
Paschke, R OC4.2
Peculis, R EP931 & OC6.3
Paci, A EP179
Pantelidis, D EP366
Paschou, S EP1139
Pedersen, B GP190
Pacini, F EP1295 & EP60
Panthagani, AP EP1192
& EP214
Pedersen, MH EP654
Padlipskaite, A EP1412
Pantoflinski, J EP1026
Paschou, SA EP423
Pedersen, SB EP654
Padure, A EP1466
Panveloski-Costa, AC
Pascu, AM EP774
Pedicelli, A EP997
Padzik, A GP118
EP716
Pascual, C EP3
Pedraza-Arévalo, S EP178,
Pagotto, U EP1166,
Papadakis, G EP1098,
Pasqualetti, P EP1050
EP472, EP698
EP1381, EP669
EP1373, EP217,
Pasquali, R EP1135,
& EP790
& EP671
EP417, EP442, EP509,
EP669, EP671 & CET1
Pedro, J EP719
Paiva, I EP1009, EP1049,
GP153 & N3.2
Passos, D EP1359
Pedroncelli, A GP187
EP44, EP57 & EP61
Papadakis, GZ OC7.3
& EP139
Pedroso de Lima, J EP198
Paiva, S EP392, EP394,
Papadopoulou, D GP131
Pastor, F EP1415
Pedroso, JC EP1356
EP61 & EP922
Papaevangelou, V EP885
Patakov, M MTE15
Peene, B EP1393
Paixa˜ o, R EP1083
Papagianni, M EP588
Patalano, R EP927
Pehlevan, E EP47
& EP243
Papakokkinou, E GP9
Patalong-Nowak, M
Pehlivan, B EP644
Paixao, AL EP468
Papanikolaou, I EP176
EP229
Peiró, I EP150, EP88,
Paja, M EP1040, EP112,
Papastathi-Boureau, C
Patel, C EP744
EP94 & GP241
EP1217 & EP128
EP1126
Patel, D GP124, GP186
Pejin, R EP245
Pajovic, M EP678
Papavasiliou, S EP1418
& OC7.3
Pekgoz, M EP1017
Pakarinen, P EP364
& GP32
Patel, N GP100
Pekic, S EP892, EP953,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP954, GP188
Peros, K EP1151
Phelan, N EP1150,
Pitchaiprasert, S EP1288
& GP197
& EP1161
EP1153 & EP487
Pittathankal, A EP103,
Peláez, N EP150
Perotti, P EP26 & GP123
Phillips, S GP135
EP1213, EP1485
Pellegata, N EP91 & EP926
Perreira, C EP1032
Pián, H EP94
& EP58
Pellegata, NS OC8.1
Perrino, M EP1408
Piętkowski, J OC9.3
Pitteloud, N GP153
Pellegrino, M EP268
& EP1432
Piantanida, E EP1451,
& S10.3
Pellegrino, T GP231
Perros, P EP1342 & S12.3
EP688 & EP691
Pivac, N EP595
Pelosini, C EP397
Perrotta, R EP794
Piasecka, B EP466
Pivonello, C EP34, EP786,
Pemovska, G EP285
Persani, L EP1222
Picado, B EP548 & EP573
EP927 & GP184
& EP875
& OC8.2
Picallo, M EP1030
Pivonello, R EP1015,
Pendovski, L GP62
Persson, A EP55
Piccinini, S OC7.4
EP1039, EP1056,
Penna-Martinez, M GP83
Pesic, M EP64
Piccolo, R EP291
EP34, EP786, EP927,
Penning, T EP730
Peso, CD EP1476
Picerno, IAM GP175
GP177, GP184
Penso, R EP184 & EP185
Pestana, A EP1357
Pichl, C EP1027
& GP187
Perazo, C EP794
& EP1449
Picon, N EP385
Piwowar, M EP1274
Percinic-Popovska, F
Petakov, M EP177, EP191,
Picu, C EP1094, EP1216
Planas, A EP150
EP779
EP80, EP892, EP953,
& EP1466
Planck, T EP1246
Perdigones, CD EP406,
EP954, EP956, GP188
Pieber, TR EP609 & GP107
Planella, JRU EP294
EP407 & EP627
& GP197
Piedade, C EP1227
Plank, J EP609
Perdomo, C EP227
Peter, P EP25
Piedrola, G GP111
Plaseski, T EP285
& GP198
Peterkova, V EP1025
Piemonti, L OC11.1
Platokouki, H EP885
Perego, S EP777
Petersén,
˚ EP1070
& OC6.2
Platonova, A EP126
Pereira, A GP197
& GP182
Pieruzzi, L EP1414
Platonova, N EP323
Pereira, B EP174
Petersen, S GS2.4
Pietila, S GP167
Platonova, O EP736
Pereira, BD EP596
Petersenn, S EP1039,
Pietri, L GP19
Plesoianu, C EP1345
Pereira, C EP1142, EP310,
GP191, OC12.2
Pigarova, E EP1028,
Poblocki, J EP229
EP783, EP788
& S14.1
EP1034, EP1036,
Pofi, R EP537 & GP149
& EP887
Petkovic, MM EP369
EP323, EP347, EP913,
Poggiogalle, E EP702,
Pereira, FA EP949
Petrangeli, E EP702
EP914 & GP157
EP713 & GP168
Pereira, H EP98
Petraviciute, M EP1276
Pignata, SA EP1443
Poglitsch, M GP2
Pereira, J EP1077,
Petre, O EP1147
Pignatelli, D EP1181,
Poiana, C EP1007,
EP1078, EP788,
Petre, OA EP1138
GP153 & GP18
EP1018, EP1067,
EP870 & GP200
Petrenaite, A EP171
Pignatti, E EP1123
EP1353, EP137,
Pereira, L EP1449
& GP211
Pigny, P OC5.3
EP1419, EP911,
Pereira, M EP1289, EP613
Petrenko, S EP749
Pilli, T EP1295 & EP60
EP980 & GP137
& GP199
Petrescu, D EP114
Piltonen, T EP1110
Pojo, M GP126
Pereira, ML EP57, EP706
& EP158
& GP55
Polat, S EP1129
& EP707
Petrescu, S EP148
Pimenta, J EP380
Polat, SB EP1002,
Pereira, SS GP18
Petris, R EP122
Pinhal, F EP1362
EP1320, EP1377,
Pereira, T EP1279,
Petrone, L OC9.5
Pinheiro, MI EP512
EP1429, EP237
EP1362 & EP267
Petrot-Keller, I GP148
Pinto, A GP23
& EP331
Pereira, TA EP350, EP824,
Petrov, V EP1025
Pinto, M EP578 & EP626
Polesel, DL EP385
GP228 & GP229
& EP346
Pinton, P EP789
Poli, G GP8
Pereira-Gurgel, VM EP949
Petrova, E EP117
Pinzani, P GP8
Pollak, M S23.3
Perera, S EP134
Petrovic, D OC13.5
Pipero, P EP571
Polledri, E EP1043
Peretianu, D EP1157
Petrovskaya, E EP695
Pirags, V EP142, EP931
Polovina, S EP694
Perez, FG EP270
Petychaki, F EP67
& OC6.3
Polovina, TS EP71 & EP81
Perez-Bravo, F EP1120
Peverelli, E EP20 & EP924
Piran, R OC6.1
Polychronidis, A EP1378
Perez-Fuentes, R OC6.5
Peynirci, H EP608
Pirelli, A GP43
Polymeris, A EP202
Perez-Olivares, L EP1044
Peyroteo, M EP1465, EP82
Pires, M EP1362
Ponce, MH EP581
Perez-Rivas, LG GP160
& EP98
Pires, S EP1227
Ponikwicka-Tyszko, D
Pergadou, H EP885
Pezzani, R GP3
Pires, V EP1359
OC7.1
Perge, P GP3
Pezzullo, L EP1407
Pirotte, B EP928
Ponirakis, G EP453
Perić, B EP172, EP463
Pfeifer, M EP1046, EP36,
Pisco, J GP90
Pontén, F GP155 & GP194
& EP549
GP39, OC10.4 & S18.3
Piskinpasa, H EP1235
Ponte, B EP820
Peric, B EP43
Pfeilsticker, A EP84
Pisoschi, M EP1157
& OC13.5
Peris, BP EP1072
Pfenninger, A GP105
& EP1158
Pontecorvi, A EP1260,
Perkovic, MN EP595
Pfleger, L EP638
Pistja, E EP645
EP1341, EP1426,
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
EP161, EP997
Prague, J GP131
Punales, M GP93 & OC2.1
Ragonese, M GP175
& OC12.5
Prakapiene, E EP164,
Punda, A EP1469
Rahman, H GP125
Pontinha, CM EP1000
EP542 & EP637
Purice, M EP1221,
Rahman, N GP118
Pontremolli, C GP77
Prakash, S GP105
EP1353, EP1364
& OC7.1
Pop, DD EP846
Prassad, V S2.3
& EP1419
Rahmayani, F EP363
Pop-Radu, CC EP241
Pratas, S EP660
Puspanathan, P EP115
Raica, M EP935
Popa, C EP1353
Prazeres, S EP1330,
Putilin, D EP455
Raileanu, C EP1345
Popa, DE EP376
EP258 & EP486
Puttanna, A EP409
Raimundo, L EP887
Popa, O EP1216
Preciado-Puga, M-d-C
Puukka, K EP1110
Rajendiran, N EP555
Popa, SVO EP206
EP666
Puzianowska-Kuznicka, M
Rajic, AS EP36, GP39
Popescu, D EP1364
Preda, A EP1094
EP577
& OC10.4
Popescu, N EP1018
Preda, C EP1073, EP213,
Rajicic, N EP884
Popik, E EP818
EP252, EP260, EP813
Qasim, B EP940
Rakovic, D EP42
Popova, D GP82
& EP961
Qayyum, M EP1092,
Ramalho, A EP1465
Popova, N EP1036
Premoli, P EP688 & EP691
EP1225, EP205
Ramazanova, L EP39
Popova, P GP78
Premosa, T EP491
& EP761
Ramishvili, L EP315
Popović-Radinović, V
Prete, A GP122
Queirós, DaPSGPSoD
Ramos, EG GP198
EP1245 & EP356
Preto, J EP174
EP477
Ramos, M EP1227
Popovic, B EP1114,
Prichystalova, H EP803
Queirós, J EP477, EP564,
Ramos-Leví, A EP574
EP166, EP168, EP177,
Prieto, A EP863
EP576, EP630, EP719
Ramos-Leví, AM EP180
EP191, EP75, EP80
Prieto-Alhambra, D GP84
& EP773
Ramos-Levi, A OC10.2
& GP139
Prior-Sánchez, I EP1392
Queiros, R EP468
Rance, B GP15
Popovic, D EP1089
& EP159
Quesada, M GP111
Randeva, H D4.1
& EP245
Procopiuc, C EP1221,
Quezado, MM GP236
Ranetti, A-E EP1132
Popovic, V EP953, EP954,
EP206, EP352 & EP817
Quinkler, M EP22, GP11,
Ranetti, AE EP1254
EP956, GP188, GS2.3
Prodanovic, J EP1024,
GP122, GP123, GP20
Rangger, C EP1445
& OC12.2
EP116 & EP709
& OC7.2
Rankov-Petrovic, B
Popovic-Brkic, V GP190
Proença, H EP1387
Quinn, L EP1052
EP1184
Popovic-Pejicic, S EP712
Prokop, J EP1226, EP133,
Quintana-Arroyo, S
Raoul, M EP939
Porcel, JÁR EP1331,
EP1446 & EP181
EP105, EP170, EP193,
Rapizzi, E EP92, EP93
EP1467 & EP563
Pronin, O GP86
EP390, EP530, EP621
& GP25
Porcel, JAR EP270
Proseva, T EP875
& EP757
Raposo, J EP562
Porksheyan, M EP415
Proverbio, MC EP1432
Quinton, R EP1239
Raposo, L EP146 & GP205
& EP73
Provvisiero, DP EP786
& GP153
Raposo, NC EP660
Portal, JJ OC11.2
& EP927
Rapposelli, S GP223
Portilla, AJ EP294
Prozorova, T EP454
Ra˘di, RA EP328
Raquel, C EP641
Portillo, CM EP569
Pruijm, M EP820
Río-Moreno, Md EP472
Rasic-Markovic, A EP1184
Portius, D EP692
& OC13.5
Ríos, MHC EP374
Rask, E EP680
Portugal, J EP1298,
Prystupiuk, L EP358,
Rıza Uysal, A EP1273
Rask, P EP680
EP1422, EP226,
EP507 & EP510
Runkorg, K EP607
Rasmussen,
˚K EP40
EP486 & EP996
Prystupiuk, M EP358,
Rached, A EP1212
Rasmussen, M GP152
Pospíšilová, H EP1170
EP507 & EP510
Radacs, M EP742
Rata˜ o, P EP1454
& EP14
Przeorska, D EP1074
Radenković, S EP1245
Rathnayake, T EP272
Potì, F EP1112
Przhiyalkovskaya, E
Radian, S EP1067
Rausei, S EP1451
Potier, L EP1310
EP1028
& GP137
Raverot, G GP120
Poulsen, PL GP17 & OC1.4
Przybylik-Mazurek, E
Radojkovic, D EP64
& OC12.2
Poupino, J EP243
EP1445
Radojkovic, M EP64
Ray, A EP343
Pournara, E GP190
Puar, T EP24
Radulescu, M EP1419
Raynor, H S4.1
Poutanen, M EP364,
Puar, TH GP160
Radzeviciene, L EP542
Raza, A EP761
EP692, OC13.3
Puca, E EP1370, EP1470,
& EP637
Razanskaite-Virbickiene, D
& OC3.4
EP2 & EP571
Rafael, A EP468 & GP222
EP550
Powell, M GP195
Pugeat, M GP137 & S18.1
Rafailidis, S GP40
Razavi, SA EP1406
Poyares, L EP716
Puglisi, S EP26 & GP175
Raffin-Sanson, ML GP19
Razzaghy-Azar, M GP164
Pozza, C GP149
Puig-Domingo, M GP57
Rafik, K EP939
Rebai, M EP667
Prada, ETA EP154
& GP84
Rafiq, B EP311
Rebelo, AF EP468
Prados-Gonzalez, ME
Puliani, G EP1050
Ragazzon, B GP13
Rebelo-Marques, A EP44
GP128
& EP1054
Raghavan, V OC11.2
Rebollo Román, EP1392
Praet, M EP1191
Pulido, P OC6.5
Ragnarsson, O GP9
Rebollo, I EP1001
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Rebollo-Román, Á EP159,
Rickard, AJ GP2
Rodríguez, CN GP89
EP1295, EP1311,
EP500, EP776, EP819
Rickers, L EP682
Rodríguez, FJ EP904
EP1452 & EP414
& EP907
Ricordi, C OC6.2
Rodríguez, JCR EP8
Rosário, F GP242
Recabarren, MP EP636
Riesco-Eizaguirre, G
Rodríguez, PC EP725
Rosa Alhambra Expósito,
& GP132
GP235
Rodríguez-Martín, A
M EP1392
Recabarren, S EP1120
Rigla, M EP165 & GP238
EP714 & EP715
Rosa, SL EP1451
Recabarren, SE EP636
Rikhsieva, N EP1106
Rodríguez-Perálvarez, M
Rosca, R EP1094, EP1176
& GP132
& EP1257
EP698
& EP1180
Recamonde-Mendoza, M
Rio-Moreno, Md GP128
Rodrigo-Cano, S EP681
Rosenberg, K EP13
OC2.1
Rios, E EP140 & EP1449
Rodrigues, A EP79
Rosenwald, A GP119
Redondo, LR EP432,
Ristic, N EP779, GP202
Rodrigues, C GP133
& OC1.1
EP433 & EP705
& GP62
Rodrigues, D EP45
Rosetti, S EP688
Refardt, J EP889 & EP918
Riva, E EP196, EP197
Rodrigues, E EP1058,
& EP691
Rego, T EP1006, EP251
& EP789
EP1206, EP140,
Ross, IL EP28
& EP725
Riva, S GP77
EP305 & EP54
Ross, RJ GP61
Reichelt, AJ EP457
Rivadeneira, F EP744
Rodrigues, F EP1459,
Ross, RJM EP879
Reimondo, G EP26
Rivera, A OC6.5
EP1463
Rossi, G EP970
Reincke, M EP52 & GP160
Rivera, NG EP569
& EP174
Rossi, L GP223
Reis, D EP897 & EP898
Rivero-Muller, A GP118
Rodrigues, I EP1330,
Rossiter, P EP295
Reiter, E EP1123
Rizk-Rabin, M GP5 & GP13
EP750, EP795, EP796
Rost, S GP119
Rejaibi, S EP1322
Rizoulis, A EP861
& EP829
Rotariu, D EP1073
Rejeb, O EP1212, EP1322,
Rizvi, A EP958, GP106
Rodrigues, M GP94
Rothman, JG GP47
EP1324, EP1328,
& GP108
Rodrigues, P EP1356,
Roussel, O EP9
EP207 & EP570
Rizvi, SSR EP1092,
EP51, EP807 & EP871
Roussel, R EP1310
Rekik, N EP1128, EP1349,
EP1225, EP205
Rodrigues, T EP704
Rovite, V EP931
EP1361, EP189,
& EP761
& EP919
Roy, S EP343
EP335, EP66 & EP770
Rizza, L GP16
Rodriguez, EG EP1373
Rozanska, A EP1441
Rella, N EP1237, EP1251
Rizzo, C GP214, GP215
Rodriguez, JCR EP459
Rozhinskaya, L EP1028,
& EP211
& GP216
Rodriguez, P EP1001
EP345, EP346, EP881
Remédio, F EP599
Rizzo, M GP108
Rodriguez, S OC1.2
& GP157
Remolar, MaÁB GP48
Rjeb, O EP1193, EP1201,
Rodriguez-Manas, L MTE1
Rubin, B GP5
Renard, C EP883
EP1208 & EP340
Rodriguez-Perez, A EP390
Rubin, C EP735
Rep, S EP1445
Rkik, N EP135
Rogatko, I EP890
Rubino, C GP148
Repaci, A EP1381
Robalo, B EP310
Rogowski, MP GP172
Ruchała, M EP1074,
Repetto, G OC5.1
Robenshtok, E EP1374
Rojas, C EP938
EP1433, EP1450
Requena, M EP1030
Roberts, R GP131
Rojek-Tre˛bicka, J EP48
& EP1474
Resende, E GP98
Robles-Cabeza, L EP1462
Roldan, E EP1001
Ruchala, M EP1252,
Resman, KG EP36
Rocío, P EP641
Romagnoli, P GP25
EP1275, EP388
Restituto, P EP227
Roca-Rodríguez, MM
Roman, DL EP952
& GP220
Reubi, JC GP185
GP71
Roman, G EP560
Rucz, K EP1410
Reyes, LM EP8
Rocha, A GP2
Román, ÁR EP1392
Rudaz, S EP782
Rezgani, I EP502
Rocha, G EP1155,
Romanelli, F GP33
Rudelle, H GP143
Reznik, Y GP12
EP1211, EP1351,
Romanowska-Prochnicka,
Rudovich, N EP1087
Rhayem, Y EP52
EP1356, EP145,
K EP469
Ruel, I EP661
Rheinheimer, J EP648
EP174 & EP51
Romeo, EL EP1118
Ruffinelli, JC GP241
Ribeiro, C EP1465,
Rocha, J EP320
Romeo, PD GP175
Ruggeri, RM EP1443
EP1475, EP82, EP98
Roche, D EP295
Romero, J OC6.5
& GP208
& OC14.3
Rochira, V EP1166,
Romero, JC GP73
Ruiz-Noa, Y EP437 & EP666
Ribeiro, I EP1049
EP1383, GP146
Romero, SG EP868
Rungby, J GP17
Ribeiro, J EP791
& GP51
Ronchi, C EP932, GP5
Runkle, I EP900
Ribeiro, K EP723
Rochtus, A GP45
& OC1.1
Ruohonen, S EP364
Ribeiro, L EP706 & EP707
Rodgers, R EP1190
Ronchi, CL EP161, EP20,
& OC4.2
Ribeiro-Oliveira, A
Rodic, G EP191
GP1, GP119, GP121
Ruohonen, ST EP692
EP1011
Rodien, P GP143
& GP22
Ruokonen, A EP1110
Riccetti, L EP1123
Rodionova, T EP1266
Ronchi, SSC OC7.2
Rurale, G EP1222
Richell, G EP1342
& EP1316
Roost, K EP104
Rusalenko, M EP556
Richter, S EP92, EP93
Rodríguez, A EP1284
Roque, C EP1088,
Russi, V EP825 & GP221
& GP25
& GP210
EP1177, EP1207,
Russo, GI GP127
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Russo, GT EP1118
Sagarribay, A EP1000
Sampaio, L EP310
Santos, J EP1459
Rusu, C EP813
& EP1062
& EP887
& EP1463
Rusu, S EP1419
Saglam, DA EP856
Sampedro-Nún˜ez, M
Santos, JG EP1422
Rutjowski, D EP577
Saglar, E EP815 & GP74
EP180 & OC10.2
Santos, K EP1029
Rutkowska, J EP17
Sahara, A EP273
Sampron, N EP1023
Santos, LR EP1357
Ruza, I EP342
Sahin, AB EP852
Samra, ABA EP160
Santos, R EP297
Ryan, J EP682
Sahin, D EP815 & GP74
& EP453
Santos, S EP1323 & EP32
Rybka, J GP72
Sahin, I EP330, EP620
Samson-Couterie, B GP15
Santos-Antunes, J EP576
Rylander, L EP1070
& EP703
& GP2
Santos-Silva, R EP1058
& GP182
Sahin, M EP1273, EP277
Samueloff, A OC4.1
Santrac, N EP1480
Ryo, M GP14
& EP967
Sana, R EP387 & EP845
& GP225
Ryu, J-S OC14.5
Sahiner, Z EP344
Sancak, S EP266
Sanxhaku, R EP765
Said, A EP1447
& EP440
Sanz-París, A EP461
Saida, F EP279
Sanches, AC EP174
& EP619
Sá, M GP98
Saidane, D EP667
Sanches, C EP82
Sapera, A EP217
Ságová, I EP1086
Saidnazirkhanova, M
Sanchez-Lechuga, B
Saponaro, F EP278,
& GP38
EP880
EP544
EP348 & GP33
Sáiz-Sátjes, M EP530
Saif, A EP1240
Sanchez-Ragnarsson, C
Saraiva, C EP1177,
Sánchez, CM EP1072
Saigí, I EP165
EP1484
EP1452 & GP222
Sánchez, EG EP569
Sailer, C EP942
Sandoval, D EP1120,
Saraiva, J EP1475 & EP45
Sánchez, IP EP474
Sainsbury, C GP104
EP636 & GP132
Sarak, T EP604
& EP602
Sainte-Catherine, D OC1.2
Sandu, K EP1373
Saranti, S EP1202
Sánchez, JRC EP708
Saiz-Satjes, M EP757
Sandu, R EP306
Sarantopoulou, V EP202
& EP717
Sajdak, D EP1119
Sane, T EP163
Sarauskas, V EP164,
Sánchez, MaBG EP432
Sakali, A EP864
Sanli, C EP1223
EP839 & GP244
& EP433
Sakcı, E EP266
Sansoni, V EP777
Sarchielli, E EP377
Sánchez-Lechuga, B
Sakka, I EP1201, EP1212
Santacruz, E EP88 & EP94
Sardella, C EP970
EP1278
& EP340
Santaguida, MG GP221
Sardinha, LB EP632
Sánchez-Sánchez, R
Sakka, V EP239
Santana, I EP704
Sari, CI GP141
EP178
Sala, GBL EP1123
Santana-Suárez, AD
Sarkinaite, M EP173
Sarnblad, S EP680
Salem, A EP762
EP530
Sarkisova, K EP561
Sérgio Neves, J EP1289,
Salenave, S EP966
Santana-Suarez, AD
Sas, T GS1.2
EP194, EP195
& GP19
EP105, EP170, EP390,
Sasic, I EP369
& GP217
Salgado, D EP788
EP621 & EP757
Sass, S EP91
Sørensen, HT GP17
Salgado, L EP1454
Santarem, R EP84
Sassi, L EP688 & EP691
Saarinen, N GP167
Salici, AG EP679
Santharam, S EP1051
Sastre, J EP1218 & EP973
Saavedra, A EP1058,
Salituro, N EP1381
Santi, D EP1107, EP1166,
Satoh, F GP14
EP1206, EP305
Salminen, S GP167
GP146 & GP51
Satti, H EP597
& EP630
Salomon, CF OC5.1
Santi-Cano, MJ EP714
Saucedo-Toral, CA EP437
Saba, L EP26
Salsamendi, JL EP247
& EP715
Sauter, N EP1015
Sabater, EMR EP1178
Saltiki, K EP1411
Santiago, A GP179
Sava, E EP143 & EP855
Sabatini, M GP172
& GP230
Santiago, Md EP904
Savasteeva, I EP556
& GP223
Salvador, J EP906, EP909
Santiago, P EP1332
Savchanka, A EP664
Sabatino, J EP688
& EP910
Santiago-Perez, A EP900
Savic, S EP111 & EP1261
& EP691
Salvatori, M GP231
Santini, F EP397
Savopoulos, C EP588
Sabico, S GP46 & GP77
Salvatori, R EP883, EP949
Santos, AC EP146
Savosteeva, I EP515
Sabino, T EP133, EP1446
& GP178
& GP205
Savvidis, C EP1202
& EP181
Salvi, M EP1342
Santos, AI EP1298
& EP859
Sablon-Gonzalez, N EP621
Salvianti, F GP8
& EP1422
Sawamura, T OC3.1
Sadowski, SM GP124
Samardzˇić, V EP356
Santos, AP EP100, EP146
Sawicka, A EP1372
& OC7.3
Samardzić, V EP1245
& EP174
& EP826
Saeger, W EP932 & GP176
Sambo, M EP1030
Santos, C EP1446 & OC5.4
Sawicka-Gutaj, N EP1252
Saez-Lopez, C EP753
Samia, E EP1154
Santos, F EP1177
& EP1275
Safak, O EP1464
Samia, OK EP120
& EP1452
Saygili, ES EP109
Safarova, M EP901
Sampaio, F EP243
Santos, FS EP1088,
& EP836
Safi, AW EP534
Sampaio, IL EP100
EP1207, EP1311,
Sayilar, EI EP758
Safi, W EP335 & EP770
Sampaio, J EP1387
EP1486, EP414,
Sayiner, ZA EP1003
Sagar, R EP280 & EP334
& EP95
EP725 & EP951
Sazonava, A EP527
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Sbardella, E EP1050,
Seki, M EP4
Sever, MJ OC10.4
Shin, JY EP236
EP1054 & GP16
Seki, T EP4
Sevimli, H EP1108
Shin, M EP233 & EP697
Sbiera, I GP121 & GP22
Seki, Y GP134
Sezer, A EP1198, EP1396,
Shin, Y EP233 & EP697
Sbiera, S EP161, EP932,
Sekiya, M GP166
EP1397, EP1399,
Shinya, F EP1242
GP1, GP119, GP121,
Selfa, SMM EP998
EP1400, EP1401,
Shiraso, S EP1242
GP22, GP5 & OC1.1
Selkina, V EP556
EP1402, EP1403,
Shirin, H EP199
Scagliotti, V OC8.5
Selleva˚ g, K EP33
EP271 & EP981
Shishkin, A EP518
Scappaticcio, L EP1121
Selmi-Ruby, S EP1449
Sfar, MT EP1236, EP1238
Shkurta, A EP765
& EP1293
Selva, D EP753
& EP833
Shoback, DM GP47
Scaroni, C EP1042
Selvarajan, R EP553
Sgromo, B EP682
Shong, YK EP1366,
& EP1056
Sema, D EP1281
Shackleton, CHL OC1.3
EP1367 & EP1421
Scarpa, L EP1445
Sematonyte, J EP1102
Shah, S EP553
Shorakae, S EP1115,
Scavello, I EP370
Semple, R EP466 & OC3.3
Shah, T OC3.5
GP135 & GP141
Schofl, C EP1020
Sen, EC EP109 & EP836
Shah, U EP58
Shrikrishnapalasuriyar, N
Schurmann, A OC2.3
Sencar, E EP1368
Shah, V EP272
EP303
Schutz, P OC11.3
Sendur, SN GP61
Shahid, G EP205
Shteinshnaider, M EP1313
Schalin-Jantti, C EP163
Sennarog˘lu, E EP538
Shahida, B EP1246
Shukla, R EP1333
Schalin-Jantti, C OC10.5
Sentosun, U EP282
Shakirov, H EP736
Shvangiradze, T EP659
Schally, AV GP151
Senyurt, M EP1108
Shalimova, A OC2.2
& EP685
Scheerer, P NSA5.1
& EP429
Shamanadze, A EP504
Shved, M EP420
Schilbach, K EP1027,
Seo, hA EP506
& EP650
Shyman, Z EP436
EP639 & GP196
Seo, JA GP91
Shamkhalova, M EP521
Shyshko, V EP527
Schipor, S EP1094,
Seo, JB EP383, EP506
& EP568
& EP663
EP1216, EP137
& GP56
Shanik, MH EP291
Siamopoulos, C EP299
& EP1466
Seo, Y-G EP700
Shao, R EP1096
Siderova, M EP1271
Schlegel, N OC1.1
Seok, JW EP729
Sharabiani, MT EP1458
Sidneva, Y EP799
Schlosser, A EP932, GP1
Sepek, M EP187
Sharefi, AA EP1398
& EP895
& GP5
Seppanen, M GP50
Shargorodsky, M EP1185
Sidorin, A EP1394
Schmid, C EP104
Sepp, K EP1388, EP1410
& EP580
Sierra, M EP1044
Schmidt, E EP1410
& EP742
Sharipova, J EP617
& GP73
Schoenmakers, N S26.2
Septier, A OC1.2
Sharma, D EP1309
Siffroi, J-P GP148
Schopohl, J EP1027,
Sequeira Duarte, J EP1049
Sharma, P EP1333
Sigaud, T OC11.5
EP1039 & GP196
Sequeira, J EP1177
Sharma, R GP166
Siggelkow, H EP353
Schreiner, J GP121
Seraphim, P GP163
Shatalov, I GP92
& OC10.1
Schuetz, P EP687
Serez, B EP1404
Shatarnova, T EP670
Sigirli, D GP161
& EP942
Serfling, G EP800
Shauly-Aharonov, M
Sigurjonsdottir, H EP19
Schuster, D EP822
Sergey, D EP1248
EP624
& EP21
Schutter Harlinde, D
Serguey, D EP73
Shebl, T EP416
Silaghi, CA EP114, EP158,
OC14.4
Serra, F EP1088, EP1359
Shelestova, E N1.1
EP328, EP398, EP399
Schwaiger, R EP639
& EP139
Shell, J GP124 & OC7.3
& EP400
& GP196
Serra, FA EP951
Shepelkevich, A EP269,
Silaghi, H EP114, EP158,
Schwambach, F EP1013
Serra, L GP238
EP286, EP480
EP328, EP398, EP399
Schwarcz, E GP9
Serra-Caetano, J EP887
& EP737
& EP400
Schwarzmayr, T EP52
& GP109
Sheriba, N EP1154
Silamikelis, I OC8.3
Schweighofer, N GP107
Serra-Prat, M GP57
& EP1299
Silea, S EP1007 & EP980
Sciammarella, C EP1407
Serraclara, A EP1044
Sherlock, M EP1041,
Silva, AL EP1448
Scillitani, A GP130
Serrano, ACR EP76
EP1150, EP1153,
Silva, C EP451, EP807
& GP33
Serrano, RN GP89
EP339, EP487, EP572,
& GP73
Scinic, O EP1302
Serrano-Blanch, R EP178
EP70 & EP798
Silva, E EP133
Sclumberger, M GP148
Serrano-Nascimento, C
Sherman, M EP661
Silva, F EP1351, EP490
Scoazec, JY S17.3
EP716
Shestakova, M EP521,
& EP492
Scoscia, MF EP1251
Sert, C GP191
EP561, EP568, EP659
Silva, J EP1218, EP1359,
Scotté, M OC11.2
Sert, M EP1241
& EP685
EP139 & EP57
Secchi, A OC6.2
Sertba¸, Y EP440
Shestakova, T EP50
Silva, L GP94
Sedman, T EP607
Sertbas, M EP565
Shibina, L EP1036
Silva, LF EP267
Sefi, W EP167
Seshadri, KG EP552
Shimano, H GP166
Silva, R EP1461, EP468
Segerstedt, E GP9
Sesmero, A EP9
Shimon, I EP1046
& EP57
Seiça, R EP704
Setti, M GP51
Shin, D EP1256
Silva, RS EP512 & GP227
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19th European Congress of Endocrinology 2017
Silva, S GP222
Sir-Petermann, T EP1120,
Smirnova, L EP540
Sordi, V S20.1
Silva, T EP57 & EP933
EP636 & GP132
Smit, J GP197
Sorin, I EP587
Silva, TNd EP1422
Sira, L EP1410
Smith, D EP1041
Sosic-Jurjevic, B GP202
Silva-Fernández, J EP11,
Siracusa, M EP1443
Smith, K GP104 & GP106
Sˇošic-Jurjević, B EP212
EP456 & EP955
Sirbu, A EP1371, EP855
Smith, L GP10, GP159,
Sˇošo, G EP1469
Silva-Nunes, J EP1446
& EP943
GP4 & S10.1
Soto, C EP3, EP9
& EP451
Sirbu, AE EP947
Smolen, A EP865
& EP952
Silveira, D EP807
Sironi, M GP77
Smolovic, B EP1283
Soto, CC EP603
Silveiro, SP EP457
Sisman, M EP1017
Snabboon, T EP1288
Soto-Moreno, A EP929
& OC2.5
Sisman, P EP1017, EP102,
Snyder, M EP744
Sottomayor, C EP129
Silvestre, C EP1083,
EP131, EP1335,
Soare, I EP943
Soua, H EP1236
EP119, EP1387,
EP333, EP336, EP608,
Soare, IS EP947
& EP1238
EP157, EP243, EP329,
EP679 & EP852
Soares, AA OC2.5
Soula, M EP754
EP897, EP898
Sitch, A GP122
Soares, P EP1357, EP1449
Soumaya, M EP780
& GP226
Sjoberg, S N1.4
& OC14.3
Sousa Santos, F EP1295
Silvestri, S EP1260
Sjogren, K S7.3
Soares, S EP1155
Sousa, A EP51
Silvius, B EP635
Sjostedt, E GP155
Sobhi, N EP219
Sousa, AM EP1356
Simó-Servat, A GP241
Skalniak, A EP1297,
Sobral, J EP51
Sousa, B EP722
Simo˜ es, H EP1219, EP57,
EP283, EP284 & OC9.3
Sobrinho-Simoes, M OC14.3
Sousa, I EP596
EP725 & EP772
Skorkiewicz, K EP1445
Sodikov, S EP1106
Sousa, L EP567
Simo˜ es, MS EP1357,
Skowronska-Jozwiak, E
Sodji, M OC11.2
Sousa, M EP1179
EP1449 & P6
GP183
Sohn, SY EP1424
Sousa, R EP1454
Simo˜ es, R EP232 & EP234
Skrobisz, J EP1252
Soidán, JLG EP365
Sousa, S EP1133, EP1155,
Simo˜ es-Pereira, J EP1142,
& EP1275
Soler, MG GP48
EP403, EP84
EP1454, EP772,
Skrobowski, A OC12.4
Sokhatska, O EP1289
& GP133
EP783, EP816
Skrodeniene, E EP550
& GP199
Souteiro, P EP1081,
& GP133
Skrzypulec-Plinta, V
Sokolowski, A EP1477
EP140, EP169, EP194,
Simaityte, P EP173
EP1119
Solak, M EP71 & EP81
EP195, EP477, EP493,
Simanaviciene, V GP244
Skuja, S GP209
Solari, D EP927
EP53, EP54, EP564,
Simeakis, G EP1411
Skuridina, D EP1034
Solari, S OC5.1
EP576, EP630
& GP230
Slagter, S EP672
Soldatovic, I EP367,
& EP719
Simeoli, C EP34 & EP786
& OC9.1
EP677 & EP678
Southall, N EP754
Simeoni, L EP807 & GP26
Slama, AB EP355
Soldevila, B GP84
Souto, SB EP1091
Simkovic, M EP837
Slavikova, E EP1344
Soler, GS EP294
Souto-Moura, C EP872
Simo, R EP753
Slezak, T GP118
Solntsava, A EP351,
Souza, B GP94
Simoes, H EP258 & GP23
Slim, I EP1428 & EP1430
EP670 & EP814
Souza, Bd EP648
Simon, T GP148
Slimane, H EP1193,
Solovov, V EP1286
Souza, L EP723
Simona, F EP587
EP1201, EP1208,
Soltész, P EP1384
Sowa-Staszczak, A
Simonds, S EP373
EP1212, EP1322,
Solter, M EP209
EP1297, EP1445
Simonelli, I EP1050
EP1324, EP1328,
& GP232
& EP283
Simoni, M EP1107,
EP207, EP340
Soltsava, A EP218
Sowinska-Przepiera, E
EP1112, EP1123,
& EP570
Soltysik, K GP67
EP229 & EP230
EP1131, EP1383,
Slimene, MFB EP1428
Somali, M EP588
Sowinski, J EP1275
GP245 & GP51
& EP1430
Someya, FN EP1447
Sˇošić-Jurjević, B EP359
Simoniene, D EP1321,
Sliwczynski, A EP577
Sondergaard, E OC1.4
Soysal-Atile, N EP446
EP1436 & EP479
Slomian, M EP1372
Song, E EP1366, EP1367
& EP842
Simpson, H GP27
Sloot, Avd GP153
& OC14.5
Sozen, M EP1167
Simsek, S EP912
Slowinska-Lisowska, M
Song, K-H EP438, EP514,
Spottl, G EP154
Simu˚ nková, K EP14
EP1160
EP554 & EP690
Spada, A EP20, EP924
Sinclair, A EP798
Slusarczyk, J GP154
Song, SO EP960
& OC7.4
Singh, AK EP701
& GP158
Song, Y OC1.5
Spagnolo, F GP175
Singh, R EP741
Sluszniak, A EP1409
Song, YD EP960
Span, P GP10
Singh, V EP1333
Smaili, M EP65
Sonmez, A EP1165
Spiroiu, C EP1254
Siolos, A EP1303, EP1307
Smajic, E EP609
& EP362
Spremovic-Radjenovic, S
& EP1417
Smajis, S EP638
Sonmez, C EP821
EP111
Siomkajło, M GP72
Smircic Duvnjak, L EP1151
Sonzogni, B EP1043
Spyropoulos, P EP136
Sipila, P OC13.3
Smircic-Duvnjak, L EP508
Soo, S-C EP272
Sˇrámková, M EP14
Sipkova, Z GP206
& EP595
Sook Kim, E EP690
Sˇrámková, M EP1143
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Sreckovic, B EP367,
Stikkelbroeck, N GP10
Suzaki, N EP1039
Tabor, VH EP1365
EP677 & EP678
Stobiecka, E EP1420
Suzuki, A EP1385
Tabur, S EP1003
Sri Venkata, M EP408
Stochholm, K OC1.4
Svard, D GP182
Tagliati, F EP789
Sriamareswaran, R EP426
Stoffel, M MTBS3
Svaikeviciene, K EP156
Tagliavini, S EP1123
Sroczynski, M EP187
Stojanoska, MM EP1024,
Svarre Nielsen, H OC13.2
& GP51
Stárka, L EP1143, EP1170
EP245 & EP956
Svensson, A-M EP55
Taha, MO EP425
& EP14
Stojanovic, M EP111,
Svilias, I EP1197
Tahir, F EP1092, EP1225,
Stępor, M EP48
EP678, EP892, EP953,
Swan, J EP13
EP205 & EP761
Stormann, S EP1027
EP954, EP956, GP188
Swarbrick, M EP1312
Taieb, A EP1229, EP646
& GP196
& GP197
Swee, DS EP29 & EP46
& EP780
Stan´ czyk, A EP48
Stojanovic, Z EP127
Sweep, F GP10
Takagi, A EP4
Stacey, H EP575
Stojkovic, M EP111
S´wider,G EP1338
Takao, T EP643
Stacul, F GP204
& EP1261
Swirska, J EP338
Takeda, Y OC3.1
Stakor, MS EP1161
Stokic, E EP1089 & EP245
Sworczak, K EP396
Takeuchi, Y GP166
Stalla, G EP912
Storey, C OC5.5
Syed, I EP1485
Takito, D EP1029
Stalla, GK GP160
Storr, H GP195
& EP58
Taliani, E EP1383
Stalvey, M GP66
Strajhar, P EP782
Sygut, J EP1474
Taliano, M GP151
Stamenkovic-Pejkovic, D
Strasburger, C GP190
Sykiotis, GP EP1373
Tallini, G EP1381
EP694
Strasburger, CJ GP192
Sykja, A EP1303 & EP223
Tam, AA EP1429
Stamm, B OC10.1
Stratakis, C EP13, GP28
Sylvetsky, N EP228
Tamatea, J EP1312
Stamm, N OC10.1
& GP68
Symington, E EP124
Tamer, G EP1243
Stancˇík, M EP1086
Stratakis, CA GP12
Syrenicz, A EP1205,
Tampouratzi, D EP217
Stancic, A EP693
& GP236
EP1336, EP229
Tampourlou, M EP1051
Stanciu, M EP1364
Strauss, L EP692 & GP167
& EP230
& GP180
& EP391
Strebkova, N EP1025
Syrenicz, M EP230
Tan, J OC11.4
Stancu, C EP1220
Strobel, R EP1244
Syska-Bielak, A EP1441
Tan, S EP724
Stanescu, B EP1220
Strom, T GP15
Székely, E EP1384
Tancic-Gajic, M EP127
Stankiewicz-Olczyk, J
Strom, TM EP52
Székely, T EP1384
& EP42
GP72
Stukens, J EP931
& EP1434
Tanda, ML EP1451 & EP688
Stanoevich, I EP1028
Suárez, ADS EP107
SzU˜cs,N EP1046
Tanday, R EP1213,
Stanojevic´, A EP356
Suarez, E OC7.5
Szabo, Z EP1410
EP1354, EP1485
Stanojlovic, O EP1114,
Subías, D EP165
Szakács, G GP44
& EP308
EP1184, GP139
Sucaliuc, A EP16 & EP240
Szanto, Z EP1134 & EP860
Tandircioglu, UA EP724
& GP140
Sucesso, MB GP227
Szczepanek-Parulska, E
Tang, J EP1
Stanworth, R EP1192
Sudar-Milovanović, E
EP1433, EP1450,
Tanimoto, M GP134
Starchenko, T EP458
EP1245
EP388 & GP220
Tanko, Z EP860
Starostina, E EP1069
Sugano, H EP840
Szekeres, S EP1410
Tanna, R EP525
Stashuk, G EP905
Sugino, K EP1385
Szeliga, K GP67
Tanrikulu, S EP1038
Stasiolek, M EP1435
Sukhanova, O EP1036
Sztefko, K EP890
& OC12.1
Stassen, L EP339
Suleiman, N EP160
Sztembis, J EP1338
Tanriverdi, F EP968
Stebbing, J EP386
Suligowska, A EP1442
Szujo, S EP1410
Tapanainen, J EP1110
Stefan, C EP262
Sumarac-Dumanovic, M
Szuman, G EP1251
& GP55
Stefanescu, AM GP21
EP367 & EP694
Szymonek, M EP1274,
Tapia, J EP681
Stefaroi, C EP838
Sun Jeong, J EP690
EP1382 & EP1409
Tapia-Castillo, A OC5.1
Steffensen, C EP63
Sun, N OC1.1
Szyska-Skrobot, D EP1382
Tapikara, Z EP362
& GP17
Sundaram, AY OC8.3
Tarach, J EP547, EP831,
Steinhauer, S GP119
Sundgren, PM EP1070
Távora, A EP51
EP850 & EP865
Steinschneider, M EP199
& GP182
T’Sjoen, G EP1019
Tarach, JS EP144 & EP338
Stejereanu, L EP763
Sung, Y-A EP925
Tóbiás, B EP1434
Tarasova, T EP913
Stelmachowska-Banas, M
Sung, YA EP1116
Tutuncu, NB EP1431
& EP914
GP173
Sunthornyothin, S
Tutuncu, Y EP538
Tarcin, OU EP47
Stelmaszewska, J GP118
EP1288
Ta¸çılar, ME EP673
Tardy, V GP19
Steponaviciute, R EP173
Susanti, VY EP363
Tabaei, K EP662
Tarigopula, G EP25
Stepto, N EP1115 & EP747
Suter-Widmer, I EP942
Tabarin, A GP120 & OC7.2
Tarsitano, MG GP149
Stettler, C EP1090
Sutulovic, N EP1184
Tabassum, S EP1016
Tartaglione, T EP991
Steven, N EP1052
Suvanto, E EP1285
& EP606
& EP997
Stevenson, J EP1084
Suwanwalaikorn, S
Tabbal, H OC1.2
Tas, B EP565
Stieg, MR GP160
EP1288
Tabor, MH EP1365
Tashmanova, A EP436
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Taskaldiran, A EP1175
Terrasi, A GP130
Tiulpakov, A EP1025,
Torres, I EP100 & EP146
Taskaldiran, I EP1175,
Terriou, L EP1369
EP345 & EP346
Torres, JFM EP183
EP384 & EP854
Terroba, C EP603
Tiwari, S EP701 & EP741
Torres, MM GP89
Taskinen, M-R GP76
Tertipi, A EP217
Tkachuk, A GP78
Torres, SG EP1178
Taskiran, B EP1375
Terzolo, M EP161, EP26,
Toba, L GP156, GP52
Torres-Arroyo, B EP11,
& EP244
GP122, GP123
& GP75
EP456 & EP955
Tassone, F EP268
& GP8
Tobiás, B EP1384
Torres-Barea, I EP1174,
Tastekin, E EP1198,
Tesic, D EP1089
Tobin, L EP696
EP1200, EP1203,
EP121, EP1396,
Tetiker, T EP1241
Tocino-Hernandez, AL
EP1287 & EP535
EP1397, EP1399,
Teulé, A EP150
EP105
Torres-Barea, IM EP858
EP1400, EP1401,
Tezuka, Y GP14
Todd, JF EP1196, GP29
& EP915
EP1402, EP1403,
Thé, AC EP841, EP899
& GP30
Torres-Rasgado, E OC6.5
EP271 & EP981
& EP975
Todorova, B EP285
Torres-Torrenteras, J
Tatli Dogan, H EP1413
Thakker, R S2.1
Tofan, M EP792 & EP809
EP753
Tauchmanova, L EP1039
Thakker, RV OC10.5
Toivanen, S EP163
Tortora, A EP1064
& GP177
Themeli, A EP645
Toivonen, R GP167
Tortosa, F EP896 & EP974
Tauni, R EP254, EP272,
Theodoropoulou, M
Tokac, M EP237
Torun, D EP1165
EP525, EP732
GP160
Tokunaga, S EP27
Torun-Jurkowska, A
& EP877
Theodorou, M EP1084
Toldy, E GP44
EP547
Tavares, C EP1449
Thoda, P EP861
Toledano-Delgado, Á
Toruner, FB EP1144
Tavares, L EP791
& EP864
EP819
Tosheva, G EP1271
Tavares, P EP1155,
Thomas, S EP1032
Tomé M EP298, EP302
Toth, M GP3
EP1211, EP1351,
Thomasius, F EP353
& EP341
Toubert, ME GP148
EP1356, EP145
Thomo, T EP495
Toma, GM EP1364
Touraine, P GP12
& EP51
Thompson, C EP1041
Tomczyk, R EP357
Tournis, S EP859
Tavares, T EP337
& EP768
Tome, M EP623
Tozzi, R EP702
Tay, WL EP29
Thordarson, H EP49
Tomic, D EP116
Trabado, S GP7
Taylor, AE EP1150,
Thordarson, HB EP33
Tomic, M EP508
Trainer, P EP1169
EP1153 & OC3.3
Thorsby, PM EP59
Tomic-Naglic, D EP1089
Tramontano, AL EP1064
Taylor, AE OC1.3
Tiaka, E EP1047
Tomlinson, J EP682,
Tran, DN EP1100, EP727
Tayyeb, S EP428
Tiano, L EP1260
EP728, EP730, EP798,
& EP738
Tazza, L EP1260
Tiberg, F GP177
GP69, GP70, OC3.3,
Tranfaglia, C GP231
Teede, H EP1115, GP135
Tiffreau, V EP1439
OC3.5 & S25.3
Tranti, T EP1123
& GP141
Tigas, S EP1172, EP299
Tomlinson, JW GP138
Trapella, C EP789
Tehrani, FR EP1125
& EP559
Tomoda, C EP1385
Trattnig, S EP638
& EP1183
Tigishvili, L EP315
Tomokuni, J EP273
Travlos, A EP1460,
Teixeira, G GP163
Timon, C EP339
Tomulescu, V GP21
EP202, EP221
Teixeira, JP EP1422
Timur, O EP1113
Tonoli, D EP782
& EP276
Teixeira, M EP100
Tinahones, F EP755,
Toogood, A EP1051,
Trenti, T GP51
& GP163
EP756, EP808
EP1052 & GP180
Treppiedi, D EP20
Teixeira, R EP1279
& EP868
Top
¸uog˘lu, C EP1453
& EP924
Teixeira, S EP496 & EP567
Tinahones-Maduen˜ o, F
Topaloglu, O EP1320,
Tresoldi, A OC7.4
Tekin, G EP421
EP1462
EP1326, EP1377,
Triana, P EP984
Tekin, S OC12.1
Tinahones-Maduen˜ o, FJ
EP1413, EP330,
Triantafillou, E EP217
Tekin, ZN EP1122
EP614 & GP71
EP620 & EP703
Trifanescu, R EP1353
Teles, L EP54 & EP169
Tino, P OC1.3
Topcuoglu, C EP1347
& EP137
Temessek, A EP502
Tinu, A-M GP21
Toporcerová, S EP1127
Trifunović, S EP212
Temizkan, S EP289
Tippisetty, S EP552
Toppari, J GP118, OC4.2,
Trifunovic, S GP62
Tenés, S EP681
& EP553
OC7.1 & S21.2
Triggiani, V GP214,
Tennagels, N GP105
Tirnovan, M EP1076,
Toprak, İD EP113
GP215 & GP216
Tenu, I EP560
EP1360 & EP188
Topsakal, S EP1405,
Trimarchi, F EP1443
Tepla, O GP86
Tirnoveanu, M EP1209
EP656, EP971
& GP208
Terakawa, N GP134
Tirosh, A EP13, GP124,
& EP972
Tripolski, M EP23
Teresa Gallego, M EP1415
GP186 & OC7.3
Torffvit, O EP557
Tripsianis, G EP1378
Terlizzese, P GP214,
Tishkovsky, S EP540
Toromanyan, E EP304
Trivin˜ o, V EP891
GP215 & GP216
& EP541
Torralvo, FS EP756
Trofimiuk-Muldner, M
Terol, E EP1415
Tissier, PL GP159
Torregrossa, L EP1414
EP1445
Terraris, D GP43
Tiszlavicz, L EP1388
& EP348
Trofimiuk-Muldner, M
Endocrine Abstracts (2017) Vol
49
19th European Congress of Endocrinology 2017
EP1026, EP283
GP138, GP203
Urbanavicius, V EP173
Vale, Sd EP1012, EP1021,
& EP284
& GP206
Urbanczuk, M EP144,
EP41, EP853 & EP897
Trojan, E GP158
Turpin-Nolan, S GP105
EP338 & EP865
Valea, A EP117, EP846
Trolle, C OC1.4
Turunen, S EP1285
Urbani, C EP970
& EP979
Troncone, G EP1407
Tutal, E EP1097, EP1368
Urboniene, J EP1276
Valeeva, E GP170
Troshina, E EP659
& EP327
Ureten, K EP684
Valeeva, F EP464, EP465,
& EP685
Tutuncu, N EP39
Urhan, M EP1455
EP617 & GP170
Trotti, E EP688 & EP691
Tutuncu, Y EP56
Urmanova, Y EP1106,
Valente, A EP562 & OC5.4
Trouillas, J EP954, GP194,
Tuzcu, AK EP937
EP880 & EP965
Valente, I EP997
GS2.6 & OC12.2
Tuzcu, S EP937
Urquhart, T MTNE1
Valente, V EP129, EP1479
Trova˜ o, E EP841, EP899
Twito, O EP1374
Ursu, HI EP1364
& EP1483
& EP975
& EP1391
Urun, V EP684
Valera, MAE EP432
Trummer, C EP1188
Twomey, P EP430
Uruno, T EP1385
& EP433
Trybek, T EP1274
Tymms, DJ EP1210
Urwyler, S OC11.3
Valero, MA EP1218
Tsagarakis, S D1.2
Tzamali, X EP202
Urwyler, SA EP687
Valickas, R EP1437
& EP1047
Tzanavari, A EP366
Uscebrka, G GP202
Valido, F EP1459
Tsakova, A GP82
Tzanela, M EP1047
Usta, R EP565
Valkusz, Z EP1388,
Tsamadias, V GP32
Tzelepi, K EP1471
Ustun, F EP118, EP1198,
EP1410 & EP742
Tsapaeva, N EP663
Tziomalos, K GP140
EP1396, EP1397,
Vallespin, E EP904
Tsatsoulis, A EP1172
Tzoulis, P EP386
EP1399, EP1400,
Valta, H OC10.5
Tschop, MH OC2.3
Tzvetkov, M EP353
EP1401, EP1402,
Valtere, A EP931
Tschiedel, B GP93 & OC2.1
EP1403, EP201,
Valtink, M EP806
Tschop, M GH1
Ušćebrka, G EP212
EP271, EP848
Valverde, M EP435
Tschopp, O EP104
Uc, ZA EP962
& EP981
van Beek, A EP402
Tselebis, A EP793
Ucan, B EP1368, EP327
Utku, OG EP684
& EP672
Tselovalnikova, T EP1057
& EP999
Utlu, M EP1113
van de Meerhaeghe, T
Tseng, C-H EP404 & GP97
Ucar, MG EP1101
Uygun, B EP322
GP41
Tseng, F-Y EP1319
Ucci, S EP825 & GP221
& GP161
Van de Velde, F EP1191
Tsentidis, C EP1008, EP38
Ucgun, AB EP1380
Uygur, M EP47
van den Broek, M EP402
& GP99
Ucgun, S EP1294
Uygur, MM EP665, EP676
Van den Bruel, A EP1393
Tsiberkin, A EP978
Uchigata, Y EP1014
& EP851
van der Horst-Schrivers,
Tsikarishvili, N EP315
Uchman, D EP908
Uysal, S EP282
ANA EP155
Tsirona, S EP1098
Ueland, G
˚ EP49
Uzieblo-Zyczkowska, B
van der Klauw, M EP672
Tsirou, E EP68
Ugalde, A EP1217
OC12.4
& OC9.1
Tsitlakidis, D EP528
Ugarte, E EP1040 & EP112
van der Lely, AJ GP116
Tsoli, M EP67
Ugolini, C EP1414
Vázquez-Borrego, M-C
& GP174
Tsoriev, T EP881
Ugur, K EP249
EP819
Van Doninck, N EP393
Tsourouflis, G EP1253
Uitterlinden, A EP744
Vázquez-Borrego, MC
van Eck, JP GP116
& GP80
Ujházi, S EP1127
EP929
van Etten, B EP155
Tsoy, U EP200 & EP978
Ulianova, I EP521
Vaarasmaki, M EP1285
Van Gaal, L OC3.5
Tuchiyama, Y EP840
Ulkar, SE EP1144
Vcˇelák, J EP1143
van Herwaarden, T GP10
Tudorache, S EP1364
Ulyana, T EP989
Vítku˚, J EP1143 & EP14
Van Koetsveld, P EP933
Tukiendorf, A EP349
Unal, B EP330
Vanˇuga, A EP1086
van Kralingen, J GP58
Tulpakov, A EP913
Unal, M EP56
& GP38
Van Meter, QL GP65
& EP914
Unay, B EP673
Vanˇuga, P EP1086
van Niel, J EP635
Tuna, MM EP1453 & EP56
Undeutsch, H OC4.2
& GP38
Van Nieuwenhove, Y
Tuncez, OE EP362
Ungureanu, M-C EP1209,
Vaca, CS EP459 & EP8
EP1191
Tungalagsuvd, A EP1156
EP961 & GP34
Vagnerova, K EP1082
Van Ooswaard, M N3.3
Tuomi, T GP76
Unlu, A EP1167, EP419,
Vainikonyte-Kristapone, J
van Pelt, A S10.2
Tupea, C EP1063
EP421 & GP96
EP1437
van Vliet-Ostaptchouk, J
Tupikowska-Marzec, M
Unluhizarci, K EP968
Vaira, V GP130
EP672 & OC9.1
GP165
Unluhizarci, K E1129
Vajauskas, D GP31
van Waateringe, R EP672
Tupikowski, K EP187
Unsal, İO EP327 & EP999
Val-Zaballos, FD EP11
& OC9.1
Turatti, W EP7
Unsal, I EP1097 & EP1368
Valadares, L EP84
vanderLely, AJ GP192
Turek-Jabrocka, R EP1026
Unsal, YA EP186
Valadas, C EP660
Vandewalle, S EP393
& OC9.3
Unuane, D GP41
Valassi, E GP36
Vanka, R EP89
Turkon, H EP1099
Unverdi, H EP317
Valdivia, C OC5.1
Vanselow, JT EP932, GP1
Turner, H EP1145,
& GP5
Urbánková, H EP1086
Vale, C GP217
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Vantyghem, M-C EP1369,
Velickiene, D EP448
Victor, M EP1298
Vita, R EP1118 & EP1171
GP120 & OC5.3
& EP449
Vidal, J OC12.3 & S15.3
Vitale, M EP1064
Vantyghem, MC EP1439
Velija-Asimi, Z EP976
Vidal-Ríos, P EP1284
Vitali, E OC7.4
Vanya, M EP731
Velikova, T GP82
& GP210
Vitellius, G GP7
Vaquero-Barrios, J-M
Velkeniers, B GP41
Vidal-Ríos, S EP1284
Vitkauskiene, A EP173
EP776
Velloso, RN EP389
& GP210
Vitorino, H EP1323
Varani, M EP1123 & GP51
Venaki, E EP793
Vidmar, G GP39 & OC10.4
& EP32
Varela, A EP719
Vendramini, MF EP380
Vidovic, J EP491
Vitti, P EP1247, EP1414,
Vargas, ML EP1481
Vendrell, CS EP1178
Vieira, A EP1362 & EP267
EP238, EP397 & S19.1
Varo, N EP227
Venegas-Moreno, E EP929
Vieira, J EP1356
Vitulli, F EP927
Varthakavi, P EP844
Venkataraman, S EP555
Viengchareun, S GP7
Vlachopapadopoulou, E
Vasar, E EP607
Venneri, MA EP537
& OC5.5
EP62
Vaschenko, E EP536
Vensa˜ o, L EP79
Vignali, E EP238, EP274
Vlad, M EP1068, EP1364,
& EP556
Ventosa, M EP603
& EP288
EP153, EP306 & GP53
Vasconcelos, C EP1088,
Ventura, M EP1009,
Vignera, SL EP1163
Vladimir, M EP1248
EP1177, EP1207,
EP1195, EP1475,
& GP127
Vladislav, C EP989
EP1311, EP1452,
EP203, EP392, EP394,
Vignozzi, L EP370, EP377
Vladoiu, S EP1094,
EP1486, EP414,
EP44, EP444, EP445,
& GP147
EP1176 & EP1180
EP887 & EP951
EP45, EP61 & GP35
Vigouroux, C OC5.3
Vlaski, J EP1089
Vasile, M EP1364
Veríssimo, D EP1359
Vijayan Melapatte, A
Vlychou, M EP483
Vasileiadou, S EP1473
& EP139
EP1052
& EP559
Vasileiou, A EP483
Vera, L EP1415 & EP1476
Vikentieva, E GP82
Vogiatzi, E EP1460,
Vasileiou, E EP1008
Vera-Llonch, M EP1263
Vikulova, O EP568
EP202, EP221
Vasileiou, V EP1411
Verdelli, C GP130
Vilaça, J EP1291
& EP276
Vasilescu, F EP16
Verdes-Sanz, G EP461
& EP1292
Vogt, B EP820 & OC13.5
Vasiliev, E EP1025
Verdi, H EP1431
Vila, G EP1010
Vogt, D EP889
Vasilieva, N EP351
Veresiu, I EP560
Vila, L EP1332
Vohra, G EP1333
Vasiliu, I EP809
Veresiu, IA EP398, EP399
Vilar, C EP841, EP899
Voicu, G EP1221
Vasiljevic, A EP954
& EP400
& EP975
Voicu, O EP1007
Vasilkova, V EP511
Vergara, A EP938
Vilar, L EP841, EP899
Vojnovic-Milutinovic, D
Vasilyev, E EP345
Verkauskiene, R EP1102,
& EP975
EP1114, GP139
& EP346
EP434, EP542
Vilardell, C EP165
& GP140
Vasovic, O GP197
& EP839
Vilas, AP GP237
Vokes, TJ EP291 & GP47
Vasoya, S EP1117
Verma, N EP741
Vilaverde, J EP496
Volante, M EP161
Vasques, M EP519
Veronesi, G EP688
& EP921
Volk, J EP814
& EP599
& EP691
Villabona, C EP150, EP88,
Volke, V EP607
Vass, A EP731
Verrijken, A OC3.5
EP891, EP94 & GP241
Volkova, N EP218, EP415,
Vassilatou, E EP1139
Verroken, C EP1019
Villanova, T GP151
EP539, EP73 & EP760
Vassiliadi, D-A EP1139
Verrua, E EP1043
Villanueva-Herraiz, SI
Volle, D S11.1
& GP122
Versari, A GP231
EP769
Volovat, C EP792 & EP809
Vasyliene, G GP31
Vershinina, M EP1036
Villas, L EP1284 & GP210
Volzke, H S21.3
Vaz de Castro, R EP1055
Vezbaviciene, V EP550
Villette, B EP966
Vorobiev, S EP695
& EP791
Vezzoli, V OC8.2
Viloria, MdM EP1331
Vorobyev, S EP1164
Vecchiola, A OC5.1
Vin˜ a, V EP3, EP9 & EP952
Vinagre, J OC14.3
Voronkova, I EP126,
Veeger, N EP402
Vin˜ uela-González, L GP71
Vinaixa, M EP435
EP318, EP323 & EP345
Vega, MM EP406, EP407,
Viana, GS EP716
Vincentis, SD EP1166
Vorotnikova, S EP1034
EP627 & EP998
Viana, J EP1330
& GP51
& EP1036
Veiga, L EP451
Vicari, ES EP1163
Vinha, E EP1077, EP1078
Vosjan-Noeverman, M
Veiga, R GP242
Vicaut, E OC11.2
& EP140
EP1045
Vela, ET GP89
Vicchio, TM EP1443
Vinogradova, A EP936
Vozdvizhenskiy, M EP1286
Velarde, AP EP878
& GP208
Vinson, G GP18
Vrkljan, M EP172, EP43,
Velasco, M EP984
Vicennati, V EP1381,
Vintila, M EP206 & EP352
EP463 & EP549
Velden, JAd GS1.3
EP669 & EP671
Violante, A EP152
Vryonidou, A EP1139,
Veldhuis, J GP131
Vicente, A EP866 & EP973
Virgolini, I EP1445
EP239 & EP423
Velez, A EP175
Vicente, N EP392
Virili, C EP825
Vujović, M EP1245
Velez, MA EP1030
Vicentini, L EP1408,
Visalli, G GP175
& EP356
Velicescu, C EP213, EP252
EP1432 & GP130
Visockiene, Z EP156,
Vujovic, A EP470
& EP260
Vicic, I EP43
EP171, GP211 & GP31
Vujovic, M EP677
Endocrine Abstracts (2017) Vol 49
19th European Congress of Endocrinology 2017
Vujovic, S EP127 & EP42
Werner, U GP105
Yahi, A EP1182
Yildiz, OB EP378
Vukovic, B EP1024,
Wernig, F EP123
Yakout, S EP263
Yildiz, SO EP821
EP116, EP245
Wessling, A EP1055,
Yakut, F EP937
Yildiz, SS EP1228
& EP709
EP1204, EP1255,
Yalcin, MM EP1144
Yilmaz Bulbul, B EP1396
Vuksanovic, M EP369
EP1340, EP243,
Yalcin, S EP1280, EP529
& EP1397
Vulpoi, C EP1073,
EP300, EP791, EP897
& EP683
Yilmaz, BA EP1144
EP1076, EP1209,
& EP898
Yalcin, Y EP1431
Yilmaz, E EP110
EP1345, EP1360,
Westen, DV GP182
Yalin, GY EP1038,
Yilmaz, FM EP1347
EP188, EP213, EP252,
Westgate, C EP798
EP1327 & OC12.1
Yilmaz, N EP1061
EP260, EP792, EP809
Wiersinga, W S6.2
Yamagami, K EP27
Ylli, A EP1470, EP495,
& EP961
Wik, H GP117
Yaman, S EP856
EP546, EP571
Vurnek, I EP172
Wikiera, B EP775
Yamanaka, Y EP643
& EP765
Wikstrom, J GP194
Yamina, A EP120
Ylli, D EP1370, EP1470,
Warn, M GP117
Wild, D GP185
& EP138
EP2, EP495, EP546
Wagner, C EP1352
Wild, V GP5 & OC1.1
Yanes, EP435
& EP765
Wahlberg, J GP9
Wilieman, M EP723
Yang, L OC7.3
Yokota, T EP273
Wajda, A EP1148
Wilkinson, IR GP61
Yang, M EP801
Yoldi, A EP869
& EP371
William, A EP1213
Yang, P-S OC14.2
Yologlu, S EP703
Wajdi, S EP77
Williams, T EP37
Yang, S OC1.5
Yoneda, T OC3.1
Walch, A EP52, GP22
Williamson, C MTE3 & OC3.2
Yang, TY GP162
Yong Kim, T OC14.5
& OC1.1
Wilusz, M EP1026
Yang, W-S EP1319
Yoo, HJ GP91
Walczyk, A EP1274,
Winhofer, Y EP638
Yano, K EP1156
Yoo, WS GP207
EP1382 & EP1409
Winston, LR OC3.2
Yarets, Y EP556
Yoon, Bk EP729
Waldmann, J OC7.2
Winzeler, B EP889, EP918
Yarman, S EP1038
Yoon, JH EP987
Walenkamp, AME EP155
& EP942
& OC12.1
Yoon, K EP605
Walicka, M EP577
Witek, P OC12.4
Yarom, N EP199
Yorulmaz, G EP1033,
Waligórska-Stachura, J
Witte, K S27.1
Yasuda, A EP4
EP110, EP12, EP1375,
EP1252
Wołkow, P OC9.3
Yatabe, J EP1014
EP1444, EP244,
Waligorska-Stachura, J
Woischke, C EP52
Yatabe, M EP1014
EP264, EP418, EP427,
EP1275
Wojtyna, E EP1441
Yavuz, DG EP47, EP665,
EP69 & EP90
Walker, BR EP802
Wojtysiak-Duma, B EP547
EP676, EP851
Yoshida, H EP1242
Wall, J EP1265
Wolczynski, S EP1104,
& GP187
Yoshimoto, R EP273
Walsh, M OC3.3
GP118 & OC7.1
Yavuz, ST EP673
Yosra, H EP1229 & EP646
Wang, H-C EP1093
Wolf, P EP638
Yaylalı, GF EP1405,
You, J GP54
Wang, L EP916
Wolffenbuttel, B EP672
EP656, EP971
You, JH EP452, EP531
Wargny, A EP1126
& OC9.1
& EP972
& GP87
Warren, ML GP47
Wong, E EP1339
Yazicioglu, O EP1326
Youcef, HS EP1315
Wasoori, SC EP526
Woods, C GP70
Yazidi, M EP1193,
Young Kim, E OC14.5
Wass, J GP180 & P1
Wook Kim, S GP219
EP1201, EP1208,
Young Park, S GP219
Watson, M EP682
Wouters, H OC9.1
EP1212, EP1322,
Young, J EP1015, GP12
Watts, NB GP47
Wright, N GP66
EP1324, EP1328,
& GP19
Wawak, E EP1282
Wu, F-J EP1103
EP207, EP340
Young, P EP211
Wawrusiewicz-Kurylonek,
Wu, J EP744
& EP570
Yu, SH EP959
N EP31
Wu, S EP426
Yedinak, C N2.1
Yuce, ZT EP968
Webb, S EP1010 & GP192
Wygoda, Z EP1420
Yeh, S GP129
Yucel, S EP620
Webb, SM GP36
Yemelyantsava, T EP670
Yudina, A EP1057
Webber, L GP131
Xanthakou, E EP136
Yenigun, M EP86
Yurekli, BS EP1194
Weber, B EP1030
Xiao, J EP754
Yeoh, P EP985
& EP1379
Webster, R EP1051
Xifra, G GP24
Yerdesova, K EP532
Yurkovets, V EP737
Weigand, I EP932, GP1
Xilola, G EP1124
Yesildal, F EP1165
Yusupovna, Z EP15
& GP5
Xu, C GP153
Yeudachkova, T EP556
Yuzbashian, E EP642,
Weigel, N OC7.5
Xydiari, K EP1202
Yi, N EP934
EP662 & OC5.2
Weinert, LS EP457
& EP859
Yigitbasi, A EP1403
Weinstein, LS OC4.2
Yildirim, A EP937
Zabalegui, A EP112,
Wejman-Matela, A EP388
Yadagiri, M EP409
Yildirim, AE EP1035
EP1217 & EP128
Wen, J GP171
Yaghmaei, F GP164
Yildiz, F EP429
Zabeen, B EP428
Wen, L GP171
Yagiz, B EP12
Yildiz, K EP478, EP566
Zabransky, M EP912
Wengrowicz, S EP1332
Yahagi, N GP166
& EP710
Zabuliene, L EP1276
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19th European Congress of Endocrinology 2017
Zadeh-Vakili, A EP1183,
Zapanti, E GP230 & GP80
Zhang, A OC1.5
Zivkovic, M EP285
EP1406, EP642,
Zapendowska-Dudek, A
Zhang, F-P EP364, EP692
Zivkovic, TB EP369
EP662 & OC5.2
EP283
& OC13.3
Zmailik, M EP511
Zafón, C GP235
Zarate, VO EP948
Zhang, M EP24, EP801
Zmau, G EP1345
Zafeiriou, G EP1473
Zarkesh, M EP1406,
& OC7.5
Zona, S GP146
Zaggia, B EP26
EP642, EP662
Zhang, P EP22, GP11
Zoric, S EP694
Zagrebaeva, O EP351
& OC5.2
& GP20
Zosin, I EP1068 & GP53
& EP670
Zarkovic, M EP111
Zhang, S EP1
Zoubir, S EP138
Zagrodna, A EP1160
& EP1261
Zhang, Y EP1096
Zubrecki, A EP731
Zaharenko, L OC6.3
Zatelli, MC EP26
Zhudro, A EP823
Zucchi, R GP172 & GP223
Zaharia, V EP213, EP260,
Zatonska, K GP165
Zibarev, A EP415
Zuhur, SS EP265
EP809 & GP34
Zazerskaya, I EP485
Zielinski, G OC12.4
Zukas, K EP542
Zaharieva, E GP82
Zdrojowy-Welna, A GP165
Ziemnicka, K EP1074,
Zukowski, L EP31
Zaheer Shah, N EP190
Zdzierak, B EP1148
EP1433, EP1450
Zulj, B EP23
Zaher, FZ EP1337
& EP371
& EP1474
Zunzunegui, NE EP1023
& EP711
Zelissen, P EP22, GP11
Zilaitiene, B EP1102,
Zuraeva, Z EP568
Zaidi, R EP1309
& GP20
EP637, EP839
Zurauskas, E EP1412
Zajickova, K EP326
Zelnyte, G EP990
& GP244
Zvirbliene, A GP244
Zak, P EP837
Zennaro, MC GP2 & GP15
Zilbermint, M EP13
Zwolak, A EP144
Zake, T GP209
Zeqja, A EP765
Zilio, M EP1042
& EP338
Zakia, T EP279
Zerbi, A OC7.4
& EP1056
Zybek-Kocik, A EP1252
Zaletel, K EP1445
Zerbini, MC GP6
Zitzmann, M EP1164
& GP220
Zalinkevicius, R EP434
Zerkiebel, N EP1087
Ziukaite, R EP171
Zygmunt, A EP1325
& EP550
Zeydabadinejad, S EP1183
& GP211
Zambelis, T EP417, EP442
Zgliczynski, W EP469
Ziv, A EP735
& EP509
& GP173
Zivanovic, J EP779
Zambo, K EP1410
Zha, B GP218
Zˇivanović, J EP212
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